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1.
Rev Sci Tech ; 39(1): 47-55, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32729579

RESUMO

The World Trade Organization (WTO) and the World Organisation for Animal Health (OIE) play an important role in supporting efforts to facilitate the safe trade of animals and animal products by promoting international regulatory cooperation among their Members. International regulatory cooperation is embedded in the Agreement on the Application of Sanitary and Phytosanitary Measures (SPS Agreement) and is an integral part of the work of the Sanitary and Phytosanitary Committee. The OIE plays a crucial part in this cooperation, as the OIE is the WTO reference organisation for international standards related to animal health and zoonoses. The SPS Agreement encourages governments to apply national sanitary measures that are consistent with OIE standards, particularly when making decisions on the importation of animals and animal products. This principle of harmonisation is key to integrating the reference frameworks of the WTO SPS Agreement and the OIE standards. This paper describes international regulatory cooperation, the principle of harmonisation and its expressions, and, finally, the various ways in which the WTO and the OIE cooperate towards the achievement of their goals.


L'Organisation mondiale du commerce (OMC) et l'Organisation mondiale de la santé animale (OIE) jouent un rôle majeur dans les efforts déployés pour faciliter des échanges internationaux sûrs d'animaux et de produits d'origine animale en encourageant leurs Membres à faire appel à la coopération réglementaire internationale. La coopération réglementaire internationale s'inscrit dans l'Accord sur l'application des mesures sanitaires et phytosanitaires (Accord SPS) de l'OMC et fait partie intégrante des travaux du Comité des mesures sanitaires et phytosanitaires. L'OIE est un acteur essentiel de cette coopération, étant reconnue par l'OMC comme l'organisation de référence pour les normes internationales en lien avec la santé animale et les zoonoses. L'Accord SPS encourage les gouvernements à faire en sorte que les mesures sanitaires nationales qu'ils appliquent soient conformes aux normes de l'OIE, en particulier lorsqu'il s'agit de décisions relatives aux importations d'animaux et de produits d'origine animale. Ce principe d'harmonisation est essentiel pour intégrer les cadres de référence que constituent à la fois l'Accord SPS de l'OMC et les normes de l'OIE. Cet article décrit la coopération réglementaire internationale, le principe d'harmonisation et ses traductions concrètes, et, enfin, les diverses modalités de la coopération entre l'OMC et l'OIE en vue de réaliser leurs objectifs.


La Organización Mundial del Comercio (OMC) y la Organización Mundial de Sanidad Animal (OIE), al promover la cooperación internacional entre sus Miembros sobre cuestiones ligadas a la reglamentación, cumplen una importante función de apoyo para facilitar el comercio seguro de animales y productos de origen animal. La cooperación internacional sobre temas de reglamentación, inscrita en el Acuerdo sobre la Aplicación de Medidas Sanitarias y Fitosanitarias (Acuerdo MSF), forma parte integrante de la labor del Comité de Medidas Sanitarias y Fitosanitarias (Comité MSF). La intervención de la OIE es fundamental en esta cooperación, puesto que es la organización de referencia para la OMC en cuanto a la normativa internacional sobre sanidad animal y zoonosis. El Acuerdo MSF promueve que los gobiernos apliquen medidas sanitarias nacionales acordes con las normas de la OIE, especialmente al adoptar decisiones sobre la importación de animales y productos de origen animal. Este principio de armonización es clave para integrar los marcos de referencia que constituyen tanto el Acuerdo MSF de la OMC como las normas de la OIE. Las autoras describen la cooperación internacional en materia de reglamentación, el principio de armonización y sus aplicaciones prácticas y, por último, las diversas maneras en que la OMC y la OIE colaboran entre sí para cumplir sus objetivos.


Assuntos
Comércio , Cooperação Internacional , Animais , Saúde Global , Organizações , Zoonoses
2.
Rev Sci Tech ; 39(1): 57-67, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32729578

RESUMO

The World Organisation for Animal Health (OIE) is a major actor in international cooperation to improve animal health and welfare throughout the world. The OIE sets international standards to support Member Countries in their efforts to prevent and control animal diseases, strengthen Veterinary Services and Aquatic Animal Health Services, and facilitate safe international trade. Member Countries face many challenges in the implementation of OIE standards. Poor governance and a lack of resources and technical capacity are often major constraints. Trade concerns raised at the World Trade Organization (WTO) can also be a signal that countries are experiencing difficulties in implementing international standards. In May 2018, the World Assembly of OIE Delegates adopted a resolution recommending the establishment of an observatory to monitor the implementation of OIE standards. This monitoring mechanism will help the OIE to improve its international standard-setting process and identify the capacity-building needs of Member Countries. Monitoring implementation will be challenging as the OIE does not prescribe a specific procedure for implementing OIE standards. World Organisation for Animal Health Member Countries use a range of approaches to implement OIE standards, because of differences in animal health situations, legal frameworks and procedures, trade profiles, and acceptable levels of risk. Given this complexity, this article proposes a 'cross-over' approach to monitoring implementation that would require the collection of information from various trusted sources, such as the World Animal Health Information System (WAHIS), the OIE Performance of Veterinary Services (PVS) Pathway mission reports and the WTO Sanitary and Phytosanitary Information Management System database. This approach aims to document what is currently happening and to identify potential patterns in Member Country practices when implementing OIE standards.


L'Organisation mondiale de la santé animale (OIE) est un acteur majeur de la coopération internationale oeuvrant à l'amélioration de la santé et du bien-être animal dans le monde. L'OIE élabore des normes internationales visant à soutenir les efforts déployés par ses Membres pour prévenir et lutter contre les maladies animales, renforcer les Services vétérinaires et les Services chargés de la santé des animaux aquatiques, et faciliter un commerce international sûr. Les Membres rencontrent de nombreuses difficultés lors de la mise en oeuvre des normes de l'OIE. Une mauvaise gouvernance et l'insuffisance des ressources et des capacités techniques constituent souvent des contraintes majeures. Les préoccupations commerciales soulevées au sein de l'Organisation mondiale du commerce (OMC) sont également révélatrices des difficultés rencontrées par les pays pour mettre en oeuvre les normes internationales. En mai 2018, l'Assemblée mondiale des Délégués de l'OIE a adopté une résolution recommandant la création d'un observatoire destiné à assurer le suivi de la mise en oeuvre des normes de l'OIE. Grâce à ce mécanisme de suivi, l'OIE sera à même d'améliorer le processus d'élaboration de ses normes internationales et d'identifier les besoins de ses Membres en matière de renforcement des capacités. Le suivi de la mise en oeuvre ne sera pas une tâche facile, dans la mesure où l'OIE ne prescrit pas de procédure spécifique pour appliquer ses normes. Les Membres de l'OIE recourent à diverses approches pour mettre en oeuvre les normes de l'OIE, dictées par des différences dans les situations zoosanitaires, les cadres et procédures juridiques, les profils commerciaux et les niveaux de risque considérés comme acceptables. Face à une telle complexité, les auteurs proposent une méthode transversale de suivi de la mise en oeuvre, qui passe par la collecte d'informations auprès de diverses sources fiables telles que le Système mondial d'information sanitaire de l'OIE (WAHIS), les rapports de mission du Processus de l'OIE pour évaluer la Performance des Services vétérinaires (Processus PVS) et la base de données de l'OMC de gestion des renseignements sanitaires et phytosanitaires. Cette approche vise à documenter ce qui se fait actuellement et à identifier d'éventuelles tendances dans les pratiques des Membres en matière de mise en oeuvre des normes de l'OIE.


La Organización Mundial de Sanidad Animal (OIE) es uno de los actores principales de la cooperación internacional para mejorar la sanidad y el bienestar animales en todo el mundo. La OIE elabora normas internacionales destinadas a apoyar el esfuerzo de los Países Miembros por prevenir y combatir las enfermedades animales, fortalecer los Servicios Veterinarios y los Servicios de sanidad de los animales acuáticos y facilitar un comercio internacional seguro. Los Países Miembros afrontan numerosos desafíos a la hora de implementar las normas de la OIE. La insuficiencia de mecanismos de gobernanza y la falta de recursos y capacidad técnica constituyen a menudo obstáculos de gran calado. Las preocupaciones comerciales expresadas ante la Organización Mundial del Comercio (OMC) también pueden ser una señal de las dificultades que afrontan los países para implementar las normas internacionales. En mayo de 2018, la Asamblea Mundial de Delegados de la OIE aprobó una resolución en la que recomendaba la creación de un observatorio para el seguimiento de la implementación de las normas de la OIE. Este mecanismo ayudará a la OIE a mejorar su proceso de elaboración de normas internacionales y a identificar las necesidades de capacidades específicas de los Países Miembros. El seguimiento de la implementación no será fácil, pues la OIE no prescribe ningún procedimiento específico para poner en práctica sus normas. Los Países Miembros utilizan modalidades distintas debido a las diferencias en cuanto a situaciones zoosanitarias, ordenamiento y procedimientos jurídicos, perfiles comerciales y niveles de riesgo aceptables. Teniendo en cuenta esta compleja situación, los autores proponen aquí un enfoque «transversal¼ de seguimiento de la implementación de las normas, que requeriría reunir información de diversas fuentes fidedignas, como el Sistema Mundial de Información Zoosanitaria (WAHIS), los informes de las misiones de evaluación de las prestaciones de los Servicios Veterinarios (Proceso PVS) de la OIE y la base de datos del sistema de la OMC de gestión de información relativa a las medidas sanitarias y fitosanitarias. Tal enfoque tiene por objetivo documentar lo que está ocurriendo actualmente e identificar posibles patrones en las prácticas de los Países Miembros al implementar las normas de la OIE.


Assuntos
Doenças dos Animais/prevenção & controle , Medicina Veterinária , Animais , Comércio , Saúde Global , Cooperação Internacional , Internacionalidade
3.
J Dairy Sci ; 102(12): 11652-11669, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31521361

RESUMO

The study aimed at the analysis of the functional status of cryopreserved bovine sperm using multicolor flow cytometry. The value of sperm functional traits as predictors of bull fertility was further evaluated through a retrospective fertility study. For this purpose, 20 Holstein-Friesian bulls serving as mature sperm donors in an artificial insemination (AI) center were selected based on their annual 56-d non-return rate (%) after at least 1,000 AI, and were accordingly classified as high (HF; nHF = 10 bulls) or low fertility bulls (LF; nLF = 10 bulls). Four to 5 cryopreserved ejaculates per bull (91 ejaculates in total) were examined immediately after thawing (0 h) and after a 3-h incubation at 38°C (3 h). A panel of 5 fluorochromes including calcein violet, propidium iodide, pycoerythrin-conjugated lectin of Arachis hypogea, Fluo-4, and cyanine dye DiIC1(5) was configured by means of a 3-laser flow cytometer, to simultaneously assess sperm esterase activity, plasma membrane integrity, acrosomal status, intracellular Ca2+ levels, and mitochondrial membrane potential, respectively. The % relative size of 18 sperm sub-populations showing 2 or more of a combination of the following features was determined: high esterase activity (Cpos), intact plasma membrane (PIneg), unstained acrosome (PNAneg), low intracellular Ca2+ levels (Fneg), and high mitochondrial membrane potential (Mpos). In both fertility groups, Mpos cells comprised more than 90 and 84% of PInegPNAneg sperm at 0 and 3 h, respectively. The percentage of CposPInegPNAnegFnegMpos sperm did not differ between HF and LF ejaculates; however, the percentage of Fneg cells within the PInegPNAneg and PInegMpos sperm populations at 0 h was higher in the HF than in the LF bulls. Applying the random forest ensemble learning method, approximately two-thirds of ejaculates could be correctly assigned to their fertility group. The fraction of Fneg sperm within the PInegMpos population at 0 h was the most important fertility predictor among the 18 defined sperm populations. In conclusion, multicolor flow cytometry offered an insight into the functional heterogeneity of cryopreserved bovine sperm. Indeed, the ability of viable sperm to retain low Ca2+ levels differed between bulls of diverse fertility. A classifier based on selected sperm populations assessed through multicolor flow cytometry could contribute to the prognosis of bull fertility after AI.


Assuntos
Bovinos/fisiologia , Criopreservação/veterinária , Fertilidade , Espermatozoides/fisiologia , Acrossomo/fisiologia , Animais , Membrana Celular/fisiologia , Citometria de Fluxo/veterinária , Inseminação Artificial/veterinária , Masculino , Estudos Retrospectivos , Motilidade dos Espermatozoides
4.
Rev Sci Tech ; 38(2): 523-536, 2019 Sep.
Artigo em Inglês, Francês, Espanhol | MEDLINE | ID: mdl-31866678

RESUMO

The World Organisation for Animal Health (OIE) develops international standards for the prevention, detection and control of aquatic animal diseases as well as the safe international trade of amphibians, crustaceans, fish, molluscs and their products. The Competent Authorities of importing and exporting countries should implement the OIE international standards by adopting the required legislation as this provides the basis for setting sanitary measures that ensure safe international trade, while avoiding unjustified sanitary barriers to trade. Based on an analysis of legislation notified by countries to the World Trade Organization (WTO) in the context of the Agreement on the Application of Sanitary and Phytosanitary Measures (SPS Agreement), the authors explore how and to what extent Member Countries use the OIE international standards when developing sanitary measures. The study develops an analytical framework for collecting and presenting countries' legislation to determine if a direct link can be demonstrated between national legislation and OIE international standards. Results show that OIE international standards are implemented through different categories of legislation which range from more general (those providing a general sanitary framework) to more specific (those setting requirements for the import of aquatic animals and aquatic animal products). However, the study illustrates the difficulty of identifying direct links between countries' legislation and OIE international standards. Nonetheless, this study is the first step in the design of an approach to better understand how OIE international standards are used by Member Countries to devise sanitary measures in the context of international trade. It further notes that increased transparency of national sanitary legislation can facilitate efforts to improve knowledge on the implementation of OIE international standards.


L'Organisation mondiale de la santé animale (OIE) prépare et publie des normes internationales relatives à la prévention, la détection et le contrôle des maladies des animaux aquatiques et à la sécurité sanitaire des échanges internationaux d'amphibiens, crustacés, poissons, mollusques et produits issus de ces espèces. Les Autorités compétentes des pays importateurs et exportateurs doivent procéder à la mise en œuvre de ces normes par le biais d'une législation appropriée, celle-ci fournissant la base pour élaborer des mesures sanitaires destinées à garantir la sécurité sanitaire des échanges internationaux et à éviter l'imposition d'obstacles injustifiés au commerce. À partir d'une analyse des notifications adressées par les pays à l'Organisation mondiale du commerce (OMC) concernant les dispositions de leur législation relevant de l'Accord sur l'application des mesures sanitaires et phytosanitaires (Accord SPS), les auteurs explorent comment et dans quelles mesures les Pays membres utilisent les normes internationales de l'OIE pour développer des mesures sanitaires. Un cadre analytique a été élaboré pour les besoins de cette étude afin de recueillir et de traiter les données relatives à la législation des pays en vue de déterminer l'existence ou non d'un lien direct entre la législation nationale et les normes internationales de l'OIE. Les résultats montrent que la mise en œuvre des normes internationales de l'OIE fait appel à diverses catégories d'instruments législatifs qui vont du plus général (ceux qui fournissent un cadre sanitaire général) au plus spécifique (dispositions relatives aux importations d'animaux aquatiques et de leurs produits). Cette étude fait néanmoins état des difficultés à déceler un lien direct entre la législation d'un pays et les normes internationales de l'OIE. Malgré tout, cette étude marque une première étape dans l'élaboration d'une approche destinée à mieux comprendre comment les Pays membres utilisent les normes internationales de l'OIE lorsqu'ils instaurent des mesures sanitaires dans le contexte des échanges internationaux. Elle fait également ressortir que l'amélioration de la transparence de la législation sanitaire d'un pays est un élément facilitateur pour mieux comprendre tous les aspects de la mise en œuvre des normes internationales de l'OIE.


La Organización Mundial de Sanidad Animal (OIE) elabora normas internacionales que regulan la prevención, la detección y el control de las enfermedades de los animales acuáticos, así como la seguridad del comercio internacional de anfibios, crustáceos, peces y moluscos y los productos derivados de ellos. Las autoridades competentes de los países importadores y exportadores deben aplicar las normas internacionales de la OIE adoptando la legislación necesaria, pues esta sienta las bases para establecer medidas sanitarias que garanticen un comercio internacional seguro, evitando a la vez toda barrera sanitaria al comercio que no esté justificada. Los autores, partiendo del análisis de los textos legislativos comunicados por los países a la Organización Mundial del Comercio (OMC) como parte del Acuerdo sobre la Aplicación de Medidas Sanitarias y Fitosanitarias (Acuerdo MSF), explican cómo y en qué medida los Países Miembros utilizan las normas internacionales de la OIE al definir medidas sanitarias. Como parte del estudio se elaboró un marco analítico destinado a recopilar y presentar la legislación de los países y a determinar, a partir de ahí, si existe un nexo directo entre la legislación nacional y las normas internacionales de la OIE. Los resultados demuestran que las normas internacionales de la OIE se implementan mediante diferentes categorías de instrumentos legales, que van desde lo más genérico (textos que sientan un marco sanitario general) hasta lo más específico (textos que establecen requisitos para importar animales acuáticos y sus derivados). Sin embargo, el estudio evidencia también la dificultad de encontrar nexos directos entre la legislación de los países y las normas internacionales de la OIE. Con todo, el estudio aquí presentado supone el primer paso hacia la concepción de un método que ayude a comprender mejor el modo en que los Países Miembros utilizan las normas internacionales de la OIE para definir medidas sanitarias que se apliquen al comercio internacional. Además, pone de manifiesto que un mayor grado de transparencia de la legislación sanitaria nacional puede facilitar los esfuerzos por conocer con mayor profundidad la forma en que se aplican las normas internacionales de la OIE.


Assuntos
Doenças dos Animais , Cooperação Internacional , Medicina Veterinária/normas , Doenças dos Animais/prevenção & controle , Animais , Comércio/normas , Saúde Global , Internacionalidade
5.
Biochemistry (Mosc) ; 81(7): 691-9, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27449615

RESUMO

The intracellular PI3K-AKT-mTOR pathway is involved in regulation of numerous important cell processes including cell growth, differentiation, and metabolism. The PI3Kα isoform has received particular attention as a novel molecular target in gene therapy, since this isoform plays critical roles in tumor progression and tumor blood flow and angiogenesis. However, the role of PI3Kα and other class I isoforms, i.e. PI3Kß, γ, δ, in the regulation of vascular tone and regional blood flow are largely unknown. We used novel isoform-specific PI3K inhibitors and mice deficient in both PI3Kγ and PI3Kδ (Pik3cg(-/-)/Pik3cd(-/-)) to define the putative contribution of PI3K isoform(s) to arterial vasoconstriction. Wire myography was used to measure isometric contractions of isolated murine mesenteric arterial rings. Phenylephrine-dependent contractions were inhibited by the pan PI3K inhibitors wortmannin (100 nM) and LY294002 (10 µM). These vasoconstrictions were also inhibited by the PI3Kα isoform inhibitors A66 (10 µM) and PI-103 (1 µM), but not by the PI3Kß isoform inhibitor TGX 221 (100 nM). Pik3cg(-/-)/Pik3cd(-/-)-arteries showed normal vasoconstriction. We conclude that PI3Kα is an important downstream element in vasoconstrictor GPCR signaling, which contributes to arterial vasocontraction via α1-adrenergic receptors. Our results highlight a regulatory role of PI3Kα in the cardiovascular system, which widens the spectrum of gene therapy approaches targeting PI3Kα in cancer cells and tumor angiogenesis and regional blood flow.


Assuntos
Fosfatidilinositol 3-Quinases/metabolismo , Androstadienos/farmacologia , Animais , Cromonas/farmacologia , Classe I de Fosfatidilinositol 3-Quinases , Classe Ib de Fosfatidilinositol 3-Quinase/deficiência , Classe Ib de Fosfatidilinositol 3-Quinase/genética , Furanos/farmacologia , Artérias Mesentéricas/fisiologia , Camundongos , Camundongos Knockout , Morfolinas/farmacologia , Neoplasias/irrigação sanguínea , Neoplasias/patologia , Neoplasias/terapia , Neovascularização Patológica , Fenilefrina/farmacologia , Fosfatidilinositol 3-Quinases/deficiência , Fosfatidilinositol 3-Quinases/genética , Inibidores de Fosfoinositídeo-3 Quinase , Piridinas/farmacologia , Pirimidinas/farmacologia , Pirimidinonas/farmacologia , Receptores Adrenérgicos alfa 1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos , Wortmanina
6.
Eur J Paediatr Dent ; 17(2): 129-35, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27377111

RESUMO

AIM: Though the use of advanced behaviour management may facilitate dental treatment in children, some patients still require comprehensive care under general anaesthesia (GA). This is especially true for young children and/or medically compromised children. Thus, this study aimed to provide information about children undergoing GA with regard to age, sex and medical conditions (ICD-10), repeated treatments, dental procedures and recall. MATERIALS AND METHODS: A total of 464 medically compromised children treated under GA in a dental university clinic between 2004 and 2012 were included. Patients` records were analysed retrospectively using SPSS (Version 21.0) and R for statistical analysis. RESULTS: More than 75% of the patients were younger than six years when receiving initial GA. The proportion of children subjected to repeated treatments was low, at 11% for a second and <2% for a third round of GA. The greatest proportion of dental care consisted of restorative therapy and tooth extractions. The recall behaviour observed between the first and second GA revealed no significant influence on the time elapsed in between events (p>0.05). CONCLUSION: Oral care in children with medical conditions is mostly caries-related, and repeated treatment may be necessary, though it was generally uncommon in this university-based study population.


Assuntos
Anestesia Geral , Serviços de Saúde Bucal , Adolescente , Criança , Pré-Escolar , Humanos , Lactente
8.
Brain Topogr ; 24(1): 78-89, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20820898

RESUMO

Greater low frequency power (<8 Hz) in the electroencephalogram (EEG) at rest is normal in the immature developing brain of children when compared to adults. Children with epilepsy also have greater low frequency interictal resting EEG activity. Whether these power elevations reflect brain immaturity due to a developmental lag or the underlying epileptic pathophysiology is unclear. The present study addresses this question by analyzing spectral EEG topographies and sources for normally developing children and children with epilepsy. We first compared the resting EEG of healthy children to that of healthy adults to isolate effects related to normal brain immaturity. Next, we compared the EEG from 10 children with generalized cryptogenic epilepsy to the EEG of 24 healthy children to isolate effects related to epilepsy. Spectral analysis revealed that global low (delta: 1-3 Hz, theta: 4-7 Hz), medium (alpha: 8-12 Hz) and high (beta: 13-25 Hz) frequency EEG activity was greater in children without epilepsy compared to adults, and even further elevated for children with epilepsy. Topographical and tomographic EEG analyses showed that normal immaturity corresponded to greater delta and theta activity at fronto-central scalp and brain regions, respectively. In contrast, the epilepsy-related activity elevations were predominantly in the alpha band at parieto-occipital electrodes and brain regions, respectively. We conclude that lower frequency activity can be a sign of normal brain immaturity or brain pathology depending on the specific topography and frequency of the oscillating neuronal network.


Assuntos
Ondas Encefálicas/fisiologia , Córtex Cerebral/crescimento & desenvolvimento , Eletroencefalografia/métodos , Epilepsia/fisiopatologia , Adulto , Mapeamento Encefálico/métodos , Córtex Cerebral/anatomia & histologia , Criança , Epilepsia/diagnóstico , Feminino , Humanos , Masculino
9.
Neuroimage ; 50(2): 837-46, 2010 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-20025981

RESUMO

Neuroimaging studies have thoroughly investigated brain regions that are recruited when we put ourselves in another person's shoes. Taking a third-person perspective (3PP) as opposed to a first-person perspective (1PP) has been associated with brain activation in the inferior parietal cortex, the medial posterior cortex and the prefrontal cortex. Here we investigate for the first time the development of the neural network that yields cognitive perspective taking. Twelve adults (aged 25-32 years) and twelve school-aged children (aged 8-10 years) were investigated using functional magnetic resonance imaging (fMRI). Behaviorally, we found a decrease of reaction time differences between 3PP and 1PP with age indicating that adults were more efficient in processing a 3PP. Despite the reaction time differences both groups were equally accurate in their judgments. Brain imaging data indicated neural activity in the left inferior parietal cortex and precuneus for adults during 3PP as compared with 1PP judgments. Children additionally showed enhanced activity in the dorsolateral prefrontal cortex and the right inferior perietal cortex. We found a significant interaction between groups and brain activation in the right dorsolateral prefrontal cortex and in the right inferior parietal cortex. These results suggest that the development of the ability to reason about another person's mind accompanies a shift in activity from frontal to posterior brain regions and from bilateral to unilateral left inferior parietal cortex.


Assuntos
Mapeamento Encefálico , Encéfalo/fisiologia , Empatia/fisiologia , Julgamento/fisiologia , Vias Neurais/fisiologia , Adulto , Criança , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Adulto Jovem
10.
Sci Rep ; 10(1): 18728, 2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-33127943

RESUMO

The visual word form area (VWFA) in the left ventral occipito-temporal (vOT) cortex is key to fluent reading in children and adults. Diminished VWFA activation during print processing tasks is a common finding in subjects with severe reading problems. Here, we report fMRI data from a multicentre study with 140 children in primary school (7.9-12.2 years; 55 children with dyslexia, 73 typical readers, 12 intermediate readers). All performed a semantic task on visually presented words and a matched control task on symbol strings. With this large group of children, including the entire spectrum from severely impaired to highly fluent readers, we aimed to clarify the association of reading fluency and left vOT activation during visual word processing. The results of this study confirm reduced word-sensitive activation within the left vOT in children with dyslexia. Interestingly, the association of reading skills and left vOT activation was especially strong and spatially extended in children with dyslexia. Thus, deficits in basic visual word form processing increase with the severity of reading disability but seem only weakly associated with fluency within the typical reading range suggesting a linear dependence of reading scores with VFWA activation only in the poorest readers.


Assuntos
Dislexia/diagnóstico por imagem , Dislexia/fisiopatologia , Processamento de Texto , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Mapeamento Encefálico , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Reconhecimento Visual de Modelos/fisiologia , Percepção Visual
11.
J Cell Biol ; 106(6): 1853-61, 1988 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2898478

RESUMO

Novel subcellular fractionation procedures and pulse-chase techniques were used to study the intracellular transport of the microvillar membrane hydrolases sucrase-isomaltase and dipeptidylpeptidase IV in the differentiated colon adenocarcinoma cell line Caco-2. The overall rate of transport to the cell surface was two fold faster for dipeptidylpeptidase IV than for sucrase-isomaltase, while no significant differences were observed in transport rates from the site of complex glycosylation to the brush border. The delayed arrival of sucrase-isomaltase in the compartment where complex glycosylation occurs was only in part due to exit from the endoplasmic reticulum. A major slow-down could be ascribed to maturation in and transit of this enzyme through the Golgi apparatus. These results suggest that the observed asynchronism is due to more than one rate-limiting step along the rough endoplasmic reticulum to trans-Golgi pathway.


Assuntos
Dipeptidil Peptidases e Tripeptidil Peptidases/metabolismo , Mucosa Intestinal/enzimologia , Complexos Multienzimáticos/metabolismo , Complexo Sacarase-Isomaltase/metabolismo , Transporte Biológico , Carbonil Cianeto m-Clorofenil Hidrazona/farmacologia , Compartimento Celular , Dipeptidil Peptidase 4 , Retículo Endoplasmático/metabolismo , Imunofluorescência , Complexo de Golgi/metabolismo , Humanos , Membranas Intracelulares/metabolismo , Cinética , Microscopia Eletrônica , Microvilosidades/enzimologia , Processamento de Proteína Pós-Traducional , Células Tumorais Cultivadas
12.
J Cell Biol ; 136(4): 935-44, 1997 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-9049257

RESUMO

The H-rev107 gene is a new class II tumor suppressor, as defined by its reversible downregulation and growth-inhibiting capacity in HRAS transformed cell lines. Overexpression of the H-rev107 cDNA in HRAS-transformed ANR4 hepatoma cells or in FE-8 fibroblasts resulted in 75% reduction of colony formation. Cell populations of H-rev107 transfectants showed an attenuated tumor formation in nude mice. Cells explanted from tumors or maintained in cell culture for an extended period of time no longer exhibited detectable levels of the H-rev107 protein, suggesting strong selection against H-rev107 expression in vitro and in vivo. Expression of the truncated form of H-rev107 lacking the COOH-terminal membrane associated domain of 25 amino acids, had a weaker inhibitory effect on proliferation in vitro and was unable to attenuate tumor growth in nude mice. The H-rev107 mRNA is expressed in most adult rat tissues, and immunohistochemical analysis showed expression of the protein in differentiated epithelial cells of stomach, of colon and small intestine, in kidney, bladder, esophagus, and in tracheal and bronchial epithelium. H-rev107 gene transcription is downregulated in rat cell lines derived from liver, kidney, and pancreatic tumors and also in experimental mammary tumors expressing a RAS transgene. In colon carcinoma cell lines only minute amounts of protein were detectable. Thus, downregulation of H-rev107 expression may occur at the level of mRNA or protein.


Assuntos
Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Genes Supressores de Tumor , Inibidores do Crescimento/genética , Inibidores do Crescimento/fisiologia , Proteínas/fisiologia , Animais , Carcinoma , Carcinoma Hepatocelular , Linhagem Celular Transformada , Neoplasias do Colo , Regulação para Baixo/fisiologia , Fibroblastos , Líquido Intracelular/metabolismo , Neoplasias Hepáticas , Especificidade de Órgãos/genética , Neoplasias Pancreáticas , Fosfolipases A2 Independentes de Cálcio , Proteínas/genética , RNA Mensageiro/biossíntese , Ratos , Células Tumorais Cultivadas , Proteínas Supressoras de Tumor
13.
Parasitol Res ; 104(6): 1459-64, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19172294

RESUMO

Glycerol derivatives are a class of compounds, which are easy and inexpensive to produce with potent anti-malarial activities against blood stages of Plasmodium falciparum in vitro. In the present study, one of these compounds, termed 1t, which had the lowest IC(50) values, was assessed in a murine malarial model. Nuclear magnetic resonance imaging and Balb/c mice infected with Plasmodium berghei ANKA strain were treated in a 4-day suppressive test. Mice received a once-daily intraperitoneal administration of 50 mg/Kg of the drug for 4 days. Although no parasitaemia clearance was reached, a slower parasite proliferation and a slightly longer survival time compared with the placebo group were observed.


Assuntos
Amino Álcoois/uso terapêutico , Antimaláricos/uso terapêutico , Malária/tratamento farmacológico , Plasmodium berghei/efeitos dos fármacos , Amino Álcoois/administração & dosagem , Amino Álcoois/farmacologia , Animais , Antimaláricos/administração & dosagem , Antimaláricos/farmacologia , Feminino , Concentração Inibidora 50 , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Parasitemia/tratamento farmacológico , Análise de Sobrevida
14.
J Dent ; 36(12): 1033-40, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18930575

RESUMO

OBJECTIVES: To determine the clinical performance of a laser fluorescence device (DIAGNOdent pen, KaVo) to discriminate between different occlusal caries depths (D(0)-D(1-4); D(0-2)-D(3,4)) in permanent molars. METHODS: In this prospective, randomized two-centre-study 120 sound/uncavitated carious sites in 120 patients were measured after visual and radiographic caries assessment. In cases of operative intervention (n=86), the lesion depths after caries removal were recorded (reference). In cases of preventive intervention (n=34), the sites were reassessed visually/radiographically after 12 months to verify the status assessed before (reference). The discrimination performance was determined statistically (Mann-Whitney test, Spearman's rho coefficient, and areas under the receiver operating characteristic curves (AUCs)). Sensitivities (SE) and specificities (SP) were plotted as a function of the measured values and cut-off values for the mentioned thresholds suggested. RESULTS: Sound sites (n=13) had significantly minor fluorescence values than carious sites (n=107) (P<0.0001) as had sites with no/enamel caries (n=63) compared to dentinal caries (n=57). The AUCs for the same discriminations were 0.92 and 0.78 (P<0.001). For the D(0)-D(1-4) threshold, a cut-off at a value of 12 (SE: 0.88, SP: 0.85) and for the D(0-2)-D(3,4) threshold at 25 (SE: 0.67, SP: 0.79) can be suggested. A moderate positive correlation between the measurements and the caries depths was calculated (rho=+0.57, P=0.01). CONCLUSION: Within this study, the device's discrimination performance for different caries depths was moderate to very good and it may be recommended as adjunct tool in the diagnosis of occlusal caries.


Assuntos
Cárie Dentária/diagnóstico , Lasers , Dente Molar/patologia , Adolescente , Adulto , Idoso , Área Sob a Curva , Criança , Cárie Dentária/diagnóstico por imagem , Cárie Dentária/prevenção & controle , Preparo da Cavidade Dentária/métodos , Esmalte Dentário/diagnóstico por imagem , Esmalte Dentário/patologia , Fissuras Dentárias/diagnóstico , Fissuras Dentárias/diagnóstico por imagem , Restauração Dentária Permanente/métodos , Dentina/diagnóstico por imagem , Dentina/patologia , Feminino , Fluorescência , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Dente Molar/diagnóstico por imagem , Estudos Prospectivos , Curva ROC , Radiografia Interproximal , Sensibilidade e Especificidade , Adulto Jovem
15.
Cancer Res ; 59(7 Suppl): 1794s-1798s, 1999 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-10197599

RESUMO

Two general features have emerged about genes that are activated after chromosomal translocations in acute forms of cancer. The protein products of these genes are transcription regulators and are involved in developmental processes, and it seems that the subversion of these normal functions accounts for their role in tumorigenesis. The features of the LMO family of genes, which encode LIM-domain proteins involved in T-cell acute leukemia through chromosomal translocations, typify these abnormal functions in tumorigenesis. For example, the LMO2 protein is involved in the formation of multimeric DNA-binding complexes, which may vary in composition at different stages of hematopoiesis and function to control differentiation of specific lineages. In T cells, enforced expression of Lmo2 causes aberrant protein complex formation that primarily seems to hinder the T-cell differentiation program. These observations underscore the conclusion that protein-protein interaction (in this case, through the LIM domain) is a key determinant in tumorigenesis. Furthermore, the study of chromosomal translocations as naturally occurring mutations has been informative about mechanisms in hematopoiesis as well as in tumor etiology.


Assuntos
Proteínas de Ligação a DNA/genética , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Leucemia Experimental/genética , Metaloproteínas/genética , Transcrição Gênica , Translocação Genética , Doença Aguda , Proteínas Adaptadoras de Transdução de Sinal , Animais , Hematopoese/fisiologia , Proteínas com Domínio LIM , Leucemia-Linfoma de Células T do Adulto/genética , Camundongos , Família Multigênica
16.
Cancer Res ; 50(24): 7942-9, 1990 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-2253236

RESUMO

The polymorphic acetyltransferase isozyme expressed in homozygous rapid acetylator inbred hamster liver cytosol was purified over 2000-fold by sequential Q-Sepharose fast-flow anion-exchange chromatography, Sephacryl S-200 high-resolution size-exclusion chromatography, Mono Q anion-exchange fast-protein liquid chromatography, and preparative polyacrylamide gel electrophoresis. The isozyme migrated as a single homogeneous monomer following both preparative and sodium dodecyl sulfate-polyacrylamide electrophoresis. The molecular weight was estimated at 34,170 following elution via size-exclusion chromatography and 35,467 following migration via sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The homogeneous polymorphic acetyltransferase exhibited a broad substrate specificity; it catalyzed the acetyl coenzyme A-dependent N-acetylation of p-aminobenzoic acid, carbocyclic arylamine carcinogens such as 2-aminofluorene, 4-aminobiphenyl and beta-naphthylamine, and heterocyclic arylamine carcinogens such as 2-aminodipyrido[1,2-a:3'2'd]imidazole and 3-amino-1-methyl-5H-pyrido[4,3-b]indole. It also readily catalyzed the acetyl coenzyme A-dependent metabolic activation (via O-acetylation) of N-hydroxy-2-aminofluorene to DNA adducts but not the metabolic activation (via intramolecular, N,O-acetyltransfer) of N-hydroxy-2-acetylaminofluorene or N-hydroxy-4-acetylaminobiphenyl to DNA adducts. Conversely, the partially purified monomorphic acetyltransferase isozyme from the same hamsters readily catalyzed the metabolic activation of N-hydroxy-2-acetylaminofluorene and N-hydroxy-4-acetylaminobiphenyl, and rates of metabolic activation of these substrates did not differ between homozygous rapid and slow acetylator liver, intestine, kidney, and lung cytosols. Heat inactivation rates for the purified polymorphic acetyltransferase isozyme were first order and indistinguishable for the acetyl coenzyme A-dependent N-acetylation and O-acetylation activities. The results strongly suggest the expression of a single polymorphic acetyltransferase product of the hamster polymorphic acetyltransferase gene that catalyzes both acetyl coenzyme A-dependent N-acetylation and O-acetylation of arylamine and N-hydroxyarylamine carcinogens but not the metabolic activation of N-hydroxy-N-acetylarylamines (arylhydroxamic acids) via intramolecular N,O-acetyltransfer. Consequently, acetylator genotype-dependent metabolic activation of N-hydroxyarylamines to a DNA adduct in hamster is catalyzed by direct O-acetylation of the hydroxyl group and not via sequential N-acetylation followed by N,O-acetyltransfer.


Assuntos
Acetiltransferases , Aciltransferases/isolamento & purificação , Arilamina N-Acetiltransferase/isolamento & purificação , Homozigoto , Intestinos/enzimologia , Rim/enzimologia , Fígado/enzimologia , Pulmão/enzimologia , Polimorfismo Genético , Aciltransferases/genética , Aciltransferases/metabolismo , Animais , Arilamina N-Acetiltransferase/genética , Arilamina N-Acetiltransferase/metabolismo , Cromatografia em Gel , Cromatografia por Troca Iônica , Cricetinae , Citosol/enzimologia , DNA/metabolismo , Eletroforese em Gel de Poliacrilamida , Genótipo , Cinética , Masculino , Mesocricetus , Peso Molecular
17.
J Innate Immun ; 8(4): 362-73, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26950764

RESUMO

Pseudomonas aeruginosa is a key opportunistic pathogen causing disease in cystic fibrosis (CF) and other lung diseases such as chronic obstructive pulmonary disease (COPD). However, the pulmonary host defense mechanisms regulating anti-P. aeruginosa immunity remain incompletely understood. Here we demonstrate, by studying an airway P. aeruginosa infection model, in vivo bioluminescence imaging, neutrophil effector responses and human airway samples, that the chemokine receptor CXCR1 regulates pulmonary host defense against P. aeruginosa. Mechanistically, CXCR1 regulates anti-Pseudomonas neutrophil responses through modulation of reactive oxygen species and interference with Toll-like receptor 5 expression. These studies define CXCR1 as a novel, noncanonical chemokine receptor that regulates pulmonary anti-Pseudomonas host defense with broad implications for CF, COPD and other infectious lung diseases.


Assuntos
Fibrose Cística/imunologia , Neutrófilos/imunologia , Infecções por Pseudomonas/imunologia , Pseudomonas aeruginosa/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Receptores de Interleucina-8A/metabolismo , Mucosa Respiratória/imunologia , Animais , Células Cultivadas , Modelos Animais de Doenças , Feminino , Interações Hospedeiro-Patógeno , Humanos , Imunidade Inata , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Espécies Reativas de Oxigênio/metabolismo , Receptores de Interleucina-8A/imunologia , Mucosa Respiratória/microbiologia , Receptor 5 Toll-Like/genética , Receptor 5 Toll-Like/metabolismo , Adulto Jovem
18.
Prostaglandins Other Lipid Mediat ; 76(1-4): 35-47, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15967160

RESUMO

Platelet-activating factor (PAF) and its receptors are involved in inflammatory-like processes of the uterus associated with increased vascular permeability. PAF is supposed to be influenced by ovarian steroid hormones. The present study was undertaken to examine whether progesterone (P(4)), estradiol (E(2)) or PAF influence the PAF receptor gene expression in perfused endometrial explants derived from ovariectomized bovine. Furthermore, we identified the cell types in which the PAF receptor gene and protein are expressed. In endometrial explants, applications of 10 nM P(4) or 10nM P(4) plus 10 nM E(2) for 24 h induced elevated transcript levels of PAF receptor in comparison to the controls or after treatment with 1 nM E(2). When explants were administered 10 nM E(2), a slight decrease in the transcript level was recorded. After treatment of explants with PAF, no significant changes in PAF receptor mRNA expression was observed compared to the control group. We demonstrate that PAF receptor immunoreactivity and mRNA are detected mainly in the luminal epithelium, epithelial cells of the superficial glands and to a lesser degree in stroma. Levels of PAF receptor mRNA in bovine endometrial explants were correlated with PAF receptor protein localization assessed by immunohistochemistry. The regulation of PAF receptor by progesterone in bovine endometrial explants suggests that PAF is involved in the physiological process of reproduction.


Assuntos
Endométrio/metabolismo , Estradiol/fisiologia , Ovariectomia , Ovário/fisiologia , Fator de Ativação de Plaquetas/fisiologia , Progesterona/fisiologia , RNA Mensageiro/metabolismo , Animais , Sequência de Bases , Bovinos , Primers do DNA , Feminino , Imuno-Histoquímica , Perfusão , Reação em Cadeia da Polimerase Via Transcriptase Reversa
19.
Oper Dent ; 40(3): 255-62, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25695643

RESUMO

OBJECTIVE: This in vitro study aimed to evaluate occlusal caries extension in relation to visual and radiographic diagnostic criteria and their clinical value to indicate operative or preventive dental care. METHODS: A total of 196 third molars with clinically sound occlusal fissures or noncavitated lesions were collected. Before microcomputed tomography (µCT) investigation, each tooth was examined visually and radiographically. Kühnisch's µCT-based caries-extension index (CE index) was used to determine the caries depth on a numeric scale (0 = sound; 0.01-0.99 = enamel caries; 1.0-1.99 = dentin caries). Sensitivities (SEs), specificities (SPs), and area under the receiver operating characteristic curve (Az value) were also calculated. RESULTS: Based on µCT data, the following mean CE index values and standard deviations (SDs) were documented according to the visual criteria: sound = 0.6 (0.4); first visible signs = 0.9 (0.4); established lesions = 1.3 (0.3); microcavities = 1.4 (0.2); dentin exposure = 1.5 (0.2); and large cavities = 1.5 (0.3). The radiographic categories according to Marthaler (enamel caries [D0-2], caries in the outer half of dentin [D3], and caries in the inner half of dentin [D4]) were related to CE index values of 0.9 (0.4), 1.4 (0.2) and 1.6 (0.4), respectively. Caries detected visually or radiographically showed an SE of 84% and an SP of 85% (Az = 0.85). When both methods were used to predict dentin involvement simultaneously, SE = 27%, SP = 100%, and Az = 0.63; this combined visual and radiographic approach was associated with a perfect specificity and no false-negative decisions. The proportion of false-positive diagnoses was moderately high, and lesion extension in these cases was mainly limited to the outer 20% of the dentin. CONCLUSIONS: Our results might be useful for differentiating between preventive and operative dental care for pits and fissures.


Assuntos
Cárie Dentária/diagnóstico por imagem , Radiografia Dentária/métodos , Microtomografia por Raio-X/métodos , Cárie Dentária/diagnóstico , Cárie Dentária/patologia , Cárie Dentária/terapia , Humanos , Técnicas In Vitro , Dente Molar/diagnóstico por imagem , Dente Molar/patologia , Selantes de Fossas e Fissuras/uso terapêutico , Sensibilidade e Especificidade
20.
Am J Med Genet ; 7(1): 27-34, 1980.
Artigo em Inglês | MEDLINE | ID: mdl-7211951

RESUMO

Haldane's rule states that one-third of the cases of an X-linked recessive lethal should represent new mutations. This rule is derived under the assumptions that there is equilibrium between mutation and selection, that mutation rates in ova and sperm are equal, and that heterozygous and homozygous normal women have the same fitness. To test this rule for Duchenne muscular dystrophy (DMD), we have examined the mothers of 55 boys with DMD (16 familial and 39 isolated cases) and classified them as carriers or noncarriers on the basis of measures of ribosomal protein synthesis (RPS). Of the 55 mothers, only nine (16.4%) are classified as noncarriers, a figure significantly different from the expected one-third. When the analysis is limited to the 39 mothers of isolated cases, 23.1% (9/39) are classified as noncarriers, still significantly different than expected under Haldane's rule. Violation of any of the assumptions under which Haldane's rule is derived could lead to deviations from the expected one-third new mutants. We find the most likely explantation to be a higher male than female mutation rate. This is supported also by the finding that maternal grandfathers in whom a mutation occurred had higher mean age at birth of the carrier daughter (33.7 +/- 1.6) than did the general population or intrapedigree controls (29.5 +/- 1.3).


Assuntos
Frequência do Gene , Distrofias Musculares/genética , Mutação , Feminino , Aconselhamento Genético , Humanos , Masculino , Idade Materna , Idade Paterna , Risco , Fatores Sexuais
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