Inter- and intralaboratory variation of in vitro diffusion cell measurements: An international multicenter study using quasi-standardized methods and materials

In vitro measurements of skin absorption are an increasingly important aspect of regulatory studies, product support claims, and formulation screening. However, such measurements are significantly affected by skin variability. The purpose of this study was to determine inter- and intralaboratory variation in diffusion cell measurements caused by factors other than skin. This was attained through the use of an artificial (silicone rubber) rate-limiting membrane and the provision of materials including a standard penetrant, methyl paraben (MP), and a minimally prescriptive protocol to each of the 18 participating laboratories. Standardized calculations of MP flux were determined from the data submitted by each laboratory by applying a predefined mathematical model. This was deemed necessary to eliminate any interlaboratory variation caused by different methods of flux calculations. Average fluxes of MP calculated and reported by each laboratory (60 +/- 27 mug cm(-2) h(-1), n = 25, range 27-101) were in agreement with the standardized calculations of MP flux (60 +/- 21 mug cm(-2) h(-1), range 19-120). The coefficient of variation between laboratories was approximately 35% and was manifest as a fourfold difference between the lowest and highest average flux values and a sixfold difference between the lowest and highest individual flux values. Intra-laboratory variation was lower, averaging 10% for five individuals using the same equipment within a single laboratory. Further studies should be performed to clarify the exact components responsible for nonskin-related variability in diffusion cell measurements. It is clear that further developments of in vitro methodologies for measuring skin absorption are required. (C) 2005 Wiley-Liss, Inc.

The effects of vehicle and region of application on in vitro penetration of testosterone through canine skin

The effects of the vehicles phosphate-buffered saline (PBS), ethanol (EtOH; 50% in PBS w/w) and propylene glycol (PG; 50% in PBS w/w) and the region of administration on in vitro transdermal penetration of testosterone was investigated in the dog. Skin was harvested from the thorax, neck (dorsal part) and groin regions of greyhounds after euthanasia and stored at -20 degrees C until required. The skin was then de-frosted and placed into Franz-type diffusion cells which were maintained at approximately 32 degrees C by a water-bath. Saturated solutions of testosterone, containing trace amounts of radiolabelled (C-14) testosterone, in each vehicle were applied to the outer (stratum corneum) surface of each skin sample and aliquots of receptor fluid were collected at 0, 2, 4, 8, 16, 20, 22 and 24 h and analysed for testosterone by scintillation counting. The maximum flux (J(max)) of testosterone was significantly higher for all sites when dissolved in a vehicle containing 50% EtOH or 50% PG, compared to PBS. In contrast, higher residues of testosterone were found remaining within the skin when PBS was used as a vehicle. This study shows that variability in percutaneous penetration of testosterone could be expected with formulation design and site of application. (C) 2004 Elsevier Ltd. All rights reserved.

A DUPLA FACE DE SALOMÃO MEMÓRIAS DE UMA ESCOLA DE ESCRIBAS NO SÉCULO X A.C.

O memóravel rei Salomão passou para a história como um sábio por excelência. Ainda na atualidade, a maioria das pessoas relaciona o seu nome com a sabedoria. Mas a partir do momento que passamos a ter conhecimento dos textos que se referem a Salomão, de como foram construídos e quais as ideologias ali presentes (tanto as favoráveis quanto as contrárias), surgem muitos questionamentos, em especial, quando se busca metodicamente dissociar a história da memória. Ao que parece a historiografia tradicional sobre Salomão, ainda encontra-se muito dependente da figura idealizada de Salomão. Resultado de uma construção feita desde a sua época, pelas mãos de seus escribas, como também em tempos posteriores, de acordo com os interesses de cada época. Concluí-se que a sabedoria de Salomão nada mais é do que uma construção ideológica. A partir dessa perspectiva, surge o desafio de buscar outra memória de Salomão, a fim de propor um caminho alternativo, que nos permita produzir uma nova historiografia a respeito de Salomão. Uma historiografia que não se firma na memória oficial , mas que siga na direção contrária, a partir das memórias dos que não se deixaram influenciar pela ideologia do poder. Dessa forma, poderemos alcançar a comprovação de nossa tese: a existência de duas memórias conflitantes a respeito de Salomão, dentro da Escola de Escribas da corte de Jerusalém no século X a.C. Infelizmente, as fontes disponíveis sobre esse assunto são realmente escassas, o que temos são textos, isto é, memórias sobre Salomão. Escolheu-se um texto crítico a Salomão. Trata-se de 1Rs 1-2, texto que pertence a chamada História da Sucessão de Davi, acreditando-se que a partir dele, consiga-se produzir uma historiografia diferente da historiografia tradicional. Concluímos que dentro da Escola de Escribas Salomônica existiam duas ideologias conflitantes. Os que eram a favor de Salomão, defendiam os interesses urbanos. Aqueles que pertenciam à escola anti-Salomônica e anti-Jerusalém, representavam os interesses dos camponeses explorados e oprimidos pelo poder.

UMA ÁNALISE EXEGÉTICA DA PORÇÃO DE MIQUEIAS 2,1-5: A SITUAÇÃO SOCIOECONÔMICA EM JUDÁ E SUAS IMPLICAÇÕES NA HERANÇA DOS CAMPONESES NA SEFELÁ JUDAÍTA NO SÉCULO VIII A.C.

Esta pesquisa procura examinar, à luz da metodologia exegética, a perícope de Miqueias 2,1-5, a fim de reconstruir o cenário no qual emergiu a dura crítica social do profeta. O texto apresenta, em sua análise literária, características de um dito profético coeso, em estilo poético. Sua estrutura encontra-se dividida em duas unidades (denúncia e castigo), sendo que cada uma das unidades possui outras duas subunidades (genérica e específica). O gênero literário harmoniza-se com um dito profético de julgamento geralmente conhecido como oráculo ai . A análise da dimensão histórica situa o acontecimento fundante em 701 a.C., na Sefelá judaíta. Numa análise investigativa do conteúdo da denúncia norteado pelo modelo teórico do modo de produção tributário, observa-se um conflito entre dois grupos. Nesse conflito, Miqueias faz uma acusação a um grupo de poder em Judá que planeja e executa ações criminosas contra a herança camponesa. O castigo descreve a conspiração e o plano divino contra esse grupo de poder. Javé havia planejado um mal idêntico ao que eles haviam cometido, desonra e privação de suas possessões. Os valores culturais de honra e vergonha subjazem a esse oráculo. Por descumprirem seus deveres junto a Javé e ao povo, os criminosos perderiam todos os seus direitos e, sobretudo, a honra perante a própria comunidade. Com base no modelo teórico do modo de produção tributário, constata-se que, na situação social em Judá no oitavo século, prevalecia um conflito entre campo e cidade. As comunidades aldeãs pagavam tributo à cidade em forma de produtos e serviços. A excessiva arrecadação de tributo e as falhas no sistema de ajuda mútua forçaram os indivíduos e famílias a contrair dívidas, a hipotecar suas terras herdadas dos pais e eventualmente perdê-las. O profeta Miqueias é o porta-voz do protesto da classe campesina que resolve reagir aos desmandos praticados pela elite citadina. Para ele, Javé escuta a queixa dos que estão sendo oprimidos e intervém na história tomando o partido do oprimido.(AU)

ANÁLISE DAS MUDANÇAS DOS FATORES DETERMINANTES DA ESTRUTURA DE CAPITAL EM FUNÇÃO DO CICLO DE VIDA DAS EMPRESAS BRASILEIRAS SÃO BERNARDO DO CAMPO

As várias teorias acerca da estrutura de capital despertam interesse motivando diversos estudos sobre o assunto sem, no entanto, ter um consenso. Outro tema aparentemente pouco explorado refere-se ao ciclo de vida das empresas e como ele pode influenciar a estrutura de capital. Este estudo teve como objetivo verificar quais determinantes possuem maior relevância no endividamento das empresas e se estes determinantes alteram-se dependendo do ciclo de vida da empresa apoiada pelas teorias Trade Off, Pecking Order e Teoria da Agência. Para alcançar o objetivo deste trabalho foi utilizado análise em painel de efeito fixo sendo a amostra composta por empresas brasileiras de capital aberto, com dados secundários disponíveis na Economática® no período de 2005 a 2013, utilizando-se os setores da BM&FBOVESPA. Como resultado principal destaca-se o mesmo comportamento entre a amostra geral, alto e baixo crescimento pelo endividamento contábil para o determinante Lucratividade apresentando uma relação negativa, e para os determinantes Oportunidade de Crescimento e Tamanho, estes com uma relação positiva. Para os grupos de alto e baixo crescimento alguns determinantes apresentaram resultados diferentes, como a singularidade que resultou significância nestes dois grupos, sendo positiva no baixo crescimento e negativa no alto crescimento, para o valor colateral dos ativos e benefício fiscal não dívida apresentaram significância apenas no grupo de baixo crescimento. Para o endividamento a valor de mercado foi observado significância para o Benefício fiscal não dívida e Singularidade. Este resultado reforça o argumento de que o ciclo de vida influência a estrutura de capital

Data compilation on the biological response to ocean acidification: environmental and experimental context of data sets and related literature

The exponential growth of studies on the biological response to ocean acidification over the last few decades has generated a large amount of data. To facilitate data comparison, a data compilation hosted at the data publisher PANGAEA was initiated in 2008 and is updated on a regular basis (doi:10.1594/PANGAEA.149999). By January 2015, a total of 581 data sets (over 4 000 000 data points) from 539 papers had been archived. Here we present the developments of this data compilation five years since its first description by Nisumaa et al. (2010). Most of study sites from which data archived are still in the Northern Hemisphere and the number of archived data from studies from the Southern Hemisphere and polar oceans are still relatively low. Data from 60 studies that investigated the response of a mix of organisms or natural communities were all added after 2010, indicating a welcomed shift from the study of individual organisms to communities and ecosystems. The initial imbalance of considerably more data archived on calcification and primary production than on other processes has improved. There is also a clear tendency towards more data archived from multifactorial studies after 2010. For easier and more effective access to ocean acidification data, the ocean acidification community is strongly encouraged to contribute to the data archiving effort, and help develop standard vocabularies describing the variables and define best practices for archiving ocean acidification data.

Sonho e cura: o culto de Asclépio em Epidauro entre os séculos IV e II a. C.

Profound changes have marked Greek society from the fourth century B.C.. Conquests, wars and epidemics altered drastically the Greek’s posture regarding his public life, his conception of gods and hence the construction of their spaces, whether sacred or profane. Through the fonts, we perceived that the cult of god Asklepeios turned very popular, in this context, for the peculiar way that the god relates to his devotees, through the dreams. We know that the dream was held, for the Greeks, as a space of real existence, it was sacred, and could be accessed in the healing rituals of Asklepios. Our work intends, thereby, to understand the curious and peculiar oniric space, mainly through the inscriptions, architectural structures of the sanctuary and the ancient texts that refer to the context of the period, because we understand that this space was the essential condition for the popularization of the cult, it placed the individual in direct contact with the divinity, a rare closeness between men and gods accepted by the greek imagery until then.

"Lancea", Lusitanian Word, and the "Lancienses" Ethnogenesis

Analysis of the word lancea, of Hispanic origin after Varro, and of place names, people´s names and personal names derived from it. It confirms that the spear was the most important weapon in the Bronze Age, belonging to the iuventus and used as heroic and divine symbol. This analysis confirms also the personality of the Lusitanians, a people related to the Celts but with more archaic archaeological, linguistic and cultural characteristics originated in the tradition of the Atlantic Bronze in the II millennium BC. It is also relevant to better know the organisation of Broze and Iron Age societies and the origin of Indo-Europeans peoples in Western Europe and of pre-Roman peoples of Iberia.

"Sub Tiberio quies"? Judaea’s Political Situation under the Prefects (6-41 c.e.), between Reality and Ideology

Deeply conflicting views on the political situation of Judaea under the Roman prefects (6-41 c.e.) have been offered. According to some scholars, this was a period of persistent political unrest and agitation, whilst according to a widespread view it was a quiescent period of political calm (reflected in Tacitus’ phrase sub Tiberio quies). The present article critically examines again the main available sources –particularly Josephus, the canonical Gospels and Tacitus– in order to offer a more reliable historical reconstruction. The conclusions drawn by this survey calls into question some widespread and insufficiently nuanced views on the period. This, in turn, allows a reflection on the non-epistemic factors which might contribute to explain the origin of such views.

Actividad física, imagen corporal y condiciones de vida. Un abordaje teórico desde los determinantes y la determinación social de la salud

El objetivo de este trabajo fue analizar la construcción social del conocimiento en Actividad física desde dos planteamientos teóricos de la salud centrando el análisis en la relación con la imagen corporal y las condiciones de vida. Se trata de un estudio teórico desde el análisis de contenido de corte narrativo de 98 artículos desarrollado en cinco etapas a través de: rastreo de documentos en bases de datos en el periodo 2000-2014, revisión de artículos, y análisis y hallazgos de significados, sentidos o contenidos. Como hallazgo importante se puede mencionar que en la literatura científica relacionada con la triada Actividad física-imagen corporal-condiciones de vida predomina la construcción del conocimiento a partir de modelos hegemónicos y dominantes que priorizan la intensidad, la frecuencia y el tiempo dedicado a la AF, la estandarización en la comparación de la apariencia física y la medición de elementos materiales en el modo de vivir de las personas, principalmente desde el abordaje de los determinantes sociales de la salud. Se concluye que es necesario revisar las poblaciones que incluyendo en los estudios al estar concentrados el conocimiento en solo unos grupos; así como se hace explícita la necesidad de revisar cuales son los aportes de la Educación Física y otras disciplinas (ciencias sociales) para una mayor comprensión teórica y práctica de la AF.

Estudio molecular en dos hermanas afectadas por ictiosis congénita autosómica recesiva : descripción de una nueva mutación causal en TGM1

Se describe la variante homocigota c.320-2A>G de TGM1 en dos hermanas con ictiosis congénita autosómica recesiva. El clonaje de los transcritos generados por esta variante permitió identificar tres mecanismos moleculares de splicing alternativos.

La cultura del trabajo y la igualdad en la Nueva Granada

Basada en los conceptos de Alexis de Tocqueville, esta investigación busca explicar de qué manera la cultura del trabajo influyó en la igualdad de condiciones. Para esto fue necesario analizar cómo la sociedad neogranadina acogía nuevas teorías y prácticas del mundo moderno liberal en su estructura socio-económica y política, haciendo indispensable, en primer lugar, realizar un estudio detallado de la situación de la Nueva Granada en los aspectos mencionados, durante finales del siglo XVIII y gran parte del siglo XIX. En principio se puede deducir que la cultura del trabajo no tuvo influencia en la igualdad de condiciones, porque la concepción protestante de la salvación del alma no halló en los neogranadinos la aceptación que requería para hacer de este un pueblo trabajador y tampoco se pudo garantizar una situación de igualdad de condiciones desde un aspecto cultural, sino que estuvo presente por medio de leyes que no eran respetadas.

Relationship Between Orofacial Function, Dentofacial Morphology, And Bite Force In Young Subjects.

The aim was to evaluate the relationship between orofacial function, dentofacial morphology, and bite force in young subjects. Three hundred and sixteen subjects were divided according to dentition stage (early, intermediate, and late mixed and permanent dentition). Orofacial function was screened using the Nordic Orofacial Test-Screening (NOT-S). Orthodontic treatment need, bite force, lateral and frontal craniofacial dimensions and presence of sleep bruxism were also assessed. The results were submitted to descriptive statistics, normality and correlation tests, analysis of variance, and multiple linear regression to test the relationship between NOT-S scores and the studied independent variables. The variance of NOT-S scores between groups was not significant. The evaluation of the variables that significantly contributed to NOT-S scores variation showed that age and presence of bruxism related to higher NOT-S total scores, while the increase in overbite measurement and presence of closed lip posture related to lower scores. Bite force did not show a significant relationship with scores of orofacial dysfunction. No significant correlations between craniofacial dimensions and NOT-S scores were observed. Age and sleep bruxism were related to higher NOT-S scores, while the increase in overbite measurement and closed lip posture contributed to lower scores of orofacial dysfunction.

Vascular Pattern In Enchondroma And Chondrosarcoma: Clinical And Immunohistologic Study.

Although cartilaginous tumors have low microvascular density, vessels are important for the provision of nutrition so that the tumor can grow and generate metastasis. The aim of this study was to assess the value of the vascular pattern classification as a prognostic tool in chondrosarcomas (CSs) and its relation with vascular endothelial growth factor (VEGF) expression. This was a retrospective study of 21 enchondromas and 57 conventional CSs. Clinical data and outcome were retrieved from medical files. CSs histologic grades (on a scale of 1 to 3) were determined according to the World Health Organization classification. The vascular pattern (on a scale of A to C) was assessed through CD34, according to Kalinski. CD105 and VEGF were also evaluated. Poor outcome was significantly associated with vascular pattern groups B and C. Higher vascular pattern were 6.5 times more frequent in moderate-grade and high-grade CSs than in grade 1 CS. On multivariate analysis, a clear correlation was found between VEGF overexpression and B/C vascular patterns. Only 18 (benign and malignant) tumors stained for CD105. The results point to the use of the vascular pattern classification as a prognostic tool in CSs and to differentiate low-grade from moderate-grade/high-grade CSs. Vascular pattern might be also used to complement histologic grade, VEGF immunostaining, and microvascular density, for indicating a patient's prognosis. Low-grade CSs develop under low neoangiogenesis, which conforms to the slow growth rate of these tumors.

Hypothalamic Inflammation And The Central Nervous System Control Of Energy Homeostasis.

The control of energy homeostasis relies on robust neuronal circuits that regulate food intake and energy expenditure. Although the physiology of these circuits is well understood, the molecular and cellular response of this program to chronic diseases is still largely unclear. Hypothalamic inflammation has emerged as a major driver of energy homeostasis dysfunction in both obesity and anorexia. Importantly, this inflammation disrupts the action of metabolic signals promoting anabolism or supporting catabolism. In this review, we address the evidence that favors hypothalamic inflammation as a factor that resets energy homeostasis in pathological states.