Clearing extracellular alpha-synuclein from cerebrospinal fluid: A new therapeutic strategy in parkinson’s disease

This concept article aims to show the rationale of targeting extracellular α-Synuclein (α-Syn) from cerebrospinal fluid (CSF) as a new strategy to remove this protein from the brain in Parkinson’s disease (PD). Misfolding and intracellular aggregation of α-synuclein into Lewy bodies are thought to be crucial in the pathogenesis of PD. Recent research has shown that small amounts of monomeric and oligomeric α-synuclein are released from neuronal cells by exocytosis and that this extracellular alpha-synuclein contributes to neurodegeneration, progressive spreading of alpha-synuclein pathology, and neuroinflammation. In PD, extracellular oligomeric-α-synuclein moves in constant equilibrium between the interstitial fluid (ISF) and the CSF. Thus, we expect that continuous depletion of oligomeric-α-synuclein in the CSF will produce a steady clearance of the protein in the ISF, preventing transmission and deposition in the brain

Análisis del plano sagital en las escoliosis idiopáticas tratadas con instrumentación Cotrel-Dubousset

Se analiza la evolución del plano sagital en 50 enfermos con escoliosis idiopática intervenidos mediante artrodesis posterior con instrumentación de Cotrel-Dubousset con un seguimiento medio de 72 meses. Se recogieron los valores evolutivos de cifosis torácica medida entre T5 y T12 y de lordosis lumbar medida entre Ll y L5. Las curvas escolióticas fueron clasificadas según King et al. Los resultados obtenidos mostraron que no existía una variación global significativa de la cifosis torácica tras la cirugía. Sólo en aquellos enfermos que previamente existía una hipocifosis torácica existía una mejoría estadísticamente significativa de la misma con la intervención. Se evidenció una clara tendencia al incremento de la cifosis torácica con el tiempo. La lordosis lumbar se mantuvo, en la mayoría de los casos, dentro de límites fisiológicos. La instrumentación de Cotrel-Dubousset ofrece ventajas evidentes respecto a instrumentaciones previas en lo que respecta a la obtención de una curva más fisiológica en el plano sagital. Permite corregir la hipocifosis torácica severa y mantener la lordosis lumbar dentro de límites normales, incluso en instrumentaciones por debajo de L3.Sagittal plane analysis of 50 patients with idiopathic scoliosis treated with Cotrel- Dubousset instrumentation was performed. Mean follow-up was 72 months. The values of thoracic kyphosis from T5 to T12 and lumbar lordosis from L1 to L5 were retrospectively reviewed. Scoliotic curves were classified according to King et al. The results showed that there was not any significant change in thoracic kyphosis after surgery. Only those patients with preoperative thoracic hypokyphosis achieved a significant realignment. There was an obvious increase of thoracic kyphosis with time. Lumbar lordosis was maintained within normal limits in the mayority of patients. Cotrel-Dubousset instrumentation achieves better sagittal alignment than previous systems. It corrects thoracic hypokyphosis and preserves lumbar lordosis, even when the instrumentation is carried out lower than L3

GLUT1 protects prostate cancer cells from glucose deprivation-induced oxidative stress

Glucose, chief metabolic support for cancer cell survival and growth, is mainly imported into cells by facilitated glucose transporters (GLUTs). The increase in glucose uptake along with tumor progression is due to an increment of facilitative glucose transporters as GLUT1. GLUT1 prevents cell death of cancer cells caused by growth factors deprivation, but there is scarce information about its role on the damage caused by glucose deprivation, which usually occurs within the core of a growing tumor. In prostate cancer (PCa), GLUT1 is found in the most aggressive tumors, and it is regulated by androgens. To study the response of androgen-sensitive and insensitive PCa cells to glucose deprivation and the role of GLUT1 on survival mechanisms, androgen-sensitive LNCaP and castration-resistant LNCaP-R cells were employed. Results demonstrated that glucose deprivation induced a necrotic type of cell death which is prevented by antioxidants. Androgen-sensitive cells show a higher resistance to cell death triggered by glucose deprivation than castration-resistant cells. Glucose removal causes an increment of H2O2, an activation of androgen receptor (AR) and a stimulation of AMP-activated protein kinase activity. In addition, glucose removal increases GLUT1 production in androgen sensitive PCa cells. GLUT1 ectopic overexpression makes PCa cells more resistant to glucose deprivation and oxidative stress-induced cell death. Under glucose deprivation, GLUT1 overexpressing PCa cells sustains mitochondrial SOD2 activity, compromised after glucose removal, and significantly increases reduced glutathione (GSH). In conclusion, androgen-sensitive PCa cells are more resistant to glucose deprivation-induced cell death by a GLUT1 upregulation through an enhancement of reduced glutathione levels. Keywords: Glut1, Prostate cancer, Glucose deprivation, Androgen receptor, Glutathione, Oxidative stres

Inhomogeneity correction of magnetic resonance images by minimization of intensity overlapping

Proceeding of: IEEE 2003 International Conference on Image Processing (ICIP), Barcelona, Spain, 14-17 Sept. 2003This work presents a new algorithm (NIC; Non uniform Intensity Correclion) for the correction of intensity inhomogeneities in magnetic resonance images. The algorithm has been validated by means of realistic phantom images and a set of 24 real images. Evaluation using previously proposed phantom images for inhomogeneity correction algorithms allowed us to obtain results fully comparable to the previous literature on the topic. This new algorithm was also compared, using a real image dataset, to other widely used methods which are freely available in the Internet (N3, SPM'99 and SPM2). Standard quality criteria have been used for determining the goodness of the different methods. The new algorithm showed better results removing the intensity inhomogeneities and did not produce degradation when used on images free from this artifact

Research at the medical imaging laboratory, CIBERSAM CB07/09/0031

The Medical Imaging Laboratory is a research group within the Hospital General Universitario Gregorio Marañón. The main research line of the group is focused towards the development and exploitation of medical imaging techniques, including the development of new processing tools for image analysis in clinical and preclinical research. The group has a multi-disciplinary profile and a priority for translational research topics, derived from real problems faced by the clinical specialists. One of the main research areas is the development of technologies for molecular imaging, some of which have been transferred to the industry and are now among the top products of the market. These systems include high-resolution PET, CT and PET-CT. Over the last years the group has developed several software tools to enable quantification of multimodal brain images using morphometric and functional data. Some research applications of these hardware and software tools are illustrated in the paper“Ministerio de Sanidad y Consumo”, CDTEAM Programa CÉNIT, Ministerio de Industria. FIS PI052271 “Ministerio de Sanidad y Consumo”. CIBER Salud Mental (CIBERSAM) “Ministerio de Sanidad y Consumo” and Fundación Mutua MadrileñaPublicad

The Spatial Extent of (U)LIRGs in the mid-Infrared I: The Continuum Emission

We present an analysis of the extended mid-infrared (MIR) emission of the Great Observatories All-Sky LIRG Survey (GOALS) sample based on 5-15um low resolution spectra obtained with the IRS on Spitzer. We calculate the fraction of extended emission as a function of wavelength for the galaxies in the sample, FEE_lambda. We can identify 3 general types of FEE_lambda: one where it is constant, one where features due to emission lines and PAHs appear more extended than the continuum, and a third which is characteristic of sources with deep silicate absorption at 9.7um. More than 30% of the galaxies have a median FEE_lambda larger than 0.5 implying that at least half of their MIR emission is extended. Luminous Infrared Galaxies (LIRGs) display a wide range of FEE in their warm dust continuum (0<=FEE_13.2um<=0.85). The large values of FEE_13.2um that we find in many LIRGs suggest that their extended MIR continuum emission originates in scales up to 10kpc. The mean size of the LIRG cores at 13.2um is 2.6kpc. However, once the LIR of the systems reaches the threshold of ~10^11.8Lsun, all sources become clearly more compact, with FEE_13.2um<=0.2, and their cores are unresolved. Our estimated upper limit for the core size of ULIRGs is less than 1.5kpc. The analysis indicates that the compactness of systems with LIR>~10^11.25Lsun strongly increases in those classified as mergers in their final stage of interaction. The FEE_13.2um is also related to the contribution of an active galactic nucleus (AGN) to the MIR. Galaxies which are more AGN-dominated are less extended, independently of their LIR. We finally find that the extent of the MIR continuum emission is correlated with the far-IR IRAS log(f_60um/f_100um) color. This enables us to place a lower limit to the area in a galaxy from where the cold dust emission may originate, a prediction which can be tested soon with the Herschel Space Telescope.Comment: 18 pages, 8 figures, accepted for publication in Ap