Thesis (Ph. D.)--University of Alabama at Birmingham, 2007. / Description based on contents viewed June 25, 2007; title from title screen. Includes bibliographical references (p. 142-148).

Fundação de Amparo a Pesquisa no Estado do Rio Grande do Sul / The compound 2,2 -dithienyl diselenide (DTDS), an organoselenium compound with thiophene moieties, has been proven to be a promising antioxidant in vitro and in vivo, as well as an antifungal and antimicrobial agent. However, its toxicity, an important point to be investigated, has not been evaluated. The objective of this study was to evaluate whether DTDS has potential toxicity in vitro or in vivo. For this reason, sulfhydryl enzyme activities, such as δ-aminolevulinic acid dehydratase (δ-ALA-D) and Na+, K+-ATPase were assessed to predict in vitro DTDS toxicity in rat brain homogenate, in addition to its thiol oxidase-like activity. In other section of experiments, DTDS was administered to rats (50 or 100 mg/kg; per orally) in order to determine toxicological parameters in vivo. Plasma samples were collected in order to measure the biochemical parameters: alanine (ALT) and aspartate (AST) aminotransferase activities and urea and creatinine levels. Besides, in brain homogenates, it was determined the activity of the enzymes δ-ALA-D and Na+, K+-ATPase, as well as lipid peroxidation levels and antioxidant defenses (catalase and superoxide dismutase activities and ascorbic acid and reduced glutathione levels). The compound DTDS inhibited in vitro both δ-ALA-D and Na+, K+-ATPase activities (IC50 2 μM and 17 μM, respectively). The DTDS inhibitory effect on δ-ALA-D and Na+, K+-ATPase activities was restored by dithiol dithiothreitol. In addition, DTDS (5-25 μM) showed a thiol oxidase-like activity. In vivo, DTDS (50 and 100 mg/kg) caused a decrease in food and water intakes and the loss of body weight, indicating systemic toxicity, even causing death of the animals. At a dose of 100 mg/kg, DTDS decreased urea levels and increased plasma alanine and aspartate aminotransferase activities. Lipid peroxidation was increased in both administered doses. Moreover, in the highest dose, DTDS inhibited δ-ALA-D activity. By contrast, neither Na+, K+-ATPase activity nor antioxidant defenses were altered in the brain of rats exposed to DTDS. In conclusion, the interaction with thiol groups of sulfhydryl enzymes seems to mediate the inhibitory effect of DTDS against δ-ALA-D and Na+, K+-ATPase activities in vitro. Furthermore, in the administered doses, DTDS causes cerebral and systemic toxicity in rats. Although other studies are necessary to give more information about this specific compound, our findings contribute to the knowledge on the toxicology of DTDS, a compound with pharmacological properties. / O composto 2,2 -disseleneto de ditienila (DSDT), um composto orgânico de selênio com grupamento tiofeno, fora comprovado como um promissor antioxidante in vitro e in vivo, assim como um agente antifúngico e antimicrobiano. Entretanto, sua toxicidade ainda não fora avaliada, representando um importante ponto a ser investigado. O objetivo deste estudo foi avaliar se o DSDT apresenta potencial toxicidade in vitro ou in vivo. Para este fim, a atividade de enzimas sulfidrílicas, como δ-aminolevulato desidratase (δ-ALA-D) e Na+, K+-ATPase fora testada para predizer a toxicidade in vitro do DSDT em homogeneizado de cérebro de ratos, bem como a sua atividade tipo-tiol oxidase. Em outra seção de experimentos, o DSDT foi administrado em ratos (50 ou 100 mg/kg; oralmente) com o intuito de determinar parâmetros toxicológicos in vivo. Amostras de plasma foram retiradas para dosagem dos parâmetros bioquímicos: atividade das enzimas alanina (ALT) e aspartato (AST) aminotrasferase e níveis de ureia e creatinina. Além disso, em homogeneizado de cérebro foram dosadas a atividade das enzimas δ-ALA-D e Na+, K+-ATPase, assim como os níveis de peroxidação lipídica e as defesas antioxidantes (atividade das enzimas catalase e superóxido dismutase e níveis de ácido ascórbico e glutationa reduzida). O composto DSDT inibiu in vitro, tanto a atividade da δ-ALA-D quanto da Na+, K+-ATPase (IC50 2μM e 17μM, respectivamente). O efeito inibitório do DSDT sobre a atividade das enzimas δ-ALA-D e Na+, K+-ATPase foi restaurado pelo ditiol ditiotreitol. Adicionalmente, DSDT (5-25μM) apresentou atividade do tipo-tiol oxidase. In vivo, o DSDT (50 e 100 mg/kg) causou uma diminuição no consumo de comida e água e perda de peso corporal, evidenciando toxicidade sistêmica, causando inclusive morte de ratos. Quando administrado na dose de 100 mg/kg, DSDT diminui os níveis de ureia e aumentou a atividade plasmática da ALT e da AST. Os níveis de peroxidação lipídica encontraram-se aumentados em ambas as doses administradas. Na maior dose, o DSDT inibiu a atividade da δ-ALA-D. Em contrapartida, nem a atividade da Na+, K+-ATPase nem as defesas antioxidantes foram alteradas no cérebro de ratos expostos ao DSDT. Em conclusão, a interação com grupos tióis de enzimas sulfidrílicas parece mediar o efeito inibitório do DSDT em relação a atividade da δ-ALA-D e da Na+, K+-ATPase in vitro. Além disso, nas doses administradas, o DSDT induz toxicidade cerebral e sistêmica em ratos. Embora outros estudos sejam necessários para fornecer mais informações sobre este composto em específico, estes dados contribuem para o conhecimento sobre a toxicologia do DSDT, um composto com propriedades farmacológicas.

Diabetes mellitus (DM) is an important health problem that affects worldwide human population and is commonly observed in small animal clinics. Many studies show that hyperglycemia is the pivotal cause of DM complications, including cataract, nephropathy and neuropathy. Hyperglycemia leads to generation of reactive oxygen species (ROS) and increases oxidative damage of lipids, DNA and proteins in many tissues. Oxidative stress is increased in cells in response to a depletion of antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT) that scavenge oxygen reactive species. Curcumin is the main component of Curcuma longa and has been used traditionally as an antidiabetic agent; and there are evidences that this substance presents high activity of ROS scavenger. Considering that diet is part of diabetic state treatment and that curcumin is considered and antioxidant agent, this study aimed to evaluate the effects of curcumin and/or insulin on oxidative stress parameters in streptozotocin-induced diabetic rats. In addition, it was performed a histopathological analysis of the liver and kidney of healthy and diabetic rats treated with these compounds. For this, the animals were divided into six groups, with six animals each: Control (C); Control/Curcumin (CCur); Diabetic/Saline (D); Diabetic/Insulin (DIns); Diabetic/Curcumin (DCur), and Diabetic/Insulin/Curcumin (DInsCur). Curcumin was diluted in corn oil and administered at the dosage of 60mg/kg once a day and insulin was administered twice a day, at the dosage of 1.5IU/rat in the morning and 2.5IU/rat in the afternoon, for a period of 30 days. In groups D and DCur, the histological analysis of the liver revealed elevated number of binucleated hepatocytes and alterations in hepatic trabeculae. In kidney there were vacuolization of tubular cells, glomerular congestion and mononuclear inflammatory focus. The treatment with insulin ameliorate renal and hepatic lesions from both DIns and DInsCur groups. Thiobarbituric acid reactive substances (TBARS) levels were increased in serum of D and DInsCur groups and in hepatic and renal tissue of group D (P<0.05). CAT activity was low in liver and kidney of groups D, DIns and DCur; there was significant increase in kidney of DInsCur group; in blood, catalase activity was high in groups D and DInsCur (P<0.05). SOD activity in blood was decreased in groups D and DInsCur and increased in groups DIns and DCur (P<0.05). In liver, SOD activity was increased in groups D and DInsCur. Delta aminolevulinic acid dehydratase (δ-ALA-D) activity was reduced in liver and kidney of group D and treatment with insulin and/or curcumin prevented the decrease of the activity in hepatic tissue from groups DIns, DInsCur and DCur, and renal tissue from groups DCur and DInsCur. Thus, treatments with curcumin or insulin prevented oxidative stress in blood of diabetic rats, through modulation of antioxidant defenses. Regarding lipid peroxidation, both substances presented positive effect in serum, liver and kidney, except in serum from group DInsCur, revealing a negative effect when curcumin and insulin were associated. With this experiment, it was possible to demonstrate the importance of insulin as primary treatment of DM, once this drug prevented cell damage in organs analyzed by histopathology. Furthermore, this study contributed to comprehend that antioxidants from medicinal plants, such as curcumin, can be used as adjuvant in treatment of this endocrinopathy and not as a single therapy. / O diabetes mellitus (DM) é um importante problema de saúde que afeta a população humana e é comumente observada na clínica de pequenos animais. Diversos estudos relatam que a hiperglicemia é a principal causa das complicações do DM, tais como catarata, nefropatia e neuropatia. A hiperglicemia causa a geração de espécies reativas de oxigênio (EROs) e aumenta o dano oxidativo de lipídios, DNA e proteínas em diversos tecidos. O estresse oxidativo está aumentado nas células como resultado da depleção de enzimas antioxidantes, especialmente a superóxido dismutase (SOD) e catalase (CAT) removedoras de EROs. A curcumina é o principal componente da Curcuma longa e tem sido usada tradicionalmente como antidiabético e há evidências científicas que esse composto apresenta uma alta atividade antioxidante. Considerando que a dieta faz parte do tratamento do paciente diabético e que a curcumina é um agente antioxidante, este estudo teve como objetivo avaliar os efeitos desse composto, associado ou não à insulinoterapia, sobre os parâmetros de estresse oxidativo em ratos diabéticos induzidos com estreptozotocina. Em adição, também foi avaliada a histopatologia do fígado e rim dos ratos sadios e diabéticos tratados com estes compostos. Para isso, os ratos foram distribuídos em seis grupos, cada um com seis animais: grupo controle (C), grupo controle curcumina (CCur), grupo diabético (D), grupo diabético curcumina (DCur), grupo diabético insulina (DIns) e grupo diabético insulina e curcumina (DInsCur). A curcumina foi diluída em óleo de milho e administrada na dose de 60mg/kg, uma vez ao dia e a insulina aplicada a cada 12 horas nas doses de 1,5UI/rato pela manhã e 2,5UI/rato à tarde por um período de 30 dias. Nos grupos D e DCur, a análise histológica do fígado mostrou número elevado de hepatócitos binucleados e alterações nas trabéculas. Nos rins, havia vacuolização das células tubulares, congestão glomerular e focos inflamatórios mononucleares. O tratamento com insulina reduziu as lesões renais e hepáticas dos grupos DIns e DInsCur. Os níveis de substâncias reativas ao ácido tiobarbitúrico (TBARS) apresentaram-se elevados no soro dos grupos D e DInsCur e nos tecidos hepático e renal do grupo D (P<0,05). A atividade da CAT foi baixa no fígado e rins dos grupos D, DIns and DCur; também houve um aumento significativo na atividade desta enzima nos rins do grupo DInsCur. Já no sangue, a atividade da CAT foi alta nos grupos D e DInsCur (P<0,05). A atividade da SOD no sangue estava reduzida nos grupos D e DInsCur e aumentada nos grupos DIns e DCur (P<0,05), já no fígado, a atividade da SOD estava aumentada nos grupos D e DInsCur. A atividade da enzima delta-aminolevulinato desidratase (δ-ALA-D) estava reduzida no fígado e rins do grupo D e o tratamento com insulina e/ou curcumina preveniu a redução da sua atividade no tecido hepático dos grupos DIns, DInsCur e DCur e no tecido renal dos grupos DCur e DInsCur. Dessa forma, observa-se que o tratamento com curcumina ou insulina preveniu o estresse oxidativo no sangue dos ratos diabéticos, através da modulação das defesa antioxidantes enzimáticas. Em relação à peroxidação lipídica, ambas substâncias apresentaram efeito benéfico no soro, fígado e rins, com exceção do soro do grupo DInsCur, revelando um efeito negativo quando a curcumina e a insulina foram associadas. Com esta investigação, foi possível demonstrar a importância do uso da insulina como tratamento de eleição do DM, visto que este fármaco foi capaz de prevenir danos celulares nos órgãos avaliados histologicamente. Além disso, este estudo contribuiu para a compreensão de que antioxidantes provenientes de plantas medicinais, como a curcumina, podem ser utilizados como adjuvantes no tratamento desta endocrinopatia e não como terapia isolada.

Made available in DSpace on 2016-08-17T18:39:29Z (GMT). No. of bitstreams: 1 2220.pdf: 1450706 bytes, checksum: 0253030468c7f8632d10be1f594463aa (MD5) Previous issue date: 2008-08-08 / Universidade Federal de Sao Carlos / Photodynamic therapy (PDT) is a modality for treatment of tumors, and uses a combination of a drug (photosensitizer) and light in the presence of the molecular oxygen to selectively damage target tissue. In the absent of one of these components, the cytotoxic effect is not observed. Since 1990, many works in the literature studies the topical application of precursors of protoporphyrin IX (PpIX) in PDT, such 5- aminolevulinic acid (ALA) and methyl aminolevulinate (MAL). The purpose of this work was realized an comparative study in vivo between two commercial and available drugs precursors of PpIX, the ALAsense (5-aminolevulinic acid - ALA) from Russian and Metvix (methyl aminolevulinate MAL) from United Kingdom. Experiments were carried out in animals to analyze the performance and the ALA photodynamic MAL in liver of rats. The fluorescence spectra of the liver were collected at pre-determined time. The time of accumulation of PpIX was observed by 2 hours and 45 minutes for the ALA and MAL for 4 hours after application of drugs in the liver. The formation, accumulation and depth of penetration of PpIX in liver tissue were determined by fluorescence spectroscopy. Using a total of 21 animals were the irradiation of the liver fotossensibilizado with ALA or MAL alone with different doses of light (20, 50, 100 and 200J/cm2) or in a combination MAL + ALA to 8%, 16% and 32 dose of 100J/cm2. Thirty hours after the lighting, the animals were killed and livers removed. The area of necrosis of the liver was assessed macroscopically and the samples were prepared for histological study, considering especially the aspects and depth of necrosis. In histological analysis were carried out many aspects of necrosis and the normal liver. The depths of necrosis were measured and the threshold dose obtained using a mathematical model proposed in the literature. Moreover, the monitoring was carried out of O2 consumption of mitochondria isolated from livers of rats, after topical administration of drugs precursors of PpIX (ALA and MAL) in order to check the influence of these substances in mitochondrial bioenergetics. The results showed a higher penetration of MAL in the tissue, as well as greater depth of necrosis when compared to the ALA. These results suggest that MAL has a tendency to better photodynamic response than ALA to the criteria studied. / Terapia Fotodinâmica (TFD) é uma modalidade terapêutica para tratamento de tumores que provoca a destruição do tecido alvo através da combinação de uma droga (fotossensibilizador) e uma fonte de luz na presença de oxigênio molecular. Na ausência de algum desses componentes, o efeito citotóxico não é observado. Desde 1990, têm-se estudado a aplicação tópica de substâncias precursoras da protoporfirina IX (PpIX) associada à TFD, como o ácido 5-aminolevulínico (ALA) e o metil aminolevulinato (MAL). O objetivo do presente trabalho foi realizar um estudo comparativo in vivo entre duas substâncias precursoras da PpIX , o ALAsense (ácido 5-aminolevulínico - ALA) da Rússia e o Metvix (metil aminolevulinato MAL) do Reino Unido. Foram realizados experimentos em animais para analisar o desempenho fotodinâmico ALA e pelo MAL em fígado de ratos. Os espectros de fluorescência do fígado foram coletados em tempos prédeterminados. O tempo de acúmulo da PpIX observado foi de 2 horas e 45 minutos para o ALA e 4 horas para o MAL após a aplicação da droga no fígado. A formação, acúmulo e a profundidade de penetração da PpIX no tecido hepático foram determinados através da espectroscopia de fluorescência. Utilizando um total de 21 animais foi realizada a irradiação do fígado fotossensibilizado com ALA ou com MAL isoladamente com diferentes doses de luz (20, 50, 100 e 200J/cm2) ou na forma combinada MAL + ALA a 8%, 16 e 32% com dose de 100J/cm2. Trinta horas após a iluminação, os animais foram mortos e os fígados removidos. A área necrosada do fígado foi avaliada macroscopicamente e as amostras foram preparadas para o estudo histológico, considerando, principalmente, os aspectos e a profundidade da necrose. Na análise histológica realizada foram observados vários aspectos da necrose e da região normal do fígado. As profundidades de necrose foram medidas e a dose limiar obtida utilizando-se um modelo matemático proposto na literatura. Além disso, foi realizado o monitoramento do consumo de O2 de mitocôndrias isoladas de fígados de ratos, após administração tópica dos medicamentos precursores da PpIX (ALA e MAL) afim de verificar a influência dessas substâncias na bioenergética mitocondrial. Os resultados obtidos mostraram uma maior penetrabilidade do MAL no tecido, bem como uma maior profundidade de necrose quando comparado ao ALA. Esses resultados sugerem que o MAL possui uma tendência a melhor resposta fotodinâmica que o ALA para os critérios estudados.

Aluminium (Al) and silicon (Si) are contaminants found in substances used in the parenteral nutrition (PN). Because of its large volume, nutrition and infusion solutions are pharmaceutical products parenterally administered, which present higher risks of adverse effects when contaminated. Insoluble and biologically inert species of hydroxyaluminosilicates (HAS) may be formed in solutions containing Al and Si when pH > 4.5. This chemical interaction is considered of great interest in biology because of its possible role in detoxification or protection against metal toxicity. In this study the Al bioavailability was investigated in the presence of Si and some PN components in vivo. Al and Si body distribution in Wistar rats was analyzed after 60 administrations of Al 0.5 mg/kg/day and/or Si 2 mg/kg/day in the presence or absence of calcium gluconate or potassium dihydrogenphosphate in concentrations similar to those used in the PN solutions. δ -Aminolevulinic acid dehydratase enzyme activity and tiobarbituric acid reactive species (TBARS) content was also evaluated in animal tissues. Tissue digestion methods were optimized for the determination of both Al and Si in the same samples by Graphite Furnace Atomic Absorption Spectrometry (GFAAS). Better Al and Si recoveries in animal tissue samples occurred after dissolution with tetramethylammonium hydroxide (TMAH) using Si 15 mg/L as modifier for Al determination and Pd 2 g/L for Si. Before the measurements, graphite furnace was coated with Zr following a specific heating program. Al accumulated in all tissues, especially in the liver, kidneys, bones and blood. Si decreased Al accumulation, this effect was less pronounced in the presence of PN components though. Si tissue accumulation was also observed, mainly when administered together with phosphate. Although Al was deposited in the tissues, pronounced toxicity effects were not observed. Increase in lipidic peroxidation was observed in a few tissues. When δ-ALA-D activity was altered, it was increased in Al treated groups, mainly in Ca gluconate treatment. As a conclusion, Si did not decrease Al deposition and therefore the metal biodisponibility amidst the NP components. / O alumínio (Al) e o silício (Si) são contaminantes encontrados em substâncias usadas na nutrição parenteral (NP). Devido ao seu grande volume, soluções de nutrição e de infusão são os fármacos, administrados por via parenteral, que apresentam mais efeitos adversos se contiverem contaminantes. Hidroxialuminosilicatos (HAS) insolúveis e biologicamente inertes podem se formar em soluções contendo Al e Si quando o pH > 4,5. Esta interação química é considerada de grande interesse no campo biológico devido ao seu possível papel na desintoxicação ou proteção contra a toxicidade do metal. Neste trabalho, foi investigada a biodisponibilidade do Al na presença do Si e de alguns componentes da NP in vivo. Primeiramente otimizou-se os métodos de abertura de tecido biológico para análise de Al e Si coexistentes nas amostras por espectromentria de absorção atômica com forno de grafite. Foi analisada a distribuição do Al e Si no organismo de ratos Wistar após 60 administrações de 0,5 mg/kg/dia de Al e/ou 2 mg/kg/dia de Si na presença ou não de gluconato de cálcio ou dihidrogenofosfato de potássio em concentrações semelhantes as usadas nas soluções de NP. Foi também avaliada a atividade da enzima δ-aminolevulinato desidratase (δ-ALA-D) e espécies reativas ao ácido tiobarbitúrico (TBARS) nos tecidos dos animais. As melhores recuperações de Al e Si nas amostras de tecido animal ocorreram após dissolução com hidróxido de tetrametilamônio (HTMA) utilizando Si 15 mg/L como modificador para determinação de Al e Pd 2 g/L para Si. Foi necessário o recobrimento do forno com Zr para a medida das amostras dissolvidas com HTMA. O Al se acumulou em todos os tecidos, principalmente no fígado, rim, osso e sangue. O Si diminuiu o acúmulo do metal nos tecidos, mas esse efeito é menos pronunciado em meio aos componentes da NP. Foi observado o depósito de Si nos tecidos, principalmente no tratamento com fosfato. Apesar do Al ter se depositado nos tecidos, não foram observados efeitos pronunciados de toxicidade. Em poucos tecidos observou-se aumento na peroxidação lipídica nos tratamentos e a atividade da enzima δ-ALA-D, quando alterada, aparece aumentada nos grupos tratados com Al, principalmente no tratamento com gluconato de Ca. Como conclusão, o Si não diminui a deposição do Al e, portanto, a biodisponibilidade do metal em meio aos componentes da NP.

Abstract The educational process behind the work done with children’s choirs has not been written about or talked about very much. Performances get natural visibility and audibility, but most of the work is done in a closed space. The pedagogical process happens behind the scenes and as a result, children and youths grow up as musicians and human beings, as individuals and as a group. The Tapiola Choir celebrates its 50th anniversary in 2013. In this doctoral thesis, I study the educational part of the work done with the choir. In particular, this thesis examines the co-operative pedagogy of Mr. Kari Ala-Pöllänen as a conductor. The specific focus is on the process of qualifying the travelling choir because this is where many pedagogical processes come together. Methodologically, my thesis is a data based case study. The data is based on an in-depth interview. The empirical part is only focused on the period (1994–2008) when Mr. Ala-Pöllänen acted as a conductor of the choir. However, in the beginning of the book I create a view of the whole frame of reference for the choir by exploring the complete archive of the Tapiola Choir and the written material about choral pedagogy. The analysis was done by searching for characters in the qualification process and by using a theory called Big Five personality domains. The results show how a co-operative way of thinking and working promoted the educational goals in all of the teaching done by conductor Ala-Pöllänen. Art and education worked hand in hand, serving the aims of both a shorter and a longer time frame. The naturally occurring interaction between both harder and softer values, in addition to the determined aim to develop the social skills of children, is emphasized in the communication. Both the artistic and educational ambition of the conductor is obvious, but yet does not appear to conflict with the teaching in practice. Many demands are made of the children and youth in a choir that is conducted co-operatively, and they get special instruction to help them with that responsibility. The basic characteristics that the conductor requires from the choir are mainly clear and they are consistent with the professional attitude and favourable prerequisites that are for collaboration. This thesis is about the pedagogical wisdom that is needed to succeed in educating a mostly heterogenic group of children. According to my survey, this is based on sufficient theoretical knowledge, an understanding of the behaviour and growth of a child and a practical personal background - all of these things are connected to the communication skills that are needed to influence a group of individuals in a cohesive manner. / Tiivistelmä Kasvatuksellisista päämääristä lapsikuorotyössä puhutaan ja kirjoitetaan vähän. Esiintymislavalla tapahtuva toiminta saa näkyvyyttä ja kuuluvuutta, mutta suurin osa työstä tapahtuu suljetussa tilassa. Juuri siellä tapahtuu se pedagoginen prosessi, jonka seurauksena lapset ja nuoret kasvavat muusikkoina sekä ihmisinä, yksilöinä ja ryhmässä. Tapiolan kuoro, espoolainen lapsi- ja nuorisokuoro täyttää 50 vuotta vuonna 2013. Väitöstutkimuksessani käsittelen kasvatuksellista toimintaa Tapiolan kuorossa ja Kari Ala-Pölläsen yhteistoiminnallista pedagogiikkaa Tapiolan kuoron johtajana. Erityinen fokus on matkakuorovalinnan prosessissa, jossa toiminnan pedagogisia sisältöjä kiteytyy. Menetelmällisesti väitöstyöni on aineistolähtöinen tapaustutkimus. Aineisto perustuu syvähaastatteluun. Empiirinen osa keskittyy Kari Ala-Pölläsen johtajakauteen 1994–2008, mutta työn alussa luon kuoron arkiston ja muun kuoropedagogisen aineiston kautta läpileikkauksen kuoron toiminnan viitekehykseen. Analyysimenetelmänä matkakuorovalinnan tarkastelussa toimii valintatilanteen kuvauksessa ilmenevien persoonallisuudenpiirteiden tarkastelu ns. viiden suuren mallin mukaisesti. Tulokset osoittavat, kuinka Kari Ala-Pölläsen johtajakaudella yhteistoiminnallinen työskentelytapa palveli kasvatuksellista tavoitetta johtajan kaikessa toiminnassa. Taide ja kasvatus tukevat toisiaan palvellen lyhyen ja pitkän aikavälin päämääriä. Kovien ja pehmeiden arvojen luonteva vuorovaikutus sekä määrätietoinen pyrkimys sosiaalisten taitojen kehittämiseen korostuvat Kari Ala-Pölläsen kommunikaatiossa. Ilmeistä tutkimukseni tulosten nojalla on kuoronjohtajan sekä taiteellinen että kasvatuksellinen kunnianhimo, mikä ei ole ristiriitaista käytännön toiminnassa. Lapsilta ja nuorilta odotetaan yhteistoiminnallisesti johdetussa kuorossa hyvin monenlaisia taipumuksia ja edellytyksiä, ja näihin heitä määrätietoisesti kasvatetaan. Persoonallisuuden piirteiden perusasiat, joita johtaja toivoo ja odottaa kuoroltaan, ovat selkeitä ja liittyvät jäsenten ammattimaiseen asenteeseen ja suotuisiin yhdessä toimimisen edellytyksiin. Onnistuminen hyvin heterogeenisen ryhmän kasvatuksessa kiteytyy pedagogiseen viisauteen. Se tarkoittaa tässä tutkimuksessa riittävää teoreettista osaamista ja lapsen käytöksen ja kehityksen ymmärtämistä, omakohtaista kokemustaustaa ja tälle perustalle rakentuvaa kommunikatiivista taitoa kohdata ja vaikuttaa samanaikaisesti yksilöistä koostuvaan ryhmään.

While the spin trapping properties of thiols have been investigated through EPR analysis and kinetics studies, few groups have studied these properties using strictly computational methods. In particular, α-lipoic acid (ALA) and its reduced form, dihydrolipoic acid (DHLA), one of the strongest endogenously produced antioxidants, show potential for being effective, naturally occurring spin traps for the trapping of reactive oxygen species. This research covers electronic structure calculations of ALA, DHLA, and their corresponding hydroxyl radical spin adducts, performed at the cc-pVDZ/B3LYP/DFT level of theory. The effects on DHLA introduced by other radicals such as ·OOH, ·OCH3, and ·OOCH3 are reported. Explicit solvation was carried out using open-source molecular packing software and was studied using MOPAC PM6 semi-empirical geometry optimizations. Complete Basis Set (CBS) limit extrapolations were performed using cc-pVXZ (X = D, T, Q) Dunning basis sets under the DFT/B3LYP level of theory, and results are compared to the literature.

The purpose of this research is to identify models of Indigenous governance: that respects Indigenous women’s ability to govern, are grounded in a sacred relationship with the land and water, and engage language and culture to guide the process. Focusing on two distinct land-based resurgence movements, including the Áse Ti Tewá:ton Program in the Onkwenhonwe (Mohawk) community of Akwesasne; and the Hui Mālama ike Ala ‘Ūlili Program in the Kanaka community of Koholālele in Pa‘auilo (Hāmākua, Hawai‘i), it is the intention of this research to understand how these communities are consciously and critically engaging ways that restore their sacred relationship to the land and water; the manner in which they are developing sustainable practices that restore traditional food and educational systems; and methods of developing the critical skills needed to address a contemporary colonial reality. Research considers existing scholarship, community-based practice and Indigenous knowledge to create an understanding of the traditional/ancestral governance practices being generated through these land-based resurgence movements. Through a comparative analysis, this research reveals how each of these communities is using Indigenous language, culture and their relationship to the land as a foundation for restoring ancestral ways of thinking, being and doing, that underlie a traditional governance model. The teachings I have gained through doing this research have given me an understanding of community-based strategies that we can use to move away from an external, violent, dependency-creating style of governance that is consistent with western political approaches to a system of Indigenous governance that upholds Indigenous traditions of agency, leadership, decision-making and diplomacy. / Graduate / 2021-03-31

Bei brachyzephalen Hunden ist der Naseneingang fehlgebildet und hochgradig stenotisch. Diese Naseneingangsstenose wird seit Jahrzehnten diagnostiziert und im Rahmen des Brachyzephalen Syndroms chirurgisch behandelt. Bereits mit dem bloßen Auge kann die äußere 1. Stenose erkannt werden, verursacht durch den äußeren Anteil der Nasenflügel, der dem Septum nahezu anliegt und so die Naris fast vollständig verschließt. Der vestibuläre Anteil des Naseneingangs ist bei brachyzephalen Hunden von außen nicht zu beurteilen. In der Computertomographie und der Endoskopie wird deutlich, dass der voluminöse Bulbus, in dem der rostrale Anteil der Flügelfalte und der innere Anteil des Nasenflügels verschmelzen, den Nasenvorhof fast vollständig obstruiert und damit unmittelbar kaudal der ersten Stenose zu einer relevanten 2. Stenose des Naseneingangs führt. Zusätzlich ist die beim gesunden Hund ausgeprägte Abduktion des vestibulären Bulbus nach lateral während der Inspiration bei brachyzephalen Hunden eingeschränkt bis völlig fehlend. Zur Korrektur der Naseneingangsstenose wird in der Literatur bis heute eine 'Keilchen-Resektion' aus dem äußeren Anteil des Nasenflügels empfohlen. Diese Operationsmethode und ihre Modifikationen konzentrieren sich auf die Korrektur der von außen sichtbaren 1. Stenose. In den letzten 10 Jahren wird von Tierbesitzern nach dieser Operation immer häufiger ein ausbleibender Operationserfolg beklagt. Ziele der Untersuchungen: Es soll eine Operationsmethode beschrieben werden, mit der beide Stenosen des komplexen Naseneingangs chirurgisch korrigiert werden können. Zur Evaluierung dieser Operation soll anhand von CT-Untersuchungen das Luft-Volumen im Naseneingang brachyzephaler Hunde prä- und sechs Monate postoperativ gemessen werden. Brachyzephale Hunde, die zur Behandlung einer schweren respiratorischen Insuffizienz überwiesen wurden, wurden in die Studie aufgenommen. Es wurde eine Computertomographie durchgeführt und das Luft-Volumen im Naseneingang mit einer speziellen Software berechnet (Phillips Intelli Space Portal, Philips Healthcare, Hamburg). Eine neue chirurgische Technik mit Teilresektion des Nasenflügels und des Bulbus der Plica alaris, die Ala-Vestibuloplastie, wird zum ersten Mal beschrieben und durch eine CT-Kontrolle nach 6 Monaten analog der präoperativen Untersuchung evaluiert. Die Operationsergebnisse von zwei Chirurgen werden verglichen und die Reproduzierbarkeit der CT-basierten Volumenbestimmung im Vestibulum nasi evaluiert. Für die Analyse der normalverteilten Daten wurde nach dem Shapiro-Wilk-Test geprüft. Signifikanzen wurden mit dem Wilcoxon-Mann-Whitney-Test beurteilt. Für die Analyse der nicht normalverteilten Daten wurde der Kruskal-Wallis Test durchgeführt, gefolgt von dem Dunn´s Multiple Comparisons Test. Die Vergleichbarkeit der Operateure und die Reproduzierbarkeit wurde nach Altmann und Bland überprüft. Das Signifikanzniveau wurde auf alpha=0,05 festgelegt. In diese retrospektive Studie wurden 20 Möpse und 30 Französische Bulldoggen eingeschlossen. Präoperativ wurde bei den Französischen Bulldoggen ein Naseneingangsvolumen links von median 235 mm³ und rechts von 258 mm³ gemessen. Bei den Möpsen wurden Volumina von links 178 mm³ und rechts 146 mm³ gemessen. Mit der Ala-Vestibuloplastie wird durch die Resektion des Bulbus der Plica alaris und der stenosierenden Nasenflügel das Luft-Volumen im Vestibulum nasi bei allen Hunden statistisch signifikant vergrößert. Sechs Monate postoperativ wurde bei den französischen Bulldoggen eine Volumenzunahme von 77 % links und rechts von 75 % gemessen. Bei den Möpsen betrug die Volumenzunahme links 85 % und rechts 71 %. Zwischen den beiden Chirurgen gab es keinen signifikanten Unterschied im Operationsergebnis. Schlussfolgerungen: Die Ala-Vestibuloplastie ist eine neue in Leipzig entwickelte Operationsmethode mit der die komplexe Fehlbildung aus Nares- und Vestibulum-Stenose der brachyzephalen Hunde effektiv und anhaltend korrigiert werden kann. Mit der computertomographischen Untersuchung der brachyzephalen Nase kann die Gesamtstenose nachgewiesen und die kleinen Volumina des Nasenvorhofs prä- und postoperativ vergleichbar und reproduzierbar bestimmt werden. Die Operation führt zu einer signifikanten Vergrößerung des luftgefüllten Naseneingangs und zu einer vollständigen Beseitigung beider Stenosen.

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