Dissertations / Theses on the topic '4-MBC'

Mestrado em Química Analítica e Controlo de Qualidade
Os filtros UV são compostos amplamente utilizados em diversos produtos, tais como protectores solares, produtos cosméticos, plásticos e têm como principal função a protecção contra a radiação UV. O 4 – MBC é um dos filtros UV mais utilizado, apresenta tendência para o bioacumulação, tendo sido detectado em águas e em peixes e alguns estudos revelam que pode ter efeitos estrogénicos. O principal objectivo deste trabalho foi avaliar a fotodegradação do 4 – MBC em águas, verificar qual o efeito das substância húmicas e do cloreto e por último identificar os produtos de degradação resultantes. Para o estudo do efeito das substâncias húmicas foram usados dois tipos de amostras: ácidos fúlvicos extraídos do rio Vouga e ácidos húmicos comerciais. Os resultados obtidos permitem concluir que o 4 – MBC sofre uma isomerização rápida, seguida de uma degradação lenta ao longo do tempo. Não se observou efeito significativo dos ácidos fúlvicos e ácidos húmicos na velocidade de degradação do 4 – MBC. No caso do cloreto os resultados sugerem que a percentagem de degradação é superior na presença deste ião relativamente à percentagem de degradação em água. No que diz respeito aos produtos de degradação foi possível detectar a formação de quatro produtos de degradação em água. No entanto, verificou-se que as substâncias húmicas e o cloreto afectam a formação dos produtos intermediários de degradação, inibindo a formação de alguns deles. A identificação destes produtos de degradação foi efectuada por espectrometria de massa tandem. Os produtos identificados não tinham sido referenciados em estudos anteriores.
The UV filters are compounds widely used in several products such as sunscreens, cosmetics, plastics and their main function is the protection against UV radiation. 4 - MBC is one of the most widely used UV filters, it has a tendency to bioaccumulate, it has been detected in waters and in fish and some studies show that it may have estrogenic effects. The main objective of this study was to evaluate the photodegradation of 4 - MBC in waters, to verify what is the effect of humic substances and chloride and finally to identify the resulting degradation products. To study the effect of humic substances two types of samples were used: fulvic acids extracted from river Vouga and commercial humic acids. The results showed that 4 - MBC undergoes a fast isomerization, followed by a slow degradation along time. There was no significant effect of fulvic and humic acids on the degradation rate of 4 - MBC. In the case of chloride the results suggest that the rate of degradation is higher in the presence of this ion relatively to the rate of degradation in water. With regard to the degradation products it was possible to detect the formation of four degradation products in water. However, it was found that the humic substances and chloride affect the formation of photo products, inhibiting the formation of some of them. The identification of these degradation products was carried out by tandem mass spectrometry. The identified products have not been referred in previous studies.

Mestrado em Biologia Marinha
Coral reefs are extremely complex and productive ecosystems, providing habitat for thousands of marine species. Despite their ecological and socio-economic importance, coral reefs are globally threatened by natural and anthropogenic impacts. The discharge of domestic and industrial wastes contributes for the introduction of xenobiotics, namely organic UV filters, in marine ecosystems such as coral reefs, contributing for their degradation over the past few decades. It is estimated that approximately 40 % of coral reefs located along coastal areas are at risk of exposure to organic UV filters such as Benzophenone-3 (BP-3) and 3-(4-methylbenzylidene) camphor (4-MBC), two widely used compounds in sunscreen lotions and personal-care products. It is therefore important to evaluate the effects of these emerging contaminants on local species inhabiting the more affected areas, namely the intertidal environments. The genus Zoanthus (Anthozoa: Hexacorallia) contains numerous species abundant in coral reefs and intertidal areas of tropical and sub-tropical regions. These photosynthetic corals, which live in symbiosis with dinoflagellates of genus Symbiodinium, might have potential application as indicator organisms. The existing research in zoanthids ecology is however scarce in comparison with other cnidarian groups. In this study, we aimed to evaluate the effects of short-term exposure of Zoanthus sp. to BP-3 and 4-MBC. Zoanthus sp. mini colonies (4 – 6 polyps) were exposed to 4 concentrations (0.5; 1, 2 and 4 mg/L) of BP-3 and 4-MBC during 96 h. After exposure, mini colonies were photographed for polyp behavioral response evaluation, the photosynthetic efficiency of photosystem II was measured in vivo, through PAM fluorometry, and finally, the Symbiodinium sp. cells were quantified and normalized to Zoanthus sp. dry weight. Results suggested that Zoanthus sp. exposure to sub-lethal and environmentally relevant concentrations of BP-3 and 4-MBC induced behavioral reactions in the polyps (increase of closed polyps with increased concentrations), decreased photosynthetic efficiency and the number of endosymbionts. Beside the polyp behavioural response, tested organic UV filters proven to have potential to induce coral bleaching. Further ecotoxicological studies should be undertaken with other compounds and with different coral species, to evaluate the effect of these emergent contaminants on coral reefs, and identify UV filter compounds less harmful to the environment.
Os recifes de coral são ecossistemas extremamente complexos e produtivos, que fornecem habitat a milhares de espécies marinhas. Apesar da sua importância ecológica e socioeconómica, os recifes de coral estão globalmente ameaçados por impactos naturais e antropogénicos. A descarga de resíduos domésticos e industriais contribui para a introdução de xenobióticos, nomeadamente filtros UV orgânicos, nestes ecossistemas marinhos, como os recifes de corais, contribuindo para sua degradação nas últimas décadas. Estima-se que aproximadamente 40 % dos recifes de corais localizados ao longo das áreas costeiras correm o risco de exposição a filtros UV orgânicos, como a Benzophenona-3 (BP-3) e 3- (4-metilbenzilideno) cânfora (4-MBC), amplamente usados em protetores solares e produtos de cuidados pessoais. Por conseguinte, é importante avaliar os efeitos destes contaminantes emergentes nas espécies que habitam as áreas mais afetadas, nomeadamente as zonas intertidais. O género Zoanthus (Anthozoa: Hexacorallia) contém inúmeras espécies abundantes em recifes de corais e áreas intertidais de regiões tropicais e subtropicais. Estes corais fotossintéticos, que vivem em simbiose com dinoflagelados do género Symbiodinium, podem ter potencial aplicação como organismos indicadores. A pesquisa existente em ecologia de zoantídeos é, no entanto, escassa, em comparação com outros grupos de cnidários. Neste estudo, procuramos avaliar os potenciais efeitos nefastos da exposição a curto prazo de Zoanthus sp. a BP-3 e 4-MBC. Expuseram-se mini colónias (4 a 6 pólipos) de Zoanthus sp. a 4 concentrações (0.5; 1; 2 e 4 mg/L) de BP-3 e 4-MBC durante 96 h. Após exposição, as mini colónias foram fotografadas para uma avaliação da resposta comportamental dos pólipos, mediu-se in vivo a eficiência fotossintética do fotossistema II, através da fluorometria de pulso modulado (PAM) e, finalmente, as células de Symbiodinium sp. foram quantificadas e normalizadas para o peso seco de Zoanthus sp.. Os resultados sugeriram que a exposição de Zoanthus sp. a concentrações sub-letais e ambientalmente relevantes de BP-3 e 4-MBC, induziu reações comportamentais nos pólipos (aumento do número de pólipos fechados com o aumento das concentrações), diminuição da eficiência fotossintética e do número de endossimbiontes. Para além da alteração comportamental dos pólipos, os filtros UV orgânicos testados provaram ter potencial para induzir o branqueamento de corais. Estudos ecotoxicológicos adicionais devem ser realizados com outros compostos e diferentes espécies de corais, para avaliar o efeito destes contaminantes emergentes em recifes de corais e também para a identificação de filtros UV menos prejudiciais ao meio ambiente.

The Bioconcentration Factor (BCF) is the principal source of information used to assess and regulate the potential hazard and risk for a chemical that has the potential to bioaccumulate in the marine environment, according to the Marine Strategy Framework Directive (MSFD). The main objective of this thesis was to estimate the BCFs of two different emerging contaminants in Ruditapes philippinarum (Manila clam) under controlled laboratory conditions: the UV filter 4-methylbenzylidene camphor (4-MBC) commonly used in skincare products, and the artificial sweetener Acesulfame potassium (ACE-K) used as a food additive. Ruditapes philippinarum organisms were exposed directly to 4-MBC and ACE-K nominal concentration of 1, 10 and 100 μg L-1 during 10 days. Bioconcentration factors (BCFs) were estimated according to 3 different models for both compounds. The 4-MBC estimated BCFs fall in range of 61553 - 539143 L Kg-1, showing that this compound is very bioaccumulative and could also undergo biomagnification in the marine food chain. On the contrary, estimated ACE-K BCF is consistently lower, in order of 7 L Kg-1 for the nominal exposure concentration of 100 μg L-1. The low ACE-K BCF could be explained by its high solubility in water and thus a rapid metabolization by clams during the experiments. In summary, future research focusing on the marine environment is needed on these two emerging compounds.

Endokrin aktive Substanzen (EACs) sind exogene Substanzen natürlichen oder synthetischen Ursprungs, die mit der Feedbackregulation hormoneller Netzwerke interferieren können und somit deren Homöostase beeinflussen. Störungen der Hypothalamus-Hypophysen-Schilddrüsenachse (HPT-Achse) haben weitreichende Konsequenzen, da Schilddrüsenhormone essentiell für die Regulation von Entwicklung, Wachstum und Stoffwechsel sind. In der vorliegenden Arbeit wurde das Wirkprofil potenter Inhibitoren der thyreotropen Achse am Beispiel von 4-Methylbenzyliden-campher (4-MBC) und Genistein (GEN) untersucht. Der UV-Filter 4-MBC wurde in der ovariektomierten Ratte als goitrogene Substanz identifiziert. 4-MBC interferiert auf Ebene von Hypothalamus und Hypophyse mit der Expression Feedback-assoziierter Gene und beeinflusst daher die Feedbackregulation der thyreotropen Achse. Darüber hinaus wird die Biosynthese von Schilddrüsenhormonen durch Inhibition des Iodidtransports bei gleichzeitig erhöhter messenger RNA (mRNA)-Konzentration des Natrium-Iodid-Symporters (NIS) durch 4-MBC beeinträchtigt. Parallel dazu lässt die verstärkte Expression des Angiogenesemarkers vascular endothelial growth factor (VEGF) nach subakuter Exposition auf die Entstehung einer Hypothyreose schließen. Die damit einhergehenden Veränderungen sind auch in peripheren Organen durch die Analyse 3,3‘,5-Triiod-L-thyronin (T3)-regulierter Zielgene dokumentiert. Zudem wurden diese Effekte maßgeblich durch die Expositionszeit beeinflusst, da nach chronischer Exposition vermutlich auch kompensatorische Prozesse eine wichtige Rolle spielen. Die gezeigten speziesspezifischen Effekte lassen sich möglicherweise auf Unterschiede in der Pharmakokinetik zurückführen, z.B. in Folge differentieller Expression von Cytochrom P450-Genen.
Endocrine active compounds (EACs) can be of natural or synthetic origin and show hormone-like effects that interfere with feedback regulation of hormonal networks. Interferences with the hypothalamic-pituitary-thyroid axis (HPT-axis) result in extensive consequences as thyroid hormones are essential for regulation of development, growth, and metabolism. In the work presented here, the active profile of potent inhibitors of the HPT-axis namely 4-methylbenzylidene-camphor (4-MBC) and genistein (GEN) was investigated. 4-MBC, a UV filter used in sunscreens and various cosmetics, was identified as a goiter causing agent using ovariectomized rats. 4-MBC acts at the level of hypothalamus and pituitary gland by modulating the expression of thyrotropin-releasing hormone (TRH) as well as thyroid-stimulating hormone (TSH) that regulate feedback on the HPT-axis. Furthermore, biosynthesis of thyroid hormones was impaired by 4-MBC secondary to the inhibition of iodide transport with concomitantly increased messenger RNA (mRNA)-levels of the sodium-iodide symporter (NIS). In parallel expression of the angiogenesis marker vascular endothelial growth factor (VEGF) was increased, indicating hypothyroidism. After the application of 4-MBC the expression of L-3,3’,5-triiodothyronine (T3)-regulated target genes was reduced in the periphery both on the mRNA and protein level. The documented species-specific effects indicate a difference in pharmacokinetics, possibly secondary to differential expression of cytochrome P450 genes. GEN is contained in soy and red clover and its mechanistic analysis was carried out in thyroid hormone receptor (TR) deficient mice (TRα0/0). The gender-dependent effects of GEN on tissue specificity did not follow an obvious pattern and warrant continuative analysis. The work presented here supports the assumption that EACs can interfere with function and regulation of the HPT-axis at levels that were previously considered safe.

Förbudsregeln, som sedan 1 januari 2019 finns implementerad i 5 kap. 4 § miljöbalken (1998:808) (MB), ställer krav på verksamheter att inte på ett otillåtet sätt försämra vattenmiljön eller äventyra att vattnet uppnår rätt kvalitet enligt miljökvalitetsnorm. Regelns stränga utformning har gett upphov till många diskussioner och kritiserats av verksamhetsutövare som menar att försämrings- och äventyrandeförbudet riskerar att hindra samhällsnyttiga verksamheter från att bedrivas.  Förbudsregeln grundar sig på Europaparlamentets och rådets direktiv 2000/60/EG (ramdirektivet för vatten) som antogs år 2000, och syftar till att medlemsstaterna ska ha gemensamma mål för en förbättrad vattenmiljö. Sverige implementerade ramdirektivet för vatten i nationell rätt, men fick kritik från kommissionen att reglerna implementerats felaktigt. År 2015 klargjorde EU-domstolen i sitt förhandsavgörande i mål C-461/13 (Weserdomen) hur reglerna i ramdirektivet för vatten ska tolkas, vilket gav Sverige vägledning i rättstillämpningen.  Det kan konstateras att det idag finns en intressekonflikt mellan en hållbar vattenmiljö och verksamhetsutövare. Den nya förbudsregeln i 5 kap. 4 § MB ställer krav på verksamhetsutövare att inte på ett otillåtet sätt försämra eller äventyra vattenmiljön. Försämringsförbudet bedöms på kvalitetsfaktornivå, vilket innebär att endast en miljökvalitetsnorm behöver försämras, med en statusklass, för att en otillåten försämring ska ha skett. Förbudsregeln har även resulterat i en utökad utredningsskyldighet av påverkan på vattenmiljön, vilket leder till en mer utdragen och kostsam tillståndsprocess för verksamhetsutövare. Reglerna om undantag i 4 kap. 11 och 12 §§ vattenförvaltningsförordningen (2004:660) (VFF) kan vara ett sätt för verksamheter att beviljas tillstånd, trots att verksamheten bryter mot förbudsregeln. Det är upp till varje vattenmyndighet och prövningsmyndighet i det enskilda fallet att avgöra om verksamheten kan beviljas tillstånd med stöd av undantagsreglerna i VFF. I dagsläget finns det inget som tyder på att förbudsregeln i 5 kap. 4 § MB hindrar verksamheter från att bedrivas, förbudsregeln förväntas dock försvåra tillståndsprocessen för verksamheter.

The national spatial planning guidelines and the subsequent legal regulation in the Natural Resources Act and the Environmental Code has been a part of the Swedish planning system for almost 40 years. In the recent years, critics have claimed that the regulations are outdated and does not work the way it was intended. This paper examines closer why it is perceived that the regulations does not work, with a focus on how the national interests are managed in the municipal planning. Why is the national interests not applied in the municipal planning as intended? Is the error in the system or in the implementation of it? The aim of this essay is to study the gap between theory and practice by studying how the land management provisions in the Environmental Code is applied in five selected municipalities. The aim is also to find interesting issues for futher studies of the topic. The problem is specified as the differense between how the legal clauses are applied and how they were intended to be applied. Amongst other aspects, the essay studies how the organisation of the municipality and the political governing affects the practice. Three methods is used. Intervention theory is used to interpret the the Environmental Code’s land management provisions, comparative analysis to identify factors which are likely to affect the municipal planning and qualitative inteview to attain deeper knowledge about how the planning is implemented in the municipalities. The land management provisions of the Environmental Code’s 3 and 4 chapters can be traced directly to the national spatial planning during the 70’s and 80’s. Since the national spatial planning until today, several system models have been used to visualize the procedure and coordination between different public agencies. In chapter 5 an intervention theory is summarized and two new models are created. Chapter 6 descibes how the five selected municipalities have specially accounted for the national interest in the comprehensive plan. Three factors are studied; how the national interests are accounted for in the comprehensive plan; if all land management provisions are accounted for; and if the municipality describes how they intend to protect the national intresets from palpable damage. The study shows that three of the municipalities specially account for the national interests in a seperated chapter or annex. Two of the municipalities acount for all management provisions and three of the municipalites descibes at least one of the protection of the national intrerest in detail. Thus, two of the municipalities are assessed to have a complete knowledge base in the comprehensive plan for continuing working with the national intrerest in detailed planning and building permit processing. (94) 7 In chapter 7 a number of factors which are believed to affect the municipalities way of account for the national interests are compared through comparative analysis. Factors such as population, access to enhanced knowledge base from a national agency and political governance is studied and compared between the municipalities. Chapter 8 presents interviews with officals and politicians in the selected municipalities and county administration. From the interviews a number of interesting topics are detected. A good knowledge and planning base is very important for the municipal planning, and the comprehensive plan is important for the land management provisions to work the way they were intended. Chapter 9 presents the conclusion of the essay. The first conclusion is that there are a lack of guidelines in the municipalities’ comprehensive plans for how to process detailed plans and building permits in areas of national interest. The second conclusion is that some national interests are descibed better than others in the comprehensive plan. The third conclusion is that the couty board is affecting the way the municipalities view the national interests.
Den fysiska riksplaneringens riktlinjer och den senare lagregleringen av dem i NRL och MB har varit en del av det svenska planeringssystemet i snart 40 år. De senaste åren har kritik riktats mot att systemet är föråldrat och inte fungerar på det vis det var tänkt. Denna uppsats undersöker närmare uppfattningen av att hushållningsbestämmelserna inte fungerar, med fokus på hur man i den kommunala planeringen hanterar riksintressena. Varför fungerar inte planeringen av riksintressena som tänkt? Ligger felet i systemet eller i tillämpningen av det? Syftet med denna uppsats är att studera vad som orsakar glappet mellan teori och praktik, genom att studera hur hushållningsbestämmelserna tillämpas i fem utvalda kommuner. Syftet med studien är också att hitta intressanta frågeställningar för vidare studier av ämnet. Problemet preciseras till skillnaden mellan tillämpningen av lagstiftningen och hur det var tänkt att tillämpas. I uppsatsen studeras bland annat hur kommuners organisation och politiska styrning påverkar tillämpningen. Tre metoder används. Interventionsteori för att tolka hushållningsbestämmelserna, komparativ analys för att identifiera faktorer som kan påverka kommunernas arbete med riksintressen och kvalitativ intervju för att uppnå fördjupad kunskap om kommunernas arbete. Hushållningsbestämmelserna i miljöbalkens 3 och 4 kapitel kan härledas direkt till riksplaneringen under 70- och 80-talet. Naturresurslagen trädde i kraft 1987, och hushållningsbestämmelserna överfördes oförändrade till Miljöbalken 1998. Flera modeller har används för att visualisera hur samordningen mellan myndigheterna ska ske, både under fysiska riksplaneringen och under senaste året. I kapitel 5 sammanfattas interventionsteorin och två systemmodeller konstrueras. I kapitel 6 beskrivs hur kommunernas särskilda redovisning av riksintressen i översiktsplanen. Tre faktorer studeras: hur riksintressena redovisas; om samtliga hushållningsbestämmelser redovisas; om kommunen beskriver hur säkerställandet av riksintresseanspråken ska ske. Studien av översiktsplanerna visar att tre av kommunerna redovisar riksintressen i ett särskilt kapitel eller bilaga. Två av kommunerna redovisar samtliga hushållningsbestämmelser och tre av kommunerna beskriver säkerställandet av åtminstone något riksintresse mer utförligt. Två av kommunerna bedöms ha ett i huvudsak fullständigt underlag i översiktsplanen för att arbeta vidare med riksintressen i planeringen och bygglovshandläggning. I kapitel 7 jämförs kommunerna i ett antal faktorer som tros påverka hur kommunen redovisat riksintressen i översiktsplanen. (94) 5 Faktorer som invånarantal, tillgång till fördjupat kunskapsunderlag och politisk styrning studeras och jämförs mellan kommunerna. I kapitel 8 redovisas intervjuer med tjänstemän och politiker i de studerade kommunerna samt de berörda länsstyrelserna. Från intervjuerna identifieras ett antal teman som viktiga att belysa. Kunskaps- och planeringsunderlaget är mycket viktigt för kommunernas planering, och översiktsplaneringen är viktig för att riksintressesystemet ska fungera. I kapitel 9 redovisas slutsatser. Slutsatsen är att det finns brister i kommunernas översiktsplaner när det gäller översiktsplanen som vägledande dokument för hur kommunen ska arbeta med områden av riksintresse i detaljplanering och bygglovshandläggning; att det finns skillnad i hur utförligt de olika riksintressena redovisas; att den kommunala organisationen kan påverka hur väl riksintressen redovisas och att det kan finnas samband mellan hur länsstyrelsen presenterar sin roll och hur kommunerna ser på sin roll.

Made available in DSpace on 2014-10-09T12:51:05Z (GMT). No. of bitstreams: 0
Made available in DSpace on 2014-10-09T14:04:29Z (GMT). No. of bitstreams: 0
Dissertação (Mestrado)
IPEN/D
Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

Ce travail de thèse s'inscrit dans un projet de développement d'une nouvelle mémoire magnétique à accès aléatoire (MRAM) dont l'élément central est une jonction tunnel magnétique (JTM). Dans ces systèmes de couches d'épaisseur nana métrique, les interfaces jouent un rôle prépondérant pour les propriétés de transport et de couplage magnétique, nécessitant une analyse fine à l'échelle du nanomètre voire atomique. La spectroscopie de pertes d'énergie des électrons (EELS) résolue spatialement est l'outil privilégié de ce travail. L'étude de systèmes industriels fonctionnels d'ALTIS Semiconductor a pour but d'évaluer leur stabilité dans le temps et aux cours des étapes de fabrication. Elle conduit à la mise en évidence d'effets limitant leur mise en production industrielle ainsi qu'à la proposition de plusieurs solutions pour y remédier. En parallèle, afin de mieux comprendre l'importance des interfaces d'une JTM, un système monocristallin Co₀,₆Fe₀,₄ / MgO / Co₀,₆Fe₀,₄ (001) a été élaboré par épitaxie par jets moléculaires, l'alliage Co₀,₆Fe₀,₄ présentant un caractère demi-métallique en fonction des symétries des états de Bloch conduisant à d'importantes polarisations de spin. La structure cristalline aux interfaces se révélant de très haute qualité, l'échantillon peut être assimilé à un système modèle permettant une analyse détaillée des structures fines des seuils L des métaux de transition et du seuil K de l'oxygène. Ces spectres expérimentaux peuvent ainsi être simulés par des calculs de diffusion multiple afin de tester l'influence de l'environnement local et de caractériser les effets d'hybridation p-d aux interfaces
The work detailed in this thesis represents an experimental contribution to the development of a new magnetic random access memory (MRAM) in which the main element is a magnetic tunnel junction (MTJ). Interfaces play a crucial role in determining the transport properties and magnetic coupling in these systems, which consist of layers having thicknesses on the order of nanometers. As such, investigation at the nanometer or even atomic scale is rnandatory. This is achieved here using spatially resolved electron energy loss spectroscopy (BELS), the dominant technique in this study. The purpose of the investigation on ALTIS Semiconductor functional industrial systems is to evaluate their stability over time as well as during the steps involved in their production. This work highlights effects restricting their industrial production and suggests solutions to counteract them. In parallel, in order to better understand the importance of the MTJ interfaces themselves, a monocrystalline Co₀,₆Fe₀,₄ / MgO / Co₀,₆Fe₀,₄ (001) system, deposited using molecular beam epitaxy, was also investigated. The Co₀,₆Fe₀,₄ alloy exhibits a half-metallic character with regards to the symmetries of the Bloch states which lead to strong spin polarization. The very high quality of the crystalline structure at the interfaces offers the possibility to consider the sample as an ideal system, allowing a detailed analysis of the fine structure of the transition metal L-edges and the oxygen K-edge. These experimental spectra can thus be simulated using multiple scattering calculations in order to test the influence of the local environment and to characterize the p-d hybridization effects at the interfaces

Die Osteoporose ist eine systemische Skeletterkrankung, die durch eine niedrige Knochenmasse und eine Verschlechterung der Mikroarchitektur des Knochengewebes mit nachfolgend erhöhter Knochenbrüchigkeit charakterisiert ist. Hauptverantwortlich für den Verlust der Knochenmasse ist vor allem der Östrogenmangel, der die mit Abstand häufigste Form, die postmenopausale Osteoporose, verursacht. Jahrelang ist diese durch die Substitution von Östrogenen therapiert worden. Die Hormonersatztherapie, die unter vielen Substanzen nachweislich das höchste antiosteoporotische Potenzial besitzt, scheidet jedoch aufgrund diverser unerwünschter Nebenwirkungen als Therapieoption aus. Daher gilt es, Therapiealternativen zur Prävention und Behandlung der Osteoporose zu finden. Als potenzielle Therapiealternativen werden in dieser Arbeit ein Phytohormon namens Daidzein und ein endokriner Disruptor namens 4-MBC an der Lendenwirbelsäule ovariektomierter und konsekutiv an Osteoporose erkrankter Sprague-Dawley-Ratten über eine Therapiedauer von 35 (5 Wochen), respektive 70 Tagen (10 Wochen), untersucht. Als Kontrolle über die Wirksamkeit der getesteten Substanzen dienten eine sojafrei behandelte sowie eine mit Östrogenen behandelte Kohorte. Phytoöstrogene sind hauptsächlich Bestandteil von Sojabohnen, Klee, Alfalfasprossen und Leinsamen. Bevorzugt binden sie an Östrogenrezeptor β, wenn auch mit einer geringeren Affinität. Eines dieser Phytoöstrogene ist Daidzein, dessen osteoprotektive Wirkung zuvor bereits vielfach nachgewiesen wurde. 4-MBC als zweite Substanz ist ein sogenannter endokriner Disruptor, der in Europa zur Herstellung von Kosmetika zugelassen ist. Bevorzugt bindet 4-MBC an Östrogenrezeptor β und seine osteoprotektive Wirkung an ovariektomierten Ratten ist ebenfalls bereits nachgewiesen. In der vorliegenden Arbeit wurden 3 Monate alte ovariektomierte Sprague-Dawley-Ratten über einen Zeitraum von 8 Wochen mit einer sojafreien Nahrung gefüttert. In dieser Zeit entwickelt die Ratte eine schwere Osteoporose. Anschließend wurde bilateral eine Tibiaosteotomie, die osteosynthetisch versorgt wurde, durchgeführt. Die Ratten wurden in 4 Gruppen eingeteilt und die sojafreie Basisnahrung um die zu testenden Substanzen 4- MBC (200 mg), Daidzein (50mg) und Östradiol (0,4mg) pro Kilogramm Körpergewicht ergänzt. Nach 5, respektive 10 Wochen wurden 12 Ratten je Futtergruppe per Dekapitation getötet und jeweils an den Lendenwirbelkörpern wurden verschiedene Untersuchungen durchgeführt. So wurde der zweite Lendenwirbelkörper mikroradiographisch analysiert, der dritte Lendenwirbelkörper wurde verascht und der vierte Lendenwirbelkörper biomechanisch getestet. Auf den erhobenen Daten basierend konnte nachgewiesen werden, dass sowohl Daidzein als auch 4-MBC einen positiven Einfluss auf das Knochengewebe während der gesamten Therapiedauer besitzen. Östradiol verzeichnet wie erwartet den größten Effekt, gefolgt von 4-MBC und Daidzein. Bezogen auf die Therapiedauer zeigte sich, dass die größere Wirkungsentfaltung innerhalb der Kurzzeittherapie zu verzeichnen ist. Nach einer Langzeittherapie zeigt die sojafrei ernährte Kontrollgruppe ebenfalls verbesserte Knochenparameter, möglicherweise zurückzuführen auf Adaptationsmechanismen der Osteoporose. 4-MBC ist von seinem osteoprotektiven Wirkungspotenzial dem der Östrogene am ähnlichsten. Eine Therapie mit 4-MBC verbessert sowohl spongiöse, als auch kortikale Knochenparameter und könnte somit als potenzielle Therapiealternative der Osteoporose dienen. Allerdings sind die Wirkungsmechanismen des endokrinen Disruptors zum gegenwärtigen Zeitpunkt noch nicht verstanden und es bedarf diesbezüglich weiterer intensiver Forschung. Ein Aspekt, der einen Gebrauch von 4-MBC als antiosteoporotisches Medikament verhindern könnte, ist das noch nicht endgültig erforschte Nebenwirkungsspektrum. Auch hier sind weitere Untersuchungen erforderlich. Daidzein zeigt insgesamt im Vergleich zu Östradiol und 4-MBC den geringsten osteoprotektiven Effekt. Als potenzielle Therapiealternative ist es 4-MBC und Östradiol unterlegen. Möglicherweise können Patienten mit osteoporosebedingten Frakturen jedoch von einer Behandlung mit Daidzein profitieren. Komrakova et al. haben 2011 an Ratten, bei denen die Tibia osteotomiert und die anschließend osteosynthetisch versorgten wurde, nachgewiesen, dass nach einer 5 wöchigen Therapie mit Daidzein die größte Kallusdichte zu verzeichnen war, während bei 4-MBC und Östradiol eine Kallusdichte aufgewiesen wurde, die der sojafreien Kontrollgruppe ähnlich war. Ob sich Daidzein als Therapieoption zur Unterstützung der Frakturheilung eignet, ist zum aktuellen Zeitpunkt noch nicht geklärt und in weiteren Untersuchungen zu eruieren. Des Weiteren gilt es, auch für Daidzein den genauen Wirkungsmechanismus zu klären und sein Nebenwirkungsspektrum zu untersuchen.

碩士
國立交通大學
分子醫學與生物工程研究所
103
Peroxynitrite (ONOO-) is an important signaling molecule in organism. It is produced from nitric oxide and superoxide radical by the diffusion-controlled reaction. Peroxinitrite is a strong oxidant and good neucleophile, it can react with different biomolecules. It has been related to a list of disease such as cardiovascular diseases, circulatory shock, diabetes, neurodegenerative disorders, and cancer. However, the effects of ONOO- in physiology and pathology remain controversial. There has been a strong demand for reliable and real-time analytical methods for ONOO- detection. The aim of this project is to design and synthesis a new fluorescent probe for detecting peroxynitrite. The design strategy of this ONOO- fluorescent probe, 4-MB, is based on the peroxynitrite anion might react with this probe by nucleophilic attack. The response time of 4-MB to react with ONOO- is about 4 minutes. 4-MB also has a good selectivity for ONOO- over other biologically relevant RNS and ROS. The detection limit of 4-MB for ONOO- is 29.8 nM. Moreover, 4-MB is successfully applied to detection of exogenous and endogenous ONOO- in living cells.

Dissertação de mestrado em Educação Especial (área de especialização em Dificuldades de Aprendizagem Específicas)
Este estudo teve por objetivos analisar longitudinalmente o desenvolvimento do nível de compreensão da leitura e a taxa de crescimento do 2.º ao 4.º ano de escolaridade do 1.º Ciclo do Ensino Básico, bem como a fiabilidade dos resultados. Participaram os alunos que constituíram a população de um distrito do norte de Portugal durante os anos letivos 2011-2012, 2012-2013 e 2013-2014. Os dados foram recolhidos com provas de Monitorização com Base no Currículo-Maze que foram realizadas em seis momentos, dois por ano letivo. O resultado de cada aluno (número total de marcações corretas) foi obtido pela mediana das classificações obtidas nos três textos que constituem a prova. Foram considerados alunos em risco, aqueles cujo resultado se encontrava abaixo ou no percentil 20, tal como sugerido pela literatura. Para tratamento, análise e interpretação dos dados recolhidos utilizou-se a estatística descritiva e inferencial. Os resultados obtidos permitiram concluir que: 1) A tragetória do nível da compreensão da leitura ao longo dos três anos letivos mostra a existência de aprendizagem; 2) Os valores da taxa de crescimento para a população foram inconsistentes ao longo dos três anos. De facto, durante o 2.º ano, observa-se uma taxa de crescimento semanal superior (0.20) à do 3.º ano (0.13) e do 4.º ano (0.16) de escolaridade; 3) A diferença do nível de compreensão entre os alunos em risco e os restantes tende a aumentar ao longo dos anos; 4) As taxas de crescimento diferem entre os alunos em risco e aqueles que não são considerados em risco. Os alunos em risco tiveram uma taxa de crescimento decrescente ao longo dos anos. Os alunos não em risco, apesar de terem baixado a taxa de crescimento semanal durante o 3.º ano de escolaridade, para 0.14, tiveram uma taxa de crescimento semanal de 0.17 no 4.º ano de escolaridade; 5) A variável género tem impacto nos resultados do 4.º ano de escolaridade; 6) A consistência interna dos itens que constituem as provas Maze é elevada, variando o coeficiente entre 0.895 e 0.943. Estas conclusões mostram a pertinência da identificação de alunos em risco, preconizado pelo modelo de Resposta à Intervenção e a utilização das provas de Monitorização com Base no Currículo-Maze, como sendo uma alternativa fiável.
The purpose of this study was to analyse the slope data of reading comprehension level and growth rate from elementary school students, in grade 2 till grade 4, and examine evidence for reliability. The population from a region in the North of Portugal participated in this project in 2011-2012, 2012-2013 and 2013-2014. CBMMaze probes were applied and data were collected on six occasions, two per year. Participants were administered three reading probes and the child’s median score was reported. Maze probes were scored by counting all correct maze choices. Students, whose results were the lowest 20%, were considered at-risk as suggested in literature. For processing, analysis of data was used the descriptive and inferential statistics. The results showed that: 1) Estimated growth lines over the three school years, reflects learning; 2) Population growth rates were changeable along the time. In fact, during grade 2 there is a higher weekly growth rate (0.20) than in grade 3 (0.13) and grade 4 (0.16); 3) Reading comprehension gap between students who are high achieving and those who are low achieving grows larger over time; 4) Growth rates differ between students at-risk and students not at risk. The risk students had a decreasing growth rate over time, while students not at risk, despite having low weekly growth rate during grade 3 (0.14), they had a weekly growth rate of 0.17 in grade 4; 5) The variable gender has an impact on grade 4 outcomes; 6) Results found high internal consistency of the probes, coefficients ranged from 0.895, to 0.943. These findings show the relevance of identifying at-risk students, stated by the Response to Intervention model and the use of Curriculum-Based Measurement-Maze, as a reliable alternative.
Fundação para a Ciência e Tecnologia (FCT) - Projeto "Monitorização do risco de Dificuldades de Aprendizagem Específicas na leitura de alunos do 4º ano e comparação com resultados destes mesmos alunos quando no 2º e 3º ano do 1º Ciclo do Ensino Básico"