45 resultados para Agents causant des dommages à l’ADN


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Thèse pour obtenir le grade de DOCTEUR DE L' UNIVERSITÉ PARIS XII, Discipline: Urbanisme Aménagement

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RESUMO: As infecções virais podem contribuir para o desenvolvimento do cancro, estando vários tumores malignos associados aos Herpesvirus (HHV). O vírus de Epstein-Barr (EBV) e o Herpesvirus 8, dois Herpesvirus, foram reconhecidos como agentes etiológicos de várias neoplasias. O astrocitoma pilocítico do cerebelo é um dos tumores cerebrais mais frequentes na criança, adolescentes e jovens adultos e a proliferação astrocitária ocorre geralmente após vários tipos de agressão, nomeadamente a infecção viral. Para investigar esta eventual interligação, estudámos 35 astrocitomas pilocíticos, pesquisando a presença dos 8 Herpesvirus. Neste estudo, foram utilizadas 10 amostras de biópsias do cerebelo de doentes que faleceram por doenças não relacionadas com infecção ou patologia tumoral. A maioria dos astrocitomas (33) eram tumores de baixa malignidade. As amostras foram analisadas por PCR (Polymerase Chain Reaction) quantitativa em tempo real (qPCR), com amplificação do gene da DNA polimerase viral. Treze astrocitomas e 7 controles revelaram pequenas quantidades de DNA viral (1-100 cópias/100ng DNA) de todos os Herpesvirus, com excepção do HHV6 A e B que estava ausente nas amostras. O EBV foi identificado em 9 dos 35 astrocitomas (26%) e em 7 dos 10 controles (70%) estando muito mais presente nos controles. As amostras positivas para o EBV foram também analisadas por imunohistoquímica, não tendo sido imunoreactivas para os anticorpos utilizados. A PCR com CODEHOP (consensus-degenerated hybrid oligonucleotide primers) foi utilizada para investigar a presença de um eventual Herpesvirus novo nestas amostras. Não foi identificada nenhuma sequência indicativa de um novo HHV por este método. 24. Em conclusão, os dados apontam para a presença de Herpesvirus, com particular relevância para o EBV, em tecido de cerebelo normal e em tumores cerebrais, embora em níveis demasiado baixos para poderem ser responsabilizados pela indução tumoral. A presença de sequências de DNA de Herpesvirus, nomeadamente do EBV, no Sistema Nervoso Central vem enriquecer a discussão sobre o significado da infecção viral na oncogénese humana, particularmente na neuro-oncogénese. ABSTRACT: Viral infections can contribute to the development of human cancer. Several human malignancies are linked with Human Herpesviruses (HHVs). Epstein-Barr virus and HHV8, two hHerpesvirus, have been recognized as etiologic agents of several neoplasms. Pilocytic astrocytoma of the cerebellum is one of the most common brain tumour in children, adolescents and young adults and astrocytary proliferation generally occurs after several types of injury, namely viral infection. To further explore this association, we have searched the tissue from 35 pilocytic astrocytoma, for all the 8 HHV. In this study, ten brain biopsies (cerebellum) from patients who died of unrelated diseases were used as controls. Most of the astrocytomas (33) were of low grade malignity. Samples were assessed by Real-time quantitative Polymerase Chain Reaction (q PCR) amplification of viral DNA polymerase gene. Thirteen astrocytoma and 7 controls showed low viral DNA levels (1-100 copies/100ng DNA) for all HHVs, with the exception of HHV6 that was absent. EBV was identified in 9 of the 35 astrocytoma (26 %) and in 7 of the 10 controls (70%) being more present in controls. EBV positive samples were also assessed by Immunohistochemistry (IHC) but none showed immunoreactivity for the antibodies used. PCR with consensus-degenerated hybrid oligonucleotide primers (CODEHOP) were also used to look for novel HHVs in these samples and no sequence indicative of a new HHV was detected. 26 Altogether the data indicate the presence of HHVs, with relevance for EBV in normal cerebellum tissue and also in brain tumours but at too low levels to be considered responsible for tumour induction. The presence of HHV DNA sequences, particularly EBV, in the studied brain tumours and control samples, further enriches the discussion about the relevance of viral infection in human oncogenesis, particularly neuro-oncogenesis.RÉSUMÉ: Les infections virales peuvent contribuer au développement du cancer. Les vírus de type Herpès sont associés à plusieurs néoplasies. Il est par exemple établi que les vírus Epstein-Barr et « human Herpesvirus 8 » (HHV-8) sont responsables de plusieurs tumeurs malignes. L´astrocytome pilocitique du cervelet est l’une des tumeurs les plus fréquentes chez les enfants, adolescents et adultes jeunes. En général la prolifération des astrocytes se produit en réponse à une agression. Posant l’hypothèse d’une agression d’origine virale, nous avons recherché la présence des 8 vírus Herpès dans les tissus de 35 astrocytomes. Dans cette étude, 10 échantillons de biopsie de cervelet de patients décédés suite à d’autres pathologies, ont été utilisés comme contrôles. La majorité des astrocytomes étaient de très basse malignité. Les échantillons ont été étudiés par PCR quantitative en temps réel, en amplifiant le gène de l’ADN-polymérase virale. Treize astrocytomes sur 35 (37%) et 7 contrôles sur 10 (70%) ont été trouvés positifs pour tous les HHV sauf l´HHV6, toujours avec un nombre de copies de polymérase virale bas (< 100 copies/100 ng d’ADN). Notamment l’EBV a été identifié 7 fois dans les contrôles (70%) et 9 fois dans les astrocytomes (26%). Les échantillons positifs pour l`EBV ont aussi été étudiés par immuno-histochimie. Aucun signal n’a été observé avec les anticorps utilisés. Enfin, une technique de PCR avec oligonucléotides dégénérés (CODEHOP ou consensus degenerated hybrid oligonucleotide primers) a été utilisée pour rechercher la présence d´un éventuel nouveau vírus Herpès dans les échantillons d’astrocytome. Aucun nouveau vírus n’a été identifié. 28 En résumé, nous avons établi la présence de vírus Herpès, en particulier l´EBV, dans le cervelet normal et dans les tumeurs du cerveau. Les quantités d’ADN viral retrouvées sont faibles et ne permettent pas d’attribuer à ces vírus la responsabilité de l’induction des tumeurs. Cependant, la présence d’ADN de vírus Herpès dans le cerveau sain ou pathologique vient enrichir la discussion sur le signification de l´infection virale dans les processus d´oncogenèse en général, et dans la neuroonco-genèse en particulier.

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This paper presents a resume of the results achieved by researchers of the Centro de Estratigrafia e Paleobiologia da U. N. L. on the Neogene of Algarve, since 1977. The detailed study of several profiles as well as that af calcareous nannoplanton, planktonic foraminifera, ostracoda, fishes and mammals allowed to obtain data and correlation elements leading to a new interpretation of the Miocene of Algarve. It was possible to date and to characterize the following units: a) Carbonate formation of Lagos-Portimão, of marine facies, ascribed to the Lower Miocene (Aquitanian? and mainly Burdigalian), possibly attaining the Lower Langhian. b) Essentially arenaceous series of continental facies with a marine intercalation of Arrifão, Olhos de Água and Auramar Hotel beach, middle Miocene (Langhian-Serravallian) in age. c) Marine (tripoli, conglomerates, sands and limestones) deposits of Tunes-Mem Moniz, Ponte das Lavadeiras (Faro), Arroteia (Fuzeta) and Luz de Tavira, corresponding, at least partially, to the first part of the upper Miocene (Lower Tortonian). d) Cacela formation with three members: The lower member (conglomerates and sands), the middle (yellow silts) and the upper ones (gray silts), uppermost Tortonian and mainly Messinian in age. An interpretation of the tectonic and paleogeographic evolution of the portuguese littoral during the Miocene is also presented considering its insertion in the meridional part of the Peninsula (Guadalquivir depression, Betic massif basins and in the spanish Levant in general). Comparisons among the Neogene vulcanism of this region and similar manifestations documented in Algarve (basanite of Figueira-Portimão, etc) are established.

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Glauconite K-Ar ages (6.88±0.4; 7.03±0.4 MY) confirm earlier reports to Upper Tortonian of silt beds near Morgadinho, Luz de Tavira and Tavira. Taking stratigraphical position and age into account it is possible now to correlate these beds with similar ones at Quelfes and Cacela (Formação de Cacela, lower member, ascribed to the upper part of N16 or to NI7 Blow's zone, Globorotalia humerosa - G. dutertrei; Tortonian to Messinian, according to the ostracod fauna). Limit between the above quoted zones is thus placed at about 7 MY. New K-Ar ages greatly improve the knowledge about Upper Miocene in eastern Algarve, and on regional tectonic evolution. This is particulary so in what concerns an intra-Tortonian phase.

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The reef levels of the gulf of Skoura belong to the reef formation of the Upper Miocene of the South-Rifan straits. A detailed analysis of the vertical distribution of various forms of colonies has led to the establishment of precise coral morphologies zonation. This palaeoecological approach leads us to distinguish between two environments in the Skoura gulf, probably corresponding to two reef episodes. The palaeogeographical implications (relationships between the Atlantic ocean and the Mediterranean sea) will be pointed out.

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The Aquitaine Basin (southwestern France) is known since long ago for its richness in marine miocene deposits of various facies. A few stratotypes concerning this period have been described in the investigated area. The stratigraphical framework has been recently revised and the study of new exposures completes our knowledge on these levels. In the present work, the authors produce a biostratigraphical distribution of about 160 species (larger and smaller foraminifera), found in the surface exposures of Aquitaine, from the topmost Oligocene (Chattian) through to Middle Miocene (including Serravallian). As a rule, the common species without significant ranges have not bcen mentioned. The microfaunas of several exposures have been thoroughly revised, which has allowed to precise the distribution of many species and induced a few modifications of the results previously produced. Synonymy problems and new taxonomical revisions have been taken into account. Of course, this work will be probably submitted to some changes according to new research on the already known exposures or other more recently discovered.

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Cahiers d'ethnomusicologie, V.22, pp. 223-237

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Resumo Uma estratégia de avaliação e prevenção de riscos na exposição a agentes químicos deve ter sempre em conta que a vigilância do ambiente de trabalho e a da saúde dos trabalhadores são aspectos complementares de uma mesma realidade – os riscos resultantes da interacção entre um agente químico e os trabalhadores a ele expostos. Se à Vigilância Ambiental compete apreciar o risco, pela caracterização do agente no ambiente de trabalho, a Vigilância Biológica pronuncia-se sobre a interacção entre o tóxico e o organismo, avaliando a resposta à agressão química e a evolução das reacções de adaptação ou de desajuste face à absorção do tóxico. Os Indicadores Biológicos, deste modo, assumem um estatuto de instrumento privilegiado na vigilância da saúde dos trabalhadores expostos, na medida em que medem a quantidade de tóxico que efectivamente penetrou e foi absorvido, ou o resultado (efeito) determinado por essa mesma dose. O presente estudo procura contribuir para a definição de um quadro metodológico de utilização dos Indicadores Biológicos na avaliação/gestão da exposição profissional ao chumbo, designadamente apreciando a variação da protoporfirina-zinco (PPZ), indicador até ao presente ainda não utilizado em Portugal. O chumbo é um metal de ocorrência natural, cujos níveis nos diversos ecossistemas resultam, principalmente, das actividades antropogénicas de natureza doméstica e industrial. A sua capacidade poluente é assinalável, representando uma fonte de exposição permanente para o homem, demonstrável pela sua constante presença no organismo apesar de não desempenhar qualquer tipo de função fisiológica. São actualmente inúmeras as suas aplicações, tornando a exposição profissional ao chumbo uma realidade vasta: indústrias de acumuladores eléctricos, de vidros, de plásticos e de munições, construção civil, manutenção e reparação automóvel e de navios, fabrico de tintas, indústrias electrónicas, fundições e actividades de soldadura são, entre outras, situações onde é uma realidade a ter em conta. A penetração dos compostos inorgânicos de chumbo no organismo efectua-se principalmente por via respiratória, não sendo, no entanto, desprezável, a sua penetração por via digestiva. As partículas absorvidas são transportadas pelo sangue principalmente ligadas aos eritrocitos (95%), distribuem-se pelos tecidos moles e depositam-se essencialmente no tecido ósseo, onde representam mais de 90% da carga corporal do total absorvido e tendo aí um elevado tempo de semi-vida (mais de 20 anos). Não é metabolizado no organismo e a sua eliminação efectua-se essencialmente por via renal,sendo igualmente excretado, em menor escala, através das fezes, do suor, da saliva, das faneras e do leite materno. O conhecimento científico evidencia que concentrações sanguíneas de chumbo entre 20 e 50 mg/dL são susceptíveis de determinar efeitos adversos no homem, podendo ser afectados o sistema hematopoiético, o sistema nervoso, o sistema cardiovascular, o sistema reprodutor e o sistema imunitário. Contudo, ainda muito há a clarificar no âmbito da toxicidade do chumbo. Os níveis de exposição a que correspondem as alterações nos diversos órgãos e sistemas continuam a ser motivo de alguma controvérsia. As características carcinogénicas e mutagénicas do chumbo são, ainda, um campo de vasta exigência de investigação. A intoxicação por chumbo e seus sais (Saturnismo) de origem ocupacional é reconhecida em Portugal como doença profissional (grupo 1 - Doenças Provocadas por Agentes Químicos, da Lista das Doenças Profissionais). É uma intoxicação do tipo crónico, fruto da absorção contínua de doses relativamente pequenas durante longo período, evidenciando-se no seu início por sinais e sintomas vagos e difusos de grande inespecificidade, que podem incluir, nomeadamente, perda de apetite, sabor metálico na boca, palidez, mal-estar e fadiga, cefaleias, mialgias e artralgias, irritabilidade, tremores finos, obstipação, cólicas abdominais, insónias, déficit da memória de curto prazo e da capacidade de concentração. Um importante conjunto de indicadores biológicos pode ser utilizado na vigilância periódica da saúde de trabalhadores nestas condições de exposição. Tais indicadores (de dose ou de efeito), encerram diferentes significados e comportam distintas exigências, competindo ao Médico do Trabalho, no âmbito dos programas de prevenção dos efeitos adversos relacionados com a exposição profissional a chumbo, seleccionar a sua utilização e interpretar a sua informação, de modo a avaliar a interacção do tóxico com o organismo numa fase de reversibilidade. O presente estudo envolveu 180 trabalhadores dos quais 110 apresentavam plumbémias (Pb-S) iguais ou superiores a 40 mg/dL. Além da Pb-S, a todos foi doseada a protoporfirina-zinco (PPZ) e efectuado o Hemograma e a cerca de 25% foi determinada a concentração do ácido d-aminolevulínico urinário (ALA-U). Os doseamentos da PPZ efectuados em amostra de sangue capilar através de um hematofluorímetro portátil revelaram-se de total fiabilidade, dando significado a uma técnica de fácil execução e baixo custo. A avaliação do tipo de colheita urinária para doseamento do ALA-U concluiu pela necessidade de recurso a urinas de 24 horas.Os resultados do estudo evidenciaram uma elevada associação entre a PPZ e a Pb-S, com uma maior magnitude e de início mais precoce do que o que registado na associação da Pb-S com o ALA-U. Revelaram, ainda, fracos níveis de associação da hemoglobina (e outros parâmetros hematológicos) com a Pb-S. E demonstraram para um cut-off de 100 mg/ dL de PPZ, taxa de falsos negativos e falsos positivos, para plumbémias a partir de 70 mg/dL, inferiores a 20%. Assim, concluiu-se que, nos protocolos de vigilância de saúde de trabalhadores expostos a chumbo, o doseamento da PPZ por hematofluorímetro, em sangue de colheita capilar, é adequado, fiável e de realização preferencial em relação ao do ALA-U. Concluiu-se, também, que a realização do hemograma apenas se justifica em situações individuais que clinicamente o tornem aconselhável. E que estes protocolos devem incluir a realização da Pb-S e da PPZ, podendo, em situações de controlo rigoroso (ambiental, biológico e clínico), basear-se apenas na determinação da PPZ reservando os outros indicadores para aprofundar a investigação médica nos casos de taxas elevadas desta ou de situações limitantes. ■ Résumée Une stratégie d’évaluation et de prévention des risques d’exposition aux agents chimiques doit toujours tenir en considération que la vigilance du lieu de travail et de la santé des travailleurs sont des aspects complémentaires d’une même réalité – les risques résultant d’une interaction entre l’agent chimique et les travailleurs exposés. Si c’est à la Vigilance Ambiantale de juger le risque, par la caractérisation de l’agent dans le lieu de travail, la Vigilance Biologique, elle, se prononce sur l’interaction entre le toxique et l’organisme, évaluant la réponse à l’agression chimique et l’évolution des réactions d’adaptation ou de rupture face à l’absorption du toxique. Les Indicateurs Biologiques assument ainsi un statut d’instrument privilégié de vigilance de la santé des travailleurs exposés, dans la mesure où ils déterminent la quantité de toxique qui a effectivement été pénétré et absorbé, ou le résultat (effet) déterminé par cette dose. Cette étude-ci cherche à contribuer à la définition d’un cadre méthodologique d’utilisation des Indicateurs Biologiques dans l’évaluation/ gestion de l’exposition professionnelle au plomb inorganique, évaluant spécialement le comportement de la protoporphirine-zinc (PPZ), indicateur pas encore utilisé au Portugal.Le plomb est un métal d’occurrence naturelle dont les niveaux dans les différents écosystèmes en résultent, principalement, des activités anthropogéniques de nature domestique et industrielle. Sa capacité polluante peut être signalée, représentant une source d’exposition permanente pour l’homme, celle-ci démontrable par sa présence continue dans l’organisme, même si elle n’y accomplit aucune fonction physiologique. Actuellement ses applications sont innombrables, faisant de l’exposition professionnelle au plomb une réalité de grande ampleur : industries d’accumulateurs électriques, de verre, de plastique et de munitions, bâtiments, manutention et réparation automobile et navale, fabrication d’encres, industries électroniques, fontes et activités de soudure sont, entre autres, des situations réelles a en tenir compte. La pénétration du plomb inorganique dans l’organisme se fait principalement par voie respiratoire, pouvant se faire également par voie digestive. Les particules absorbées sont transportées par le sang, surtout liées aux érythrocytes (95%), se repartent à travers les tissus mous et se déposent essentiellement dans le tissu osseux, où elles représentent plus de 90% de la charge corporelle de ce qui a été absorbé et ont un temps de demi-vie élevé (plus de 20 ans). Le plomb n’est pas métabolisé dans l’organisme et son élimination se fait essentiellement par voie rénale, pouvant tout de même, à une moindre échelle, être excrété dans les fèces, de la sueur, de la salive, des ongles, des cheveux et du lait maternel. La connaissance scientifique met en évidence que des concentrations sanguines de plomb entre 20 et 50 mg/dL sont susceptibles de déterminer des effets adverses dans l’homme, pouvant les systèmes hématopoïétique, nerveux, cardiovasculaire, reproducteur et immunitaire en être affectés. Cependant, il en reste beaucoup à éclaircir dans le domaine de la toxicité du plomb. Les niveaux d’exposition auxquels correspondent les modifications des divers organes et systèmes, demeurent toujours sujet de quelque controverse. Les caractéristiques carcinogèniques et mutagèniques du plomb restent toujours un champ d’investigation d’une grande exigence. L’intoxication par le plomb et ses sels (Saturnisme) d’origine occupationnelle est reconnue, au Portugal, comme une maladie professionnelle (groupe 1- Maladies Provoquées par des Agents Chimiques, de la Liste des Maladies Professionnelles). C’est une intoxication du tipe chronique, due à l’absorption continue de doses relativement petites pendant une longue période, mise en évidence à travers des signes et des symptômes vagues et diffus sans grande spécificité, lesquels peuvent inclure, particulièrement, le manque d’appétit, goût métallique dans la bouche, pâleur, malaise et fatigue, céphalées, myalgies et arthralgies, irritabilité, tremblements fins, constipation, coliques abdominales, insomnies, déficit de la mémoire à court terme et de la capacité de concentration.Un ensemble important d’indicateurs biologiques peut être employé dans la vigilance périodique de la santé des travailleurs dans ces conditions d’exposition. Ces indicateurs (de dose ou d’effet) renferment différentes significations et comportent diverses exigences, devant le Médecin de Travail, dans le domaine des programmes de prévention des effets adverses qui sont en relation avec l’exposition professionnelle au plomb, sélectionner son utilisation et interpréter son information de façon à évaluer l’interaction de l’élément toxique avec l’organisme à un stade de réversibilité. L’étude ci-présent engloba 180 travailleurs desquels 110 présentaient des plombémies (Pb-S) égales ou supérieures à 40 mg/dL. À part la Pb-S, la protoporphyrine-zinc (PPZ) leur a été prise en dosage et un Hémogramme fut effectué et fut déterminé l’acide d- aminolévulinique urinaire (ALA-U) sur environ 25% des travailleurs. Le dosage de la PPZ efectué en échantillon de sang capillaire par un fluorimètre portable, s’est accomplit d’une fiabilité total, donnant du sgnificat à une téchnique de facile execution et bas prix. L’évaluation de la prise urinaire par dosage du ALA-U conclut au besoin d’un recours aux urines de 24 heures Les résultats de l’étude ont mis en évidence une association élevée entre la PPZ et la Pb- S, avec une intensité majeure et de début plus précoce par rapport à celui qui fut registré lors de l’association de la Pb-S avec la ALA-U. Ces résultats ont également montré de faibles niveaux d’association entre l’hémoglobine (et autres paramètres hématologiques) et la Pb-S. Ils ont démontré aussi, une valeur de cut-off de 100 mg/dL de PPZ, des taux de faux négatifs et faux positifs, pour des plombémies de 70 mg/dL, inférieurs à 20%. On peut donc conclure que dans les protocoles de vigilance de la santé des travailleurs exposés au plomb, le dosage de la PPZ par fluorimetrie dans le sang capillaire est adéquat, fiable et de réalisation préférentielle par rapport à celui du ALA-U. On peut également conclure que la réalisation de l’hémogramme ne se justifie que dans les cas individuels où, cliniquement, celui-ci est conseillé. De plus, ces protocoles doivent inclure la réalisation de la Pb-S et de la PPZ, pouvant, en cas de contrôle rigoureux (ambiantal, biologique et clinique), s’appuyer que dans la détermination de la PPZ réservant les autres indicateurs pour approfondir l’investigation médicale dans les cas où les taux de celle-ci sont élevés ou dans les cas de situations limitantes. ■ Summary Any strategy to evaluate and prevent the risks of chemical agents exposure must always regard the work environment and workers health as complementary aspects of one reality - the resulting risks from the interaction between the chemical agent and the exposed workers. It is the responsibility of Environmental Monitoring to evaluate the risks of exposure by the characterization of the chemical agent in the work environment. Biological Monitoring, on the other hand, pronounces itself over the toxin and body interaction, evaluating human response to the chemical aggression and the body adaptations to the toxic absorption. Biological Exposure Indices (BEI) assume, therefore, a privileged status among exposed workers' health monitoring instruments, as they measure the actual penetrated and absorbed toxic quantity and the effect it produces. This research study aims to contribute to the definition of a methodological strategy on the utilization of BEI’s in evaluating inorganic lead's occupational exposure, more specifically appreciating the zinc protoporphyrin (ZPP) variation, an index that has never been taken under consideration in Portugal until now. Lead is a natural metal whose ecosystem’s levels are mainly due to domestic and industrial anthropogenic activities. Its pollutant capacity is notable, representing a permanent exposure risk shown by its constant presence in the human body, although it has no physiologic function. Nowadays, lead's applications are countless, turning its professional exposure a huge reality: storage batteries industries, glass industries, plasterers and munitions industries, building construction, ships and motor car maintenance and repairing, ink manufacture, electronics industries, foundries and other soldering activities are, among so many other, realities to attend to. Respiration is the main cause of human body's inorganic lead absorption, although digestive pathway must not to be ignored. The absorbed particles are transported by blood, essentially bounded to erythrocytes (95%). It is distributed by soft tissues and settled mainly on bone tissues, where it represents approximately 90% of the total body charge and has a high half-life time (more than 20 years). It is not metabolized by the organism, its elimination being effectuated by renal activity and, in smaller scale, through lees, sweat, saliva, nails, hair and maternal milk.Scientific knowledge shows that concentrations of lead in blood between 20 e 50 mg/dL are susceptible to determine adverse effects in man and able to affect the hematopoietic system, the nervous system, the cardiovascular system, the reproductive system and the immunological system. Nevertheless, there's still much to be learned and clarified about lead's toxicity. The correlation between exposure levels and human's systems and organs alteration levels continues to be a centre of controversies. Still, lead's carcinogenic and mutagenic characteristics continue to be a high demanding research field. Intoxication by lead and its compounds (saturnism), from occupational origin, is recognized in Portugal as an occupational disease, included in Group 1 - Chemical Agents Caused Diseases, on the Occupational Diseases List. It is a chronic intoxication caused by a continuous absorption of small doses, throughout a long period of time. Its signs and symptoms are diffuse and imprecise, of great unspecificity, such as loss of appetite, metallic flavor in the mouth, paleness, ailment and fatigue, headaches, myalgia and arthralgia, irritability, thin tremors, constipation, abdominal pain, insomnias, short memory loses and inability to concentrate. A considered number of BEI’s can be used in Periodic Health Monitoring of workers in such exposure conditions. Such BEI (dose indices or effect indices) provide different meanings and imply different procedures, being Occupational Doctors responsibility, in the context of lead related adverse effects preventive programmes, to select and interpret its information, in order to evaluate the interaction between toxic and organism in a reversible phase of the toxic action. The present research study involved 180 workers, 110 of which presented blood lead levels (PbB) above or equal to 40 mg/dL. Besides PbB, all workers has been evaluated for zinc protoporphyrin levels (PPZ) and submitted to a haemogram. About 25% of the workers were selected for d-aminolevulinic urinary acid (ALA-U) determination. The evaluation of PPZ, by a portable hematofluorometer using capillary blood samples, turned out to be an easy procedure with low costs and total warrantability. As in regard for ALA- U procedure, it was concluded the necessity of 24 hours urine samples. This research results underlined a strong connection between ZPP and PbB, which was found to to be stringer and to begin earlier than it was registered for PbB and ALA-U association. The same study also revealed a low association level between PbB and hemoglobin or other hematological indices. It was also verified less than 20% of false negatives and false positives cases when admitted a ZPP 100 mg/dL cut off value for PbB³ 70 mg/dL. As in result it was concluded that in Health Monit

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Les rapports complexes entre les différentes façons de faire circuler les idées et les informations ne datent pas de nos jours. A toutes les époques, les messages qui circulent emploient toutes sortes de véhicules et de langages, très souvent complémentaires. Ces véhicules et ces langages n'ont peut-être rien d'extraordinaire. Ils appartiennent au monde des gestes de tous les jours, des gestes qui se répètent et dont la répétition est elle-même importante pour la construction du sens de chaque message. Ces gestes qui sont répétés, qui sont attendus et qui sont reconnus incluent des sons, des images, des comportements, des mots, ou des citations. Il y a donc un rapport qui s'y établit entre répétition et nouveauté, rapport dans lequel la répétition fournit chaque fois une nouvelle information, même si elle est déjà attendue, tandis que leur absence peut représenter l'anxiété, ou même le scandale.

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Resumo: Os profissionais de saúde podem estar expostos a vários factores indutores de stress crónico nomeadamente de natureza profissional destacando-se, entre os seus possíveis efeitos, a diminuição da resposta de anticorpos após administração de vacinas, entre as quais, a vacina contra a gripe. Uma vez que os trabalhadores da saúde estão expostos a factores indutores de stress e, simultaneamente, a agentes biológicos cujos efeitos poderão ser prevenidos pela vacinação, é pertinente estudar a influência do stress na resposta imunitária à vacina contra a gripe em enfermeiros. Constituíram objectivos deste trabalho: (1) estudar a associação entre a presença de stress crónico em enfermeiros hospitalares e a “insuficiente” resposta imunitária à vacina contra a gripe, avaliada um mês após a vacinação (T1); (2) estudar a associação entre a presença de stress crónico em enfermeiros hospitalares e a redução dos títulos de anticorpos dirigidos às hemaglutininas seis meses após a vacinação (T6) e (3) identificar algumas características das unidades de internamento e do trabalho dos participantes que possam estar associadas à presença de stress crónico e estudar a sua possível associação com a resposta imunitária à vacina contra a gripe. Realizou-se um estudo caso-controlo incorporado num estudo de coortes e a amostra em estudo foi constituída por 136 enfermeiros saudáveis (83,8% sexo feminino; média de idades de 33anos) de um hospital universitário. Realizaram-se entrevistas individuais e aplicaram-se as versões portuguesas dos questionários The General Health Questionnaire (GHQ12) e Maslach Burnout Inventory – Human Services Survey (MBI-HSS) para determinação da presença de stress crónico pelo método da triangulação, no início do estudo (T0) e realizou-se a recolha de dados relativos à caracterização de elementos de trabalho nas unidades de internamento. Foi administrada a vacina contra a gripe e determinou-se os títulos de anticorpos dirigidos às hemaglutininas de cada estirpe componentes da vacina contra a gripe utilizada em 2007, antes da vacinação, um mês e seis meses após a vacinação. Não se encontrou associação, ao nível de significância de 5%, entre a presença de stress e a “insuficiente” resposta à vacina contra a gripe, avaliada pela taxa de indivíduos que apresentaram um aumento, ao fim de um mês, inferior a quatro vezes os títulos de anticorpos antes da vacinação. No entanto, encontrou-se uma maior proporção de indivíduos com stress no grupo de participantes em que ocorreu uma diminuição do título de anticorpos dirigidos à hemaglutinina AH1 (ac AH1) em T6, quando comparado com o respectivo grupo controlo. A diferença entre grupos foi estatisticamente significativa, quando se avaliou a presença de stress pelo método da triangulação usando a entrevista (p=0,006), pelo método da triangulação usando o GHQ12 (p=0,045) e ainda usando a combinação dos três critérios (p=0,001). Após análise multivariada, verificou-se que a associação entre a presença de XXVI stress e a redução dos ac AH1 em T6 manteve significado estatístico (respectivamente, p= 0,010, p= 0,042 e p=0,002) e apresentou odds ratio ajustados, em função de cada um dos métodos de avaliação da presença de stress, de 3,643, de 2,733 e de 5,223. A quantidade de trabalho percepcionada como sobrecarga constituiu o factor indutor de stress mais vezes referido (58,8% da amostra e 61,8% dos enfermeiros de unidades de internamento), seguida dos conflitos entre profissionais. O contacto com o sofrimento e a morte de doentes foram identificados em quarto lugar pela amostra, mas em segundo pelos enfermeiros de unidades de internamento. Nesses, verificou-se uma associação positiva entre trabalhar em Serviços onde o número de doentes falecidos foi muito elevado e a presença de stress, medido pelo método da triangulação usando a entrevista (p=0,039), usando o GHQ12 (p=0,019), usando a escala de exaustão emocional do MBI-HSS (p=0,012) e pela combinação dos três métodos (p=0,014). Verificou-se também uma associação positiva entre a presença de stress, identificada pelo método da triangulação usando a escala de exaustão emocional do MBI-HSS, e o trabalho em serviços de internamento onde a percentagem de doentes idosos (p=0,025) e a taxa de letalidade (p=0,036) foram elevadas. Contudo, não se encontrou associação entre a exposição muito frequente ao sofrimento e à morte de doentes e a redução do título de ac AH1 em T6. Possivelmente, a exposição a esse factor indutor de stress, apesar de estar relacionada com a presença de stress nos enfermeiros de serviços de internamento, não foi suficientemente intenso para, por si só, estar associada à redução do título de ac AH1 em T6. A associação encontrada entre a presença de stress crónico e a redução do título de anticorpos AH1 em T6 vem apoiar a resposta à questão de investigação inicialmente colocada de que o stress poderá influenciar negativamente a manutenção dos títulos de anticorpos, mesmo em indivíduos adultos não idosos. Assim, o risco de um enfermeiro com stress apresentar redução do título de anticorpos dirigidos à hemaglutinina da estirpe AH1N1 – A/Solomon Islands/3/2006 ao fim dos seis meses do estudo, foi 3,6, 2,7 ou 5,2 vezes superior ao de um enfermeiro sem stress, consoante o critério de stress ter sido determinado, respectivamente, pelo método da triangulação usando a entrevista, pelo método da triangulação utilizando o GHQ12 ou pela combinação dos três critérios. Summary: Health workers may be exposed to various factors causing chronic stress namely those related directly to their activity, in particular the decrease in the capacity of the response of antibodies after the administration of the vaccines, amongst others the Influenza vaccine. Since health workers are exposed to factors causing stress and at the same time biological agents, whose effects may be prevented through vaccination, it is important to study the influence of stress in the immunity response to the Influenza vaccine on nurses. The aims of this study are: (1) to examine the relation between chronic stress in hospital nurses and the “insufficient” immunity response to the Influenza vaccine, assessed at one month after vaccination (T1); (2) to examine the relation between chronic stress in hospital nurses and the decrease of the hemagglutinin titles of antibodies six months after vaccination (T6); (3) to identify some characteristics of internment units and the work of the participants that may be related to the presence of chronic stress and to study its possible relation with the immunity response to the Influenza vaccine. A control-case study, integrated in a coortes study, was carried out and the sample under analysis consisted of 136 healthy nurses (83,8% female; average age 33 years old) from a university hospital. Several individual interviews were conducted and the portuguese versions of General Health Questionnaire (GHQ12) and Maslach Burnout Inventory – Human Services Survey (MBI-HSS) was applied in order to determine the presence of chronic stress, using the triangulation method at the beginning of the study (T0). Data concerning the particular features of the internment units was collected. The Influenza vaccine was administered and the titles of hemagglutinin antibodies of each strain composing the Influenza vaccine used in 2007, before vaccination, and a month and six months after vaccination, were determined. There was no statistically relevant (5%) relation between stress and the “insufficient” immune response to the Influenza vaccine, according to the rate of individuals that showed, after a month, a level of antibodies concentration lower than four times the level prior to the vaccination. Nevertheless, there was a greater number of individuals with stress in the group of participants in which there was a decrease of the hemagglutinin titles of antibodies AH1 (ac AH1) in T6, when compared to the control group under study. The difference between groups was statistically relevant when assessing the presence of stress by triangulation method using the interview (p=0,006), by triangulation method using the GHQ12 (p=0,045) and by the combination of the three criteria (p=0,001). After multivariate analysis, it was verified that the XXVIII relation between the presence of stress and the reduction of the ac AH1 in T6 was statistically relevant (respectively, p= 0,010, p= 0,042 and p=0,002) and the odds ratio were, according to each of the methods used to assess the presence of stress, 3,643, 2,733 and 5,223. Overwork was the most emphasised stress-causing factor (58,8% of the sample and 61,8% of the nurses working in the Internment Units), followed by conflicts arousing among co-workers. Witnessing the suffering and death of patients was ranked as the fourth cause of stress, but the second by the nurses of the internment units. The former revealed a positive connection between working in the services, where there was a high rate of deaths, and the presence of stress, when assessing the presence of stress by triangulation method using the interview (p=0,039), the GHQ12 (p=0,019), the MBI-HSS emotional exhaustion scale (p=0,012) and by the combination of the three criteria (p=0,014).There was also a connection between the presence of stress, identified by the method of triangulation using the MBI-HSS emotional exhaustion scale, and working in the internment units, where the percentage of elderly people (p=0,025) and the mortality rate (p=0,036) were high. However, there was no connection between frequent exposure to suffering and death in patients and the reduction of ac AH1 titles, in T6. Although one can establish a connection between stress in nurses working in the internment units and the aforementioned stress-causing factor, the exposure to that factor was not, per se, intense enough to reduce the ac AH1 title in T6. The relation found between the presence of chronic stress and the reduction of AH1 antibodies titles in T6, corroborates the hypothesis that stress can negatively influence the title of antibodies, even in non-elderly adults. Thus, and according to the criteria used to define stress, by the triangulation method using the interview, by the triangulation method using the GHQ12 or the combination of the three criteria respectively, the risk of a nurse suffering from stress showing a reduction in the title of hemagglutinin antibodies for the strain AH1N1 – A/Solomon Islands/3/2006 six-month after Influenza vaccine was 3,6, 2,7 or 5,2 times greater than on a nurse suffering from no stress at all. Résumé: Les professionnels de la santé peuvent être exposés à différents facteurs inducteurs de stress chronique de nature professionnelle. On remarque, parmi les effets possibles, une baisse de la réponse des anticorps après l´administration de vaccins, comme en particulier, le vaccin de la grippe. Lorsque les professionnels de la santé ont été exposés à des facteurs inducteurs de stress, et de manière simultanée, à des agents biologiques dont les effets pourront être prévenus par la vaccination, il est pertinent d´étudier l´influence du stress dans la réponse immunitaire au vaccin de la grippe chez les infirmiers. Ils ont constitué des objectifs d´études et de discussion : (1) étudier l´association entre la présence de stress chronique chez les infirmiers, en milieu hospitalier, et la “insuffisant” réponse immunitaire au vaccin de la grippe, vérifiée à un mois après la vaccination (T1); (2) étudier l´association entre la présence de stress chronique chez les infirmiers, en milieu hospitalier, et la réduction de la teneur des anticorps dirigé à la hémaglutinina six mois après la vaccination (T6) (3) identifier certaines caractéristiques des unités d´internement, et étudier les aspects du travail des participants, qui puissent être associée à la présence de stress chronique et étudier sa possible association avec la réponse immunitaire au vaccin de la grippe. Une étude cas-contrôle incorporée dans une étude de groupe a été réalisée et un échantillon, pour étude, a été constitué par 136 infirmiers sains (83,8% de sexe féminin, âge moyen 33 ans) travaillant dans un hôpital universitaire. Des entretiens individuels ont été réalisés et les versions portugaises des questionnaires de General Health Questionnaire (GHQ12) et Maslach Burnout Inventory- Human Service Survey (MBI-HSS) ont été utilisés pour déterminer la présence de stress chronique grâce à la méthode de triangulation, au début de l´étude (T0) et un relevé de données relatives à la caractérisation d´éléments de travail dans les unités d´internement a été fait. Le vaccin de la grippe a été administré et les teneurs en anticorps dirigés aux hémaglutininas de chaque composant du vaccin de la grippe pour 2007 ont été déterminés, avant la vaccination et un mois et six mois après. On n´a pas trouvé d´association, à un niveau significatif de au moins 5%, entre la présence de stress et la “insuffisant” réponse au vaccin de la grippe, évaluée par le taux d´individus qui ont présenté une augmentation, à la fin du mois, inférieur à quatre fois la teneur des anticorps par rapport à avant la vaccination. Cependant , on a trouvé une plus grande proportion d´individus victimes de stress dans le groupe des participants où il y a eu une baisse de la teneur des anticorps dirigé à la hémaglutinina AH1 (ac AH1) en T6, après comparaison avec le respectif groupe de contrôle. La différence entre les groupes a été statistiquement significative lorsqu´on a vérifié la présence de stress grâce à la méthode de triangulation, en utilisant l´entretien (p=0,006), par la méthode de triangulation en utilisant le GHQ12 (p=0,045) et en utilisant aussi la combinaison des trois critères (p=0,001). Après une analyse XXX multivariée, on a vérifié que l´association entre la présence de stress et la réduction des ac AH1 en T6 a conservé un signifié statistique (respectivement, p=0,010, p=0,042 et p=0,002) et a présenté des odds ratio ajustés, en fonction de chacune des méthodes de vérification de la présence de stress de 3,643, de 2,733 et de 5,223. La quantité de travail perçue comme une surcharge constitue le facteur inducteur de stress le plus souvent cité (58,8% de l´échantillon et 61,8% des infirmiers des unités d´internement), suivi par les conflits entre professionnels. Le contact avec la souffrance et la mort des patients a été placé en quatrième position par l´échantillon, mais en deuxième position par les infirmiers des unités d´internement. Dans ces cas, on a vérifié une association évidente entre le fait de travailler dans des services où le nombre de patients décédés a été très élevé et la présence de stress, identifiée par la méthode de triangulation, en utilisant l´entretien (p=0,039), le GHQ12 (p=0,019), l´échelle de fatigue émotionnelle du MBI-HSS (p=0,012) et en utilisant aussi la combinaison des trois critères (p=0,014). On a aussi vérifié une association positive entre la présence de stress, identifiée par la méthode de triangulation, en utilisant l´échelle de fatigue émotionnelle du MBI-HSS et le travail dans des services d´internement où le pourcentage de malade âgés (p=0,025) et le taux de mortalité ont été élevés (p=0,036). Malgré tout, on n´a pas trouvé d´association entre l´exposition très fréquente à la souffrance et à la mort des patients et la réduction de la teneur de ac AH1 en T6. Probablement l´exposition à ce facteur inducteur de stress, bien qu´elle soit liée à la présence de stress chez les infirmiers des services d´internement, n´a pas été suffisamment intense pour, en elle-même, être associée à la réduction de la teneur ac AH1 enT6. L´association trouvée entre la présence de stress chronique et la réduction de la teneur des anticorps AH1 en T6 vient renforcer l´hypothèse que le stress pourra influencer négativement la manutention des teneurs en anticorps même chez les individus adultes jeunes. Donc le risque qu´un infirmier stressé présente une réduction de la teneur en anticorps dirigés à la hémaglutinina de le composant AH1N1-A/Solomon Island/3/2006 à la fin des six mois d´études a été 3,6, 2,7 ou 5,2 fois supérieure à celui d´un infirmier sans stress, après avoir déterminé le critère de stress, respectivement par la méthode de triangulation utilisant l´entretien, par la méthode de triangulation utilisant le GHQ12 ou par la combinaison des trois critères.

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The reef levels of the gulf of skoura belong to the reef formation of the Upper Miocene of the South-Rifan straits. A detailed analysis of the vertical distribution of various forms of colonies has led to the establishment of precise coral morphologies zonation. This palaeoecological approach leads us to distinguish between two environments in the Skoura gulf, probably corresponding to two reef episodes. The palaeogeographical implications (relationships between the Atlantic ocean and the Mediterranean sea) will be pointed out.

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The Aquitaine Basin (southwestem France) is known since long ago for its richness in marine miocene deposits ofvarious facies. A few stratotypes concerning this period have bccn described in the investigated area. The stratigraphical framework has becn recently revised and the study of new exposures completes our knowledge on these levels. In the present work, the authors produce a biostratigraphical distribution of about 160 species (Iarger and smaller foraminifera), found in the surface exposures of Aquitaine, from the topmost Oligocene (Chattian) through to Middle Miocene (including Serravallian). As a rule, the common species without significant ranges have not bcen mentioned. The microfaunas of several exposures have been thoroughly revised, which has allowcd to precise the distribution of many species and induced a few modifications of the results previously produced. Synonymy problems and new taxonomical revisions have been taken into account. Of course, this work will be probably submitted to some changes according to new research on the already known exposures or other more recently discovered.

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The Mid Miocene marine formations of Salles area (former "Sallomacian" stage) have been studied again from numerous outcrops and cores. The deep structural framework influences notably of the characteristics and distribution of the deposits, which are neritic. The stratigraphy is stated precisely thanks to the planktonic fauna and floradetailed examination (probably Serravallian zones NN6 - N12). Several paleobiofacies are reconstituted from the rich invertebrate faunas, which give also paleoclimatic data.

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Similarly to other organisms, Vertebrates changed during the Cenozoic Era. Mammals are the only ones to change quickly; their well mineralised bones and teeth are often fossilised. They are highly diverse and even isolated teeth can be identified. They are thus a good tool for establishing a biochronological framewoork. Among Mammals, Rodents with a short lifetime evolve more quickly than the large Mammals. In Europe, the first elaborated zonation was investigated by the Regional Committee on Neogene Stratigraphy and issued as the MN Zonation (Mammals Neogene) by Mein, 1976. During the following years, progress in knowledge lead to new charts. The latest one resulted from collective work (de Bruijn et al., 1992). Bîochronology gives relative data; if we desire to have numerical age estimates, we must correlate these results with radiometrie data, marine biostratigraphîcal units or the Geomagnetic Polarity Time Scale. For Europe, these results are summarised by Steininger et al. (1989-1996) and Steininger (1999). After some recents developments on MN Zonation, here is discussed the succession of Neogene small mammals Portuguese localities. Fortunately these localities are in majority inbedded in marine context. Their assigment to MN Zones is proposed and correlations with the spanish Aragonian Scale (Daams el al., 1999) are also suggested. In fact, some differences appear between Portugal and Aragonian assemblages, probably for ecological reasons. Therefore, the MN zonation is always useful for short and long distance biochronological correlations.

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The Domerian sections from the Lusitanian Basin of São Pedro de Muel, Rabaçal and Tomar have provided us with more than 1100 Ostracods belonging from 18 genus and about 48 species. The faunal diversity and density of the associations decrease in space (from Tomar to Rabaçal and São Pedro de Muel) and time, with favourable environments for the proliferation of Ostracods at the lower part of the sections (Stokesi subzone) and more hostile at the upper part (Ragazzonii subzone). The Monestieri and Nitescens horizons and the Subnodosus subzone are characterized by a typical assemblage of Ostracods. The palaeoecological Ostracod indexes reveal the fluctuations of the oxygenation, temperature, depth and hydrodynamism of the water, on the different sections and on the whole platform. They display a diachronous cooling in the Lower Domerian series. In the upper part of the Middle and in the Upper Domerian, the deeper, less oxygenated and cooler waters prevent the development of the Ostracod faunas.