Dissertations / Theses on the topic 'Thiosulfate'

In this research polyethylenimine coated iron oxide magnetic nanoparticles (PEI-MNPs), as a novel adsorbent, was evaluated for the adsorption of gold from thiosulfate leaching solutions that contain gold, copper and calcium thiosulfate. This novel adsorbent can simply be separated from the solution using an external magnetic field, followed by gold adsorption. Gold elution from the adsorbent was simple and rapid.

With growing environmental and occupational safety concerns over the use of cyanide in gold processing, more acceptable alternatives are receiving increased interest. The most promising of the possible alternatives is thiosulfate. However, as activated carbon is not an effective substrate for the adsorption of the gold thiosulfate complex, the thiosulfate process lacks a proven in-pulp method for recovering dissolved gold. Anion exchange resins offer a possible route for in-pulp recovery. This thesis describes work aimed at evaluating the effectiveness of commercially available anion exchange resins for the recovery of gold from thiosulfate leach liquors and pulps. It was found that Strong-base resins are superior at accommodating the gold thiosulfate complex compared to Weak-base resins, which means Strong-base resins have a greater capacity to compete with other anions in leach solutions. Strong-base resins were therefore the preferred choice of resin for recovery of gold from thiosulfate leach solutions and pulps. Work with a selected commercial Strong-base resin showed that competing polythionates (particularly tri- and tetrathionate) lower the maximum possible loading of gold but that gold is selectively recovered over other base-metal anions in typical leach solutions. From kinetic experiments, it was found that competing polythionates did not affect the initial rate of loading of gold but displaced the loaded gold at long times. Thus it would be important to minimise the contact time of the resin with the pulp. Equilibrium loading isotherms of gold in the presence of competing anions could be analysed by treating the ion exchange reaction as a simple chemical reaction. However, a stoichiometry and equilibrium quotient which does not follow that normally used for anion exchange, was required to describe the experimental data. A single value for the equilibrium constant also cannot be used to describe the data over the range of concentrations for a given competing anion. The order of selectivity of the anions for the anion exchange resin could be explained by the difference in structure and the charge of each anion. The rate of loading of gold is controlled by mass transport in the aqueous phase in the presence of weakly competing anions such as sulfate and thiosulfate. An attempt was made to describe the more complex loading curves obtained in the presence of stronger competing anions such as sulfite, trithionate and tetrathionate in which it was found that the loading of gold increased to a maximum before declining to a lower equilibrium value. The difference in the rate of loading between the macroporous and gel anion exchange resins was explained by the difference in the location of their functional groups. Operation of a small-scale resin-in-pulp plant showed that gold could be recovered from a leach pulp to yield loadings of gold of up to 6000 mg L-1 and loadings of copper below 100 mg L-1. Under ideal conditions, the gold concentration in the barren pulp could contain less than 0.01 mg L-1. Throughout the trial it was shown that loaded copper would be displaced by gold which would result in the loading of copper falling from 2000 mg L-1 in the last stage to lower than 100 mg L-1 on the resin in the first stage. It was observed that some of the dissolved gold precipitated or adsorbed on the solids during leaching. Some of this adsorbed gold was found to be recovered by the anion exchange resins that would have reported to the tails if a solid/liquid separation method was employed. Gold was efficiently eluted with a nitrate solution and the two-step elution process using aerated ammonia followed by nitrate effectively stripped all the copper and gold from the resin. This process was found not to materially affect the equilibrium gold concentration on the resin after eight cycles, thus allowing the resin to be recycled without the need for regeneration. Electrochemical studies showed that the gold thiosulfate complex was reduced on stainless steel from a nitrate solution. Conventional electrowinning could therefore be used to recover the gold from the eluant.

Thiosulfate is a promising alternative for leaching silver sulfide ores such as those at the epithermal Yanacocha deposit. These ores suffer from low silver recovery, high mercury extraction and environmental challenges when treated with conventional cyanide. In this study, cupric-ammonia, ferric-ethylenediaminetetraacetic acid (EDTA), ferric-oxalate and ferric-citrate are tested with thiosulfate in a series of rotating disk experiments with silver sulfide and with ore from Yanacocha. This thesis publishes experimental evidence that supports the use of thiosulfate with different additives as a potential alternative to conventional cyanidation for silver sulfide leaching. The leaching of silver sulfide by cupric-ammonia thiosulfate can occur either by the substitution of cupric or cuprous for silver. The cupric catalyzed reaction is favored due to a thermodynamic barrier to the cuprous reaction. Rotating disk experiments demonstrate that cupric-ammonia leaching is under mixed chemical/diffusion control. The leaching rate is maximized by stabilizing cupric in solution with ammonia and increasing the availability of thiosulfate for silver dissolution. The addition of EDTA to this system decreased the leaching rate of the silver sulfide disk by lowering the cupric reactivity, but accelerated silver leaching of the ore, likely due to the prevention of passive oxide film formation on sulfides. Ferric complexes used were found to be very unreactive towards thiosulfate, but are reduced by sulfides present in the ore. Ferric-EDTA was the most effective oxidant of the three for leaching silver sulfide with thiosulfate. Silver recovery of the ground ore in batch leaching tests is low due to quartz locking of silver, with cupric-ammonia and ferric-EDTA leaches exposed to air recovering 31% and 26% after 24 hours, respectively. Cyanidation recovered 34% silver with a 95% confidence interval of 28-37%. The slightly lower recovery by thiosulfate may be due to silver minerals which are not amenable to thiosulfate leaching.

Flower bud abortion, or "blasting" was shown to be at least partially caused by treating plants with ethephon, a chemical that releases ethylene. In floricultural greenhouses, ethylene could accumulate to levels that could induce commercially significant levels of flower bud injury. Silver thiosulfate (STS) was shown to be a potent inhibitor of ethephon injury. STS at (1 to 2 mM) could be applied as early as the visible bud stage (approximately 5 to 6 weeks before flowering) without phytotoxic effects. Using current silver prices, the material cost for our treatment is less than 0.4 cents per plant. Based on these results, a preventative STS application could potentially reduce much of the flower bud abortion seen in commercial greenhouses.

Stable and isolable alkanethiolate-stabilized Pt nanoparticles (PtNP) were synthesized using the two-phase thiosulfate method with sodium S-alkylthiosulfate as ligand precursor. The mechanistic formation of octanethiolate-capped PtNP (Pt-SC₈) from both sodium S-octylthiosulfate and 1-octanethiol ligands was investigated by using ¹H NMR and UV-vis spectroscopy, which revealed the formation of different Pt complexes as the reaction intermediates. The partially poisoned PtNP with thiolate monolayer ligands was further investigated for the hydrogenation of various alkynes to understand the organic ligands-induced geometric and electronic surface properties of colloidal Pt nanoparticle catalysts. In addition, alkanethiolate-capped Pd nanoparticles (PdNP) were prepared using reversed thiosulfate addition method with S-octylthiosulfate as ligand precursor. Various synthetic conditions were applied to the modified two-phase method in order to control the average core size and surface ligand density. The obtained nanoparticles were characterized by ¹H NMR, UV-vis spectroscopy, infrared spectroscopy (IR), thermogravimetric analysis (TGA), and transmission electron microscopy (TEM).

A replicated field study was conducted at the Maricopa Agricultural Center in 1992 investigating Upland cotton lint yield and fiber quality response to foliar applied potassium thiosulfate. Applications were applied at early, peak, and late bloom. There were no significant yield or lint quality response by treatment.

This research was undertaken to study the suitable physico-chemical conditions for the selective recovery of gold and silver from simulated thiosulfate leach liquors containing copper, gold or silver, ammonia and thiosulfate using three anion exchange resins. In particular, the effect of chemical variables such as thiosulfate, cupric ion and ammonia concentrations and the solution potential of the system on the batch loading of silver and gold onto the resins have been investigated in detail. Pourbaix diagrams have been constructed to understand the stability of this complex system under various Eh and pH conditions. The experimental results indicate that IRA-400 resin has the highest capacity for both silver and gold compared to IRA-68 and IRA-94. All the three resins investigated are not selective to silver and gold over copper. The elution studies using ammonium thiosulfate solutions have revealed that selective elution of silver from copper is not possible, while some selectivity can be achieved between gold and copper. (Abstract shortened with permission of author.)

Hydrogen sulfide (H2S) is an endogenous gasotransmitter that regulates vascular function and blood pressure, and also protects the heart from injury associated with myocardial infarction (MI). The mitochondrial enzyme thiosulfate sulfurtransferase (TST) has a putative role in the breakdown of H2S but its role in the cardiovascular system is unknown. I hypothesised that TST reduces cardiovascular H2S availability and that inhibiting TST activity may therefore ameliorate cardiovascular pathology. In the heart, TST was expressed by cardiomyocytes and vascular smooth muscle cells. Tst-/- mice all survived to adulthood and had normal cardiac structure and function. Cardiac and hepatic H2S breakdown rates were reduced and H2S levels were higher in the blood of Tst-/- mice. However, in heart tissue, protein levels for the H2S-activated Nrf2 downstream targets, thioredoxin (Trx1) and heme oxygenase-1 (HO-1) were comparable. In contrast, protein levels for the cardiac specific H2S-synthetic enzyme, cystathionine gamma lyase (CSE) was reduced, suggesting a homeostatic negative feedback mechanism to maintain H2S at non-toxic levels. Respiration, measured using an oxygen-sensing electrode was normal in isolated mitochondria from whole Tst-/- compared to control C57BL6 hearts. Endothelial nitric oxide synthase (eNOS) protein expression was lower in Tst-/- hearts, highlighting potential cross talk between H2S and nitric oxide (NO) signalling. TST was expressed in whole aorta homogenates and in isolated endothelial cells from aorta and small intramuscular vessels of the hindlimb from C57BL/6N control mice. Myography and western blotting revealed a greater influence of NO in aorta from Tst-/- mice that was associated with increased phosphorylation of the activating serine1177 residue of eNOS (PeNOSSer1177). NO plays a lesser role in resistance arteries, but in comparison to control vessels, small mesenteric vessels from Tst-/- mice was more reliant on small and intermediate calcium activated potassium channels for relaxation. Tst-/- mice were normotensive, despite this alteration in the regulation of vascular tone. However, metabolic cage experiments identified that Tst-/- mice presented with diuresis, polydipsia, and increased urinary electrolyte excretion of sodium, potassium and chloride, possibly to compensate for increased vascular tone in order to maintain stable blood pressure. To investigate the role of TST in regulating the response to pathological challenge, MI was induced by coronary artery ligation (CAL). In control mice, gene expression of CSE was downregulated by 2 days after CAL, but TST expression was 12-fold increased, suggesting regulation of H2S bioavailability during the acute MI-healing phase. Tst-/- male mice had a 40% greater incidence of cardiac rupture during infarct healing and surviving Tst-/- mice had greater left ventricular dilatation and impaired function compared to controls. Ex vivo, isolated perfused hearts from Tst-/- mice were more susceptible to ischaemia/ reperfusion injury, suggesting an additional role of TST in determining cardiomyocyte susceptibility to injury. In conclusion, these data indicate that cardiovascular H2S bioavailability is regulated through degradation by TST. The data presented here provide evidence for significant tissue specific crosstalk between H2S synthetic and degradative mechanisms and between H2S and other local regulatory mechanisms, including ion channels and NOS. We infer TST has a physiological role in the kidney where its loss leads to changes in renal electrolyte and water handling, although other compensatory mechanisms prevent a change in blood pressure. Under conditions of pathological challenge following MI, loss of TST is detrimental, illustrating its key role in removal of H2S. The data refute the original hypothesis that TST inhibition would be protective against cardiovascular pathology. Further studies in mice with tissue specific deletion of TST are now required to more fully reveal the cardiovascular role of TST.

Inorganic sulfur-oxidising Bacteria are present throughout the Proteobacteria and inhabit all environments of Earth. Despite these facts they are still poorly understood in terms of taxonomy, physiology, biochemistry and genetics. Using phylogenetic and chemotaxonomic analysis two species that were erroneously classified as Thiobacillus trautweinii spp. in 1921 and 1934 are in fact novel chemolithoheterotrophic species for which the names Pseudomonas trautweiniana sp. nov. and Achromobacter starkeyanus sp. nov. are proposed, respectively. These species were found to oxidise thiosulfate in a “fortuitous” manor when grown in continuous culture and increases in maximum theoretical growth yield (YMAX) and maximum specific growth rate (μMAX) were observed. Cytochrome c linked thiosulfate-dependent ATP production was confirmed in both species, confirming “true” chemolithoheterotrophy. Evidence is presented that the ATP concentration governs the benefits of chemolithoheterotrophy. There were significant changes in enzyme activities, including enzymes of the TCA cycle that might be affecting amino acid synthesis. This is strong evidence that chemolithoheterotrophy gives a strong physiological boost and evolutionary advantage over strictly heterotrophic species. An autotrophic species that was historically placed in Thiobacillus was also shown to be a novel species for which the name Thermithiobacillus parkerianus sp. nov. is proposed. The enzyme profiles of Thermithiobacillus parkerianus differed significantly between different inorganic sulfur growth substrates and was the first time all TCA cycle enzymes were assayed in a member of the Acidithiobacillia. The properties of thiosulfate dehydrogenase varied significantly between Pseudomonas sp. Strain T, Achromobacter sp. Strain B and Thermithiobacillus sp. ParkerM both in terms of optimal parameters and the effect of inhibitors. This evidence adds to the increasing body of work indicating there to be at least two thiosulfate dehydrogenases present in the Bacteria.

In the Caron process, nickeliferous laterite ores undergo a pyrometallurgical pre-treatment step, in which their nickel and cobalt content is reduced to the metallic state. This is followed by leaching in ammoniacal-carbonate solutions, where metallic nickel and cobalt dissolve by forming complexes with ammonia. Since the reductive pre-treatment step also results in some metallic iron being formed, nickel and cobalt are present in the pre-reduced ore mainly as ferro-alloys. As a result, the dissolution behaviour of metallic nickel and cobalt is strongly influenced by the behaviour of metallic iron. In particular, the passivation of iron has been identified as a potential factor contributing to the relatively low metal value recoveries suffered by the process (80-82% nickel and 50-60% cobalt). The present study consists of an investigation into various heterogeneous reactions involving metallic iron and ions commonly found in Caron leach liquors, namely nickel(II), cobalt(II), copper(II) and thiosulfate, in order to identify interactions which may adversely affect the extraction efficiency. The study was carried out using a combination of electrochemical and surface characterisation techniques, as well as thermodynamic calculations. Metallic iron was found to generally dissolve in ammoniacal-carbonate solutions by forming ferrous ammine complexes, but a few specific conditions were found to promote its spontaneous passivation: the presence of copper(II) ions and the presence of both cobalt(II) and thiosulfate ions. In the presence of copper(II) ions, the passivation process was promoted by the cementation and subsequent redissolution of metallic copper, as confirmed by surface characterisation studies. However, when thiosulfate ions were also present, passivation was not observed and the formation of a partially adherent layer containing metallic copper dendrites and cuprous sulfide took place on the iron surface. In the presence of both cobalt(II) and thiosulfate ions, the passivation process, which was not observed when either species was present on its own, was promoted by the formation of an amorphous cobalt sulfide or polysulfide species. The loss of cobalt from the leach solution into this layer was identified as another potential factor contributing to the poor cobalt extractions suffered by the process.

La Mercaptopyruvate Sulfurtransférase (MPST) et la Thiosulfate Sulfurtransférase (TST) sont deux enzymes jouant un rôle central dans la détoxification des cyanures. Un défaut d'activité, d'origine génétique, de ces enzymes pourrait être à l'origine de variations interindividuelles de susceptibilité à la toxicité des cyanures et être impliqué dans la genèse et/ou l'évolution de maladies héréditaires. Notre travail a consisté à évaluer la nature et l'étendue de la variabilité de la séquence nucléotidique des gènes de ces deux enzymes dans une population d'individus sains et de patients atteints de deux pathologies intestinales à composante environnementale et génétique, à l'aide d'une stratégie basée sur le couplage de l'analyse du polymorphisme de conformation de fragments d'ADN simple brin générés par réaction de polymérisation en chaîne (PCR-SSCP) et du séquençage. Ce travail nous a permis d'identifier de nombreux variants de ces gènes. L'étude in vitro et in vivo des conséquences fonctionnelles de ces variants sur l'expression des gènes et l'activité des enzymes codées a ensuite été effectuée. Les résultats de ce travail démontrent pour la première fois l'existence d'un polymorphisme génétique fonctionnel de la MPST et de la TST. Les conséquences cliniques de ces polymorphismes restent à démonter
The Mercaptopyruvate Sulfurtransférase (MPST) and the Thiosulfate Sulfurtransférase (TST) are both key enzymes in cyanide detoxification. A deficiency of genetic origin in MPST or TST activity would lead to interindividual variability in susceptibility to cyanide and, consequently, could be involved in the pathogenesis of environmental diseases (ulcerative colitis and Crohn disease). The present work consisted first in the mutational screening of the MPST and TST genes in DNA samples from large groups of healthy individuals and patients, using a PCR-SSCP strategy and sequencing. This strategy allowed us to identify numerous polymorphisms in both genes. The functional consequences of some of the identified polymorphisms were then assessed by in vitro and in vivo assays. Our findings revealed for the first time the existence of a functional genetic polymorphism of MPST and TST. The clinical relevance of these genetic polymorphisms remains to be analysed

Salmonella enterica is an important cause of food poisoning and is responsible for approximately a billion human infections each year. Disease manifestation in humans varies from severe systemic enteric (typhoid) fever to self-limiting gastroenteritis depending upon the infecting S. enterica serovar. S. Typhimurium is responsible for acute gastroenteritis in humans but causes a typhoid-like disease in mice and thus serves as an important model for studying the pathogenesis of systemic salmonellosis. Following ingestion, S. Typhimurium employs a variety of virulence mechanisms to survive within its host and establishes infection in the intestinal tract by invading the epithelial cells. Recent studies have revealed the importance of sulfur compounds in the intestine, such as tetrathionate and thiosulfate for the disease progression. S. Typhimurium is capable of utilising these sulfur compounds as terminal electron acceptors for its anaerobic respiration and thus gains a growth advantage over host microbiota during infection. However, the regulation of sulfur availability within S. Typhimurium and the mechanisms involved in mitigating cellular sulfide toxicity are not well-defined. During this study, we have identified the sstRA operon in S. Typhimurium encoding a deduced SmtB/ArsR family of transcriptional regulatory protein (SstR) and a deduced rhodanese-family sulfurtransferase (SstA) and demonstrated a role in mitigating the effects of cellular sulfide toxicity. SstR has been confirmed to act as a transcriptional repressor from the sstRA operator-promoter and the SstR-dependent repression is alleviated by low pH and sulfide stress (sodium thiosulfate), consistent with a role for SstR in sensing sulfide stress to trigger gene expression. Electrophoretic mobility shift assays confirm binding of purified SstR to the sstRA operator-promoter region. Furthermore, a conserved pair of cysteine residues within SstR was identified to be crucial for alleviating SstR-mediated repression, with the substitution of either cysteine causing constitutive repression. This is consistent with SstR inducer-responsiveness involving a thiol-based redox switch. Importantly, S. Typhimurium mutants lacking the sstRA operon have reduced tolerance to sulfide stress, consistent with the sstRA operon having a role in cellular sulfide detoxification. Work is continuing to further characterise the roles of sstR and sstA in S. Typhimurium on their contributions to infections.

O objetivo deste trabalho é a extração de Au, Ag, Cu e Zn a partir de dois tipos de lodos galvânicos utilizando um processo híbrido de sulfatação seletiva e lixiviação com tiossulfato de sódio e amônio. Nos experimentos realizados, o lodo galvânico foi misturado com um agente promotor de sulfato (enxofre, sulfato de ferro ou pirita) e foi tratado por processos pirometalúrgicos a temperaturas até 750◦C. Nesta fase, este agente sulfatante é oxidado térmicamente, transformando a atmosfera do forno e os óxidos metálicos em sulfatos solúveis em água. Depois disso, os sulfatos foram tratados por lixiviação com água para a recuperação de Ag, Cu, Ni e Zn. Como o ouro não forma sulfatos nesta reação, foi realizada uma segunda fase de lixiviação utilizando tiossulfato de sódio e de amônio, reagentes eficazes e menos prejudiciais ao ambiente do que o cianeto. Diferentes parâmetros foram analisados como qual agente promotor de sulfatação apresentou a maior recuperação de metais em solução, a proporção ótima lodo galvânico/ agente sulfatação, a temperatura de forno, o tempo de aquecimento no forno e o tempo de lixiviação. Além disso, uma comparação da recuperação de ouro com cianeto e tiossulfato de sódio e de amônio foi realizada. A configuração que demonstrou a melhor recuperação de metal em solução tinha uma proporção de 1: 0,4 de lodo galvânico/enxofre, uma temperatura de forno de 550◦C, um tempo de aquecimento de 90 minutos e um tempo de lixiviação em água de 15 minutos. Usando estes parâmetros, as taxas de recuperação de 75% de prata, 68% de cobre, 52% de Ni e 67% de Zn foram obtidas. A lixiviação de tiossulfato de sódio resultou em uma recuperação de 78% do Au, próximos aos valores obtidos utilizando cianeto.
The purpose of this work is the selective extraction of Au, Ag, Cu and Zn from two types of galvanic sludge using a mixed process of sulfate roasting and sodium thiosulfate and ammonium thiosulfate leaching. In the experiments, the sludge was mixed with a sulfate promoter (sulfur, iron sulfate or pyrite) and treated by pyrometallurgical processes at temperatures up to 750◦C. At this stage, this agent is thermally oxidized, turning the furnace atmosphere and the metallic oxides into water-soluble sulfates. Afterward, the sulfates can be treated by leaching with water for recovery of Ag, Cu, Ni and Zn. The gold does not form sulfates in this reaction and was recovered through a second leaching stage using sodium and ammonium thiosulfate, an effective reagent and less harmful to the environment than cyanide. Different parameters as the sulfate promoter that achieves the highest recovery of metals, the proportion of galvanic sludge to sulfating agent, the temperature, the heating time in the oven and the leaching time were evaluated. Additionally, a comparison of gold recovery using cyanide versus sodium and ammonium thiosulfate was performed. The configuration that showed the best metal recovery included a 1:0.4 ratio of sludge to sulfur, an oven temperature of 550◦C, a roasting time of 90 minutes and a water leaching time of 15 minutes. Using these parameters, recovery rates of 75 % of the silver, 68% of the copper, 52% of Ni and 67% of the Zn were obtained. The sodium thiosulfate leaching resulted in a recovery of 78% of the Au, close to the values obtained using cyanide.

L’objectif global de cette thèse était d’étudier, à partir de la cohorte des patients du centre de référence PXE du CHU d’Angers, différente aspects du phénotype cardiovasculaire (CV) du PXE. Ainsi, dans un premier travail, nous avons pu montrer dans l’étude GOCAPXE, que les calcifications ectopiques seraient un processus actif pouvant être détecté par une imagerie moléculaire utilisant un traceur spécifique de l’activité ostéoblastique, le 18-Fluorure de Sodium (18F-NaF); que ce processus était détectable avant même que ces calcifications ne soient visibles par les techniques d’imageries classiques; que ce processus était localisé aux zones habituellement lésées dans le PXE : les plis de flexion et le cou pour la peau et l’artère fémorale superficielle pour le vaisseau. Cette technique mériterait d’être validée dans une étude longitudinale et son rôle en tant biomarqueur diagnostique et de suivi serait ainsi envisageable. Le deuxième travail de cette thèse a été d’étudier les conséquences morphologiques et fonctionnelles d’une augmentation chronique de la pression artérielle chez les patients PXE. Cette question était pertinente car dans la littérature, la question d’une hypertension artérielle (HTA) chez les PXE reste controversée. Nous avons ainsi montré pour la première fois que dans un modèle d’HTA induite par le Deoxycorticostérone (DOCA)-Salt chez la souris Abcc6-/- cette augmentation de la pression artérielle induisait un remodelage CV avec à la fois de la fibrose et des calcifications dystrophiques. Les résultats de cette étude suggèrent la nécessité d’un contrôle optimal de la pression artérielle chez les patients PXE. Le troisième travail de cette thèse a été de caractériser une lésion de la carotide interne détectée avec une fréquence élevée dans la cohorte angevine. Nous avons pu montrer que cette anomalie était une hypoplasie de la carotide interne d’origine probablement congénitale. Chez les patients de la cohorte angevine, cette lésion était associée à des anévrismes intracrâniens mais nous n’avons pas retrouvé d’association avec la survenue d’accident vasculaire cérébral. Ainsi, les résultats de cette étude invitent les praticiens prenant en charge des patients PXE à la rechercher systématiquement dans le bilan vasculaire d’un patient PXE. Si une telle lésion est retrouvée, une imagerie vasculaire intracrânienne devrait être proposée à la recherche d’anévrismes et leur prise en charge discuté en concertation multidisciplinaire. Enfin, le dernier travail a permis de montrer qu’un traitement systémique par le Thiosulfate de Sodium (STS), utilisé dans la calciphylaxie rénale, était efficace sur la régression des calcifications artérielles et cutanées chez une jeune garçon ayant un phénotype CV gravissime résultant de la combinaison délétères de plusieurs gènes pathogènes du spectre PXE Ce traitement mériterait d’être validé dans un essai thérapeutique chez l’humain mais aussi la démonstration de ses mécanismes d’action dans le modèle murin Abcc6-/-. Nous suggérons d’utiliser ce traitement en cas de PXE sévère et rapidement progressif notamment sur le plan vasculaire. Au terme de ce travail de thèse, nous avons montré que le gène ABCC6 était impliqué dans le remodelage vasculaire à la fois au niveau développemental (Hypoplasie Carotidienne) mais aussi acquis (Fibrose, Calcification Cardiaque Dystrophique). Nous avons montré aussi que les calcifications dans le PXE étaient tissus et localisations spécifiques, que ces calcifications étaient actives. Enfin nous avons ouvert la porte à un traitement des formes graves du PXE avec le Thiosulfate de Sodium. Une approche thérapeutique multimodale ciblant plusieurs mécanismes concourant aux calcifications seraient judicieux à évaluer dans les futurs essais cliniques
Since the discovery of the ABCC6 gene in 2000, mutations are at the origin of PseudoxanthomeElastic (PXE), knowledge of genetics, pathophysiology, phenotypic characterizations have has mademajor advances, notably with the Discovery in 2013 of the fundamental role of Pyrophosphateinorganic (PPi) as a deficient anti‐calcifying factor in patients. The overall goal of this thesis was tostudy, from the cohort of patients at the center of PXE reference of the CHU d'Angers, differentaspects of cardiovascular phenotype (CV) of PXE. Thus, in a first work, we were able to show in thestudy GOCAPXE, that ectopic calcifications would be a active process that can be detected by imagingUsing a specific activity tracer Osteoblastic, 18‐sodium fluoride (18F‐NaF); that this process wasdetectable even before these calcifications are not visible by conventional imaging techniques; thatthis process was localized to areas usually injured in the PXE: flexion folds and neck for skin and thesuperficial femoral artery for the vessel. This technique should be validated in a study longitudinaland its role as a diagnostic biomarker In this way, monitoring and monitoring could be considered.The second work of this thesis was to study the morphological consequences and functional of achronic increase in blood pressure in PXE patients. This question was relevant because in theliterature, the question of a high blood pressure (hypertension) in PXE remains controversial. Wehave thus shown for the first time that in a model of HTA induced by the Deoxycorticosterone(DOCA)‐Salt in Abcc6‐/‐ this increase in blood pressure led to a CV remodeling with both fibrosis andcalcifications dystrophic. The results of this study suggest need for optimal control of blood pressurein patients. The third work of this thesis was to characterize a lesion of the internal carotid detectedwith high frequency in the Angevine cohort. We have could show that this abnormality washypoplasia of the Probably congenital internal carotid. In the patients of the angevine cohort, thislesion was associated with intracranial aneurysms but we have not found in association with theoccurrence of vascular accident brain. Thus, the results of this study invite practitioners supportingPXE patients to search for it systematically in the vascular balance of a PXE patient. If such a lesion isfound, vascular imaging Intracranial should be proposed to research Aneurysms and theirmanagement discussed in consultation multidisciplinary. Finally, the latest work has made it possibleto show that systemic treatment with Thiosulphate Sodium (STS), used in renal calciphylaxia, waseffective on the regression of arterial calcifications and skin in a young boy with a phenotype CVGravel resulting from the deleterious combination of several pathogenic genes of the PXE spectrumThis treatment would deserve be validated in a human therapeutic trial but also the demonstrationof its mechanisms of action in the Abcc6‐/‐murin model. We suggest using this treatment for severeand rapidly progressive PXE especially on the vascular plane.At the end of this thesis work, we showed that the ABCC6 gene was involved in vascular remodelingat both at the developmental level (Carotid Hypoplasia) but also acquired (Fibrosis, CardiacCalcification Dystrophic). We also showed that calcifications in PXE were tissues and locationsspecific, that these calcifications were active. Finally we have opened the door to a treatment ofsevere forms of PXE with Sodium Thiosulphate. An approach multimodal therapy targeting multiplemechanisms this would be useful to evaluate in future clinical trials