Submitted by Celso Magalhaes (celsomagalhaes@ufrrj.br) on 2018-09-20T17:04:32Z No. of bitstreams: 1 2016 - Nubia Valle Mezzavilla.pdf: 2915573 bytes, checksum: f7b585622179c2b55f0b4f83a2d41bda (MD5) / Made available in DSpace on 2018-09-20T17:04:32Z (GMT). No. of bitstreams: 1 2016 - Nubia Valle Mezzavilla.pdf: 2915573 bytes, checksum: f7b585622179c2b55f0b4f83a2d41bda (MD5) Previous issue date: 2016-06-29 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico - CNPQ / Studies of aluminum tolerance in seedlings aroeira-vermelha (Schinus terebinthifolius R.) were held in a growth chamber in the Department of Plant Science ? Laboratory of Chemistry of Rhizosphere in the Agronomy Institute of University Federal Rural of Rio de Janeiro. Experiments were carried out with different concentrations of aluminum in simple nutrient solution (with calcium) and a complete nutrient solution with concentrations range from 0, 25, 50, 100, 200, 400 and 800 ?M in the solution and in soil Oxisol which was added liming, P, K, and micronutrients. The liming varied from (zero, 500, 1000.2000 and 4000 kg ha-1 and with100, 60, 30 kg ha-1 of phosphorus, potassium and micronutrient Br-12, respectively), and a control treatment without liming, P, K and micronutrients. The evaluations were based on analysis of root growth using the root length parameters, root growth rate, relative and evaluated root elongation also shoot length, dry weight of shoot and root, stem diameter, pH of the rhizosphere and soil . It was found that it is important to time days after sowing, before the transfer of seedlings to the nutrient solution; it is indicated 18 days after sowing for simple nutrient solution and 15 days after sowing for complete solution. Root growth rate and relative root elongation are methods that should be recommended in studies with plants aroeira-vermelha. Complete diluted and balanced nutrient solutions, should be recommended in aluminum toxicity studies in this species rather than simple solutions only with calcium due to low potential for seed storage. Low concentration of Al simple solution led to increase root growth. The root length of Schinus terebinthifolius R. seedlings grown nutrient solutions paralyzed in concentration 131.87 87 ?M of Al. In the simple nutrient solution was only possible to establish the critical level of toxicity using the root growth rate obtaining the value of 88, 42 87 ?M aluminum. Schinus terebinthifolius R. response the application of liming and P, K and micronutrients when grown in a soil Oxisol substrate, and the dosage of 2164.64 kg ha-1 of lime, dosing which was obtained the highest root length. For dry weight of shoot of seedlings, only 1831.50 Kg ha-1 of lime was enough to hit the highest value / Os estudos da toler?ncia ao alum?nio em pl?ntulas de aroeira-vermelha (Schinus Terebinthifolius R.) foram realizados, em c?mara de crescimento no Laborat?rio de Qu?mica da Rizosfera no Departamento de Fitotecnia, Instituto de Agronomia da Universidade Federal Rural Rio de Janeiro. Foram realizados experimentos com diferentes concentra??es de Al em solu??o nutritiva simples (com c?lcio) e completa com concentra??es que variaram de 0, 25, 50, 100, 200, 400 e 800 ?M na solu??o e em solo Latossolo vermelho amarelo onde foi adicionado calagem, P, K, e micronutrientes. As dosagens de calagem variaram de tratamentos com calagem (0, 500, 1000, 2000 e 4000 Kg ha-1, sendo adicionados 100, 60 e 30 Kg ha-1de fosforo, pot?ssio e de micronutriente BR-12 respetivamente), al?m de um tratamento controle, sem calagem, P, K e micronutrientes. As avalia??es foram baseadas na an?lise do crescimento radicular utilizando os par?metros comprimento radicular, taxa de crescimento radicular, elonga??o radicular relativa e avaliados tamb?m o comprimento da parte a?rea, massa seca da parte a?rea e radicular, di?metro do colo, pH da rizosfera e do solo. Foi verificado que ? importante o tempo de dias ap?s a semeadura, antes da transfer?ncia das pl?ntulas para a solu??o nutritiva, sendo indicados 18 dias ap?s a semeadura para solu??o nutritiva simples e 15 dias ap?s a semeadura para solu??o completa. A taxa de crescimento radicular e a elonga??o radicular relativa s?o m?todos que devem ser recomendados em estudos com plantas de aroeira-vermelha. Solu??es nutritivas completas, dilu?das e balanceadas, devem ser recomendadas em estudos de toxidez de alum?nio nesta esp?cie ao inv?s de solu??es simples apenas com c?lcio, devido ao baixo potencial de reserva da semente. Baixas concentra??es de Al na solu??o simples, estimulou o crescimento de raiz. O comprimento de raiz de pl?ntulas de aroeira crescidas em solu??es nutritivas completas paralisou seu crescimento na concentra??o de 131,87 ?M de Al. Na solu??o simples s? foi poss?vel estabelecer o n?vel cr?tico de toxidez utilizando a taxa de crescimento radicular, obtendo o valor de 88,42 ?M de alum?nio. A aroeira respondeu a aplica??o de calagem, P, K e micronutrientes quando crescida em solo Latossolo Vermelho Amarelo, sendo a dosagem de 2164,64 Kg ha-1 de calc?rio a que obteve o maior comprimento radicular. Para a massa seca da parte a?rea somente 1831,50 Kg ha-1 de calc?rio foi suficiente para ser atingido o maior valor.

Em 2006 foi realizado um estudo preliminar para avaliar a exposição a metais em pescadores do Alto São Francisco, no estado de Minas Gerais, Brasil. Os pescadores das cidades de Três Marias, principal foco de pesquisa, e Morada Nova de Minas, como controle, foram avaliados sob o ponto de vista clínico e laboratorial, através de exames bioquímicos e dosagens de Pb-S, Cd-V, As-V, Zn-V e Mn-V. Os resultados das avaliações apresentaram diferenças estatisticamente significativas para o zinco e o arsênio, entre os dois grupos avaliados. Para o chumbo e o manganês, as diferenças não foram, estatisticamente, relevantes. Para o cádmio os dados foram idênticos para ambas populações. Embora os estudos para verificar a contaminação por metais tenham sido feitos, ainda não há evidências de comprometimento da saúde dos pescadores pela contaminação de metais. / A preliminar study to estimate the exposure to metals by fishermen at the High San Francisco River area in Minas Gerais State, in Brazil, had been accomplished in 2006. The fishemen at Tres Marias and Morada Nova county in Minas Gerais State (used a control group), had been evaluated under a clinical and laboratorial point ofview, through a biochemical analysis and Pb-B; Cd -D, As -D, ZnD and Mn-D determinations. The results apparently presented a significant statistical differences related to Zinc and Arsenic among the evaluated fisherman groups. It was not found statistically relevant differences for Manganese and Lead. For urinary Cd, the results were identical at both cities. Although the possibility of exposure by those metals have been studied, there are no evidences of fishermen\'s health implications yet.

Cyanobacteria is perhaps the phylum that profit the most from the escalating hypereutrophication of continental waters. The resulting cyanobacterial blooms may accumulate a variety of potent toxins. Cylindrospermopsin (CYN) is a cyanotoxin known for inhibiting protein synthesis, and producing oxidative stress as well as DNA damage in eukaryotic cells. Since the toxin\'s molecular mechanisms and targets are still unclear, we purified the cyanotoxin from our lab strains and employed a shotgun proteomics approach to reveal the major changes in HepG2 cells at sublethal doses of CYN (1 µM for 6, 12 and 24h). Metabolically labeled cells were stimulated and lysed after each treatment, their tryptic digests were separated by nano HPLC and analyzed by high-resolution tandem mass spectrometry (HRMS) on data dependent acquisition mode. We scanned an average of 4000 proteins in every sample throughout the three timepoints. Cholesterol biosynthesis and transport was mostly downregulated throughout the timepooints of the experiment. Downregulation of proteins related to ubiquitination (e.g. UBE2L3) and proteolysis pathways (e.g. PSMA2) was observed in the proteomics dataset, and these results were validated by western blot. Transcription, translation and cell cycle processes showed convoluted regulation dynamics involving known cell cycle regulators like PCNA. Downregulation of mitochondrial enzymes, oxidative stress and damage to the mithochondrial inner membrane was early evidenced after a 6 hrs treatment and validated using a JC-1, a mitochondrial membrane potential probe. The resulting dataset gives us a first glimpse of the protein groups affected at the early stage of CYN cell intoxication. / Cianobactéria é o filo que mais se beneficia da crescente hipereutrofização das águas continentais. As florações de cianobactérias resultantes podem acumular potentes toxinas. A Cilindrospermopsina (CYN) é uma cianotoxina conhecida por inibir a síntese protéica e produzir estresse oxidativo, além de danos ao DNA em células eucarióticas. Os mecanismos moleculares e alvos de toxicidade aguda desta toxina ainda não são claros. Por esse motivo adoptamos uma abordagem de proteômica quantitativa baseada em descoberta para revelar as principais alterações nas células HepG2 em doses subletais de CYN (1 µM para 6, 12 e 24h). As proteinas dos hepatócitos foram marcadas metabolicamente, foram estimuladas com a toxina e os digestos trípticos foram analisados por espectrometria de massa em tandem de alta resolução (HRMS) no modo de aquisição dependente de dados. Escaneamos uma média de 4000 proteínas ao longo dos intervalos de tempo. A biosintese e transporte do colesterol foi inibida durante a maior parte do tratamento com a toxina. Proteínas e enzimas relacionadas com o processo de ubiquitinação (ex. UBE2L3) e proteólise (ex. PSMA2) foram inibidas, e alterações nas proteínas envolvidas nesses processos foram validadas por meio de Western Blot. Os processos de transcrição, tradução e ciclo celular mostraram uma dinâmica de regulação complexa, envolvendo reguladores e disruptores do ciclo celular como por exemplo PCNA. Danos à membrana mitocondrial e evidência de estresse oxidativo foram detectados após 6 horas de tratamento, e essas mudanças no proteoma foram validados por meio do corante JC-1 (test que detecta mudanças no potencial da membrana mitocondrial). O banco de dados resultante nos dá um primeiro vislumbre das proteinas afetados no estágio inicial da intoxicação celular pela CYN.

Corantes e pigmentos são utilizados no mundo todo para alterar a percepção visual de diversos bens de consumo. Dentre esses compostos se destacam os corantes que possuem grupamentos azo ou nitro como cromóforo. Muitas dessas substâncias são potencialmente tóxicas, seja na sua forma original seja após a biotransformação, com ênfase aos efeitos mutagênicos e/ou carcinogênicos. Este trabalho teve como objetivo investigar as rotas metabólicas e avaliar o perfil toxicológico parcial dos corantes Disperso Amarelo 9 e Sudan III. O Sudan III é um corante azóico e que embora tenha estrutura química muito semelhante ao Sudan I, um carcinógeno humano, existem poucos dados na literatura a respeito de sua toxicidade. Vale ressaltar que o Sudan III é um corante de alimentos banido da maioria dos países, porém tem sido repetidamente detectado em alimentos industrializados como adulterante. Já o corante Disperse Yellow 9 é amplamente utilizado principalmente pelas indústrias têxteis, porém não foram encontrados dados na literatura sobre seu potencial tóxico. Foram realizados estudos espectroeletroquimicos capazes de simular reações de oxidação e redução que ocorrem em organismos vivos, além de sistema exógeno de metabolização (S9). A mutagenicidade dos corantes foi avaliada pelo ensaio de Samonella (utilizando as linhagens TA98, TA1535, TA100 e YG1042, com e sem S9) e por meio da avaliação da capacidade de ligação com o DNA e a guanosina in vitro. Ainda, verificou-se a indução de morte celular em condrócitos bovinos. Nossos resultados mostraram que as condições de oxidação (eletroquímica ou após a reação com S9) e redução foram capazes de modificar o grupamento cromóforo tanto do corante Sudan III quanto do Disperso amarelo 9, e esse efeito é esperado em organismos vivos, podendo formar derivados tóxicos. O corante Sudan III é capaz de se ligar ao DNA de forma estável, mais especificamente com a base nitrogenada guanosina, enquanto o Disperso Amarelo 9 se liga fracamente ao DNA e não com a guanosina. O corante Sudam III exibiu fraca mutagenicidade e apenas com a linhagem TA1535. Por outro lado, Disperso Amarelo 9 foi positivo para as linhagens TA1535 e YG1042, e o efeito foi mais pronunciado após a ativação metabólica. Ambos os corantes induziram à morte dos condrócitos de forma tempo e concentração dependente. Assim, ambos os corantes foram considerados tóxicos, tanto na sua forma original quanto após biotransformação e podem levar a riscos à saúde humana e ao ecossistema quando de sua exposição. / Dyes and pigments are applied worldwide to change the visual perception of many products. Among these compounds, dyes containing azo and nitro bond as chromophore are very important groups. A wide range of these substances are potentially toxic either in its original form or after biotransformation leading to mutagenic / or carcinogenic effects. The aim of the present study was to investigate the metabolic pathways involving the chromophore group and also to evaluate the toxicological profile of Disperse Yellow 9 and Sudan III dyes. Sudan III is an azo dye that has a very similar chemical structure to Sudan I a known carcinogen. Despite, there are few data about Sudan III toxicity in the literature. It is important to point out that Sudan III is banned from most worldwide food industry it has been frequently detected as an adulterant in a large amount of processed food. The literature has no information about the toxicity potential of Disperse Yellow although it is widely and mainly used by textile industries. On the present we performed a spectroeletrochemical method capable of simulating bio- reactions able to occur on living organisms such as oxidation and reduction, also exogen metabolization system (S9) were applied. The mutagenicity of the dyes was evaluated by Salmonella assay (using strains TA98, TA1535, TA100 and YG1042, with and without S9). The ability of causing stable bonds to DNA and guanosine were also tested in vitro. Also the capacity of inducing cell death on bovine chondrocytes was investigated. Our results indicated that the oxidation reactions (spectroeletrochemical method or after S9 reaction) and also the reduction reactions were able to modify the chromophore group for the studied dyes Sudan III and Disperse Yellow 9, this effect could be expected in living organisms and may also generate toxic products. Sudan III is capable of binding to DNA and forming stable aducts, specifically to the nitrogenated base guanosine, while Disperse Yellow 9 binds weakly to DNA and does not react with guanosine. Low mutagenicity was observed for strain TA1535 for Sudan III dye. Besides, strains TA1535 and YG1042 gave positive responses for Disperse Yellow, the effect was pronounced after metabolic activation. Death of chondrocytes was observed for both dyes demonstrating time and concentration dependency. Toxicity was observed for both dyes, before and after biotransformation, this effect may lead to risks on human health and also for the environment.

Este trabalho apresenta a pesquisa de interação de organismos aquáticos com metais, especificamente cobre e cádmio assim como da combinação deles. Para tanto, descreve-se um protocolo baseado em ensaios de toxicidade com tilápias Oreochromis niloticus, desenvolvido com a finalidade de estabelecer a concentração letal 50 (CL50) 96h. Como recurso adicional, focando a translocação de metais, foram utilizadas soluções enriquecidas isotopicamente de 65Cu (99,7%) e 111Cd (95,5%), as quais foram aplicadas através de injeções intraperitoneais. As concentrações dos metais nos tecidos e nas frações citosólicas do fígado, brânquias e músculo foram determinadas a partir dos extratos preparados em solução tampão tris-HCl 50 mmolL-1, agentes redutores e antiproteolíticos, na proporção 3:1 (m/v). Adicionalmente, foram determinados os teores de proteínas totais seguidos da etapa de isolamento das metalotioneínas. As concentrações letais (CL50) 96h calculadas pelo método Trimmed Spearman-Karber (95% de confiança), foram iguais a 20,13, 3,53 e 1,36 mg L-1 para cádmio, cobre e cobre+cádmio respectivamente. Estes valores indicam uma significativa diferença na sensibilidade dos organismos aos diferentes tratamentos. Observou-se uma redução na bioconcentração dos metais em função da concentração do metal e do tecido analisado, esta é maior para o Cu do que para o Cd e menor para o musculo em relação a brânquia e ao fígado. Os teores de proteínas totais nos tecidos foram determinados e os valores encontrados estiveram entre 3,25 mg/mL para fígados e 11,83 mg/mL para músculo. A presença de MTs nos diferentes tecidos e respectivos tratamentos, foi pesquisada empregando-se eletroforese capilar e separação de proteínas utilizando a eletroforese em gel de poliacrilamida. Por ambas as técnicas eletroforéticas foi possível identificar as metalotioneínas. Contudo, as análises dos extratos dos tecidos por espectrometria de massas, MALDI-TOF/TOF (matrix-assisted laser desorption/ionization) e ESI-MS (electrospray tandem mass spectrometry ) não mostraram-se adequadas para identificação de metalotioneínas / This paper discuss the interactions of Cd, Cu and it mixture upon aquatic organisms. To reach for these goals lethal 50 (LC50) acute toxicity 96h assays were carried out. In order to assess for the metals translocation in fish, isotopically enriched solutions of 65Cu (99,7%) and 111Cd (95,5%), were used, through an intra-peritoneal injections. Metals concentrations in tissue and in the citossolic fractions of liver, and muscular tissue were analysed in the 50 mmol-1 tris-HCl buffer solutions, reducing and un-proteolitic (3:1) solutions. In addition the total protein content were determinate, followed by the metalothyonein isolation. Lethal concentrations were calculated by the Spearman-Karber method at 95% confidence interval, as 20.13, 3.53 and 1.36 mgL-1 for Cd, Cu and Cd+Cu respectively, which denote differences in organisms sensitivity according to the treatment. Metal bio-concentration was reduced depending on the analyte concentration and kind of tissue, being higher to Cu than to Cd. Total protein concentration varied from 3.35 mg L-1 for liver to 11.83 mg L-1 in the muscular tissue. The occurrence of MTs in tissues and in all treatments were investigated by using both, capillary electrophoresis and gel of polyacrilamide. In all situations the occurrence and identification of Mts were verified, but even with MALDI-TOF/TOF (matrix-assisted laser desorption/ionization) and ESI-MS (electronspray tandem mass spectrometry), or actual instrumental facilities no satisfactory results were obtained, being not possible the identification of MTs in the analysed samples

Visando detectar alternativas de manejo para a lagarta-do-cartucho-do-milho, Spodoptera frugiperda (Lepidoptera: Noctuidae), realizou-se, primeiramente, uma triagem em extratos etanólicos preparados das estruturas (folhas, ramos e sementes) de diferentes espécies de Annonaceae (Annona cacans, A. montana, A. mucosa, A. reticulata, A. sylvatica e Duguetia lanceolata). Com base nessa etapa inicial, constatou-se que o extrato etanólico das sementes de A. mucosa (ESAM) foi o mais promissor, causando significativa toxicidade aguda (CL50 e CL90 de 842,97 e 1.882,00 mg kg-1, respectivamente) e pronunciada inibição do desenvolvimento larval (toxicidade crônica), após sete dias de exposição a dietas tratadas. Na CL50, o ESAM reduziu as viabilidades larval e pupal e o peso de pupas com 24 horas, e aumentou a duração da fase larval. No entanto, o ESAM não ocasionou efeito fagodeterrente para larvas de quarto ínstar de S. frugiperda, embora tenha reduzido o consumo ao longo do tempo. Feito isso, a eficácia de ESAM foi comparada com inseticidas comerciais de origem natural (Azamax® 1,2 EC) e sintética (Premio® SC). Nessa comparação, o ESAM (na CL90) apresentou eficácia similar (equitóxico) aos dois produtos comerciais (utilizados na dose registrada para o controle do inseto-praga). A seguir, foi realizado o fracionamento biomonitorado através de diferentes técnicas cromatográficas que conduziu ao isolamento da acetogenina roliniastatina-1, identificada (com base em técnicas espectroscópicas) como componente majoritário da fração mais ativa do extrato etanólico de A. mucosa. Roliniastatina-1 foi então novamente ensaiada frente a larvas de S. frugiperda e ocasionou significativos efeitos agudos (mortalidade larval) e crônicos (redução do desevolvimento larval). Por fim, investigou-se a bioatividade de uma formulação à base de acetogeninas (Anosom® 1 EC) recentemente registrada, tanto isoladamente quanto em mistura com uma formulação à base de limonoides (Azamax® 1,2 EC). Anosom® 1 EC, testado na CL90 estimada (2.959,00 mg kg-1) e Azamax® 1,2 EC, testado na concentração registrada para o controle do inseto-praga (4.000,00 mg kg-1), causaram significativa mortalidade larval, sem ocorrer diferença entre os tratamentos tanto quando testados isoladamente como em mistura binária. Anosom® 1 EC (na CL50) provocou ainda aumento significativo das mortalidades larval e pupal e da duração da fase larval, bem como redução do peso pupal do inseto. Dessa forma, derivados de Annonaceae podem constituir um componente útil para o manejo integrado de S. frugiperda em condições de campo. / A screening with ethanolic extracts prepared from structures (leaves, branches and seeds) from different species of Annonaceae (Annona cacans, A. montana, A. mucosa, A. reticulate, A. sylvatica and Duguetia lanceolata) aiming to detect management alternatives for Spodoptera frugiperda (Lepidoptera: Noctuidae) was done. Based on this initial phase, it was verified that the ethanolic extract from seeds of A. mucosa (AMSE) was the most promising one, causing significant acute toxicity (LC50 and LC90 of 842.97 and 1,822.00 mg kg-1, respectively) and pronounced inhibition of larval development (chronic toxicity) after a 7-day exposition to treated diets. At LC50, AMSE decreased larval and pupal viabilities and also the pupal weight at 24 hours, and increased the larval phase duration. However, AMSE didn\'t cause antifeedant effect for 4-instar S. frugiperda larvae, though it decreased consumption throughout the time. After that, AMSE efficacy was compared to commercial pesticides from natural (Azamax® 1.2 EC) and synthetic (Premio® SC) origin. In this confrontation, AMSE (at LC90) showed efficacy similar to that of commercial products (used at registered dose for S. frugiperda control). Then, the bioguided fractionation using different chromatographic techniques which led to isolation of acetogenin rolliniastatin-1 identified as the majoritary compound of the most active ethanolic extract from A. mucosa. After that, rolliniastatin-1 was again tested against S. frugiperda larvae and caused significant acute (larval mortality) and chronic (decrease of larval development) effects. Finally, the bioactivity of a newly-registered acetogenin-based (Anosom® 1 EC) formulation was investigated, both separately and mixed with a limonoid-based formulation (Azamax® 1.2 EC). Anosom® 1 EC, tested at estimated LC90 (2,959.00 mg kg-1) and Azamax® 1.2 EC, tested at registered dose for S. frugiperda (4,000.00 mg kg-1) led to significant larval mortality, without happening any differences between treatments either tested separately or in a binary mixture. Anosom® 1 EC (at LC50) also led to significant increase of larval and pupal mortality and larval phase, as well as insect pupal weight decrease. Thus, Annonaceae derivates can be a useful component for S. frugiperda integrated management under field conditions.

L’exposition à des polluants environnementaux est considérée comme l’un des facteurs pouvant expliquer l’augmentation exponentielle des maladies métaboliques dans le monde. Parmi ces polluants, plusieurs études épidémiologiques suggèrent une association entre exposition au cadmium (Cd) et incidence et sévérité des cas de diabète, mais le sujet reste controversé. Des travaux expérimentaux sur des modèles animaux montrent qu’une exposition au Cd induit des effets divers sur le métabolisme du glucose. Toutefois, ces études ont été réalisées avec des doses de Cd relativement fortes et avec des modèles d’exposition peu réalistes. De plus, très peu de données sont disponibles sur l’effet de l’exposition maternelle sur la descendance. L’objectif de ces travaux était donc d’étudier les possibles altérations du métabolisme du glucose après une exposition orale à des doses faibles de Cd, chez des rats adultes ainsi que sur des jeunes rats exposés via leur mère. Nos résultats montrent qu’à des niveaux de Cd proche des doses de références sans effets chez le rat, les femelles adultes présentent des perturbations du niveau d’insuline plasmatique ainsi qu’une légère diminution de la sensibilité à l’insuline. Ces effets diabétogènes ne sont pas retrouvés chez les mâles. Les résultats de notre seconde étude indiquent que l’exposition maternelle au Cd, pendant la gestation et la lactation, induit des modifications métaboliques précoces chez les descendance, 21, 26 et 60 jours après la naissance. A 21 jours, la tolérance au glucose est altérée. A 26 jours, la sensibilité périphérique à l’insuline est transitoirement restaurée mais la fonction pancréatique est impactée. Enfin, à 60 jours, le défaut de sensibilité à l’insuline est compensé par une sécrétion accrue. Ces travaux mettent en évidence les effets d’une exposition à doses faibles de Cd sur le métabolisme du glucose et renforcent l’idée que l’environnement périnatal, en particulier l’exposition aux polluants, impacte la santé de la descendance, à plus ou moins long terme. Au-delà de ces résultats, ces travaux portent une réflexion sur l’intérêt et la difficulté à mettre en place des modèles animaux d’exposition pertinents, pour répondre à l’enjeu de l’évaluation des risques de l’exposition chronique au Cd. / The exposure to environmental pollutants is considered one of the factors that could explain the exponential increase in metabolic illnesses worldwide. Among these pollutants, many epidemiological studies suggest a link between Cadmium (Cd) exposure and the occurrence and severity of diabetes, although the subject remains controversial. Experimental work on animals shows that exposure to Cd induces various effects on glucose metabolism. However, these studies were performed with relatively high doses of Cd and with unrealistic exposure models. In addition, very little data are available on the effect of maternal exposure and effect on descendants. The aim of this work was to study possible alterations in glucose metabolism after oral exposure to low doses of Cd in adult rats as well as in young rats exposed via their mothers. Results show that when exposed to Cd levels close to no-observed-effect reference values in rats, female rats show disturbances in plasma insulin level and a slight decrease in insulin sensitivity. These diabetogenic effects are not found in male rats. The results of the second study indicate that maternal exposure to Cd during pregnancy and lactation induces early metabolic changes in the offspring, 21, 26 and 60 days after birth. At 21 days, glucose tolerance is altered. At 26 days, the peripheral insulin sensitivity is transiently restored but the pancreatic function is impacted. Finally, at 60 days, the lack of insulin sensitivity is compensated by increased secretion. This work demonstrates the effects of low doses of Cd on glucose metabolism and reinforces the idea that the perinatal environment, in particular exposure to pollutants, affects the health of offspring in the long term. Beyond these results, this work allows the reader to reflect on the interest and difficulty of setting up relevant experimental animal models, in order to tackle the issue of risk assessment of chronic Cd exposure.

The advent of effective oral, molecular-targeted drugs in oncology has changed many incurable malignancies such as chronic myeloid leukemia into chronic diseases similar to coronary artery disease and diabetes mellitus. Oral agents including monoclonal antibodies, kinase inhibitors and hormone receptor blockers offer cancer patients incremental improvements in both overall survival and quality of life. As it is imperative to recognize and manage side effects of platelet inhibitors, beta blockers, statins, HIV drugs, and fluoroquinolones by all healthcare providers, the same holds true for these newer targeted therapies, patients may present to their generalist or other subspecialist with drug-related symptoms. Cardiovascular adverse events are among the most frequent, and potentially serious, health issues in outpatient clinics, and among the most frequent side effects of targeted chemotherapy. Data support improved patient outcomes and satisfaction when primary care and other providers are cognizant of chemotherapy side effects, allowing for earlier intervention and reduction in morbidity and health care costs. With the implementation of accountable care and pay-for-performance, improved communication between generalists and subspecialists is essential to deliver cost-effective patient care.

Les particules fines émises par l'activité humaine sont la cause de diverses pathologies pulmonaires et cardiaques. Les particules de taille inférieure à 100 nm, appelées nanoparticules, sont particulièrement nocives car une fois inhalées, elles peuvent atteindre les alvéoles pulmonaires, lieux des échanges gazeux. Dans les alvéoles, les nanoparticules entrent d'abord en contact avec le surfactant pulmonaire. Ce fluide biologique tapisse les cellules épithéliales des alvéoles sur une épaisseur de quelques centaines de nanomètres et est composé de phospholipides et de protéines, les phospholipides étant assemblés sous forme de vésicules et corps multi-lamellaires. Dans ce travail, nous avons sélectionné des nanoparticules modèles de nature différente connues pour leur toxicité cellulaire (latex, oxydes métalliques, silice). Leur interaction avec un fluide pulmonaire mimétique administré aux prématurés (Curosurf®) a été étudiée en détail par microscopie optique et électronique, et par diffusion de la lumière. Nous avons mis en évidence que cette interaction est non spécifique et d'origine électrostatique. La diversité des structures hybrides obtenues entre particules et vésicules témoigne cependant de la complexité de cette interaction. En contrôlant cette interaction, nous avons formulé des particules couvertes d’une bicouche supportée de Curosurf® qui possèdent des propriétés remarquables de stabilité et de furtivité en milieu biologique.Dans une seconde partie, nous avons étudié le rôle du surfactant pulmonaire sur l’interaction entre particules et cellules épithéliales alvéolaires (A459). A l'aide d'expériences de biologie cellulaire réalisées in vitro, nous avons observé que la présence de surfactant diminue de manière significative le nombre de particules internalisées par les cellules. Dans le même temps, nous avons constaté une augmentation importante de la viabilité cellulaire. Une conclusion majeure de notre travail concerne la mise en évidence du rôle protecteur joué par le surfactant pulmonaire dans les mécanismes d'interaction des nanoparticules avec l'épithélium alvéolaire / Particulate matter emitted by human activity are the cause of various pulmonary and cardiac diseases. After inhalation, nanoparticles (ie particles smaller than 100 nm) can reach the pulmonary alveoli, where the gas exchanges take place. In the alveoli, the nanoparticles first encounter the pulmonary surfactant which is the fluid that lines the epithelial cells. Of a few hundreds of nanometers in thickness, the pulmonary fluid is composed of phospholipids and proteins, the phospholipids being assembled in multilamellar vesicles. In this work, we considered model nanoparticles of different nature (latex, metal oxides, silica). Their interaction with a mimetic pulmonary fluid administered to premature infants (Curosurf®) was studied by light scattering and by optical and electron microscopy. We have shown that the interaction is non-specific and mainly of electrostatic origin. The wide variety of hybrid structures found in this work attests however of the complexity of the phospholipid/particle interaction. In addition, we succeeded in formulating particles covered with a Curosurf® supported bilayer. These particles exhibit remarkable stability and stealthiness in biological environment. In a second part, we studied the role of the pulmonary surfactant on the interactions between nanoparticles and alveolar epithelial cells (A459). With cellular biology assays, we observed that the number of internalized particles decreases dramatically in presence of surfactant. At the same time, we found a significant increase in the A459 cell viability. Our study shows the importance of the pulmonary surfactant in protecting the alveolar epithelium in case of nanoparticle exposure

This study was designed to observe the effects of selenium from plant material in sheep after a single, oral dose. Purified sodium selenite and selenomethionine were given as positive controls. The plant Symphyotrichum spathulatum (Western Mountain Aster) was collected, analyzed for selenium content, and administered orally to sheep at varying doses according to body weight. Clinical signs were observed for 7 days during which time whole blood, serum, and expired air were collected. Following euthanasia, tissues were collected for histopathological analysis and mineral analysis. Clinical signs were less apparent than expected and included depression and mild dyspnea in sheep receiving the highest doses of selenium as plant material, whereas pathologic lesions were prominent. Acute myocardial degeneration and necrosis was most severe in the highest dose animals, but present to lesser degrees as dose decreased. Pulmonary lesions of edema and congestion were less frequently observed. Thirteen animals died prior to study completion. Selenium concentration in tissues, brain, liver, kidney cortex, atrium, ventricle, and skeletal muscle, increased with increasing dose of plant material. Treatment had a significant impact on selenium concentration in all tissues collected for mineral analysis (P < 0.01). Whole blood and serum were collected to study the toxicokinetics of selenium in these sheep. Serum kinetic parameters that increased significantly with increasing dose included the elimination rate constant, peak selenium concentration, and area under the selenium concentration versus time curve. Serum kinetic parameters that significantly decreased with increasing dose included the absorption and elimination half-lives. Whole blood kinetic parameters that increased significantly with increasing dose included the elimination rate constant, peak selenium concentration, and area under the curve. Expired air was collected to study the respiratory toxicokinetics of selenium in the sheep. The selenium concentration in expired air from sheep receiving selenomethionine was significantly greater than all other treatments (P < 0.0001) at all collection time points. But an intriguing finding was the dramatic differences in elimination profile curves as selenium dose increased with the plant material. The highest dose group elimination curve continually increased through all collection time points. All other groups dosed with plant material saw a decrease in selenium elimination by the last collection time point.