No description available.

Ce mémoire porte sur l’étude de pyrophosphates de calcium hydratés (CPP : Ca2P2O7•nH2O), composés rencontrés dans des micro-calcifications pathologiques associées à l’arthrose et, dans certains cas, responsables d’arthropathie destructive. Ces cristaux, présents dans les articulations de patients arthritiques, possèdent un fort potentiel inflammatoire susceptible d’engendrer une dégradation aigüe du cartilage. Cependant, les mécanismes de formation des phases de CPP et d’activation de leur potentiel inflammatoire n’ont pas encore été entièrement décrits. Nous nous sommes intéressés à l’étude des conditions de formation des différentes phases de pyrophosphates de calcium hydratés in vitro ainsi qu’à la caractérisation fine de chacune des phases d’intérêt biologique avec des outils de laboratoire et de grands instruments afin de mieux comprendre leurs propriétés physico-chimiques et d’améliorer leur identification in vitro et in vivo. Dans un premier temps, un protocole de synthèse a été établi permettant la synthèse de quantités importantes de chacune des phases pures de CPP (CPP amorphe, CPP dihydratés monoclinique et triclinique et CPP tétrahydraté). Les conditions de synthèse associées à la formation de chacune de ces phases, pH et température notamment, ont été explorées. Des échantillons purs ont été utilisés comme références pour les différentes études physico-chimiques et structurales qui ont ensuite été menées. Les échantillons de référence ont été caractérisés finement, d’un point de vue structural avec notamment la résolution de plusieurs structures cristallines (diffraction des rayons X et des neutrons, sur poudre et monocristal) mais aussi au travers de différentes analyses spectroscopiques (spectroscopies FTIR et Raman, RMN du solide) et d’analyses de la morphologie des cristaux (microscopies électroniques à balayage et en transmission, diffraction électronique). Chacune de ces analyses complémentaires, couplées à des modélisations ab initio, a permis de préciser les hypothèses suggérant un rôle de la surface des cristaux dans le potentiel inflammatoire de ces phases. Une troisième partie est consacrée à l’exploration de différentes techniques de synthèse mettant en œuvre différents milieux (cristallisation en solution et en gel). Ces expériences ont permis d’établir des comparaisons avec les processus de formation observés in vivo et d’évolution in vitro à haute température des phases de CPP. Finalement des études ex vivo de cartilages calcifiés seront présentées, mettant en évidence les avantages de ces techniques de caractérisation de laboratoire comme outils de diagnostic. Ce travail permet ainsi de préciser les mécanismes physico-chimiques liés aux différentes phases de CPP in vitro et in vivo afin de mieux comprendre la formation de ces phases et leur potentiel inflammatoire associé, tout en améliorant les possibilités de diagnostic des arthropathies microcristallines. / The present work concerns the study of hydrated calcium pyrophosphates (CPP: Ca2P2O7•nH2O), a group of phases detected in pathological microcalcifications and associated with arthritis. These crystals are frequently observed in the synovial fluid of arthritic patients and they were described as having a high inflammatory potential which could induce a severe degradation of cartilage. However, the mechanisms involved in the formation of the CPP crystals and the activation of their inflammatory potential are not fully understood. This work is focused on the study of the synthesis conditions of CPP in vitro and on the fine characterization of CPP phases of biological interest using laboratory equipments and large-scale facilities. The aim of this work was to describe the physico-chemical properties of these materials, including inflammatory potential, and to improve their identification in vivo and in vitro. First, a synthesis protocol was designed for the production of significant amounts of pure samples for each of the CPP phases (amorphous CPP, monoclinic and triclinic dihydrated CPP and tetrahydrated CPP). Different conditions, including pH and temperature, were studied to achieve the synthesis of reference materials. These samples were precisely characterized using complementary techniques to determine their crystalline structures (powder and single crystal X-ray diffraction and neutron diffraction) as well as using spectroscopic (FTIR and Raman spectroscopies, MAS-NMR) and morphologic analyses (SEM, TEM and electron diffraction). These analyses, combined with ab initio modeling, clarified the hypotheses concerning the role of the crystal surface on the adsorption properties of CPP crystals and their inflammatory potential. The third part of this thesis is focused on the study of CPP synthesis conditions, by using different experimental setups to study crystallization in solution and in gel. A comparison with in vivo formation processes and in vitro high temperature evolution phenomena of these phases was established based on the results of these experiments. Finally, ex vivo analyses of pathological cartilage are presented, highlighting the advantages of different laboratory characterizations as medical diagnostic tools. This work contributes to clarify the physico-chemical characteristics of CPP phases in vitro and in vivo, to improve the knowledge on the formation and the evolution of these phases, their properties including inflammatory potential, and to facilitate their identification in vivo.

<p> The magnetic structures of antiferromagnetic manganese pyrophosphate and copper pyrophosphate have been determined by single crystal neutron diffraction techniques. More detailed features of the magnetic structure have been determined by nuclear magnetic resonance (NMR). A discrepancy between previous NMR measurements on Mn2P2o7 and the single crystal neutron measurements was resolved by postulating a low temperature crystallographic phase transition. Information about the dependence of the transferred hyperfine interaction upon the separation of the relevant ions is obtained for Cu2P2o7 from the NMR data and from previously determined deviations from a higher symmetry phase. The origin of the magnetic anisotropy energy in Cu2P2o7 is discussed. </p> / Thesis / Doctor of Philosophy (PhD)

No description available.

There is considerable potential for the use of thin film shape memory alloys in the field of microtechnology due to their high power to volume ratio. The main obstacles for fabrication arise mainly due to the narrow regime over which shape memory behaviour is observed and the paucity of process techniques. Shape memory transition in brass only occurs in the alloy composition range 38.5 - 41.6 wt %% zinc. This study used a pyrophosphate electrolyte containing Cu2P2O7, Zn2P2O7 salts and an excess of K4P207 and KNO3, for brass deposition as a replacement for cyanide electrolytes because it is non-toxic and noncorrosive. A rotating disc electrode was employed to systematically examine polarisation data and a rotating cylinder electrode was employed to produce thin brass films and deduce the current efficiencies of copper, zinc and brass deposition with respect to deposition potential. Thin films were plated between 5- 301im, they all displayed a smooth, uniform homogenous deposit with no precipitates or oxide inclusions. The current efficiencies were found to be < 45% for copper, < 15% for zinc and between 10 - 30% for brass. The microstructural characterisation of the Cu-Zn thin alloys was undertaken by X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray fluorescence (EDAX), transmission electron microscopy (TEM) and differential scanning calorimetry (DSC). XRD showed all the electrodeposited Cu-Zn alloys to have same phase composition as those predicted by the equilibrium phase diagram for Cu-Zn. This confirmed the existence of the parent p-phase within the shape memory composition range, which undergoes the martensitic transformation. TEM showed these foils to be composed of a matrix of a, p and martensite nano sized grains (< 40nm) co-existing with a sparse distribution of larger grains (200-300nm). The larger grains were always martensite in nature, recognisable by their twinning planes. Differential scanning calorimetry analysis shows evidence of a martensitic transformation change for the thin brass films.

Tissue thiamin diphosphate was assayed enzymatically utilizing purified brewer's yeast apotransketolase. With this assay ten uumoles of thiamin diphosphate could be detected. Total thiamin was fluorometrically measured. For one to three days rats were placed under conditions of stress, consisting of loud noise treatment, emotional stress, deprivation of paradoxical sleep, and swimming to exhaustion, respectively. The body weight was markedly decreased at the end of the respective experimental periods except with the loud noise treated group, compared with the corresponding controls. Following two to three such consecutive treatments, the adrenal weight also showed a significant increase. Thiamin diphosphate and total thiamin in liver was significantly decreased after one day's exposure to loud noise. On the other hand, thiamin diphosphate and total thiamin in brain and liver were not significantly affected by the other treatments tried in this study .

<P> Taxol, a highly functionalized and complex diterpene belonging to the taxane group, possesses strong antitumor activity against various cancers, especially in cases of advanced ovarian and breast cancers. Because of the unique mechanism of action and the unusual chemical structure, taxol may represent the prototype of a new class of chemotherapeutic agents. The non-clinical work up to date on taxol is described in this thesis, including natural resources, chemical synthesis and chemical manipulation of taxol. </p> <p> The biosynthesis of taxol has not yet been studied. The hypothesis proposed for the biosynthetic sequence involves cyclization of geranylgeranyl pyrophosphate (GGPP) into hydrocarbon intermediates, which are then further transformed into taxol. In order to study the biosynthesis of taxol, [^14C]-labelled GGPP was prepared. Through the use of this labelled precursor in incubations with cell-free extract of yew labelled biosynthetic intermediates which are formed can be isolated and identified, hence leading to further understanding of the biosynthesis of taxol. </p> <p> The synthesis of [16,17-^14C]geranylgeranyl pyrophosphate was achieved in eight steps starting from commercially available geranylgeraniol. The alcohol was protected as the acetate derivative and the terminal double bond selectively epoxidized. The epoxide was opened to the diol, which was then cleaved. The resulting aldehyde was coupled to [^14C] isopropyltriphenylphosphonium ylid in a Wittig reaction, giving [16,17-14C]geranylgeraniol after deprotection of the acetate group. The alcohol was converted into the chloride derivative and subsequently to [16,17-14C]geranylgeranyl pyrophosphate. </p> / Thesis / Master of Science (MSc)

Les chondrocalcinoses articulaires (CCA) sont des arthropathies microcristallines caractérisées par la présence de cristaux de pyrophosphate de calcium dihydratés (PPCD) au sein du cartilage. Il existe trois formes de CCA : les formes familiales, transmises de façon autosomique dominante, et les formes sporadiques, dont la probabilité d'apparition augmente avec l'âge, et les formes secondaires à d'autres pathologies, comme l'hyperparathyroïdie. Le gène Ank code un transporteur exportant le pyrophosphate inorganique (PPi) hors des cellules. Un lien est clairement établi entre des mutations dans la séquence codante du gène Ank et les formes familiales de CCA Nous avons étudié la contribution du gène Ank dans la production de PPi par les chondrocytes articulaires stimulés avec du transforming growth factor-ß1 (TGF-ß1), leur sensibilité a ce facteur de croissance augmentant avec le l'âge des patients. Nous avons également, vu la présence fréquente des cristaux de PPCD chez les patients arthrosiques, et l'influence du niveau d'expression d'Ank dans la chondrogenèse, voulu élucider la possible implication d'Ank dans la perte du phénotype du chondrocyte articulaire, retrouvée dans l'arthrose. Enfin, nous avons étudié le rôle du calcium sur les effets du TGF-ß1 dans la production d'ePPi, l'hypercalcémie étant souvent retrouvée dans les tableaux cliniques d'hyperparathyroïdisme. Ces travaux ont permis de mettre en évidence le rôle majeur d'ANK en cas sensibilité accrue du chondrocyte au TGF-ß1. De plus, le PPi transporté par ANK influence le phénotype du chondrocyte articulaire. Enfin, le calcium joue un rôle crucial sur les effets inducteurs du TGF-ß1 dans la production de PPi. / Articular chondrocalcinosis (CCA) are microcrystalline arthtopathies characterized by the presence of calcium pyrophosphate dihydrate crystals (CPPD) in the cartilage. There are 3 forms of CCA, including the familal forms, dependent upon an autosomal dominant transmission mechanism, the sporadic forms, whose probability of occurrence increases with ageing, and the metabolic forms, secondary to other pathologies like hyperparathyroidism. The Ank gene encodes a transporter which exports inorganic pyrophosphate (PPi) outside the cells. A link is well established between mutations in the coding sequence of the Ank gene and the familial forms of CCA. We studied, on one hand, the contribution of the Ank gene in the production of PPi by articular chondrocytes stimulated with transforming growth factor-ß1 (TGF-ß1), since the sensitivity of chondrocytes to this growth factor increases with ageing. On the other hand, since CPPD are often associated with osteoarthritis (OA), and since Ank expression levels influences the chondrogenesis, we elucidated the possible implication of Ank in the loss of the articular chondrocytes phenotype observed during OA. Finally, we analyzed the role of calcium on the TGF-ß1 effects on ePPi production, hypercalcaemia being often found during hyperparathyroidism. This work allowed demonstrating, on one hand, the predominant role of ANK in the situations of chondrocytic hypersensitivity to TGF-ß1. On the other hand, the PPi exported by ANK influences the expression of articular chondrocytic markers. Finally, calcium plays a crucial role in the inducer effects of TGF-ß1 in the production of PPi.

No description available.

Concentrated kaolin clay slurries are found in a number of industrial operations including mine tailings surface disposal, underground paste backfill, and riverbed dredging. An understanding of the impact of solids concentration and addition of chemical species on slurry rheology is of importance to designers of pipeline transport and waste disposal systems. A project to determine the rheology of an idealized industrial kaolin clay slurry using a concentric cylinder viscometer and an experimental pipeline loop was undertaken. Additional laboratory test work including particle size analysis, slurry pH, calcium ion concentration in the slurry supernatant and particle electrophoretic mobility measurements were completed to aid in the understanding of their effects on the slurry rheology. The slurries were prepared in varying kaolin clay solids concentrations with reverse osmosis water. A flocculant, dihydrated calcium chloride (CaCl2 ¡¤ 2H2O), was added to the reverse osmosis water in concentrations equivalent to those found in typical industrial hard water supply. A dispersant, tetra-sodium pyrophosphate (TSPP, Na4P2O7) was used to disperse the clay particles for selected slurries. It was found that the kaolin clay slurries, in the absence of TSPP, exhibited yield stresses and could be characterized with either the two-parameter Bingham or Casson continuum flow models. Increasing the clay concentration in the slurry, while keeping the mass ratio of flocculant to kaolin constant, increased both the yield and plastic viscosity parameters. There was generally good agreement between the rheological parameters obtained in the Couette flow viscometer and that in the pipeline loop. In slurries for which it was possible to obtain turbulent flow, the transition to turbulent flow was predicted accurately by the Wilson & Thomas method for both Bingham and Casson models. It was possible to eliminate the yield stress of a slurry with the addition of the dispersing agent TSPP. The calcium ion content of the supernatant extracted from the slurries proved to be a indicator of the degree of flocculation. When exposed to extended periods of high shear conditions in the pipeline loop, slurries with clay concentrations of 17% by volume solids or greater exhibited an irreversible increase in apparent viscosity with time. An attempt was made to investigate this irreversible thickening characteristic. Laboratory tests did not reveal any appreciable differences in particle size, electrophoretic mobility, calcium ion concentration or pH with this irreversible change. The shear duration test shows the importance of using the appropriate shear environment when testing high solids concentration kaolin clay slurries