Descripción anatómica del espacio rectogenital: fascia de Denonvilliers y espacio rectovaginal

Desde el siglo pasado hasta la actualidad persiste un debate con respecto a la posible existencia y composición de un septo rectovaginal independiente situado medialmente entre la pared rectal y la vaginal. Se ha creído que el septo rectovaginal representa el análogo femenino de la fascia masculina prostato-perineal descrita por primera vez por el anatomista francés Denonvilliers en 1836. Asimismo, ha existido un largo debate acerca de la existencia, definición y composición de la fascia de Denonvilliers. Existe controversia acerca de si es posible identificar esta estructura durante una cirugía in vivo, así como de sus relaciones exactas con la fascia propia del recto y en cuál es el plano de disección anterior ideal durante la excisión total del mesorrecto en el tratamiento del cáncer de recto. En los años siguientes a la descripción de la fascia de Denonvilliers, anatomistas y ginecólogos como Unlenhuth o Milley y Nichols, han defendido la existencia de un septo rectovaginal basándose en estudios de disección anatómica realizados en cadáveres en fresco y fijados con formol, tanto de adultos como fetos. Otros, como Ricci y Thom, han negado su existencia basando su evidencia en estudios histológicos que no se correspondían con la disección anatómica macroscópica observada. En la actualidad, los textos anatómicos y quirúrgicos no son homogéneos en cuanto a la descripción de este concepto, y su existencia se ha implicado en el diagnóstico y tratamiento de patología del suelo pélvico origen de defecación obstructiva. Para intentar esclarecer este debate y unificar conceptos anatómicos, hemos propuesto la realización de un estudio anatómico descriptivo sobre pelvis de cadáveres. El objetivo principal de este estudio es, por una parte, evaluar la existencia o no de un septo o tabique rectovaginal mediante la disección de dichas pelvis, así como evaluar la composición histológica de los tejidos del espacio rectovaginal de cada pelvis para correlacionar los hallazgos macroscópicos con los microscópicos. Y por otro, evaluar la localización exacta y límites precisos de la fascia de Denonvilliers así como describir los planos de disección del mesorrecto anterior en relación con esta fascia. El estudio anatómico se ha realizado tanto en pelvis de sexo femenino y masculino de cadáveres fijados en formol, todas ellas obtenidas a través del Departamento de Anatomía y Embriología de la Universidad de Medicina y Odontología de Valencia. Todas las pelvis han sido seccionadas en un plano medio sagital, incorporando el eje medio del canal anal para permitir una correcta visualización de las estructuras en cada una de las hemipelvis sin provocar daño al espacio retrorrectal y al espacio rectogenital. Se ha realizado una disección cuidadosa del espacio rectogenital recogiendo en una base de datos los diferentes hallazgos anatómicos macroscópicos de cada pelvis estudiada. El estudio histológico de los tejidos del espacio rectogenital de las pelvis ha sido realizado con ayuda de un mismo patólogo del Servicio de Anatomía Patológica del Hospital General de Valencia. Los resultados obtenidos se han puesto en común con los resultados publicados hasta la fecha en la literatura científica intentando dar respuesta a nuestra hipótesis de trabajo e intentando unificar conceptos anatómicos usualmente mal empleados por cirujanos coloproctólogos y ginecólogos dedicados a la patología del suelo pélvico

Modulation of cholesterol homeostasis by antiproliferative drugs in human pterygium fibroblasts.

PURPOSE. The authors have previously shown that the growth of cultured fibroblasts obtained from primary pterygia was associated with an increase in cholesterol esterification, suggesting that alterations of cholesterol homeostasis may be involved in the development and progression of this disorder. This investigation was conducted to determine whether antiproliferative agents such as pioglitazone (PIO) and everolimus (EVE) may inhibit proteins involved in the cholesterol ester cycle and the proliferation of pterygium fibroblasts (PF). METHODS. Quiescent normal conjunctival fibroblasts and PFs were treated with or without inhibitors of cell proliferation (PIO and EVE) or with inhibitors of cholesterol esterification— progesterone (Pg) and Sandoz compound (SaH)—and then were stimulated to growth by 10% fetal calf serum (FCS). Cell proliferation was assessed by counting cells. Trypan blue uptake was used to determine cell viability. mRNA and protein levels were determined by reverse transcription‐polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. RESULTS. PIO and EVE significantly abolished the increase in cholesterol esters, acyl-coenzyme A cholesterol acyltransferase (ACAT1), and multidrug resistance protein (MDR1) mRNA observed in growing cells. Each inhibitor upregulated ATP-binding cassette-A1 (ABCA1), neutral cholesterol ester hydrolase (NCEH) mRNA, and caveolin-1 expression in a manner similar to that of specific inhibitors of cholesterol esterification such as Pg and SaH. CONCLUSIONS. Intracellular modifications of cholesterol homeostasis may be relevant to pterygium development. Moreover, antiproliferative agents such as PIO and EVE may represent a potential topical medication in the prevention and inhibition of pterygium growth at an early stage, probably by modulation of cholesterol ester metabolism. (Invest Ophthalmol Vis Sci. 2007;48:3450‐3458) DOI:10.1167/iovs.06-105

Cholesterol esterification during differentiation of mouse erythroleukemia (Friend) cells

Cholesterol is an essential constituent of all mammalian cell membranes and its availability is therefore a prerequisite for cellular growth and other functions. Several lines of evidence are now indicating an association between alterations of cholesterol homeostasis and cell cycle progression. However, the role of cholesterol in cell differentiation is still largely unknown. To begin to address this issue, in this study we examined changes in cholesterol metabolism and in the mRNA levels of proteins involved in cholesterol import and esterification (multi-drug resistance, MDR-3) and acylCoA: cholesterol acyltransferase (ACAT) and cholesterol export (caveolin-1) in Friend virus-induced erythroleukemia cells (MELC), in the absence or in the presence of the chemical inducer of differentiation, hexamethylene bisacetamide (HMBA). FBS-stimulated growth of MELC was accompanied by an immediate elevation of cholesterol synthesis and cholesterol esterification, and by an increase in the levels of MDR-3 and ACAT mRNAs. A decrease in caveolin-1 expression was also observed. However, when MELC were treated with HMBA, the inhibition of DNA synthesis caused by HMBA treatment, was associated with a decrease in cholesterol esterification and in ACAT and MDR-3 mRNA levels and an increase in caveolin-1 mRNA. Detection of cytoplasmic neutral lipids by staining MELC with oil red O, a dye able to evidence CE but not FC, revealed that HMBA-treatment also reduced growth-stimulated accumulation of cholesterol ester to approximately the same extent as the ACAT inhibitor, SaH. Overall, these results indicate for the first time a role of cholesterol esterification and of some related genes in differentiation of erythroid cells

acat1 cav 1 and prp expression in brains and skin fibroblasts from sarda breed sheep with scrapie resistant and scrapie susceptible genotype

Scrapie is an infective ovine neurodegenerative disease; the only identified component of the infectious agent being an aberrant isoform (PrPSc) of the cellular prion protein (PrPC). So far, no means for ante-mortem diagnosis are available for Scrapie as well as for any other mammal Transmissible Spongiform Encephalopaties. We recently found a strong relationship between cell susceptibility to scrapie-infection and intracellular cholesterol homeostasis alterations. In brain tissues as well as in ex vivo cultures of skin fibroblasts and PBMCs from healthy and scrapie-affected sheep carrying a scrapie-susceptible (ARQ/ARQ) genotype, the levels of cholesterol esters were consistently higher than in tissues and cultures derived from animals with a scrapie-resistant (ARR/ARR) genotype. Moreover, both uninfected and scrapie-affected ARQ/ARQ sheep showed abnormally low levels of high density lipoprotein-cholesterol (HDL-C) in their plasma, as compared to ARR/ARR animals. We now show that intracellular accumulation of cholesterol esters in fibroblasts derived from scrapie-susceptible sheep was accompanied by parallel alterations in the expression level of genes and gene products (ACAT1 and Cav-1) that are involved in the pathways leading to intracellular cholesterol esterification and trafficking. Comparative analysis of PrPc mRNA, showed an higher expression level in cells from animals carrying susceptible genotype, with or without Scrapie. Preliminary experiments also revealed the presence of PK-resistant PrP isoforms in the latter cultures. The data reported in the present paper suggest that accumulation of cholesterol esters in peripheral cells, together with the altered expression of some proteins implicated in intracellular cholesterol homeostasis, might serve to identify a distinctive lipid metabolic profile associated with increased susceptibility to develop prion disease following infection

Altered cholesterol ester cycle in ex vivo skin fibroblasts from Alzheimer patients

Recent studies in both animal and cell models of Alzheimer's disease (AD) indicated that sub-cellular cholesterol distribution seems to regulate amyloid-beta (A[beta]) generation in the brain. In particular, cholesterol-esters (CE), rather than total cholesterol levels, appear directly correlated with A[beta] production. Here we observed that, similarly to brain cells, skin fibroblasts obtained from AD patients produce and accumulate more CE than skin fibroblasts from age-matched healthy controls do. AD fibroblasts also exhibited a 2 fold increase in the expression of ACAT1, in addition to lower levels of SREBP2, nCEH, Caveolin-1 and ABCA1 mRNA levels, all of which are involved in the CE cycle. HMGCoA-reductase and LDL-receptor mRNAs levels did not show statistically significant changes in AD, compared to non-AD, cells. Furthermore, although APP mRNA did not significantly vary, neprilysin (NEP), the most important enzyme in the proteolysis of A[beta], was expressed at very low levels in skin fibroblasts of sporadic AD patients. Our results contribute to the concept that AD may be the consequence of a basic and systemic defect in the CE cycle. Moreover, our results identify new possible targets for the diagnosis, prevention, and cure or, at least, amelioration of the symptoms of AD

Multi-Temporal X-Band Radar Interferometry Using Corner Reflectors: Application and Validation at the Corvara Landslide (Dolomites, Italy)

From the wide range of methods available to landslide researchers and practitioners for monitoring ground displacements, remote sensing techniques have increased in popularity. Radar interferometry methods with their ability to record movements in the order of millimeters have been more frequently applied in recent years. Multi-temporal interferometry can assist in monitoring landslides on the regional and slope scale and thereby assist in assessing related hazards and risks. Our study focuses on the Corvara landslides in the Italian Alps, a complex earthflow with spatially varying displacement patterns. We used radar imagery provided by the COSMO-SkyMed constellation and carried out a validation of the derived time-series data with differential GPS data. Movement rates were assessed using the Permanent Scatterers based Multi-Temporal Interferometry applied to 16 artificial Corner Reflectors installed on the source, track and accumulation zones of the landslide. The overall movement trends were well covered by Permanent Scatterers based Multi-Temporal Interferometry, however, fast acceleration phases and movements along the satellite track could not be assessed with adequate accuracy due to intrinsic limitations of the technique. Overall, despite the intrinsic limitations, Multi-Temporal Interferometry proved to be a promising method to monitor landslides characterized by a linear and relatively slow movement rates

Navigating surgical anatomy of the Denonvilliers' fascia and dissection planes of the anterior mesorectum with a cadaveric simulation model

Anterior dissection of the rectum in the male pelvis represents one of the most complex phases of total meso-rectal excision. However, the possible existence of different anatomical planes is controversial and the exact anatomical topography of Denonvilliers' fascia is still debated. The aim of the study is to accurately define in a cadaveric simulation model the existence and boundaries of Denonvilliers' fascia, identifying the anatomical planes suitable for surgical dissection. The pelvises of 31 formalin-preserved male cadavers were dissected. Careful and detailed dissection was carried out to visualize the anatomical structures and the potential dissection planes, simulating an anterior meso-rectum dissection. Denonvilliers' fascia was identified in 100% of the pelvises, as a single-layer fascia that originates from the peritoneal reflection and descends until its firm adhesion to the prostate capsule. The fascia divides the space providing an anterior and a posterior plane. Anteriorly to the fascia, during the caudal dissection, its firm adhesion to the prostate capsule forces to section it sharply. The cadaveric simulation model allowed an accurate description of Denonvilliers' fascia, defining several planes for anterior dissection of the meso-rectum

Exploitation of satellite A-DInSAR time series for detection, characterization and modelling of land subsidence

In the last two decades, advanced differential interferometric synthetic aperture radar (A-DInSAR) techniques have experienced significant developments, which are mainly related to (i) the progress of satellite SAR data acquired by new missions, such as COSMO-SkyMed and ESA’s Sentinel-1 constellations; and (ii) the development of novel processing algorithms. The improvements in A-DInSAR ground deformation time series need appropriate methodologies to analyse extremely large datasets which consist of huge amounts of measuring points and associated deformation histories with high temporal resolution. This work demonstrates A-DInSAR time series exploitation as valuable tool to support different problems in engineering geology such as detection, characterization and modelling of land subsidence mechanisms. The capabilities and suitability of A-DInSAR time series from an end-user point of view are presented and discussed through the analysis carried out for three test sites in Europe: the Oltrepo Pavese (Po Plain in Italy), the Alto Guadalentín (Spain) and the London Basin (United Kingdom). Principal component analysis has been performed for the datasets available for the three case histories, in order to extract the great potential contained in the A-DInSAR time serie

accumulation of cholesterol esters in ex vivo lymphocytes from scrapie susceptible sheep and in scrapie infected mouse neuroblastoma cell lines

Our studies on the role of cholesterol homeostasis in the pathogenesis of scrapie in sheep, revealed abnormal accumulation of cholesterol esters in brains and in ex vivo skin fibroblasts from genetically scrapie-susceptible, as compared to sheep with resistant genotype. We now report that PBMCs isolated from scrapie-susceptible sheep, as well as mouse neuroblastoma cell lines persistently infected with two different mouse-adapted strains of scrapie, showed similar alterations with up to 3-fold higher cholesterol ester levels than their resistant or uninfected counterparts. Treatments with drugs that interfere with intracellular cholesterol metabolism strongly reduced accumulation of cholesterol esters in scrapie-infected cell lines, whereas had significantly lower, or no effect, in uninfected cell line. These data add support to our hypothesis that accumulation of cholesterol esters may represent a biological marker of susceptibility to prion infection and a potential molecular target for prion inhibitors

Application of multi-sensor advanced DInSAR analysis to severe land subsidence recognition: Alto Guadalentín Basin (Spain)

Multi-sensor advanced DInSAR analyses have been performed and compared with two GPS station measurements, in order to evaluate the land subsidence evolution in a 20-year period, in the Alto Guadalentín Basin where the highest rate of man-induced subsidence (> 10 cm yr−1) of Europe had been detected. The control mechanisms have been examined comparing the advanced DInSAR data with conditioning and triggering factors (i.e. isobaths of Plio-Quaternary deposits, soft soil thickness and piezometric level).This work is financially supported by the DORIS project (Ground Deformation Risk Scenarios: an Advanced Assessment Service) funded by the EC-GMES-FP7 initiative (Grant Agreement 423 no. 242212). ALOS PALSAR images were provided by the project JAXA-1209. Part of this work is supported by the Spanish Government under project TEC2011-28201-C02-02 and TIN2014-55413-C2-2-P and by the project 15224/PI/10 from the Regional Agency of Science and Technology in Murcia. Additional funding was obtained from the Spanish Research Program through the projects AYA2010-17448, ESP2013-47780-C2-1-R and ESP2013-47780-C2-2-Rand by the Ministry of Education, Culture and Sport through the project PRX14/00100