A exposição a estressores incontroláveis leva a alterações comportamentais e bioquímicas significativas que parecem envolver um mau funcionamento da via serotoninérgica Núcleo Mediano da Rafe (NMnR)-Hipocampo Dorsal, mediada por receptores de tipo 5-HT1A (5-HT1aR), sugerindo que as associações aprendidas, relacionadas à exposição ao estresse e suas conseqüências emocionais, não foram desconectadas. Estudos na literatura sugerem que processos de memória são tempo-dependentes e podem ser alterados pela administração de drogas no momento de sua formação ou evocação. Assim, o objetivo do trabalho foi investigar se a interferência na neurotransmissão serotoninérgica mediada por 5-HT1aR, no NMnR, em diferentes momentos com relação à exposição ao estresse de nado forçado pode prevenir ou atenuar os efeitos desse estressor. Ratos Wistar machos (n=5-13/grupo) receberam duas injeções intra-NMnR de Salina (Sal), 8-OH-DPAT (DPAT; 3nmoles/0,2µL; agonista 5-HT1aR) e/ou WAY100635 (WAY; 0,3nmoles/0,2µL; antagonista 5-HT1aR) compondo os grupos experimentais: Sal+Sal, Sal+DPAT, WAY+Sal, WAY+DPAT. As drogas foram administradas em três condições experimentais distintas: antes da pré-exposição ao nado forçado; antes do teste em animais submetidos à pré-exposição; ou antes do teste em animais não pré-expostos. O teste ocorreu 24 horas após a pré-exposição. O tempo de latência para o primeiro episódio de imobilidade (LAT) e o tempo total gasto imóvel (IMO) foram registrados. Somente animais com sítios de injeção confirmados foram usados na análise (ANOVA de uma via seguida por teste post hoc de Duncan). Nossos resultados sugerem que o tratamento com 8-OH-DPAT antes da pré-exposição ou do teste em animais estressados previne ou atenua, respectivamente, as consequências comportamentais da exposição prévia ao estresse de nado forçado. Além disso, nossos dados sugerem que tanto a interferência no processo de aquisição da memória aversiva quanto da evocação da mesma são em parte mediados por 5-HT1aR. / Exposure to uncontrollable stressors leads to significant behavioral and biochemical changes which has been associated to mal functioning of the Median Raphe Nucleus (NMnR) Dorsal Hippocampus serotonergic pathway, mediated by receptor type 5-HT1A (5-HT1aR), suggesting that learned associations related to exposure to stress and emotional consequences from such exposure were not disconnected. Published studies suggest that memory processes are time-dependent and can be changed by the administration of drugs at the time of its formation or retrieval. The objective of the present study was to investigate whether interference with serotonergic neurotransmission mediated by 5-HT1aR in NMnR at different times in relation to exposure to forced swim stress could prevent or reduce the effects of this stressor. Male Wistar rats (n = 5-13/grupo) received two intra-NMnR injections of Saline (Sal), 8-OH-DPAT (DPAT; 3nmoles / 0.2 mL; 5-HT1aR agonist) and / or WAY100635 (WAY; 0.3 nmol / 0.2 mL; 5-HT1aR antagonist) composing the experimental groups: Sal + Sal, Sal + DPAT, WAY + Sal, WAY + DPAT. The drugs were administered in three different experimental conditions: before preexposure to forced swim; before testing in animals subjected to preexposure; or before testing in animals not preexposed. The test occurred 24 hours after preexposure. The latency to the first episode of immobility (LAT) and the total time spent immobile e (IMO) were registered. Only animals who had their sites of injection confirmed were used in the analysis (one-way ANOVA followed by post hoc test Duncan). Our results suggest that treatment with 8-OH-DPAT before preexposure or testing in stressed animals prevents or attenuates, respectively, the behavioral consequences of prior exposure to forced swim stress. Furthermore, our data suggest that both the interference in the acquisition of aversive memory, and the retrieval of the same are partly mediated by 5-HT1aR.

Neste trabalho, um sensor eletroquímico avançado baseado em eletrodo de grafite de lápis modificado via eletropolimerização do monômero de N,N\'-bis(salicilideno)etilenodiaminoníquel(II) na presença de nanopartículas de Ni(OH)2 suportadas em carbono (chamado aqui de poli[Ni(salen)] e Ni(OH)2C) foi desenvolvido e investigado para quantificação de furosemida (FUR) em meio alcalino. O sensor eletroquímico e seus componentes foram extensivamente caracterizados por técnicas físico-químicas, enquanto que o processo de oxidação da furosemida foi investigado por espectroscopia no infravermelho com transformada de Fourier in situ (FTIV in situ). Estes resultados indicam que a oxidação da furosemida nestas condições leva à formação de 2-amino-4-cloro-5-sulfamoilbenzoato e 5-hidroxi-furano-2-carboxilato. A resposta eletroquímica do eletrodo de grafite modificado (EGM) para a determinação de furosemida foi medida por voltametria cíclica (VC). A curva de calibração (mudança de corrente de pico voltamétrico versus concentração de FUR) apresentou uma faixa linear de 2,5 × 10-10 mol L-1 a 2,7 × 10-9 mol L-1 com um limite de detecção calculado tão baixo quanto 1,45 × 10-10 mol L-1 nas condições otimizadas, que é menor do que os valores relatados na literatura. A sensibilidade ultrabaixa obtida com sensor desenvolvido foi atribuída a um efeito sinérgico entre o filme de poli[Ni(salen)] e as nanopartículas de Ni(OH)2/C. / In this work, an advanced electrochemical sensor based on pencil graphite electrode modified via electropolymerization of the N,N\'-bis(salicylidene)ethylenediaminonickel(II) monomer in the presence of carbon supported Ni(OH)2 nanoparticles (here called as poly[Ni(salen)] and Ni(OH)2/C) was developed and investigated for furosemide (FUR) quantification in alkaline medium. The electrochemical sensor and its components were extensively characterized by physico-chemical techniques, while the furosemide oxidation process was investigated by in situ Fourier transform infrared spectroscopy (in situ FTIR). These results indicate that the oxidation of furosemide in these conditions leads to the formation of 2-amino-4-chloro-5-sulfamoylbenzoate and 5-hydroxy-furan-2-carboxylate. The electrochemical response of the modified graphite electrode (MGE) for the determination of furosemide was measured by cyclic voltammetry (CV). The calibration curve (change of voltammetric peak current vs. FUR concentration) presented a linear range from 2.5 × 10-10 mol L-1 to 2.7 × 10-9 mol L-1 with a calculated limit of detection as low as 1.45 × 10-10 mol L-1 under the optimized conditions, which is lower than values reported in the literature. The ultra-low sensitivity obtained with the MGE sensor was attributed to a synergistic effect between the poly[Ni(salen)] film and Ni(OH)2/C nanoparticles.

<p>Cancer or malignant tumors has a high death frequency in many countries. Nowadays many research facilities are dedicated to find new substances and techniques which would lead to better cancer therapies. Seven years ago a research team from Finland made a remarkable connection between vitamin D deficiencies and an increased chance of getting prostate cancer. The research investigating this statement has lead to findings of a new non-classical effect of the calcium controlling vitamin, 1,25(OH)2D3. This effect involves anti-proliferatory effects and more importantly apoptotic effects resulting in the hope of finding a new drug that can cure prostate cancer with the smallest amount of harm to the body.</p><p>In an attempt to find out if the signalling pathway of this apoptotic effect is fast or slow, an experiment designed to detect when the apoptotic protein caspase-3 is induced has been performed. Cells from the cell line LNCaP has been cultured and incubated with 1,25(OH)2D3 and after 0min - 48h an assay was performed to detect the relative amounts of caspase-3 present in every sample. The optimal time period (48h) was then subjected to three different concentrations of 1,25(OH)2D3 and read in the same way as the previous samples. The results showed an increase in caspase-3 expression as early as 2 min, but disappear to be seen again at 24h and are more profound in 48h samples. The caspase-3 expression was also seen to form a possible exponential curve in dose-response.</p>

Dans le cadre du projet DISPATMO (étude de prévision des risques de pollution liés à la dispersion atmosphérique de produits chimiques), des études de risques liés aux incendies et explosions dus aux produits chimiques ont été menées. L’objectif de cette thèse était de réaliser une étude cinétique et mécanistique approfondie afin de déterminer la dégradation en phase gazeuse de l'un des principaux constituants du solvant Tiflex, acétate de 1-méthoxy-2-propyle (MPA), par les radicaux OH et les atomes de Cl. En outre, les constantes de vitesse de réaction de OH et Cl avec une série d' acétates d’alcoxyle largement utilisés dans l'industrie du revêtement et la peinture, l'acétate de méthoxy-2-butyle (2MBA), l'acétate de méthoxy-3-butyle (3MBA), l'acétate de méthoxy-éthyle (MEA), l'acétate d'éthoxy-éthyle (EEE) et l’acétate de n-pentyle (n-PA), ont été déterminées. Les expériences ont été conduites en utilisant la technique de photolyse laser pulsée couplée à la fluorescence induite par laser, un réacteur à écoulement à basse pression couplé à un spectromètre de masse et une chambre de simulation atmosphérique couplé à GC-FID, FTIR et GC-MS en utilisant les méthodes absolue et relative. Les données cinétiques ont été utilisées pour déterminer les expressions Arrhenius pour évaluer le devenir environnemental des composés étudiés tels que leur durée de vie et le potentiel de formation d'ozone. D'autre part, le mécanisme réactionnel a été étudié et les principaux produits de dégradation et leurs rendements ont été déterminés en présence de NO. Les spectres d’absorption UV-Vis de MPA, 2MBA et 3MBA ont également été déterminés afin d'évaluer le potentiel de photolyse de ces composés dans l’atmosphère. Les paramètres cinétiques et mécanistiques ainsi que les durées de vie troposphérique déterminés sont utilisés comme données d'entrée dans les modèles de simulation atmosphériques photochimiques et dans les modèles de dispersion atmosphérique de produits chimiques pour évaluer leur impact atmosphérique. / In the context of DISPATMO project (forecast study of pollution risks related to the atmospheric dispersal of chemicals), risk studies linked to the fires and the explosions due to chemical storage were conducted. The purpose of this thesis was to perform a thorough kinetic and mechanistic study to determine the gas phase degradation of one of the main component of Tiflex solvent, the 1-methoxy 2-propyl acetate (MPA). Furthermore, the rate coefficients of OH and Cl with a series of alkoxy acetates widely used in painting and coating industries, 2-methoxy-butyl acetate (2MBA), 3-methoxybutyl acetate (3MBA), methoxy ethyl acetate (MEA), ethoxy ethyl acetate (EEA) and n-pentyl acetate (n-PA), were determined. The experiments were performed employing the pulsed laser photolysislaser induced fluorescence technique, a low pressure flow tube reactor coupled with a quadrupole mass spectrometer and an atmospheric simulation chamber coupled with a GC-FID, a FTIR and a GC-MS using complementary absolute and relative rate methods. The kinetic data were used to derive the Arrhenius expressions as well as to evaluate the environmental fate of the studied compounds such as their lifetimes and the Photochemical Ozone Creation Potential. Besides, the reaction mechanism was investigated, while the major degradation products and their yields were determined in presence of NO. In addition, the UV-Vis absorption cross sections of MPA, 2MBA and 3MBA were measured in order to evaluate their potential photolysis in the atmosphere. The investigation of the chemical processes and the tropospheric lifetimes of the compounds are used as input data in photochemical atmospheric simulation models and in chemical agent atmospheric dispersion models to evaluate their atmospheric impact.

Les travaux présentés dans cette thèse concernent le développement d’un procédé de stockage d’énergie thermique haute température par voie thermochimique en vue d’une application dans une centrale solaire à concentration. Un état de l’art des technologies de stockage d’énergie thermique haute température par voie thermochimique a permis de définir le couple réactionnel et la technologie les mieux adaptés au procédé. Ainsi, la réaction réversible Ca(OH)2(s) = CaO(s) + H2O(g) est mise en oeuvre dans un réacteur à lit fluidisé. Une étude expérimentale a permis de démontrer la faisabilité du procédé en stockant et en déstockant l’énergie à une même température et en mettant en oeuvre 50 cycles de charge/décharge de l’énergie sans perte de réversibilité. L’utilisation d’un modèle monodimensionnel couplant les phénomènes chimiques, thermiques et hydrodynamiques à l’intérieur du réacteur a permis de mettre en évidence l’influence des conditions opératoires sur les performances du système. Les premiers pas vers une extrapolation industrielle font l’objet de la dernière partie de ces travaux, en présentant l’analyse énergétique d’une centrale solaire à concentration intégrant le procédé de stockage développé et en présentant une étude expérimentale mettant en oeuvre un solide de type industriel dans le réacteur. / This PhD thesis concerns the development of a high temperature thermochemical heat energy storage process for an application in concentrated solar power plants. A literature review allows the identification of both the best reaction couple and technology to operate the process. Thus, the Ca(OH)2(s) = CaO(s) + H2O(g) reversible reaction is carried out in a fluidized bed reactor. The experimental study demonstrated the process feasibility. Thermal energy has been charged and discharged at the same temperature and 50 cycles have been performed without any loss of reversibility. A 1D model coupling the chemical, thermal and hydrodynamic phenomena inside the reactor has been developed to study the operating parameter effects on the process performance. The last section of this work deals with the first steps towards an industrial scale-up. An energetic analysis of a concentrated solar power plant integrating the developed storage process is detailed as well as the reactions implementation with an industrial solid.

Bakgrund: Vitamin D finns i två olika former, det animaliska D3 (kolekalciferol) och det vegetabiliska D2 (ergokalciferol). Det har rått olika åsikter bland läkarkåren och allmänheten om vilken av de två formerna som är mest potent för att höja 25(OH)D-statusen i blodet, det värde som mäts för att avgöra vitamin D-halten i kroppen. Då vitamin D-brist är vanligt förekommande bland befolkningen i Norden är det viktigt att veta vilken form som har bäst effekt och som därför bör användas för att behandla och förebygga vitamin D-brist. Det har även betydelse för veganer som inte äter det animaliska D3, där rekommendationen kanske behöver ändras. Syfte: Syftet med studien var att ta reda på om det finns någon skillnad i potensen av D2 respektive D3 för att höja 25(OH)D-statusen i blodet och i så fall, att hitta möjliga orsaker till denna skillnad. Metod: Sex relevanta vetenskapliga originalartiklar, som har undersökt effekten av D2 vs. D3 på 25(OH)D-statusen i blodet, hittades i databasen PubMed. Studierna genomfördes mellan 2008 och 2017. Studiedeltagarna var vuxna friska människor. Resultat: Fyra av studierna pekade på att D3 var mer effektivt än D2 för att höja 25(OH)D-statusen. En studie kom fram till att det inte fanns någon skillnad i potensen mellan D2 och D3 och en studie visade att D2 var mer effektivt jämfört med D3 när det gällde daglig behandling med låga doser men att D3 uppvisade bättre effekt vid behandling med höga doser med två eller fyra veckors avstånd. Slutsats: Majoriteten av studierna visade en bättre effekt av D3 än D2 för att höja 25(OH)D-nivåer i blodet. De blandade resultaten samt det begränsade antalet studier och deltagare gör att det inte är möjligt att kunna komma fram till en tydlig slutsats. / Background: Vitamin D comes in two different forms, D3 from animals (cholecalciferol) and D2 from plants (ergocalciferol). There has been different opinions among physicians and the general public about which of the calciferols is more potent to raise 25(OH)D-levels in the blood, which is the value that is measured to determine the vitamin D-status in the body. Since vitamin D deficiency is common among the people of the Nordic countries it is important to know which form has the best effect and should be used to treat and prevent vitamin D deficiency. Furthermore, it is relevant for vegans who do not eat the animalic D3, where recommendations might have to be changed. Aim: The aim of the study was to find out if there were differences in potency of D2 vs. D3 to raise 25(OH)D status in the blood and if so, to find possible explanations for those differences. Methods: Six relevant original articles that examined the effect of D2 vs. D3 on 25(OH)D status in the blood, were found in the database PubMed. The studies where published between the years 2008 and 2017. The participants were healthy adults. Results: Four of the studies suggested that D3 is more effective than D2 in order to raise the 25(OH)D status. One study concluded that there is no difference in the effectiveness of D2 vs D3 and one study showed that D2 is more effective than D3 when it comes to daily treatment but that D3 has a better effect than D2 when treatment happens on a two or four weekly basis with large doses. Conclusion: Most of the articles suggested a better effectiveness of D3 than D2 to raise 25(OH)D levels in the blood. However, besides the mixed results, the number of studies and participants was too small to come to a clear conclusion.

Cancer or malignant tumors has a high death frequency in many countries. Nowadays many research facilities are dedicated to find new substances and techniques which would lead to better cancer therapies. Seven years ago a research team from Finland made a remarkable connection between vitamin D deficiencies and an increased chance of getting prostate cancer. The research investigating this statement has lead to findings of a new non-classical effect of the calcium controlling vitamin, 1,25(OH)2D3. This effect involves anti-proliferatory effects and more importantly apoptotic effects resulting in the hope of finding a new drug that can cure prostate cancer with the smallest amount of harm to the body. In an attempt to find out if the signalling pathway of this apoptotic effect is fast or slow, an experiment designed to detect when the apoptotic protein caspase-3 is induced has been performed. Cells from the cell line LNCaP has been cultured and incubated with 1,25(OH)2D3 and after 0min - 48h an assay was performed to detect the relative amounts of caspase-3 present in every sample. The optimal time period (48h) was then subjected to three different concentrations of 1,25(OH)2D3 and read in the same way as the previous samples. The results showed an increase in caspase-3 expression as early as 2 min, but disappear to be seen again at 24h and are more profound in 48h samples. The caspase-3 expression was also seen to form a possible exponential curve in dose-response.

Abstract The aim of the present study was to examine associations between serum 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D[(1,25(OH)2D]—the circulating and active forms of vitamin D—and periodontal infection. The data were gathered from a case-control study (63 periodontitis patients and 30 periodontally healthy controls) and an intervention study among individuals with type 1 diabetes mellitus (T1DM, 80 patients at the baseline and 65 after periodontal treatment). The periodontal data and the levels of serum 25(OH)D, 1,25(OH)2D and parathyroid hormone (PTH) were available. A third data set included periodontal data and the serum level of 25(OH)D of 1262 non-smoking and non-diabetic 30–49-year-old individuals (Health 2000 Survey). Serum 25(OH)D analyses were done using enzyme-linked immunoassay and radioimmunoassay, 1,25(O)2D analyses using enzyme-immunoassay after purification of 1,25(OH)2D by immunoextraction and PTH analyses using electrochemiluminescence immunoassay. In the case-control study individuals with a low serum 1,25(O)2D level were more likely to belong to the periodontitis group than to the periodontally healthy group and an inverse association was observed between serum 1,25(OH)2D and severity of periodontitis at the baseline of the intervention study. Serum 1,25(OH)2D increased significantly after periodontal treatment in the T1DM patients; a finding that was considered suggestive of a causal relationship between serum 1,25(OH)2D and periodontal infection. Also, serum PTH increased after periodontal treatment; this increase, which was statistically significant (p = 0.016) in patients with moderate or severe periodontitis, may partly account for the earlier observed post-treatment increase in serum 1,25(OH)2D level. Possible explanations for low serum 1,25(OH)2D in periodontal infection may be increased degradation of 1,25(OH)2D, increased use of 1,25(OH)2D, or decreased hydroxylation of 25(OH)D The association between serum 25(OH)D level and periodontal infection was weak, if existent. An inverse association between serum 25(OH)D and the severity of periodontal infection was observed only in the T1DM patients. Among individuals with low plaque level, those in higher 25(OH)D quintiles tended to have fewer teeth with deepened periodontal pockets than those in lower quintiles; a finding which was interpreted to mean a slight protective role of 25(OH)D against periodontal infection. / Tiivistelmä Tutkimuksen tarkoituksena oli selvittää seerumin 25-hydroksivitamiini D:n [25(OH)D, D-vitamiinin varastomuoto] ja 1,25-dihydroksivitamiini D:n [1,25(OH)2D, D-vitamiinin aktiivinen muoto] tasojen yhteyttä parodontiumin alueen infektiosairauksiin. Tulokset perustuvat kolmeen tutkimusasetelmaan: tapaus-verrokki-tutkimus (63 parodontiitti-potilasta, 30 verrokkia), interventio-tutkimus [80 tyypin 1 diabetes mellitus (T1DM) potilasta, joista 65 osallistui seurantaan parodontologisen hoidon jälkeen] ja poikittaistutkimus Terveys 2000 tutkimuksen osa-aineistossa (1262 30-49 vuotiasta tupakoimatonta ei-diabeetikkoa). Tapaus-verrokki- ja interventiotutkimuksissa tutkittiin myös seerumin parathormoonin (PTH) yhteyttä parodontaali-infektioon sekä PTH:n vaikutusta seerumin 1,25(OH)2D tasoon infektion hoidon jälkeen. D-vitamiinin ja PTH:n tasot määritettiin immunologisin menetelmin. Yhteyksiä tutkittiin käyttäen vakioituja monimuuttujamalleja. Tapaus-verrokki-tutkimuksessa yksilöt, joilla seerumin 1,25(OH)2D taso oli alhainen, kuuluivat todennäköisemmin parodontiitti- kuin verrokkiryhmään. Interventiotutkimuksen alkutilanteessa seerumin 1,25(OH)2D:n ja parodontaali-infektion vaikeusasteen välillä vallitsi tilastollisesti merkittävä käänteinen yhteys ja taso nousi merkittävästi infektion hoidon jälkeen. Myös seerumin PTH taso nousi parodontaali-infektion hoidon jälkeen; nousu oli tilastollisesti merkittävä (p = 0.016) pitkälle edennyttä parodontiittia sairastavilla. Interventiotutkimuksen tulokset viittaavat kausaaliseen yhteyteen 1,25(OH)2D:n ja parodontaali-infektion välillä. Alhainen seerumin 1,25(OH)2D pitoisuus infektion vallitessa voi selittyä sen suurella käytöllä immuunipuolustukseen infektion aikana tai lisääntyneellä hajoamisella. Tason nousu hoidon jälkeen tukee edellä mainittua. PTH on 25(OH)D:n hydroksylaation pääsäätelijä ja 1,25(OH)2D:n nousua hoidon jälkeen voi osittain selittää myös seerumin PTH tason kohoaminen. Seerumin 25(OH)D:n ja parodontaali-infektion välillä havaittu yhteys oli heikko, mutta ei täysin sulje pois 25(OH)D:n suojaavaa vaikutusta. Käänteinen yhteys löytyi vain interventiotutkimuksen alkutilanteessa T1DM potilailla. Infektion hoito ei vaikuttanut 25(OH)D tasoon. Terveys 2000 tutkimuksen osa-aineistossa havaittiin hyvän suuhygienian omaavilla jonkin verran alhaisempi määrä syventyneitä ientaskuja ylemmissä kuin alemmissa 25(OH)D kvintiileissä.

We report a Raman technique applicable for the in situ analysis of the development of hydrogen bonds in the liquid water‐rich phase just before the onset of gas hydrate formation. Herewith, the phase transition as well as the working principle of hydrate formation inhibitors and promoters can be analyzed.

The Master´s thesis deals with description of the influence of cobalt additive on positive electrode parameters for Ni-Cd accumulators. Trough the use of Electrochemical Quartz Crystal Microbalance are analysed the effects which decline effective life of positive electrode during accelerated cycling. Theoretical part describes important characteristics of Ni-Cd accumulators, the working principle and effects which are in progress on positive electrode during cycling. The next part deals with description of system EQCM and the pricnciples of doping active mass with cobalt additive. Practical part consists of EQCM system calibration and electrochemical measurements. The principal aim is detection of the influence of cobalt additve on active mass during cycling in different electrolytes. From the results of measurements is set the optimal amount of cobalt additive.