Efecto de un nuevo xanthanólido sesquiterpeno sobre la activación de mastocitos inducida por neurópeptidos pro-inflamatorios

Los mastocitos son células del tejido conectivo que participan en la génesis y modulación de las respuestas inflamatorias celulares. En trabajos previos hemos demostrado que xanthatina (xanthanólido sesquiterpeno aislado de Xanthium cavanillesii Schouw) inhibe la activación de mastocitos inducida por secretagogos experimentales. Sin embargo, se desconoce su efecto sobre la activación de mastocitos inducida por estímulos fisiopatológicos. Estos estímulos incluyen, entre otros, los neuropéptidos pro-inflamatorios sustancia P y neurotensina, responsables de una de las principales vías de inflamación neurogénica. El objetivo del presente trabajo fue estudiar el efecto de xanthatina sobre la activación de mastocitos inducida por sustancia P y neurotensina. Mastocitos peritoneales de rata se incubaron con: 1) PBS (basal); 2) sustancia P (100 Fm); 3) neurotensina (50 Fm); 4) xanthatina (8-320 Fm)+sustancia P; 5) xanthatina (8-320 Fm)+neurotensina. La viabilidad de los mastocitos se evaluó con azul tripán. En las soluciones de incubación se cuantificó serotonina liberada (marcador de activación). En las células se cuantificó serotonina remanente (no liberada) y se analizó la morfología celular por microscopía óptica y electrónica de transmisión. Tratamiento estadístico: ANOVA-1 y Tukey-Kramer. La incubación de mastocitos con xanthatina inhibió (P<0,01), en forma dosisdependiente, la liberación de serotonina inducida por sustancia P y neurotensina, sin modificar la viabilidad celular. Los mastocitos tratados con neuropéptidos mostraron características morfológicas de degranulación, mientras que la morfología de los mastocitos tratados con xanthatina+neuropéptido fue semejante a los basales. En conclusión, xanthatina inhibe la activación de mastocitos inducida por sustancia P y por neurotensina. Este sesquiterpeno podría representar una nueva alternativa en el tratamiento de las inflamaciones neurogénicas.The present study was designed to examine the effects of a novel natural xanthanolide with anti-ulcer and anti-inflammatory properties (xanthatin) on mast cell activation induced by pro-inflammatory peptides, such as substance P and neurotensin. Peritoneal mast cells from male adult were purified in Percoll, preincubated in the presence of xanthatin and then challenged with the mast cell activators substance P (100 Fm) or neurotensin (50 Fm). Concentration-response studies of mast cell serotonin release evoked by pro-inflammatory neuropeptides, evaluation of mast cell viability and morphology by light and electron microscopy, and drug stability analysis by thin layer chromatography (TLC) were performed. Serotonin release studies, carried out together with morphological studies, showed the effectiveness of xanthatin to stabilize mast cells. The present study provides the first strong evidence in favour of the hypothesis that xanthatin inhibits substance P- and neurotensin-induced serotonin release from peritoneal mast cells, acting thus as a mast cell stabilizer. Our findings may provide an insight into the design of novel pharmacological agents which may be used to regulate the mast cell response in neurogenic inflammation.Fil: Vargas, P.. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histologia y Embriología Mendoza. "Dr. Mario H. Burgos"Fil: Martino, E.. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Área de Anatomía NormalFil: Fogal, T.. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histologia y Embriología Mendoza. "Dr. Mario H. Burgos"Fil: Tonn, C.. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química.Fil: Penissi, A.. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histologia y Embriología Mendoza. "Dr. Mario H. Burgos

Cervicothoracic Intradural Arachnoid Cyst Misdiagnosed as Motor Neuron Disease

Recognizing syndromes which mimic ALS is crucial both to avoid giving this diagnosis erroneously and since there may be appropriate treatments. We report a 63-year-old woman diagnosed with possible ALS five years ago based on upper and lower motor neuron signs with typical electrophysiology and normal cranial MRI. At reassessment, spinal MRI revealed a cervicothoracic cyst with cord compression that was successfully treated neurosurgically. Histopathology confirmed an arachnoid origin as suspected from MRI. Spinal cysts may mimic ALS and need to be thoroughly excluded by appropriate imaging

A comparative assessment of biomass ash preparation methods using X-ray fluorescence and wet chemical analysis

X-ray fluorescence (XRF) spectroscopy is a rapid method used to determine the composition of biomass ash, but the accuracy of the method is sensitive to various factors including ash preparation methods. In this study different types of biomass ash were examined by using wet chemical analysis (WCA) and compared with the respective XRF results. The biomass ash was initially prepared in accordance with the European Standard method at 550 °C. At this low combustion temperature the amount of residual unburned carbon is significant. To eliminate this, the ashes were heated at higher temperatures: a batch of twenty biomass ashes were heated at 850 °C and a batch of five heated to 815 °C. At these higher temperatures there may be loss of inorganic components by vaporisation. Variation in these effects may lead to unreliable results. The relationship between XRF and WCA results are given by regression equations. The ashes processed at 815 °C show better agreement between the two analysis methods

Heat flow and calculus on metric measure spaces with Ricci curvature bounded below - the compact case

We provide a quick overview of various calculus tools and of the main results concerning the heat flow on compact metric measure spaces, with applications to spaces with lower Ricci curvature bounds. Topics include the Hopf-Lax semigroup and the Hamilton-Jacobi equation in metric spaces, a new approach to differentiation and to the theory of Sobolev spaces over metric measure spaces, the equivalence of the L^2-gradient flow of a suitably defined "Dirichlet energy" and the Wasserstein gradient flow of the relative entropy functional, a metric version of Brenier's Theorem, and a new (stronger) definition of Ricci curvature bound from below for metric measure spaces. This new notion is stable w.r.t. measured Gromov-Hausdorff convergence and it is strictly connected with the linearity of the heat flow.Comment: To the memory of Enrico Magenes, whose exemplar life, research and teaching shaped generations of mathematician

EGFR Gene Overexpression Retained in an Invasive Xenograft Model by Solid Orthotopic Transplantation of Human Glioblastoma Multiforme Into Nude Mice

Orthotopic xenograft animal model from human glioblastoma multiforme (GBM) cell lines often do not recapitulate an extremely important aspect of invasive growth and epidermal growth factor receptor (EGFR) gene overexpression of human GBM. We developed an orthotopic xenograft model by solid transplantation of human GBM into the brain of nude mouse. The orthotopic xenografts sharing the same histopathological features with their original human GBMs were highly invasive and retained the overexpression of EGFR gene. The murine orthotopic GBM models constitute a valuable in vivo system for preclinical studies to test novel therapies for human GBM

The Life Cycle Analysis Toolbox

The life cycle analysis toolbox is a valuable integration of decision-making tools and supporting materials developed by Oak Ridge National Laboratory (ORNL) to help Department of Energy managers improve environmental quality, reduce costs, and minimize risk. The toolbox provides decision-makers access to a wide variety of proven tools for pollution prevention (P2) and waste minimization (WMin), as well as ORNL expertise to select from this toolbox exactly the right tool to solve any given P2/WMin problem. The central element of the toolbox is a multiple criteria approach to life cycle analysis developed specifically to aid P2/WMin decision-making. ORNL has developed numerous tools that support this life cycle analysis approach. Tools are available to help model P2/WMin processes, estimate human health risks, estimate costs, and represent and manipulate uncertainties. Tools are available to help document P2/WMin decision-making and implement programs. Tools are also available to help track potential future environmental regulations that could impact P2/WMin programs and current regulations that must be followed. An Internet-site will provide broad access to the tools

National Evaluation of the Weatherization Assistance Program: Preliminary Evaluation Plan for Program Year 2006

The U.S. Department of Energy's (DOE's) Weatherization Assistance Program was created by Congress in 1976 under Title IV of the Energy Conservation and Production Act. The purpose and scope of the Program as currently stated in the Code of Federal Regulations (CFR) 10CFR 440.1 is 'to increase the energy efficiency of dwellings owned or occupied by low-income persons, reduce their total residential expenditures, and improve their health and safety, especially low-income persons who are particularly vulnerable such as the elderly, persons with disabilities, families with children, high residential energy users, and households with high energy burden' (Code of Federal Regulations, 2005). DOE sponsored a comprehensive evaluation of the Program in the early 1990's to provide policy makers and program implementers with up-to-date and reliable information they needed for effective decision making and cost-effective operations. Oak Ridge National Laboratory (ORNL) managed the five part study which was based primarily on data from Program Year (PY) 1989 and supplemented by data from 1991-92 (Brown, Berry, and Kinney, 1994). In more recent years, ORNL has conducted four metaevaluations of the Program's energy savings using studies conducted by individual states between the years 1990-1996 (Berry, 1997), 1996-1998 (Schweitzer and Berry, 1999), 1993-2002 (Berry and Schweitzer, 2003), and 1993-2005 (Schweitzer, 2005). DOE announced through its Weatherization Program Notice 05-1 (DOE, 2004) that it would undertake a new national evaluation of the Program because the Program that was evaluated comprehensively in the early 1990's is vastly different from the Program of today. The Program has incorporated new funding sources, management principles, audit procedures, and energy-efficiency measures in response to findings and recommendations resulting from the 1989 National Evaluation, the Weatherization Plus strategic planning process, and other federal, state, and local initiatives. For example, the use of computerized audits has increased, cooling and baseload measures have been added, weatherization approaches tailored to the unique construction characteristics of mobile homes have been developed, the weatherization of large multifamily buildings has expanded and become more sophisticated, the flexibility to improve 'energy-related' health and safety has been provided, and leveraging with utilities, other state programs, and owners of large multifamily buildings has increased considerably. The Department of Energy tasked ORNL with planning the new evaluation in light of its experience in conducting the previous national evaluation and the metaevaluations. This preliminary evaluation plan, developed by ORNL, documents how the new national evaluation will be performed. In the remaining portion of this section, the purpose and fundamental questions the evaluation will address are identified and how these questions were derived is discussed

NATIONAL EVALUATION OF THE WEATHERIZATION ASSISTANCE PROGRAM DURING THE ARRA PERIOD: PROGRAM YEARS 2009-2011

This report describes the third major evaluation of the Program, encompassing program years 2009 to 2011. In this report, this period of time is referred to as the ARRA Period. This is a special period of time for the Program because the American Recovery and Reinvestment Act (ARRA) of 2009 has allocated $5 billion of funding for the Program. In normal program years, WAP s annual appropriation is in the range of$200-250 million, supporting the weatherization of approximately 100,000 homes. With the addition of ARRA funding during these program years, the expectation is that weatherization activity will exceed 300,000 homes per year. In addition to saving energy and reducing low-income energy bills, expanded WAP funding is expected to stimulate the economy by providing new jobs in the weatherization field and allowing low-income households to spend more money on goods and services by spending less on energy

Leptomeningeal metastasis from solid tumours: EANO-ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up

• This Clinical Practice Guideline provides recommendations for managing leptomeningeal metastases from solid tumours. • The guideline covers clinical, imaging and cytological diagnosis, staging and risk assessment, treatment and follow-up. • A treatment and management algorithm is provided. • The author panel encompasses a multidisciplinary group of experts from different institutions and countries in Europe. • Recommendations are based on available scientific data and the authors’ collective expert opinion