Isolation of mineralizing Nestin+ Nkx6.1+ vascular muscular cells from the adult human spinal cord

Background: The adult central nervous system (CNS) contains different populations of immature cells that could possibly be used to repair brain and spinal cord lesions. The diversity and the properties of these cells in the human adult CNS remain to be fully explored. We previously isolated Nestin(+) Sox2(+) neural multipotential cells from the adult human spinal cord using the neurosphere method (i.e. non adherent conditions and defined medium). -- Results: Here we report the isolation and long term propagation of another population of Nestin(+) cells from this tissue using adherent culture conditions and serum. QPCR and immunofluorescence indicated that these cells had mesenchymal features as evidenced by the expression of Snai2 and Twist1 and lack of expression of neural markers such as Sox2, Olig2 or GFAP. Indeed, these cells expressed markers typical of smooth muscle vascular cells such as Calponin, Caldesmone and Acta2 (Smooth muscle actin). These cells could not differentiate into chondrocytes, adipocytes, neuronal and glial cells, however they readily mineralized when placed in osteogenic conditions. Further characterization allowed us to identify the Nkx6.1 transcription factor as a marker for these cells. Nkx6.1 was expressed in vivo by CNS vascular muscular cells located in the parenchyma and the meninges. -- Conclusion: Smooth muscle cells expressing Nestin and Nkx6.1 is the main cell population derived from culturing human spinal cord cells in adherent conditions with serum. Mineralization of these cells in vitro could represent a valuable model for studying calcifications of CNS vessels which are observed in pathological situations or as part of the normal aging. In addition, long term propagation of these cells will allow the study of their interaction with other CNS cells and their implication in scar formation during spinal cord injury.

Úlceras en Extremidades Inferiores de Etiología Vascular y Pie Diabético

En el siguiente trabajo se proporcionará una clasificación detallada de las úlceras vasculares y pie diabético, así como de su fisiopatología y epidemiología, posibles complicaciones, métodos diagnósticos, pautas de prevención y tratamiento, y por último, se añade un apartado, con la finalidad de conseguir la comprensión por parte del lector de la repercusión de las úlceras en la calidad de vida del paciente.

Vascular endothelial growth factor regulates melanoma cell adhesion and growth in the bone marrow microenvironment via tumor cyclooxygenase-2

Background: Human melanoma frequently colonizes bone marrow (BM) since its earliest stage of systemic dissemination, prior to clinical metastasis occurrence. However, how melanoma cell adhesion and proliferation mechanisms are regulated within bone marrow stromal cell (BMSC) microenvironment remain unclear. Consistent with the prometastatic role of inflammatory and angiogenic factors, several studies have reported elevated levels of cyclooxygenase-2 (COX-2) in melanoma although its pathogenic role in bone marrow melanoma metastasis is unknown. Methods: Herein we analyzed the effect of cyclooxygenase-2 (COX-2) inhibitor celecoxib in a model of generalized BM dissemination of left cardiac ventricle-injected B16 melanoma (B16M) cells into healthy and bacterial endotoxin lipopolysaccharide (LPS)-pretreated mice to induce inflammation. In addition, B16M and human A375 melanoma (A375M) cells were exposed to conditioned media from basal and LPS-treated primary cultured murine and human BMSCs, and the contribution of COX-2 to the adhesion and proliferation of melanoma cells was also studied. Results: Mice given one single intravenous injection of LPS 6 hour prior to cancer cells significantly increased B16M metastasis in BM compared to untreated mice; however, administration of oral celecoxib reduced BM metastasis incidence and volume in healthy mice, and almost completely abrogated LPS-dependent melanoma metastases. In vitro, untreated and LPS-treated murine and human BMSC-conditioned medium (CM) increased VCAM-1-dependent BMSC adherence and proliferation of B16M and A375M cells, respectively, as compared to basal medium-treated melanoma cells. Addition of celecoxib to both B16M and A375M cells abolished adhesion and proliferation increments induced by BMSC-CM. TNF alpha and VEGF secretion increased in the supernatant of LPS-treated BMSCs; however, anti-VEGF neutralizing antibodies added to B16M and A375M cells prior to LPS-treated BMSC-CM resulted in a complete abrogation of both adhesion-and proliferation-stimulating effect of BMSC on melanoma cells. Conversely, recombinant VEGF increased adherence to BMSC and proliferation of both B16M and A375M cells, compared to basal medium-treated cells, while addition of celecoxib neutralized VEGF effects on melanoma. Recombinant TNFa induced B16M production of VEGF via COX-2-dependent mechanism. Moreover, exogenous PGE2 also increased B16M cell adhesion to immobilized recombinant VCAM-1. Conclusions: We demonstrate the contribution of VEGF-induced tumor COX-2 to the regulation of adhesion-and proliferation-stimulating effects of TNFa, from endotoxin-activated bone marrow stromal cells, on VLA-4-expressing

Microglia in the cerebral and cerebellar cortices in individuals with autism

In this thesis, we explore the density of the microglia in the cerebral and cerebellar cortices of individuals with autism to investigate the hypothesis that neuroinflammation is involved in autism. We describe in our findings an increase in microglial density in two disparate cortical regions, frontal insular cortex and visual cortex, in individuals with autism (Tetreault et al., 2012). Our results imply that there is a global increase in the microglial density and neuroinflammation in the cerebral cortex of individuals with autism.

We expanded our cerebellar study to additional neurodevelopmental disorders that exhibit similar behaviors to autism spectrum disorder and have known cerebellar pathology. We subsequently found a more than threefold increase in the microglial density specific to the molecular layer of the cerebellum, which is the region of the Purkinje and parallel fiber synapses, in individuals with autism and Rett syndrome. Moreover, we report that not only is there an increase in microglia density in the molecular layer, the microglial cell bodies are significantly larger in perimeter and area in individuals with autism spectrum disorder and Rett syndrome compared to controls that implies that the microglia are activated. Additionally, an individual with Angelman syndrome and the sibling of an individual with autism have microglial densities similar to the individuals with autism and Rett syndrome. By contrast, an individual with Joubert syndrome, which is a developmental hypoplasia of the cerebellar vermis, had a normal density of microglia, indicating the specific pathology in the cerebellum does not necessarily result in increased microglial densities. We found a significant decrease in Purkinje cells specific to the cerebellar vermis in individuals with autism.

These findings indicate the importance for investigation of the Purkinje synapses in autism and that the relationship between the microglia and the synapses is of great utility in understanding the pathology in autism. Together, these data provide further evidence for the neuroinflammation hypothesis in autism and a basis for future investigation of neuroinflammation in autism. In particular, investigating the function of microglia in modifying synaptic connectivity in the cerebellum may provide key insights into developing therapeutics in autism spectrum disorder.

Estudio de caso: intervención en el área de educación física para avanzar en la inclusión de un alumno con parálisis cerebral

En este trabajo se propone mediante dos sesiones de Educación Física, la inclusión educativa de un alumno con parálisis cerebral mediante actividades y juegos. Previa a esta programación, se destaca la relevancia que tiene la inclusión a nivel social y el eco que está logrando en la comunidad educativa. Centrándonos en su análisis conceptual y haciendo referencia al alumnado con necesidades educativas especiales, se numeran la infinidad de beneficios existentes para todo el grupo. Analizados sus beneficios y teniendo en cuenta las adaptaciones necesarias, se presentan las actividades mencionadas con anterioridad y se resaltan las conclusiones extraídas.

Simulation of shock-induced bubble collapse with application to vascular injury in shockwave lithotripsy

Shockwave lithotripsy is a noninvasive medical procedure wherein shockwaves are repeatedly focused at the location of kidney stones in order to pulverize them. Stone comminution is thought to be the product of two mechanisms: the propagation of stress waves within the stone and cavitation erosion. However, the latter mechanism has also been implicated in vascular injury. In the present work, shock-induced bubble collapse is studied in order to understand the role that it might play in inducing vascular injury. A high-order accurate, shock- and interface-capturing numerical scheme is developed to simulate the three-dimensional collapse of the bubble in both the free-field and inside a vessel phantom. The primary contributions of the numerical study are the characterization of the shock-bubble and shock-bubble-vessel interactions across a large parameter space that includes clinical shockwave lithotripsy pressure amplitudes, problem geometry and tissue viscoelasticity, and the subsequent correlation of these interactions to vascular injury. Specifically, measurements of the vessel wall pressures and displacements, as well as the finite strains in the fluid surrounding the bubble, are utilized with available experiments in tissue to evaluate damage potential. Estimates are made of the smallest injurious bubbles in the microvasculature during both the collapse and jetting phases of the bubble's life cycle. The present results suggest that bubbles larger than 1 μm in diameter could rupture blood vessels under clinical SWL conditions.

Alteración de lípidos en la enfermedad de Alzheimer. Estudio en tejido cerebral humano postmortem mediante MALDI-IMS.

En el presente estudio, se analizó la distribución lipídica de 3 áreas de hipocampo (CA1, subiculum y giro dentado) en muestras cerebrales de pacientes con enfermedad de Alzheimer y se comparó con muestras de sujetos sin patología neurológica. Las muestras de tejido de cerebro humano postmortem de la región de hipocampo, fueron procesadas mediante la técnica MALDI-IMS.

Efficacy and safety of autologous platelet rich plasma for the treatment of vascular ulcers in primary care: Phase III study

Background: Vascular ulcers are commonly seen in daily practice at all levels of care and have great impact at personal, professional and social levels with a high cost in terms of human and material resources. Given that the application of autologous platelet rich plasma has been shown to decrease healing times in various different studies in the hospital setting, we considered that it would be interesting to assess the efficacy and feasibility of this treatment in primary care. The objectives of this study are to assess the potential efficacy and safety of autologous platelet rich plasma for the treatment of venous ulcers compared to the conventional treatment (moist wound care) in primary care patients with chronic venous insufficiency (C, clinical class, E, aetiology, A, anatomy and P, pathophysiology classification C6). Design: We will conduct a phase III, open-label, parallel-group, multicentre, randomized study. The subjects will be 150 patients aged between 40 and 100 years of age with an at least 2-month history of a vascular venous ulcer assigned to ten primary care centres. For the treatment with autologous platelet rich plasma, all the following tasks will be performed in the primary care setting: blood collection, centrifugation, separation of platelet rich plasma, activation of coagulation adding calcium chloride and application of the PRP topically after gelification. The control group will receive standard moist wound care. The outcome variables to be measured at baseline, and at weeks 5 and 9 later include: reduction in the ulcer area, Chronic Venous Insufficiency Quality of Life Questionnaire score, and percentage of patients who require wound care only once a week. Discussion: The results of this study will be useful to improve the protocol for using platelet rich plasma in chronic vascular ulcers and to favour wider use of this treatment in primary care.

Efeito agudo dos exercícios resistidos sobre a reatividade vascular e adipocitocinas de mulheres com sobrepeso e obesidade

Introdução O exercício resistido (ER) agudo parece resultar em importantes efeitos sobre a liberação de substâncias vasoativas e sobre o controle endotélio-dependente do tônus vascular. Objetivos O objetivo do presente estudo foi avaliar os efeitos agudos de um ER isolado sobre a pressão arterial (PA), frequência cardíaca (FC), fluxo sanguíneo do antebraço (FSA), condutância vascular (CV), respostas endotelial e inflamatória de mulheres jovens com sobrepeso/obesidade (Sp/Ob). Materiais e Métodos As voluntárias foram separadas em grupos: controle (n = 16) e Sp/Ob (n = 16). Ambos os grupos realizaram cinco séries de 10 repetições com 70% de uma repetição máxima (1-RM) no exercício de flexão unilateral do cotovelo. A PA, FC e o FSA (medido por pletismografia por oclusão venosa), foram avaliados em repouso e durante uma hora após o ER em ambos os grupos. Adipocitocinas e endotelina-1 (ET-1) foram avaliadas em repouso nos dois grupos e após o ER apenas no grupo Sp/Ob. Resultados O grupo Sp/Ob apresentou massa corporal e IMC significativamente maiores que o controle (p<0,05). Surpreendentemente, o grupo Sp/Ob apresentou relação cintura-quadril significativamente menor (p<0,05). As diferenças entre grupos nas PAs diastólica e média observadas antes do ER (repouso) foram também observadas imediatamente e 20 minutos após a sessão de ER (p<0,05). Ambos os grupos apresentaram reduções significativas na PA diastólica imediatamente após a sessão de ER (p<0,01). A PA média apresentou redução significativa imediatamente após a sessão de ER apenas no grupo controle (p<0,05). O grupo Sp/Ob apresentou valores de FSA significativamente maiores que o controle em repouso (p<0,05), em 20 (p<0,01) e em 40 (p<0,01) minutos após o ER. A CV não apresentou diferença em repouso, porém em 20 e 40 minutos após o ER, o grupo Sp/Ob apresentou valores significativamente maiores (p<0,01). Em repouso e imediatamente após a sessão de ER, não foram observadas diferenças entre o grupo controle e o grupo Sp/Ob na vasodilatação endotélio-dependente. Deve-se ressaltar que em 30 minutos após a realização do ER, o grupo Sp/Ob apresentou maior vasodilatação endotélio-dependente que o controle (p<0,05). Surpreendentemente, a vasodilatação endotélio-independente em repouso era menor no grupo controle quando comparado ao grupo Sp/Ob (p<0,05). Entretanto, não foi observada diferença significativa entre os grupos 50 minutos após a sessão de ER. Como esperado, o grupo Sp/Ob apresentou valores significativamente menores de adiponectina (p<0,01) e significativamente maiores de IL-6 e leptina que o grupo controle (p<0,001). Foram observadas reduções significativas nos valores de IL-6 (p<0,05) e leptina (p<0,01), enquanto a ET-1 (p<0,05) apresentou aumento significativo. Conclusões Em conclusão, a realização do ER resultou em melhora aguda do FSA, da CV e da vasodilatação endotélio-dependente concomitantemente com mudanças no perfil inflamatório e ET-1 de mulheres saudáveis com Sp/Ob.

Cerebral hemodynamics during graded Valsalva maneuvers

The Valsalva maneuver (VM) produces large and abrupt changes in mean arterial pressure (MAP) that challenge cerebral blood flow and oxygenation. We examined the effect of VM intensity on middle cerebral artery blood velocity (MCAv) and cortical oxygenation responses during (phases I-III) and following (phase IV) a VM. Healthy participants (n = 20 mean +/- SD: 27 +/- 7 years) completed 30 and 90% of their maximal VM mouth pressure for 10 s (order randomized) whilst standing. Beat-to-beat MCAv, cerebral oxygenation (NIRS) and MAP across the different phases of the VM are reported as the difference from standing baseline. There were significant interaction (phase * intensity) effects for MCAv, total oxygenation index (TOI) and MAP (all P < 0.01). MCAv decreased during phases II and III (P < 0.01), with the greatest decrease during phase III (-5 +/- 8 and -19 +/- 15 cm.s(-1) for 30 and 90% VM, respectively). This pattern was also evident in TOI (phase III: -1 +/- 1 and -5 +/- 4%, both P < 0.05). Phase IV increased MCAv (22 +/- 15 and 34 +/- 23 cm.s(-1)), MAP (15 +/- 14 and 24 +/- 17 mm Hg) and TOI (5 +/- 6 and 7 +/- 5%) relative to baseline (all P < 0.05). Cerebral autoregulation, indexed, as the % MCAv/%MAP ratio, showed a phase effect only (P < 0.001), with the least regulation during phase IV (2.4 +/- 3.0 and 3.2 +/- 2.9). These data illustrate that an intense VM profoundly affects cerebral hemodynamics, with a reactive hyperemia occurring during phase IV following modest ischemia during phases II and III.

Desarrollo de un prototipo de exoesqueleto básico activado con una señal cerebral.

[ES]En este documento se estudia el desarrollo de una aplicación electrónica para la ayuda a gente con movilidad reducida a través de unos sensores cerebrales que permitan el análisis de la iniciativa de la persona a realizar acciones que de otra manera no podría realizar. El concepto completo consiste en el diseño del sensor que el paciente se colocaría en la cabeza, el tratamiento de la información extraída y la actuación por medio de una solución mecánica, como un conjunto cilindro-pistón para el futuro desarrollo de un sistema de ayuda a la movilidad.

La Educación Física como medio de inclusión para el alumnado con parálisis cerebral.

[ES] El presente trabajo ha estudiado la eficacia de la asignatura de Educación Física dentro del Sistema Educativo Español como método de inclusión para el alumnado con Parálisis Cerebral. Hemos realizado la Fundamentación Teórica sobre la Educación Física y la Parálisis Cerebral y hemos explicado la metodología utilizada hasta ahora en las clases (LOCE 2002 y LOMCE 2014) con el objetivo de lograr la integración de estas personas en las clases de E. Física y en la sociedad. Además, hemos llevado a cabo un caso práctico en el que se asistió a una clase de Educación Física con un paralítico cerebral en el Instituto Valle del Ebro (Tudela, Navarra), con el fin de analizar, tanto la clase impartida por el profesor, como la situación que vivía el alumno dentro de la misma. Los resultados de algunas investigaciones avalan que aún queda mucho camino por recorrer en esta área de intervención, Orta Tierra, J.; Badia Corbella, M.; Mayán, Núñez Mª Teresa entre otros. Por último, hemos propuesto el modelo de intervención metodológica por proyectos (procesos) en la EF de la próxima década, con vistas a su posible utilización con alumnos que presenten este trastorno.