Évaluation de la toxicité du béryllium en fonction de la forme chimique et de la taille des particules

Le béryllium (Be) est un métal dont les propriétés physiques et mécaniques sont très recherchées, notamment dans les secteurs spatial, énergétique et électronique. Les principaux effets associés à l’exposition au Be sont la sensibilisation et la bérylliose chronique. La prévalence des effets associés au Be suggère que les risques sont, entre autres, fonction de sa spéciation. Par ailleurs, il semble que les particules fines constituent la fraction d’intérêt pour l’occurrence de tels effets. Dans cette étude nous avons vérifié l’hypothèse que la forme chimique et la taille des particules du Be jouent un rôle majeur au niveau de la toxicité et de l’apparition d’effets spécifiques à une exposition au Be. Les effets spécifiques se traduisent, entre autres, par la formation de granulomes inflammatoires pulmonaire, par la prolifération de lymphocytes TCD4+ et la production de cytokines de type Th1. Pour chacune des trois formes chimiques visées par la présente étude (le Be métallique ou Be, l’oxyde de Be ou BeO et l’alliage Be aluminium ou BeAl), la toxicité a été évaluée à la suite d’une exposition subchronique par inhalation oro-nasale à des particules fines (F) et totales (T). À cette fin, un modèle animal (souris) a été utilisé. Au total, 245 souris ont été utilisées. Elles ont été subdivisées en sept groupes de 35 souris. Un groupe a servi de contrôle, alors que chacun des six autres a été exposé soit à des particules fines soit à des particules totales, pour chacune des trois formes chimiques de Be (Be-F, Be-T, BeO-F, BeO-T, BeAl-F, BeAl-T). La durée d’exposition pour chacun des groupes s’est étendue sur 3 semaines, 5 jours par semaine, 6 heures par jour. Le niveau d’exposition des souris était de 250 µg/m3. L‘urine des souris a été recueillie avant et durant l’exposition. Au moment du sacrifice, plusieurs tissus (poumon, rate, foie et reins) ainsi que des échantillons de sang ont été prélevés puis immédiatement congelés jusqu’à leur analyse pour la détermination de leur teneur en Be. De plus, certains poumons et rates ont été analysés pour l’évaluation de la sensibilité immunologique et de l'inflammation pulmonaire. Cette étude d’exposition subchronique est la première étude murine qui étudie les effets toxiques de différentes tailles particulaires sur les changements pathologique et immunologique similaires à ceux observés chez l’humain. Cette étude a permis de constater qu’il existait des différences importantes au niveau de la toxicité du Be d’après les différentes tailles particulaires à l’étude. Ces différences seraient reliées au dépôt des particules de Be dans les voies respiratoires et également à la capacité des voies respiratoires à les éliminer totalement ou partiellement. La clairance respiratoire est fonction, notamment, du site de déposition et du caractère soluble ou non des particules. Cette recherche aura également permis de démontrer que les souris C3H/HeJ représentent un bon modèle pour l’étude des effets toxicologiques et immunologiques d’une exposition au Be. De plus, nos résultats démontrent que la sévérité des lésions pulmonaires causées par le Be, tel que l’infiltration interstitielle de lymphocytes et la formation de granulomes non-caséeux, augmente avec le temps de résidence pulmonaire des particules de Be. Combinés à d’autres résultats, nos résultats contribueront à guider les actions de prévention relativement à l’exposition au Be, incluant éventuellement la révision de la valeur limite de l’exposition et possiblement l’établissement de valeurs limites en fonction de la forme chimique et de la taille des particules.

Influence de la taille de départ, de l’état d’agglomération et de la dose de nanoparticules de dioxyde de titane (TiO2) inhalées sur la réponse pulmonaire chez le rat

En raison de leur petite taille, les nanoparticules (NP) (< 100 nm) peuvent coaguler très rapidement ce qui favorise leur pénétration dans l’organisme sous forme d’agglomérats. L’objectif de cette recherche est d’étudier l’influence de l’état d’agglomération de NP de dioxyde de titane (TiO2) de trois tailles de départ différentes, 5, 10-30 ou 50 nm sur la toxicité pulmonaire chez le rat mâle (F344) exposé à des aérosols de 2, 7 ou 20 mg/m3 pendant 6 heures. Dans une chambre d’inhalation, six groupes de rats (n = 6 par groupe) ont été exposés par inhalation aiguë nez-seulement à des aérosols ayant une taille primaire de 5 nm, mais produits sous forme faiblement (< 100 nm) ou fortement (> 100 nm) agglomérée à 2, 7 et 20 mg/m3. De façon similaire, quatre autres groupes de rats ont été exposés à 20 mg/m3 à des aérosols ayant une taille primaire de 10-30 et 50 nm. Les différents aérosols ont été générés par nébulisation à partir de suspensions ou par dispersion à sec. Pour chaque concentration massique, un groupe de rats témoins (n = 6 par groupe) a été exposé à de l’air comprimé dans les mêmes conditions. Les animaux ont été sacrifiés 16 heures après la fin de l’exposition et les lavages broncho-alvéolaires ont permis de doser des marqueurs d’effets inflammatoires, cytotoxiques et de stress oxydant. Des coupes histologiques de poumons ont également été analysées. L’influence de l’état d’agglomération des NP de TiO2 n’a pu être discriminée à 2 mg/m3. Aux concentrations massiques de 7 et 20 mg/m3, nos résultats montrent qu’une réponse inflammatoire aiguë est induite suite à l'exposition aux aérosols fortement agglomérés. En plus de cette réponse, l’exposition aux aérosols faiblement agglomérés à 20 mg/m3 s’est traduite par une augmentation significative de la 8-isoprostane et de la lactate déshydrogénase. À 20 mg/m3, les effets cytotoxiques étaient plus importants suite à l’exposition aux NP de 5 nm faiblement agglomérées. Ces travaux ont montré dans l'ensemble que différents mécanismes de toxicité pulmonaire peuvent être empruntés par les NP de TiO2 en fonction de la taille de départ et de l’état d’agglomération.

Salinity influences glutathione S-transferase activity and lipid peroxidation responses in the Crassostrea gigas oyster exposed to diesel oil

Biochemical responses in bivalve mollusks are commonly employed in environmental studies as biomarkers of aquatic contamination. The present study evaluated the possible influence of salinity (35, 25,15 and 9 ppt) in the biomarker responses of Crassostrea gigas oysters exposed to diesel at different nominal concentrations (0.01, 0.1 and 1 mLL(-1)) using a semi-static exposure system. Salinity alone did not resulted in major changes in the gill`s catalase activity (CAT), glutathione S-transferase activity (GST) and lipid peroxidation levels (measured as malondialdehyde. MDA), but influenced diesel related responses. At 25 ppt salinity, but not at the other salinity levels, oysters exposed to diesel showed a strikingly positive concentration-dependent GST response. At 25 ppt and 1 mLL(-1) diesel, the GST activity in the gills remained elevated, even after one week of depuration in clean water. The increased MDA levels in the oysters exposed to diesel comparing to control groups at 9, 15 and 35 ppt salinities suggest the occurrence of lipid peroxidation in those salinities, but not at 25 ppt salinity. The MDA quickly returned to basal levels after 24 h of depuration. CAT activity was unaltered by the treatments employed. High toxicity for 1 mLL(-1) diesel was observed only at 35 ppt salinity, but not in the other salinities. Results from this study strongly suggest that salinity influences the diesel related biomarker responses and toxicity in C. gigas, and that some of those responses remain altered even after depuration. (C) 2011 Elsevier B.V. All rights reserved.

Salinity influences glutathione S-transferase activity and lipid peroxidation responses in the Crassostrea gigas oyster exposed to diesel oil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Influence of gasoline inhalation on the enantioselective pharmacokinetics of fluoxetine in rats

Fluoxetine is used clinically as a racemic mixture of (+)-(S) and (-)-(R) enantiomers for the treatment of depression. CYP2D6 catalyzes the metabolism of both fluoxetine enantiomers. We aimed to evaluate whether exposure to gasoline results in CYP2D inhibition. Male Wistar rats exposed to filtered air (n = 36; control group) or to 600 ppm of gasoline (n = 36) in a nose-only inhalation exposure chamber for 6 weeks (6 h/day, 5 days/week) received a single oral 10-mg/kg dose of racemic fluoxetine. Fluoxetine enantiomers in plasma samples were analyzed by a validated analytical method using LC-MS/MS. The separation of fluoxetine enantiomers was performed in a Chirobiotic V column using as the mobile phase a mixture of ethanol:ammonium acetate 15 mM. Higher plasma concentrations of the (+)-(S)-fluoxetine enantiomer were found in the control group (enantiomeric ratio AUC(+)-(S)/(-)-(R) = 1.68). In animals exposed to gasoline, we observed an increase in AUC0-∞ for both enantiomers, with a sharper increase seen for the (-)-(R)-fluoxetine enantiomer (enantiomeric ratio AUC(+)-(S)/(-)-(R) = 1.07), resulting in a loss of enantioselectivity. Exposure to gasoline was found to result in the loss of enantioselectivity of fluoxetine, with the predominant reduction occurring in the clearance of the (-)-(R)-fluoxetine enantiomer (55% vs. 30%). Chirality 25:206-210, 2013. © 2013 Wiley Periodicals, Inc. Copyright © 2013 Wiley Periodicals, Inc.

Elf magnetic field influence on ION Channels studied by Patch Clamp Technique: exposure set up and "Whole Cell" measurements on Potassium currents

The aim of this thesis was to study the effects of extremely low frequency (ELF) electromagnetic magnetic fields on potassium currents in neural cell lines ( Neuroblastoma SK-N-BE ), using the whole-cell Patch Clamp technique. Such technique is a sophisticated tool capable to investigate the electrophysiological activity at a single cell, and even at single channel level. The total potassium ion currents through the cell membrane was measured while exposing the cells to a combination of static (DC) and alternate (AC) magnetic fields according to the prediction of the so-called ‘ Ion Resonance Hypothesis ’. For this purpose we have designed and fabricated a magnetic field exposure system reaching a good compromise between magnetic field homogeneity and accessibility to the biological sample under the microscope. The magnetic field exposure system consists of three large orthogonal pairs of square coils surrounding the patch clamp set up and connected to the signal generation unit, able to generate different combinations of static and/or alternate magnetic fields. Such system was characterized in term of field distribution and uniformity through computation and direct field measurements. No statistically significant changes in the potassium ion currents through cell membrane were reveled when the cells were exposed to AC/DC magnetic field combination according to the afore mentioned ‘Ion Resonance Hypothesis’.

Chamber evaluation of a personal organic vapor dosimeter at ppb concentrations of VOCs, varying temperatures and humidities with 24 -hour exposures

An exposure system was constructed to evaluate the performance of a personal organic vapor dosimeter (3520 OVM) at ppb concentrations of nine selected target volatile organic compounds (VOCs). These concentration levels are generally encountered in community air environments, both indoor and outdoor. It was demonstrated that the chamber system could provide closely-controlled conditions of VOC concentrations, temperature and relative humidity (RH) required for the experiments. The target experimental conditions included combinations of three VOC concentrations (10, 20 and 200 $\rm\mu g/m\sp3),$ three temperatures (10, 25 and 40$\sp\circ$C) and three RHs (12, 50 and 90% RH), leading to a total of 27 exposure conditions. No backgrounds of target VOCs were found in the exposure chamber system. In the exposure chamber, the variation of the temperature was controlled within $\pm$1$\sp\circ$C, and the variation of RH was controlled within $\pm$1.5% at 12% RH, $\pm$2% at 50% RH and $\pm$3% at 90% RH. High-emission permeation tubes were utilized to generate the target VOCs. Various patterns of the permeation rates were observed over time. The lifetimes and permeation rates of the tubes differed by compound, length of the tube and manufacturer. By carefully selecting the source and length of the tubes, and closely monitoring tube weight loss over time, the permeation tubes can be used for delivering low and stable concentrations of VOCs during multiple days.^ The results of this study indicate that the performance of the 3520 OVM is compound-specific and depends on concentration, temperature and humidity. With the exception of 1,3-butadiene under most conditions, and styrene and methylene chloride at very high relative humidities, recoveries were generally within $\pm$25% of theory, indicating that the 3520 OVM can be effectively used over the range of concentrations and environmental conditions tested with a 24-hour sampling period. Increasing humidities resulted in increasing negative bias from full recovery. Reverse diffusion conducted at 200 $\rm\mu g/m\sp3$ and five temperature/humidity combinations indicated severe diffusion losses only for 1,3-butadiene, methylene chloride and styrene under increased humidity. Overall, the results of this study do not support the need to employ diffusion samplers with backup sections for the exposure conditions tested. ^

Blade pitch control malfunction simulation in a wind energy conversion system with MPC five-level converter

This paper is on a wind energy conversion system simulation of a transient analysis due to a blade pitch control malfunction. The aim of the transient analysis is the study of the behavior of a back-to-back multiple point clamped five-level full-power converter implemented in a wind energy conversion system equipped with a permanent magnet synchronous generator. An alternate current link connects the system to the grid. The drive train is modeled by a three-mass model in order to simulate the dynamic effect of the wind on the tower. The control strategy is based on fractional-order control. Unbalance voltages in the DC-link capacitors are lessen due to the control strategy, balancing the capacitor banks voltages by a selection of the output voltage vectors. Simulation studies are carried out to evaluate not only the system behavior, but also the quality of the energy injected into the electric grid.

Uncertainty based Multi-Robot Cooperative Triangulation

The paper presents a multi-robot cooperative framework to estimate the 3D position of dynamic targets, based on bearing-only vision measurements. The uncertainty of the observation provided by each robot equipped with a bearing-only vision system is effectively addressed for cooperative triangulation purposes by weighing the contribution of each monocular bearing ray in a probabilistic manner. The envisioned framework is evaluated in an outdoor scenario with a team of heterogeneous robots composed of an Unmanned Ground and Aerial Vehicle.

Análise comparativa de sistemas de classificação de doentes de reabilitação

RESUMO - Caracterização do problema: A inadequação e ineficácia do sistema de financiamento ―por diária‖ dos cuidados de reabilitação resultaram na necessidade de criação de sistemas de classificação de doentes de reabilitação em regime de internamento, em muitos países. Também em Portugal é necessário implementar um sistema de financiamento, baseado num sistema de classificação de doentes, ajustado pela complexidade e necessidade de cuidados destes doentes. Objectivos: Caracterização dos cuidados de reabilitação em Portugal, e do actual sistema de financiamento destes doentes; realização de uma revisão de literatura dos sistemas de classificação de doentes de reabilitação já existentes, de modo a compreender quais as variáveis de agrupamento utilizadas e qual a capacidade de previsão dos custos destes mesmos sistemas; perceber a importância da implementação de um dos sistemas de classificação em Portugal, e quais as suas vantagens. Metodologia: Da revisão de literatura efectuada, foram encontrados quatro sistemas de classificação de doentes implementados e/ou em vias de serem implementados como base para um sistema de financiamento, nos EUA, Austrália e Canadá. Foi efectuada uma extensa caracterização e análise crítica dos mesmos. Conclusões: Podemos concluir, que dos poucos sistemas de classificação de doentes de reabilitação existentes, optou-se pelo estudo de uma possível adopção do sistema norte-americano para a realidade portuguesa, por ser o único sistema de classificação já utilizado para fins de financiamento para todos os doentes de reabilitação desde 2002, o que inclui mais variáveis de decisão na classificação dos doentes, e o que permite a maior previsão dos custos dos doentes em termos percentuais.

Development of Photorefractive Polymers: Evaluation of Photoconducting and Electro-optic Properties

This Thesis discussed molecules suitable for photorefractive effect. Out of the molecules studied, only one system was used to make photorefractive polymers system. Other molecules, especially, the electro-optic polymer, Poly(3-methacrloyl-1-(4'-nitro-4-azo-1'-phenyl)phenylalanine-co- methyl methacrylate) can be subjected to more detailed studies to explore the possibilities of using them for electro-optic applications. Though not included in the thesis, the efficient photoconductor, Poly(6-tert-butyl-3- phenyl-3,4-dihydro-2H-1,3-benzoxazine) sensitized with C60, which was described in Chapter 3 showed a low magnitude photovoltaic effect. This hints at the possibility of using this system for organic solar cells also. The thesis presented the initial observation of photorefractive effect in a polybenzoxazine based polymer system. A detailed analysis of the effect of C60, ECZ and DR1 can be carried out to check for the possibility of a high efficiency photorefractive system.

Generalised prime systems with periodic integer counting function

We study generalised prime systems (both discrete and continuous) for which the `integer counting function' N(x) has the property that N(x) ¡ cx is periodic for some c > 0. We show that this is extremely rare. In particular, we show that the only such system for which N is continuous is the trivial system with N(x) ¡ cx constant, while if N has finitely many discontinuities per bounded interval, then N must be the counting function of the g-prime system containing the usual primes except for finitely many. Keywords and phrases: Generalised prime systems. I

Amor intellectualis diaboli

An essay on love and liberty in the writings of Gillian Rose, Marquis de Sade, Max Horkheimer and Theodor W. Adorno, written in response to the following provocation: "Encore un effort. A banderole publicitaire carries the breathless descriptions of the new fashions for 1968, when anything goes and details place the accent on this or that part of the body and its adornment: a pair of shoes that come off in a struggle, for example, the heel of one snapped off; a striking checked shirt, with two buttons undone; a light-coloured trench coat (perfect for a May day); a blouson-style jacket that allows easy freedom of movement; place casual slacks worn with an ankle boot. Beauty is in the streets as fashion becomes democratic (or so say the houses of haute couture), while the philosopher of the boudoir extorts us once again to make an effort if we wish to be republicans. Here, to an assembled crowd of sensitive men and women, which petit-maitre or dangerous man of principles would suggest that the only moral system to reinforce political revolution is that of libertinage, the revenge of nature's course against the aberrations of society?"

Diagnóstico ecotoxicológico dos efluentes lançados no complexo estuarino do Jundiaí/Potengi, Natal/RN

Untreated effluents that reach surface water affect the aquatic life and humans. This study aimed to evaluate the wastewater s toxicity (municipal, industrial and shrimp pond effluents) released in the Estuarine Complex of Jundiaí- Potengi, Natal/RN, through chronic quantitative e qualitative toxicity tests using the test organism Mysidopsis Juniae, CRUSTACEA, MYSIDACEA (Silva, 1979). For this, a new methodology for viewing chronic effects on organisms of M. juniae was used (only renewal), based on another existing methodology to another testorganism very similar to M. Juniae, the M. Bahia (daily renewal).Toxicity tests 7 days duration were used for detecting effects on the survival and fecundity in M. juniae. Lethal Concentration 50% (LC50%) was determined by the Trimmed Spearman-Karber; Inhibition Concentration 50% (IC50%) in fecundity was determined by Linear Interpolation. ANOVA (One Way) tests (p = 0.05) were used to determinate the No Observed Effect Concentration (NOEC) and Low Observed Effect Concentration (LOEC). Effluents flows were measured and the toxic load of the effluents was estimated. Multivariate analysis - Principal Component Analysis (PCA) and Correspondence Analysis (CA) - identified the physic-chemical parameters better explain the patterns of toxicity found in survival and fecundity of M. juniae. We verified the feasibility of applying the only renewal system in chronic tests with M. Juniae. Most efluentes proved toxic on the survival and fecundity of M. Juniae, except for some shrimp pond effluents. The most toxic effluent was ETE Lagoa Aerada (LC50, 6.24%; IC50, 4.82%), ETE Quintas (LC50, 5.85%), Giselda Trigueiro Hospital (LC50, 2.05%), CLAN (LC50, 2.14%) and COTEMINAS (LC50, IC50 and 38.51%, 6.94%). The greatest toxic load was originated from ETE inefficient high flow effluents, textile effluents and CLAN. The organic load was related to the toxic effects of wastewater and hospital effluents in survival of M. Juniae, as well as heavy metals, total residual chlorine and phenols. In industrial effluents was found relationship between toxicity and organic load, phenols, oils and greases and benzene. The effects on fertility were related, in turn, with chlorine and heavy metals. Toxicity tests using other organisms of different trophic levels, as well as analysis of sediment toxicity are recommended to confirm the patterns found with M. Juniae. However, the results indicate the necessity for implementation and improvement of sewage treatment systems affluent to the Potengi s estuary

Parameter-dependent Lyapunov functions for state-derivative feedback control in polytopic linear systems

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)