Introdução: à despeito da evolução dos aspectos técnicos do tratamento dialítico ao longo das últimas décadas, hipotensão intradialítica (HID) continua a ocorrer em uma parcela significante das sessões. Esquemas alternativos de diálise, especificamente sessões prolongadas e/ou frequentes tem se mostrado benéficas e se associam a um melhor controle da pressão arterial e da anemia, maior remoção de fósforo, regressão da hipertrofia ventricular esquerda, melhor controle de hipervolemia e aumento da sobrevida dos pacientes. A adoção destes métodos mais intensivos, entretanto, não é unânime e a maior parte da população em diálise no mundo realiza hemodiálise (HD) convencional 3 x semana. A HD convencional está associada à HID e à remoção ineficaz de fosfato. Como as pernas são a principal fonte de fluido extracelular removido durante o HD, procurou-se reduzir a HID e aumentar a remoção de fosfato usando exercício com cicloergômetro e compressão pneumática, o que potencialmente proporcionariam maior retorno venoso dos membros inferiores, preservando o fluxo sanguíneo central e também fazendo com que mais fosfato pudesse chegar ao dialisador, facilitando sua eliminação. Métodos: este é um estudo com intervenção, cruzado, onde foram avaliados 21 pacientes, em 3 diferentes sessões de HD: controle, exercício com cicloergômetro durante os primeiros 60 minutos de HD e compressão pneumática durante os primeiros 60 minutos de HD. Os dados avaliados foram: distribuição de fluidos (através de bioimpedância), pressão arterial hora a hora durante a HD, parâmetros bioquímicos e de remoção de fosfato (através de quantificação direta do dialisado). HID foi definida como uma queda na pressão arterial média (PAM) >= 20 mmHg. Resultados: não houve diferença na taxa de ultrafiltração (p = 0,628), delta de peso (p = 0,415), delta de água corporal total, intracelular e extracelular entre controle, cicloergômetro e compressão pneumática (p = 0,209, p = 0,348 e p = 0,467, respectivamente). Comparando controle, cicloergômetro e compressão pneumática, o delta de PAM foi menos negativo durante a compressão pneumática [-4,7 (-17,2, 8,2), -4,7 (-20,5, -0,2) e -2,3 (-8,1,9,0) mmHg, respectivamente; p = 0,021]. HID ocorreu em 43%, 38% e 24% dos pacientes em controle, cicloergômetro e compressão pneumática, respectivamente (p = 0,014). A remoção de fosfato não aumentou com nenhuma intervenção (p = 0,486). A remoção mais elevada de fosfato foi dependente da ultrafiltração, fosfato sérico pré-diálise e PTH mais elevado. Conclusão: A compressão pneumática durante a primeira hora de diálise foi associada a menor HID, embora não tenha sido observado efeito nos parâmetros de distribuição de fluidos. Nenhuma das intervenções testadas, seja exercício ou compressão pneumática conseguiu aumentar a remoção de fosfato / Introduction: Despite the evolution of the technical aspects of dialysis over the last decades, intradialytic hypotension (DIH) continues to occur in a significant proportion of the sessions. Alternative dialysis schemes such as prolonged and / or more frequent sessions have been shown to be beneficial and are associated with better control of blood pressure and anemia, greater phosphorus removal, regression of left ventricular hypertrophy, better control of hypervolemia, and increased survival of patients. The adoption of these methods, however, is not unanimous and the majority of the dialysis population worldwide are on conventional hemodialysis (HD) 3x week. Conventional HD is associated with DIH and it is also ineffective to remove phosphate. Since the legs are the main source of extracellular fluid removed during HD, we sought to reduce DIH and increase phosphate removal by using cycling exercise and pneumatic compression, which would potentially provide greater venous return from the lower limbs, preserving blood flow, and also offering more phosphate to the dialyser, facilitating its elimination. Methods: We evaluated 21 patients in a randomized crossover fashion in which each patient underwent 3 different HD: control; cycling exercise during the first 60-min; and pneumatic compression during the first 60-min. Data obtained included bioelectrical impedance, hourly blood pressure measurement, biochemical parameters, and directly quantification of phosphate through the dialysate. DIH was defined as a drop in mean arterial pressure (MAP) >= 20 mmHg. Results: There was no difference in ultrafiltration rate (p=0.628), delta weight (p=0.415), delta of total, intracellular and extracellular body water among control, cycling and pneumatic compression (p=0.209, p=0.348 and p=0.467, respectively). Delta MAP was less changed by pneumatic compression when compared to control, cycling and pneumatic compression, respectively [-4.7 (-17.2, 8.2), -4.7 (-20.5, -0.2) and -2.3 (-8.1,9.0) mmHg; p=0.021]. DIH occurred in 43%, 38% and 24% of patients in control, cycling and pneumatic compression, respectively (p=0.014). Phosphate removal did not increase in any intervention (p=0.486). Higher phosphate removal was dependent on ultrafiltration, pre-dialysis serum phosphate and higher PTH. Conclusion: Pneumatic compression during the first hour of dialysis was associated with less DIH, albeit no effect on fluid parameters was observed. Neither exercise nor pneumatic compression increased phosphate removal

Le retraitement des déchets radioactifs est un problème crucial de nos jours. Ce travail est dédié au développement de nouveaux systèmes d'extraction des radionucléides sur la base de solvants "verts", les liquides ioniques (LI). Dans ce but, des LI ont été fonctionnalisés avec des motifs variés : oxyde de phosphine, carbamoyl oxyde de phosphine et fragments malonamides. De même, les plateformes calix[4]arènes ont été utilisées pour la synthèse de LI fonctionnalisés (LIF) et de leurs précurseurs. Des LIF de deux types (cationiques et anioniques) ont été obtenus.Les LIF synthétisés ont été testés pour l'extraction liquide/liquide de radionucléides. Il a été montré que l'extraction est bien due aux motifs extractants. Toutefois, la charge de l'ion modifié influence l'extraction.Différentes expériences d'extraction et une modélisation mathématique ont été effectuées pour déterminer les mécanismes d'extraction. Ces études ont montré que chacun des systèmes d'extraction est caractérisé par un ensemble d'équilibres d'extraction différent, basés essentiellement sur l'échange cationique. / Radioactive waste treatment is a crucial problem nowedays. This work was dedicated to the development of the new extracting systems for radionuclides on the basis of "green" solvents Ionic Liquids {Ils). For this purpose Ils were functionalized with various extracting patterns: phosphine oxide, carbamoyl phosphine oxide groups and malonamide fragment. Also the calix[4]arene platforms were used for the synthesis of functionalized ionic liquids (Fils) and their precursors. The Fils of both types cationic and anionic have been obtained. The synthesized Fils were tested for the liquid-liquid extraction of radionuclides. lt was found that extraction well occurs due to the extracting patterns, however a charge of a modified ion influences extraction.The various extracting experiments and mathematical modelling have been performed to determine the mechanisms of extraction. These studies showed that each extracting system is characterized by a different set of extracting equilibria, based mostly on cationic exchange.

The conditioning effect in metabolomic studies is the phenomenon of initial variation of analytical results in the first 5-10 injections of a biological sample in chromatographic systems. The deviation manifests itself as a drift in retention time, peak area and in multivariate analysis. It is a major quality assurance problem in the metabolomic field and if not accounted for would result in high analytical variance. The aim of this study was to investigate the conditioning effect and to gain further knowledge about it. The study was carried out on UPLC of hydrophilic liquid chromatography (HILIC) type coupled to quadrupole time of flight (QTOF) MS. A systematic study was designed to investigate the effects of the age of the analytical column. An investigation into certain matrix components as a possible cause of the conditioning effect was made. Different sample preparation methods were investigated. One result showed that no conditioning could be seen and the system appeared stable from the first injection. Differences in sample composition between samples with conditioning effect and samples without conditioning effect were investigated. No correlation between conditioning effect and levels of certain matrix compounds could be found. More studies of correlation between sample composition and the amount of conditioning occurring is needed. Some samples appear to have no retention time drift but have a significant drift in peak area and in multivariate analysis. This is an indication that the conditioning effect should be analysed in more ways than one before determining if a system is stable.

Le procédé hydrométallurgique le plus utilisé pour extraire l'uranium VI des minerais phosphoriques met en jeu un mélange synergique de deux molécules extractantes : HDEHP et TOPO. Si les combinaisons synergiques sont connues dans le domaine de l'extraction liquide/liquide, les mécanismes qui pilotent la synergie d'extraction sont encore mal décrits. Une approche multi-échelle a été utilisée pour décrire ces mécanismes, combinant deux descriptions qui diffèrent par leur centre d'intérêt, respectivement l'ion pour l'approche moléculaire et les agrégats d'extractants pour l'approche supramoléculaire. Ces deux approches ont parallèlement été rationnalisées par des calculs de dynamique moléculaire. La description obtenue permet de rendre compte de la synergie via la structure des complexes et des agrégats formés pour différents ratios HDEHP/TOPO. De la même façon, des composés bifonctionnels, qui combinent deux fonctions extractantes au sein de la même molécule ont été étudiés et comparés au système HDEHP/TOPO pour identifier l'origine de l'augmentation des performances d'extraction et de sélectivité. / Uranium VI is commonly extracted from phosphoric ores by a well-known process exploiting the synergistic mixture of two extractant molecules : HDEHP and TOPO. In the field of liquid-liquid extraction, synergistic combinations are common but the mechanisms at the origin of the synergy are not well understood. A multi-scale approach has been used to describe these mechanisms, combining two different descriptions : the molecular scale focuses on the ion point of view, while the supramolecular scale focuses on extractants' aggregation. These two approaches have been rationalized by molecular dynamics computations. The results allow describing the synergy through the structure of the complexes and aggregates. With the same approach, some bifunctional compounds, combining the two extracting sites in one molecule, have been studied and compared to the HDEHP/TOPO system in order to identify the origin of their increased capacities in extraction and selectivity.

This master thesis deals with the potential influence of the waste dump Hrádek u Pacova and the wastewater treatment plant Brno – Modřice on surroundings using the optimized non-target screening method of organic pollutants in water and sediments. The experimental part is focused on the identification of organic compounds in samples of ground water from monitoring wells, the surface water from stream and pond and in sediment samples collected from streams in the vicinity of municipal waste dump. Organic compounds were also identified in water and sediment samples from the river Svratka near the municipal waste water treatment plant Modřice. The sequential liquid – liquid extraction was used for the isolation of organic compounds in water samples. Organic compounds in sediment samples were isolated by pressurized solvent extraction (PSE) with subsequent fractionation of the extract using column chromatography. Final analysis determination was performed using comprehensive orthogonal two-dimensional gas chromatography with mass spectrometric detection (GCxGC-TOF MS).

(EN) This work has been focused on the development and optimization of analytical methodology, using high performance liquid chromatography with diode array detection (HPLC-DAD) and high performance liquid chromatography with diode array and tandem mass spectrometric detection (HPLC-DAD-MS/MS) for the determination of amatoxins (α- and β-amanitin) and phalotoxins (phallacidin and phalloidin) in the crude extract from cap of Amanita phalloides with the option to later use for clinical purposes. In order to guarantee the reliability of the analytical results the influence of various parameters on the quality of the separation and the determination of toxins was studied. The developed HPLC-DAD method achieves good linearity in the concentrations range 1 - 100 µg/ml, with correlation coefficients higher than 0,997. Limits of detection (LOD) and quantitation (LOQ) were calculated for all the studied toxins with following values: for α-amanitin 0,90 µg/ml (LOD); 2,99 µg/ml (LOQ), β-amanitin 1,07 µg/ml (LOD); 3,56 µg/ml (LOQ), phallacidin 2,17 µg/ml (LOD); 7,26 µg/ml (LOQ) and phalloidin 0,79 µg/ml (LOD); 2,64 µg/ml (LOQ). Key words: Amanita phalloides,-amanitin,-amanitin, phallacidin, phalloidin, solid-liquid extraction, HPLC-DAD, HPLC-DAD-MS/MS .

Sulfate-reducing bacteria (SRB) frequently occur in the deep granitic rock aquifers at the Äspö Hard Rock Laboratory (Äspö HRL), Sweden. The new SRB strain Desulfovibrio äspöensis could be iso-lated. The objective of this project was to explore the basic interaction mechanisms of uranium, curium, neptunium and plutonium with cells of D. äspöensis DSM 10631T. The cells of D. äspöensis were successfully cultivated under anaerobic conditions as well in an optimized bicarbonate-buffered mineral medium as on solid medium at 22 °C. To study the interaction of D. äspöensis with the actinides, the cells were grown to the mid-exponential phase (four days). The collected biomass was usually 1.0±0.2 gdry weight/L. The purity of the used bacterial cultures was verified using microscopic techniques and by applying the Amplified Ribosomal DNA Restriction Enzyme Analysis (ARDREA). The interaction experiments with the actinides showed that the cells are able to remove all four actinides from the surrounding solution. The amount of removed actinide and the interaction mechanism varied among the different actinides. The main U(VI) removal occurred after the first 24 h. The contact time, pH and [U(VI)]initial influence the U removal efficiency. The presence of uranium caused a damaging of the cell membranes. TEM revealed an accumulation of U inside the bacterial cell. D. äspöensis are able to form U(IV). A complex interaction mechanism takes place consisting of biosorption, bioreduction and bioaccumulation. Neptunium interacts in a similar way. The experimental findings are indicating a stronger interaction with uranium compared to neptunium. The results obtained with 242Pu indicate the ability of the cells of D. äspöensis to accumulate and to reduce Pu(VI) from a solution containing Pu(VI) and Pu(IV)-polymers. In the case of curium at a much lower metal concentration of 3x10-7 M, a pure biosorption of Cm(III) on the cell envelope forming an inner-sphere surface complex most likely with organic phosphate groups was detected. To summarize, the strength of the interaction of D. äspöensis with the selected actinides at pH 5 and actinide concentrations ≥10 mg/L ([Cm] 0.07 mg/L) follows the pattern: Cm > U > Pu >> Np.

Die Effektivität der Reaktivextraktion als Verfahren zur Stoffabtrennung aus wässrigen Lösungen mit organischen Lösungsmitteln lässt sich durch den Zusatz weiterer Stoffe deutlich steigern. Das können Co-Ionen, Lösungsvermittler und Stoffe sein, die die Phasengrenzfläche beeinflussen. Wichtigste Vertreter der letzteren Gruppe sind Tenside, die die Grenzflächenspannung zwischen den Phasen verringern. Sie werden in der industriellen Technik bereits seit Jahrzehnten mit gleich bleibendem Erfolg angewandt. Dabei sind die Vorgänge an der Phasengrenze, die durch die Tenside beeinflusst werden, noch nicht vollständig geklärt. In diesem Umfeld ist auch die vorliegende Arbeit entstanden. Sie soll bereits am Lehrstuhl vorliegende Arbeiten ergänzen. Gegenstand der Untersuchungen ist der Einfluss von Tensiden auf die Extraktion von Schwermetallionen im elektrischen Feld, hier untersucht an dem kationischen Tensid Hexadecyltrimethylammoniumbromid (CTAB). Als Untersuchungsmethode wird die Polarographie verwendet. Der Ladungsdurchtritt durch die Grenzfläche Wasser/Quecksilber und deren Beeinflussung durch das Tensid werden für die Metallionen von Zink, Cadmium, Blei und Chrom bei unterschiedlichen pH-Werten untersucht. Es zeigt sich, dass die Modifizierung der Grenzfläche nur einen Teil der Beeinflussung ausmacht, weitere entstehen durch die chemische Modifizierung der vorhandenen Spezies. Weiterhin kann abgeleitet werden, dass trotz chemischer Verwandtschaft der eingesetzten Systeme eine klare Vorhersage der Beeinflussung nur begrenzt möglich ist. Der grundlegende Trend von Systemen mit chemisch ähnlicher Zusammensetzung ist zwar der gleiche, jedes System reagiert jedoch individuell in Abhängigkeit der genauen stofflichen Zusammensetzung und der Versuchsbedingungen, so dass stets konkrete Voruntersuchungen notwendig erscheinen.

Solvents play a crucial role in the Active Pharmaceutical Ingredient (API) manufacturing and are used in large quantities. Most of the industries incinerate the waste solvents or send it to waste management companies for destruction to avoid waste handling and cross-contamination. It is not a cost effective method and also hazardous to the environment. This study has been performed at AstraZeneca’s API manufacturing plant at Sodertalje, Sweden. In order to find a solution, a solvent recovery system is modeled and simulated using ASPEN plus and ASPEN batch modeler. The waste streams were selected based on the quantity and cost of the solvents present in them. The solvent mixture in the first waste stream was toluene-methanol in which toluene was the key-solvent whereas in the second waste stream, isooctane-ethyl acetate was the solvent mixture in which isooctane was the key-solvent. The solvents in the waste stream were making an azeotrope and hence it was difficult to separate them using conventional distillation techniques. Liquid-Liquid Extraction with water as a solvent followed by batch distillation was used for the first waste stream and Pressure Swing Distillation was used for the second waste stream. The design was optimized based on cost analysis and was successful to deliver 96.1% toluene recovery with 99.5% purity and 83.6% isooctane recovery with 99% purity. The purity of the solvents was decided based on the quality conventions used at AstraZeneca so that it can be recovered and recycled in the same system. The results were favorable with a benefit of €335,000 per year and preventing nearly one ton per year carbon dioxide emissions to the environment. A theoretical study for the recovery system of toluene-methanol mixture was performed. The proposed design was an integration of pervaporation to the batch distillation. A blend of polyurethane / poly(dimethylsiloxane) (PU / PDMS) membrane was selected for the separation of methanol and toluene mixture. The results of preliminary calculations show 91.4% toluene recovery and 72% methanol recovery with desired purity.

Peanut skins are a low-value byproduct of peanut blanching operations. They have been shown to contain significant levels of phenolic compounds with demonstrated antioxidant properties. The effects of two types of extraction methods: solid-liquid extraction (SLE) and microwave-assisted extraction (MAE) on the recovery of phenolic compounds from peanut skins were investigated. Response surface methodology was used to optimize extraction conditions based on total phenolic content (TPC), ORAC (oxygen radical absorbance capacity) activity and <i>trans</i>-resveratrol content. The protective effect of peanut skin extracts (PSE) against hydrogen peroxide (H₂O₂)-induced oxidative stress in human brain microvascular endothelial cells (HBMEC) and the effect of PSE on lipid oxidation in commercial peanut butter were also evaluated. In the SLE method, EtOH was found to be the most efficient extraction solvent followed by MeOH, water and EA. Despite EtOH extracts having a higher TPC, samples extracted with MeOH demonstrated slightly higher ORAC activity. Resveratrol was identified in MeOH extracts but was not found in EtOH, water or EA extracts. In the MAE procedure, the maximum predicted TPC under the optimized conditions was 144 mg phenols/g skins compared to 118 mg/g with SLE. The maximum predicted ORAC activity was 2789 μmol TE/g as opposed to 2149 μmol TE/g with the SLE method. MAE was able to extract more phenolic compounds (with higher antioxidant activity) in a faster time than the SLE procedure. In addition, resveratrol was identified in PSE derived from MAE although at relatively low levels. PSE were found to have some protective effects against oxidative stress in HBMEC. Higher doses of PSE appeared to have a slightly cytotoxic effect. However, the data were highly variable which made it difficult to arrive at any definitive conclusions regarding the potential benefits of PSE in preventing oxidative damage to cells. In the PB experiment, hexanal levels over the storage period were not high enough for the samples to be considered oxidized. However, hexanal values of PB samples treated with PSE were lower than the control throughout storage, which suggests that PSE may provide some protection against oxidation of PB. / Ph. D.