Abordaxe fisioterápico no asma infantil

[Resumen] Objetivo: analizar qué intervenciones se están llevando a cabo por parte de la fisioterapia en la patología del asma. Material y métodos: revisión de artículos en los cuales se lleven a cabo intervenciones de fisioterapia en niños asmáticos. La búsqueda se efectuó en las bases de datos Pubmed, PEDro, Web of Science y Scopus, seleccionando artículos publicados entre 2013 y 2017 en lengua inglesa, portuguesa y española. Resultados: se seleccionaron 6 artículos, la mayoría de calidad intermedia, con variabilidad en el número de sujetos en cada estudio. La población que se seleccionó comprende desde el nacimiento hasta los 18 años. Las terapias fisioterápicas empleadas son variables. Se realiza en todos los casos un tratamiento enfocado al abordaje de las capacidades físicas por medio de diferentes programas de entrenamiento que cada estudio enfocó de forma diferente. Los aspectos más evaluados han sido la función pulmonar, la calidad de vida y la disnea, medidos a través de diferentes test y pruebas funcionales. Se obtienen resultados positivos en el manejo del asma con cada uno de estos programas de entrenamiento físico. Conclusiones: existen múltiples programas de intervención fisioterápica sobre el asma. Se llevan a cabo programas de entrenamiento de la musculatura inspiratoria, entrenamiento aeróbico, anaeróbico, de fuerza y equilibrio por parte de la fisioterapia en el abordaje de esta patología y todos presentan beneficio sobre ella. Asimismo, se objetivó que el programa de tratamiento que engloba un entrenamiento basado en ejercicio aeróbico y ejercicios respiratorios presenta una mayor eficacia.[Abstract] Objective: to analyze what interventions are being carried out by physiotherapy in the pathology of asthma. Material and methods: review of articles in which physiotherapy interventions are carried out in asthmatic children. The search was carried out in the Pubmed, PEDro, Web of Science and Scopus databases, selecting articles published between 2013 and 2017 in English, Portuguese and Spanish. Results: Six articles were selected, most of intermediate quality, with variability in the number of subjects in each study. The population that was selected comprises from birth to 18 years. The physiotherapeutic therapies used are variable. In all cases, a treatment focused on addressing physical abilities is carried out through different training programs that each study focused on differently. The most evaluated aspects have been pulmonary function, quality of life and dyspnea, measured through different tests and functional tests. Positive results are obtained in the management of asthma with each of these physical training programs. Conclusions: There are multiple programs of physiotherapy intervention on asthma. Training programs for inspiratory musculature, aerobic, anaerobic, strength and balance training are carried out by physiotherapy in the approach to this pathology and all have benefit over it. Likewise, it was found that the treatment program that includes a training based on aerobic exercise and breathing exercises is more effective.[Resumo] Obxectivo: analizar que intervencións se están a facer por parte da fisioterapia na patoloxía da asma. Material e metodoloxía: revisión de artículos nos que se fagan intervencións de fisioterapia en nenos asmáticos. A búsqueda efectuouse nas bases de datos Pubmed, PEDro, Web of Science y Scopus, seleccionando artículos publicados entre 2013 y 2017 en lingua inglesa, portuguesa e española. Resultados: seleccionáronse 6 artigos, a maioría de calidade intermedia, con variabilidade no número de suxeitos en cada estudo. A poboación que se seleccionou comprende dende o nacemento ata os 18 anos. As terapias fisioterápicas empregadas son variables. Realizouse en todos os casos un tratamento enfocado á abordaxe das capacidades físicas por medio de diferentes programas de entrenamento que cada estudo enfocou de forma diferente. Os aspectos máis avaliados foron a función pulmonar, a calidade da vida e a disnea, medidos a través de diferentes test e probas funcionais. Obtéñense resultados positivos no manexo do asma con cada un destes programas de entrenamento físico. Conclusións: existen múltiples programas de intervención fisioterápica sobre a asma infantil. Lévanse a cabo programas de entrenamento da musculatura inspiratoria, entrenamiento aeróbico, anaeróbico, de forza e equilibrio por parte da fisioterapia no abordaxe desta patoloxía e todos presentan beneficio sobre ela. Así mesmo obxectivouse que o programa de tratamento que engloba un entrenamento baseado no exercicio aeróbico e exercicios respiratorios presenta unha maior eficacia.Traballo fin de grao (UDC.FCS). Fisioterapia. Curso 2017/201

Colorectal Cancer Stem Cells Are Enriched in Xenogeneic Tumors Following Chemotherapy

Patients generally die of cancer after the failure of current therapies to eliminate residual disease. A subpopulation of tumor cells, termed cancer stem cells (CSC), appears uniquely able to fuel the growth of phenotypically and histologically diverse tumors. It has been proposed, therefore, that failure to effectively treat cancer may in part be due to preferential resistance of these CSC to chemotherapeutic agents. The subpopulation of human colorectal tumor cells with an ESA(+)CD44(+) phenotype are uniquely responsible for tumorigenesis and have the capacity to generate heterogeneous tumors in a xenograft setting (i.e. CoCSC). We hypothesized that if non-tumorigenic cells are more susceptible to chemotherapeutic agents, then residual tumors might be expected to contain a higher frequency of CoCSC.Xenogeneic tumors initiated with CoCSC were allowed to reach approximately 400 mm(3), at which point mice were randomized and chemotherapeutic regimens involving cyclophosphamide or Irinotecan were initiated. Data from individual tumor phenotypic analysis and serial transplants performed in limiting dilution show that residual tumors are enriched for cells with the CoCSC phenotype and have increased tumorigenic cell frequency. Moreover, the inherent ability of residual CoCSC to generate tumors appears preserved. Aldehyde dehydrogenase 1 gene expression and enzymatic activity are elevated in CoCSC and using an in vitro culture system that maintains CoCSC as demonstrated by serial transplants and lentiviral marking of single cell-derived clones, we further show that ALDH1 enzymatic activity is a major mediator of resistance to cyclophosphamide: a classical chemotherapeutic agent.CoCSC are enriched in colon tumors following chemotherapy and remain capable of rapidly regenerating tumors from which they originated. By focusing on the biology of CoCSC, major resistance mechanisms to specific chemotherapeutic agents can be attributed to specific genes, thereby suggesting avenues for improving cancer therapy

ROBO4-Mediated Vascular Integrity Regulates the Directionality of Hematopoietic Stem Cell Trafficking

Despite the use of hematopoietic stem cells (HSCs) in clinical therapy for over half a century, the mechanisms that regulate HSC trafficking, engraftment, and life-long persistence after transplantation are unclear. Here, we show that the vascular endothelium regulates HSC trafficking into and out of bone marrow (BM) niches. Surprisingly, we found that instead of acting as barriers to cellular entry, vascular endothelial cells, via the guidance molecule ROBO4, actively promote HSC translocation across vessel walls into the BM space. In contrast, we found that the vasculature inhibits the reverse process, as induced vascular permeability led to a rapid increase in HSCs in the blood stream. Thus, the vascular endothelium reinforces HSC localization to BM niches both by promoting HSC extravasation from blood-to-BM and by forming vascular barriers that prevent BM-to-blood escape. Our results uncouple the mechanisms that regulate the directionality of HSC trafficking and show that the vasculature can be targeted to improve hematopoietic transplantation therapies

Acute and endothelial-specific Robo4 deletion affect hematopoietic stem cell trafficking independent of VCAM1.

Hematopoietic stem cell (HSC) trafficking is regulated by a number of complex mechanisms. Among them are the transmembrane protein Robo4 and the vascular cell adhesion molecule, VCAM1. Endothelial VCAM1 is a well-known regulator of hematopoietic cell trafficking, and our previous studies revealed that germline deletion of Robo4 led to impaired HSC trafficking, with an increase in vascular endothelial cell (VEC) numbers and downregulation of VCAM1 protein on sinusoidal VECs. Here, we utilized two Robo4 conditional deletion models in parallel with Robo4 germline knockout mice (R4KO) to evaluate the effects of acute and endothelial cell-specific Robo4 deletion on HSC trafficking. Strikingly similar to the R4KO, the acute deletion of Robo4 resulted in altered HSC distribution between the bone marrow and blood compartments, despite normal numbers of VECs and wild-type levels of VCAM1 cell surface protein on sinusoidal VECs. Additionally, consistent with the R4KO mice, acute loss of Robo4 in the host perturbed long-term engraftment of donor wild-type HSCs and improved HSC mobilization to the peripheral blood. These data demonstrate the significant role that endothelial Robo4 plays in directional HSC trafficking, independent of alterations in VEC numbers and VCAM1 expression

Clonal and Quantitative In Vivo Assessment of Hematopoietic Stem Cell Differentiation Reveals Strong Erythroid Potential of Multipotent Cells.

Hematopoiesis is arguably one of the best understood stem cell systems; however, significant challenges remain to reach a consensus understanding of the lineage potential, heterogeneity, and relationships of hematopoietic stem and progenitor cell populations. To gain new insights, we performed quantitative analyses of mature cell production from hematopoietic stem cells (HSCs) and multiple hematopoietic progenitor populations. Assessment of the absolute numbers of mature cell types produced by each progenitor cell revealed a striking erythroid dominance of all myeloid-competent progenitors assessed, accompanied by strong platelet reconstitution. All populations with myeloid potential also produced robust numbers of red blood cells and platelets in vivo. Clonal analysis by single-cell transplantation and by spleen colony assays revealed that a significant fraction of HSCs and multipotent progenitors have multilineage potential at the single-cell level. These new insights prompt an erythroid-focused model of hematopoietic differentiation