Endothelial to mesenchymal transition (EndoMT) in the pathogenesis of Systemic Sclerosis-associated pulmonary fibrosis and pulmonary arterial hypertension. Myth or reality?

Systemic Sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and multiple internal organs and severe functional and structural microvascular alterations. SSc is considered to be the prototypic systemic fibrotic disorder. Despite currently available therapeutic approaches SSc has a high mortality rate owing to the development of SSc-associated interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), complications that have emerged as the most frequent causes of disability and mortality in SSc. The pathogenesis of the fibrotic process in SSc is complex and despite extensive investigation the exact mechanisms have remained elusive. Myofibroblasts are the cells ultimately responsible for tissue fibrosis and fibroproliferative vasculopathy in SSc. Tissue myofibroblasts in SSc originate from several sources including expansion of quiescent tissue fibroblasts and tissue accumulation of CD34+ fibrocytes. Besides these sources, myofibroblasts in SSc may result from the phenotypic conversion of endothelial cells into activated myofibroblasts, a process known as endothelial to mesenchymal transition (EndoMT). Recently, it has been postulated that EndoMT may play a role in the development of SSc-associated ILD and PAH. However, although several studies have described the occurrence of EndoMT in experimentally induced cardiac, renal, and pulmonary fibrosis and in several human disorders, the contribution of EndoMT to SSc-associated ILD and PAH has not been generally accepted. Here, the experimental evidence supporting the concept that EndoMT plays a role in the pathogenesis of SSc-associated ILD and PAH will be reviewed

Role of growth factors in the pathogenesis of tissue fibrosis in systemic sclerosis.

The most severe clinical and pathologic manifestations of systemic sclerosis (SSc) are the result of a fibrotic process characterized by the excessive and often progressive deposition of collagen and other connective tissue macromolecules in skin and numerous internal organs. The mechanisms involved in the initiation and progression of the remarkable fibrotic process in SSc remain largely unknown. Extensive recent studies have indicated that a variety of polypeptide growth factors play a crucial role in this process. The most commonly implicated growth factors include transforming growth factor beta (TGF-β), connective tissue growth factor (CTGF), platelet derived growth factor (PDGF), and vascular endothelial growth factor (VEGF). Here, the experimental evidence supporting the participation of various growth factors in the pathogenesis of the fibrotic process in SSc and the molecular mechanisms involved will be reviewed

Incidencia de la organización de la fuerza de ventas en el Desarrollo empresarial del Restaurante Toro Bravo del Municipio de Matagalpa del año 2016

En el presente trabajo se aborda sobre el tema la incidencia de la organización de la fuerza de ventas en el desarrollo empresarial del restaurante Toro Bravo del municipio de Matagalpa, durante el año 2016 para posteriormente identificar los componentes, mecanismos aplicados en función de las ventas y desarrollo empresarial que ha tenido el restaurante. Se debe recordar la importancia que tiene realizar este tipo de investigación ya que se vive un mundo cambiante y a medida que el tiempo pasa los `productos y servicios van cambiando y adaptándose a lo que el consumidor prefiere. Recordando que es una investigación cualitativa con elementos cuantitativos se han identificado todos aquellos aspectos relevantes que utiliza la administración de ventas en el desarrollo de la empresa. Esta investigación relevo que el restaurante Toro Bravo aplica mecanismo como la promoción y publicidad en función de las ventas, así como el fortalecimiento de las habilidades del personal que integran la empresa todos estos aspectos han sido de vital importancia para el crecimiento y desarrollo empresarial del restaurante Toro Bravo en el mercad

Molecular mechanisms of endothelial to mesenchymal cell transition (EndoMT) in experimentally induced fibrotic diseases.

Several recent studies have demonstrated that endothelial to mesenchymal transition (EndoMT), a newly recognized type of cellular transdifferentiation may be an important source of myofibroblasts during the development of experimentally induced pulmonary, cardiac and kidney fibrosis. EndoMT is a complex biological process induced by members of the transforming growth factor (TGF-β) family of regulatory polypeptides in which endothelial cells adopt a mesenchymal or myofibroblastic phenotype acquiring motile and contractile properties and initiating expression of mesenchymal cell products such as α smooth muscle actin (α-SMA) and type I collagen. Although these experimental studies provide compelling evidence for the participation of EndoMT in the development of experimentally-induced fibrotic processes the precise role of EndoMT in the pathogenesis of human fibrotic disorders requires confirmation and validation from studies of human clinical pathologic conditions. Such confirmation should lead to a change in the paradigm of the origin of profibrogenic myofibroblasts involved in human fibrotic diseases. Further understanding of the molecular mechanisms and the regulatory pathways involved in EndoMT may lead to the development of novel therapeutic approaches for the incurable and often devastating fibrotic disorders

Mechanically and chemically robust ZIF-8 monoliths with high volumetric adsorption capacity

The resultant monoliths are mechanically robust structures and present up to 3 times higher volumetric adsorption capacities than the conventional, powder MOF.This work was funded by the EPSRC IAA Partnership Development Award (RG/75759). D.F.-J. thanks the Royal Society for funding through a University Research Fellowship. T.D.B would like to thank Trinity Hall for funding and Professor Anthony Cheetham for use of lab facilities and equipmentThis is the accepted manuscript of a paper published in the Journal of Materials Chemistry A (Tian T, Velazquez-Garcia J, Bennett TD, Fairen-Jimenez D, Journal of Materials Chemistry A, 2015, 3, 2999-3005, doi:10.1039/c4ta05116e). The final version is available at http://dx.doi.org/10.1039/c4ta05116e

Estudio clinicopatologico de trastornos genito-urinarios en un rebaño ovino del estado de México. México

Con el objeto de evaluar y documentar el caso clínico - patológico de un ovino remitido para diagnostico al CIESA , se realizó una valoración clínica, estudios anatomopatológico e histopatológico y otros complementarios , debido a las co ndiciones y características de presentación de cuatro casos similares en un rebaño ovino , con similitud en los signos clínicos . El principal problema detectado se relacionó a un problema de: U retritis supurativa y a cistitis hemorrágica no supurativa. La importancia del presente caso es la presencia de agentes bacterianos que pueden afectar de manera importante la producción del ganado ovino, a través de lesiones o alteraciones inaparentes que deben considerarse en el manejo y eficiencia reproductiva de u n rebaño

Endothelial Cells Expressing Endothelial and Mesenchymal Cell Gene Products in Lung Tissue From Patients With Systemic Sclerosis-Associated Interstitial Lung Disease.

OBJECTIVE: To examine whether lung endothelial cells (ECs) from patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) express mesenchymal cell-specific proteins and gene transcripts, indicative of the occurrence of endothelial-to-mesenchymal phenotypic transition (EndoMT). METHODS: Lung tissue from 6 patients with SSc-associated pulmonary fibrosis was examined by histopathology and immunohistochemistry. Confocal laser microscopy was utilized to assess the simultaneous expression of EC and myofibroblast molecular markers. CD31+CD102+ ECs were isolated from the lung tissue of 2 patients with SSc-associated ILD and 2 normal control subjects, and the expression of EC and mesenchymal cell markers and other relevant genes was analyzed by quantitative polymerase chain reaction, immunofluorescence microscopy, and Western blotting. RESULTS: Immunohistochemical staining revealed cells expressing the EC-specific marker CD31 in the subendothelial, perivascular, and parenchymal regions of the lungs from all SSc patients. Confocal microscopy identified cells displaying simultaneous expression of von Willebrand factor and α-smooth muscle actin in small and medium-sized arterioles in the SSc lung tissue but not in normal control lungs. CD31+CD102+ ECs isolated from SSc lungs expressed high levels of mesenchymal cell-specific genes (type I collagen, type III collagen, and fibronectin), EC-specific genes (type IV collagen and VE-cadherin), profibrotic genes (transforming growth factor β1 and connective tissue growth factor), and genes encoding EndoMT-related transcription factors (TWIST1 and SNAI2). CONCLUSION: Cells coexpressing EC- and mesenchymal cell-specific molecules are present in the lungs of patients with SSc-associated ILD. CD31+CD102+ ECs isolated from SSc lungs simultaneously expressed mesenchymal cell- and EC-specific transcripts and proteins. Collectively, these observations demonstrate the occurrence of EndoMT in the lungs of patients with SSc-associated ILD

Description of twelve cases of nephrogenic fibrosing dermopathy and review of the literature

ABSTRACT Objectives: To review the clinical and laboratory features of twelve cases of nephrogenic fibrosing dermopathy (NFD) studied at our institution and of 70 previously described cases in the literature. Methods: Clinical evaluation and laboratory studies of twelve patients with NFD associated with chronic hemodialysis or peritoneal dialysis for end-stage renal disease and a review of 23 previous publications describing 70 patients with this disease. Results: Eleven patients undergoing chronic hemodialysis and one patient undergoing chronic peritoneal dialysis for end-stage renal failure developed a severe and progressive cutaneous fibrotic process with woody induration of legs, thighs, hands and forearms, and severe loss of motion and flexion contractures in multiple joints. Several patients displayed systemic involvement including fibrosis of muscles, myocardium and lungs and marked elevations of the erythrocyte sedimentation rate and/or C reactive protein. Three patients died within two years of onset of symptoms. A review of previously published reports of this disorder confirmed the presence of systemic involvement and a poor prognosis with a high rate of mortality. Conclusions: The analysis of twelve cases and a review of 70 previously described cases indicate that NFD is a severe and usually progressive systemic fibrotic disease affecting the dermis, subcutaneous fascia and striated muscles. It also appears that the disease can cause fibrosis of lungs, myocardium and other organs

Skin changes: A taxonomic approach to the interaction between visitors and residents in receiving communities

Las migraciones en el mundo, dentro de las cuales se pueden considerar los viajes y el turismo, presentan condiciones nuevas así como distintos patrones de movilidad. Los desplazamientos generan particularidades en las relaciones y comportamientos que se verifican entre los participantes, que pueden y deben ser diferenciados en los análisis para una mejor comprensión de esas interacciones y los factores que entran en juego. Los visitantes tienen, además, una dinámica que está conformada por factores diferenciables donde la cultura nacional y la de fuera se encuentran, dando lugar a manifestaciones específicas de esas interacciones. En este texto se busca una aproximación teórica conceptual a la dinámica que se manifiesta en esas interacciones y busca una taxonomía derivada de la complejidad establecida en las interacciones y que se encuentran más allá de la categorización de turistas y anfitriones. Los aportes surgidos de las teorías de la interacción social permiten recuperar ciertos niveles de complejidad presentes en los tipos de interacción donde se ponen en juego posibilidades interpretativas desde los diferentes marcos culturales de los participantes así como desde sus posiciones en las relaciones sociales estructuradas. Este es un elemento que se constituye en el eje de las interacciones y de las interpretaciones entre residentes y viajeros (migrantes), ya sean estos transitorios ---turistas--- o turisgrantes---, personas que combinan ambas condiciones porque su calidad migratoria resulta ser simultáneamente transitoria y su conducta es cercana a la del migrante