No description available.

A incorporação do gadolínio diretamente no combustível de reatores nucleares para geração de eletricidade é importante para compensação da reatividade e para o ajuste da distribuição da densidade de potência, permitindo ciclos de queima mais longos, com intervalo de recarga de 18 meses, otimizando-se a utilização do combustível. A incorporação do Gd2O3 sob a forma de pó homogeneizado a seco diretamente com o pó de UO2 é o método comercialmente mais atraente devido à sua simplicidade . Contudo, este método de incorporação conduz a dificuldades na obtenção de corpos sinterizados com a densidade niínima especificada, devido a um bloqueio no processo de sinterização. Pouca informação existe na literatura específica sobre o possível mecanismo deste bloqueio, restrita principalmente à hipótese da formação de uma fase (U,Gd)O2 rica em gadolínio com baixa difusividade. Este trabalho tem como objetivo a investigação do mecanismo de bloqueio da sinterização neste sistema, contribuindo para o esclarecimento da causa deste bloqueio e na elaboração de possíveis soluções tecnológicas. Foi comprovado experimentalmente que o mecanismo responsável pelo bloqueio é baseado na formação de poros estáveis devido ao efeito Kirkendall, originados por ocasião da formação da solução sólida durante a etapa intermediária da sinterização, sendo difícil a sua eliminação posterior, nas etapas finais do processo de sinterização. Com base no conhecimento deste mecanismo, possíveis propostas são apresentadas na direção da solução tecnológica do problema de densificação característico do sistema UO2-Gd203. / The incorporation of gadolinium directly into nuclear power reactor fuel is important from the point of reactivity compensation and adjustment of power distribution enabling thus longer fliel cycles and optimized fuel utilization. The incorporation of Gd2O3 powder directly into the UO2 powder by dry mechanical blending is the most attractive process because of its simplicity. Nevertheless, processing by this method leads to difficulties while obtaining sintered pellets with the minimum required density. This is due to blockages during the sintering process. There is little information in published literature about the possible mechanism for this blockage and this is restricted to the hypothesis based on formation of a low difiiisivity Gd rich phase (U,Gd)O2. The objective of this investigation has been to study the blockage mechanism in this system during the sintering process, contributing thus, to clarify the cause for the blockage and to propose feasible technological solutions. Experimentally it has been shown that the blocking mechanism is based on pore formation because of the Kirkendall effect. Formation of a solid solution during the intermediate stage of sintering leads to formation of large pores, which are difficult to remove in the final stage of sintering. Based on this mechanism, technical solutions have been proposed to resolve densification problems in the UO2-Gd2O3 system.

A nefrotoxicidade induzida por contraste (NIC) é responsável por cerca de 11% de todas as causas de injúria renal aguda no ambiente hospitalar e tem sido atribuída exclusivamente aos contrastes iodados. Contudo, os contrastes à base de gadolínio recentemente estão sendo reportados como potenciais indutores de nefrotoxicidade em pacientes de alto risco. A fisiopatologia da NIC está relacionada à geração de hipóxia na medula renal vinculada à disfunção endotelial, e ao estresse oxidativo, alterações que têm sido fortemente associadas à deficiência de vitamina D (dVD), condição que encontra-se altamente prevalente na população atual, mesmo em países de clima tropical. O objetivo desse estudo foi testar a hipótese de que a dVD é um potencial fator de risco para NIC. Para isso, ratos Wistar foram mantidos em dieta padrão ou livre de vitamina D por 30 dias. A seguir, CI (diatrizoato 76%), Gd (gadoterato de meglumina) ou soro fisiológico 0,9% foram infundidos por via endovenosa. Seis grupos foram avaliados (n=12/grupo): Sham, CI, Gd, dVD30, dVD30+CI e dVD30+Gd. Após 48h da infusão dos contrastes, os animais foram submetidos ao experimento de clearance de Inulina, para estimar o ritmo de filtração glomerular (RFG), a análise da expressão proteica no tecido renal de angiotensinogênio (AGT), renina e da óxido nítrico sintase endotelial (eNOS), e ao exame histológico. O estado redox foi avaliado por meio da medida das espécies reativas ao ácido tiobarbitúrico (TBARS, marcador de peroxidação lipídica), e dos níveis de glutationa reduzida (GSH, antioxidante endógeno) sistêmico e renal. Comparado ao grupo Sham, os animais dVD30 apresentaram menores níveis séricos de 25(OH)D total (3,96±0,8 vs. 44,87±1,7 ng/mL, p < 0,001), níveis semelhantes de cálcio e fósforo plasmáticos e aumento da expressão renal de AGT e renina. O RFG foi similar nos grupos Sham, CI e Gd. Entretanto, o RFG foi significantemente menor nos grupos dVD30+CI e dVD30+Gd e esta redução esteve associada ao aumento no tecido renal da expressão de AGT e à redução da eNOS, combinado à acentuada elevação da razão TBARS/GSH no tecido renal. Apesar da alteração na função renal com a infusão dos contrastes, a morfologia renal permaneceu preservada. Foram feitos dois grupos adicionais (n=5/grupo) mantidos em dVD por 60 dias. Após administração dos contrastes, uma maior queda do RFG foi observada, sugerindo que uma dVD mais prolongada agrava ainda mais a queda do RFG. Coletivamente, nossos resultados indicam que a dVD é um potencial fator de risco para NIC iodado e de gadolínio em consequência do desequilíbrio intrarrenal de substâncias vasoativas por meio da ativação do sistema renina-angiotensina e do estresse oxidativo / Contrast-induced nephropathy (CIN) account for about 11% of all causes of acute kidney injury in hospitalized patients and has been attributed exclusively to iodinated contrast media. However, gadolinium-based contrast agents are reported recently as potential inducers of nephrotoxicity in high risk patients. Pathophysiology of CIN is related to hypoxia in the renal medulla associated with endothelial dysfunction and oxidative stress, changes that have been strongly linked to vitamin D deficiency (VDD), condition that is highly prevalent in the current population, even in tropical countries. This study tested the hypothesis that VDD is a predisposing factor for iodinated and gadolinium contrast media nephrotoxicity. To this end, male Wistar rats were fed standard or vitamin D-free diet for 30 days (VDD30). Then, IC (diatrizoate 76%), Gd (gadoterate meglumine) or saline were administered intravenously and six experimental groups were obtained: Sham, IC, Gd, VDD30, VDD30+IC and VDD30+Gd. Renal hemodynamics, redox status, histological and immunoblot analysis were evaluated 48h after contrast or vehicle infusion. Compared to Sham, VDD30 rats presented lower levels of total 25(OH)D (3.96 +- 0.8 vs. 44.87 ± 1.7 ng/mL, p < 0,001), similar plasma levels of calcium and phosphorus and higher renal renin and angiotensinogen expression. Inulin clearance-based estimated glomerular filtration rate (GFR) was not different among Sham, IC and Gd groups. However, GFR was significantly reduced in VDD30+IC and VDD30+Gd groups and this reduction was associated with higher renal angiotensinogen and lower eNOS abundance combined with higher kidney thiobarbituric acid reactive substances and lower glutathione levels. Conversely, worsening of renal function was not accompanied by abnormalities on kidney structure or increased infiltration of inflammatory cells. Rats on a VDD for 60 days displayed a greater fall in GFR after contrast administration, suggesting that the longer the period of VDD, the worst the impact of contrast media on renal function. Collectively, our findings suggest that VDD is a potential risk factor for contrast nephropathy due to imbalance in intrarenal vasoactive substances by renin-angiotensin system activation and oxidative stress

La radiothérapie anticancéreuse repose sur trois grands principes: 1) restriction anatomique de l'irradiation ; 2) fractionnement temporel du traitement; 3) traitement de tissus plus sensibles aux rayonnements que les tissus sains environnants. Sous ces principes se cache un idéal: celui de déposer plus d'énergie de rayons X (RX) dans les tumeurs, en préservant les tissus sains adjacents. Objectif difficile à atteindre puisqu'une des causes d'échec de ce traitement est la poursuite de l'évolution tumorale. Le rayonnement synchrotron pourrait-il être plus efficace? Les variations des coefficients d'interactions rayonnement-matière, en fonction de l'énergie des RX et du numéro atomique du matériau, montrent que certaines énergies et certains matériaux sont préférables pour obtenir un maximum d'interactions et d'énergie déposée. Le rayonnement synchrotron permet de sélectionner précisément ces énergies, grâce à sa très grande intensité. Ses caractéristiques spectrales (énergie des RX entre 10 et 100 keV) permettent de déclencher l'effet photoélectrique, avec un maximum de probabilité, sur des éléments lourds introduits au voisinage de cellules tumorales. Il a été montré que: 1) la tomodensitométrie par rayonnement synchrotron est une technique d'imagerie quantitative, potentiellement puissante pour la radiothérapie car elle assure in vivo la mesure de la concentration intratumorale d'agent de contraste (I ou Gd); 2) en présence d'agent de contraste iodé l'effet létal des RX sur la survie cellulaire est augmenté et le gain de radiosensibilisation dépend de l'énergie des RX; 3) à l'échelle cellulaire, la létalité de l'irradiation peut être encore optimisée en transportant des atomes lourds (I, Pt) au cœur de l'ADN, cible biologique de l'irradiation. Ce renforcement de l'efficacité létale des RX de basses énergies, grâce à une interaction physique ciblée sur un agent pharmacologique, est un concept original en radiothérapie anticancéreuse.

L'étude des systèmes ternaires U - Cu - X (X = Si ou Ge) a permis de mettre en évidence trois nouvelles phases: U3Cu4Si4, U3Cu4Ge4 et UCuGe1,77. Leurs propriétés structurales et magnétiques ont été étudiées et les structures magnétiques des deux premières ont été déterminées. La substitution du cuivre au silicium dans la solution solide UCuxSi2-x (0,28 ≤ x ≤ 0,96) est à l'origine de transitions structurales et magnétiques selon les séquence α-ThSi2(quadratique) → AlB2(hexagonal) → Ni2In(hexagonal) et non magnétique → ferromagnétique → antiferromagnétique. L'évolution des propriétés magnétiques reflète la compétition entre les interactions de type Kondo et RKKY. Désordre cristallographique et frustrations magnétiques sont à l'origine d'un état "verre de spin" au passage ferro-antiferromagnétique. Les propriétés structurales et magnétiques des composés GdNi3X2 (X =Ga, Al, Sn) se sont avérées fortement dépendantes de la nature de l'élément X et du traitement thermique des échantillons. L'augmentation de la taille de X favorise une transition structurale de type CaCu5 → HoNi2,6Ga2,4 ainsi qu'un passage ferro → antiferromagnétique. Une structure cristallographique modulée commensurable (équivalente à une surstructure aHoNi2,6Ga2,4 × aHoNi2,6Ga2,4 × 2cHoNi2,6Ga2,4) est observée pour GdNi3Al2. L'insertion d'hydrogène dans Gd3Ni6Al2 et GdNi3Al2 affaiblit considérablement les interactions magnétiques.

<p>One of the main obstacles to maintaining patients with short bowel syndrome on parenteral nutrition, or successfully transplanting these patients with a small bowel graft, is the many severe infections that occur. Evidence is accumulating that translocating bacteria from the patient’s bowel causes a significant part of these infections. In this thesis bacterial translocation is studied in a Thiry-Vella loop of defunctionalised small bowel in the rat. </p><p>Bacterial translocation to the mesenteric lymph nodes (MLNs) occurs in almost 100% of the rats after three days. No systemic spread of bacteria is observed unless there is additional immunosupression with depletion of Kupffer cells in the liver. However, blocking the function of α/β T cells does not increase the translocation. Removal of MLNs does not either aggravate bacterial translocation in the Thiry-Vella loop model. Conversely, after small bowel transplantation translocating bacteria spread systemically if the MLNs are removed. </p><p>The Thiry-Vella loop should also be a suitable model for the testing of potentially translocation-inhibiting substances. Reinforcement of the intestinal barrier with glutamine or phosphatidylcholine proved insufficient in decreasing bacterial translocation. Even selective bowel decontamination with tobramycin failed to abolish bacterial translocation. Thus, it seems that the driving force for translocation in this model is strong regardless of the relatively small trauma of intestinal defunctionalisation.</p><p>Flow cytometric studies of the immune cells in the spleen MLNs showed a decrease in MHC class II positive T cells in the MLNs of the Thiry-Vella loop. Concurrently the number of macrophages increased with time as observed by immunohistochemistry. The fraction of MHC class II negative macrophages increased in the spleens of rats treated with glutamine. </p><p>In conclusion, the Thiry-Vella loop model offers possibilities of immunological as well as mechanistic studies on bacterial translocation from small intestine.</p>

No description available.

In der vorliegenden Arbeit wird die Einkristallzüchtung nach dem Czochralskiverfahren von GdCa4O(BO3)3 (GdCOB) beschrieben. Aus insgesamt 18 Zuchtversuchen, bei denen auch die Ziehgeschwindigkeit zwischen 1 und 3mm/h variiert wurde, wurden erfolgreich nahezu perfekte Einkristalle gewonnen. In einigen Kristallen traten jedoch auch Risse oder Einschlüsse auf. Diese enthielten neben Iridium vom Tiegelmaterial auch andere Phasen des Gd2O3–B2O3–CaO-Systems, sowie P und Yb, deren Herkunft unklar ist. Als Hauptziehrichtung wurde die kristallographische b-Achse gewählt, ergänzt durch einige Experimente in der c-Richtung. In den drei kristallographischen Hauptrichtungen wurden die thermischen Ausdehnungskoeffizienten von GdCOB bestimmt. Diese können in zwei nahezu lineare Bereiche unterteilt werden: von Zimmertemperatur bis etwa 850° C und von 850 bis 1200° C, wobei die Koeffizienten im Hochtemperaturbereich deutlich höher sind (unter 850° C: alpha_a=11.1, alpha_b=8.6, alpha_c=13.3 10^-6/K, oberhalb 850° C: alpha_a=14.1, alpha_b=11.7, alpha_c=17.8 10^-6/K). Daraus ergibt sich, dass ein Phasenübergang höherer Ordnung vorliegen muss. Als mögliche Ursache wurde mittels HT-Raman Spektroskopie ein Ordnungs-Unordnungs-Übergang identifiziert, während dessen die BO3-Gruppen in der Struktur leicht rotieren. Weitere Untersuchungen mittels thermodynamischer Methoden führten zu schwachen, aber eindeutigen Signalen, die diesem Effekt ebenfalls zuzuordnen sind. Obwohl das Material ein vielversprechender Kandidat für piezoelektrische Anwendungen im Hochtemperaturbereich ist, wurde dieser Effekt bisher unzureichend beschrieben. Dieses Verhalten, kombiniert mit den anisotropen thermischen Ausdehnungskoeffizienten, könnte eine der Ursachen für das Vorkommen von Rissen in den Kristallen während der Synthese darstellen. Spektroskopische Untersuchungen ergaben einen großen Transparenzbereich von 340 bis 2500nm (29 400–4000 cm^-1), was für optische Anwendungen von großer Bedeutung ist. / In a series of 18 growth experiments, GdCa4O(BO3)3 (GdCOB) single crystals were successfully grown by the Czochralski method. They have a well-ordered structure, as revealed by single crystal structure analysis. Although the main growth direction was along the crystallographic b-axis, some experiments were conducted using the cdirection. Pulling velocities were varied between 1 and 3mm/h. Except for a few crystals with cracks or elongated "silk-like" inclusions consisting of multiphase impurities, most of the obtained crystals are of good quality. Those inclusions contain iridium, deriving from the crucible, P and Yb with unclear source, and other phases from the system Gd2O3–B2O3–CaO. Thermal expansion coefficients of GdCOB were determined in the directions of the crystallographic axes and found to be approximately linear in two temperature ranges: from 25° C to around 850° C, and from 850 to 1200° C, with the latter range showing significantly higher coefficients (below 850° C: alpha_a=11.1, alpha_b=8.6, alpha_c=13.3 10^-6/K, and above 850° C: alpha_a=14.1, alpha_b=11.7, alpha_c=17.8 x10^-6/K). This sudden increase of thermal expansion coefficients indicates a phase transition of higher order. An order-disorder transition in form of the rotation of BO3-triangles in the structure was made tentatively responsible for this transition, as revealed by HT-Raman spectroscopy. This transition was also detected by DSC-methods but appeared to result in very weak effects. Although the material is thought to represent a promising candidate for high temperature piezoelectric applications (noncentrosymmetric space group Cm), this effect of change in specification has not been described and it is unknown whether it has influence on the piezoelectric properties. Furthermore, this characteristic behaviour in combination with anisotropic coefficients may be the reason for the development of cracks during cooling of crystals, making the growth difficult. Spectroscopic investigation revealed a wide transparency range from 340 to 2500nm (29 400–4000 cm^-1) of GdCOB, which is a very important property for optical applications.

One of the main obstacles to maintaining patients with short bowel syndrome on parenteral nutrition, or successfully transplanting these patients with a small bowel graft, is the many severe infections that occur. Evidence is accumulating that translocating bacteria from the patient’s bowel causes a significant part of these infections. In this thesis bacterial translocation is studied in a Thiry-Vella loop of defunctionalised small bowel in the rat. Bacterial translocation to the mesenteric lymph nodes (MLNs) occurs in almost 100% of the rats after three days. No systemic spread of bacteria is observed unless there is additional immunosupression with depletion of Kupffer cells in the liver. However, blocking the function of α/β T cells does not increase the translocation. Removal of MLNs does not either aggravate bacterial translocation in the Thiry-Vella loop model. Conversely, after small bowel transplantation translocating bacteria spread systemically if the MLNs are removed. The Thiry-Vella loop should also be a suitable model for the testing of potentially translocation-inhibiting substances. Reinforcement of the intestinal barrier with glutamine or phosphatidylcholine proved insufficient in decreasing bacterial translocation. Even selective bowel decontamination with tobramycin failed to abolish bacterial translocation. Thus, it seems that the driving force for translocation in this model is strong regardless of the relatively small trauma of intestinal defunctionalisation. Flow cytometric studies of the immune cells in the spleen MLNs showed a decrease in MHC class II positive T cells in the MLNs of the Thiry-Vella loop. Concurrently the number of macrophages increased with time as observed by immunohistochemistry. The fraction of MHC class II negative macrophages increased in the spleens of rats treated with glutamine. In conclusion, the Thiry-Vella loop model offers possibilities of immunological as well as mechanistic studies on bacterial translocation from small intestine.

Parmi les nanoparticules aptes à accompagner la radiothérapie en clinique, les nanoparticules à base d'oxyde de gadolinium paraissent pertinentes, de part leur multimodalité en imagerie et leur effet radiosensibilisant prouvé in vitro et in vivo. Cet effet de radiosensibilisation est exceptionnel notamment sur des cellules cancéreuses radiorésistantes de la lignée SQ20B (carcinome squameux tête et cou) et uniquement pour des doses modérées de nanoparticules (aux alentours de 0.6 mM en Gd). Les clichés de microscopie électronique ont montré que ce maximum de radiosensibilisation est dû à une internalisation maximale des particules dans le cytoplasme, notamment par macropinocytose. Ce mécanisme d'internalisation est caractérisé par la formation de vésicules de grandes tailles, ou macropinosomes. Il se produit suivant deux étapes : la formation d'agglomérats de nanoparticules à proximité de la membrane cellulaire puis la récupération de ceux-ci par les lamellipodes de la cellule. La première étape est fortement dépendante des caractéristiques physicochimiques des particules, plus particulièrement leur potentiel zêta qui détermine la taille de l'agglomérat, et de la distance les séparant de la cellule. Dans des gammes de taille et de distance à la membrane optimales aux concentrations modérées, l'agglomérat peut être récupéré par les lamellipodes de la cellule. Il s'en suit une protubérance sur la membrane plasmique formant un macropinosome contenant les agglomérats de nanoparticules. Cet endosome précoce suivra ensuite le schéma d'endocytose classique dans le cytoplasme en fusionnant avec des corps multivésiculaires, uniquement visible en microscopie électronique à transmission, pouvant contenir des enzymes de dégradation détruisant leur contenu. Ces enzymes rendent le pH acide à l'intérieur de la vésicule. Plus les nanoparticules sont proches du noyau cellulaire plus leur effet radiosensibilisant sera efficace. Les espèces oxygénées réactives (ROS) et les électrons Auger et secondaires peuvent atteindre l'ADN du noyau plus facilement. A faibles doses (<0.4 mM) très peu de nanoparticules sont internalisées et un effet linéaire de la radiosensibilisation est observé jusqu'à 0.6 mM. A fortes doses (> 0.7 mM) les nanoparticules forment une couronne autour de la membrane cellulaire agissant comme écran, empêchant ainsi les ROS et les électrons générés de pouvoir atteindre l'ADN et induire des cassures, le noyau étant situé à quelques micromètres de la membrane cellulaire. Les résultats obtenus ouvrent la voie sur la nécessité de contrôler l'internalisation cellulaire des nanoparticules en contrôlant leur chimie, laissant envisager ainsi des opportunités prometteuses dans le domaine de la radiothérapie assistée par nanoparticules délivrant de faibles doses de radiation aux patients.