Thesis (Ph.D. in Clinical Science) -- University of Colorado at Denver and Health Sciences Center, 2006. / Typescript. Includes bibliographical references (leaves 107-128). Free to UCDHSC affiliates. Online version available via ProQuest Digital Dissertations;

Thesis (PhD) -- Macquarie University, Division of Environmental and Life Sciences, Dept. of Chemistry and Biomolecular Sciences, 2007. / Bibliography: leaves 295-322.

Thesis (M.S.)--Rutgers University, 2007. / "Graduate Program in Biomedical Engineering." Includes bibliographical references (p. 80-85).

Thesis ( Ph.D) -- McMaster University, 2001. / Includes bibliographical references. Also available via World Wide Web.

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Oxidative stress is imbalance between oxidant and antioxidant levels in living systems. Human cells are protected from reactive oxygen species by endogenous enzymatic antioxidants. Most of these compounds require particular redox metals in their structures as cofactors to allow them to scavenge the free radicals such as Cu, Zn-SOD, Mn-SOD and catalase (Fe). The aim of this study was to quantify these metals in human cells to evaluate their effectiveness as novel biomarkers for measuring oxidative stress. The metals (Zn, Cu, Fe, Mn) were measured in vitro in skeletal muscle cells (C2C12) which were incubated under hypoxia/hyperoxia conditions generated by varying oxygen level from 1%-60% for 24 and 48 hours. Two methods were used to perform the analysis. ICP-MS was applied to liquid samples to quantify Zn, Cu, Fe and Mn in cell populations. And LA-ICP-MS was employed to solid samples to measure their intensity in individual cells. The data acquired from both techniques are positively correlated confirming the reliability of the two approaches. All elements of interest were successfully measured except Mn which was not detected in single cells using LA-ICP-MS due to the limit of detection. Interestingly, the results showed that their concentration increased dramatically in cells grown at 25%-60% O2, the most significant increase was in Cu at 60%O2. None showed any increase at 5%-15% O2 indicating normoxia states. At 1%O2, all elements except Fe showed a significant increase and the most remarkable growth was in Mn. More interestingly, increasing incubation to 48 hours for liquid samples had differing effects on the elements. Zn and Cu concentrations were unaffected by increasing incubation time except at 60%O2 where they showed further growth. In contrast, Mn concentration grew sharply over oxygen levels of 30%-50% with no further effect at 1%, while Fe concentration decreased at 1%O2 and grew steadily over oxygen levels of 5%-60%. It can be concluded that all four elements were significantly affected by stress conditions applied to cells, but at different rates. Importantly, a novel analytical method was introduced in this current study since there have been no previous reported investigations measuring changes in concentration of redox-active elements in human cells subjected to different controlled oxidative stress conditions in vitro.

As the most widely dispersed fauna around the world, insects are exposed to a range of stresses within their environments. Oxidative stress causes a disturbance of the balance between production of free radicals and antioxidant response, which leads to various physiological changes in an organism. Despite this, there are several of defense mechanisms, which include in particular the main antioxidant enzymes AKH. In this thesis, I tried to contribute especially to understand the physiological nature of telomere elongation after exposure to free radicals.

Introdução: A Insuficiência Hepática Aguda Grave (IHAG) é uma síndrome clínica rara, caracterizada por uma disfunção grave e súbita das células do fígado. A tioacetamida (TAA) é uma hepatotoxina, cuja administração em ratos causa a morte de células hepáticas por necrose centro lobular e promove o aumento da formação de espécies reativas de oxigênio (ERO). A glutamina é um aminoácido precursor para a síntese de glutationa. Objetivo: Avaliar o efeito antioxidante da glutamina em modelo experimental IHAG induzida por TAA em ratos. Métodos: Foram utilizados ratos machos Wistar, divididos em 4 grupos por tempo de avaliação: controle, glutamina (25 mg/kg), tioacetamida (400 mg/kg) e animais que receberam tioacetamida e glutamina. Os animais foram avaliados em 24, 36 e 48 horas. Foi coletado sangue para análises de AST, ALT, FA, BT e CRE e amostras de fígado para avaliar a lipoperoxidação (TBARS), a atividade das enzimas antioxidantes (SOD, GPx, CAT e GST), avaliação histológica e análise imuno-histoquímica de NF-kB, TNF-a e iNOS. Resultados: Os níveis de TBARS e a atividade das enzimas antioxidantes SOD e GST mostraram-se significativamente diminuídos nos animais dos grupos tratados com glutamina quando comparados com os animais dos grupos TAA. A atividade da CAT mostrou-se aumentada nos animais que receberam a glutamina em comparação aos animais dos grupos TAA. A atividade da GPx diminuiu significativamente nos grupos tratados com glutamina quando avaliada em 36 e 48 horas quando comparada com os animais dos grupos TAA, nestes tempos. O dano tecidual e a expressão de NF-kB, TNF-a e iNOS foram significativamente menores nos animais tratados com glutamina. Conclusão: A tioacetamida causa alterações em alguns parâmetros bioquímicos, histológicos e no processo inflamatório, por sua vez a glutamina exerce ação protetora ao fígado dos danos gerados pela tioacetamida no modelo de IHAG. / Introduction: Severe acute liver failure (SALF) is a rare clinical syndrome characterized by severe and sudden dysfunction of liver cells. The administration of the hepatotoxin thioacetamide (TAA) in rats causes the death of liver cells by necrosis and lobular center promotes increased formation of reactive oxygen species (ROS). Glutamine is a precursor for the synthesis of glutathione amino acid. Objective: To evaluate the antioxidant effect of glutamine in IHAG experimental model in rats induced by TAA. Methods: Male Wistar rats were divided into 4 groups by evaluation period: control, glutamine (25 mg / kg), thioacetamide (400 mg / kg) and animals that received thioacetamide and glutamine. Animals were evaluated at 24, 36 and 48 hours. Blood was collected for analysis of AST, ALT, ALP, BT and CRE and liver samples to assess lipid peroxidation (TBARS), the activity of antioxidant enzymes (SOD, GPx, CAT and GST), histological and immunohistochemical analysis NF-kB, iNOS and TNF-a. Results: The levels of TBARS and the activity of antioxidant enzymes SOD and GST were significantly decreased in animals in groups treated with glutamine compared with those for groups TAA. CAT activity was shown to be increased in animals receiving glutamine compared to groups TAA. The GPx activity decreased significantly in the groups treated with glutamine when evaluated at 36 and 48 hours compared with those for groups TAA in these times. The tissue damage and the expression of NF-kB, iNOS and TNF-a were significantly lower in animals treated with glutamine. Conclusion: The thioacetamide causes changes in some biochemical, and histological parameters in the inflammatory process, in turn glutamine exerts protective of the liver damage caused by thioacetamide in IHAG model action.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O objetivo deste estudo in vitro foi avaliar quantitativamente a mudança de cor de fragmentos dentais humanos, após a técnica de clareamento vital, variando-se o tipo de fonte de luz catalisadora. Dezoito dentes terceiros molares inclusos recém-extraídos foram seccionados no sentido mésio-distal, e a porção vestibular dos mesmos foi preparada para assumir a forma de um retângulo de 7mm de comprimento e 5mm de largura, sendo totalmente suportada por dentina. Os espécimes foram fixados sobre um suporte de acrílico pela dentina. Uma cavidade preparada no sentido cérvico-oclusal e restaurada com resina composta foi usada como barreira dividindo os espécimes ao meio, ficando uma parte servindo como controle (lado A) e outra como tratamento (lado B). Os espécimes foram aleatoriamente distribuídos em três grupos (n= 6). O grupo 1 (G1) foi tratado com um gel de peróxido de hidrogênio a 35% (Lase Peroxide-DMC) por 60 minutos em seis ciclos de 10 minutos cada. O grupo 2 (G2) recebeu o mesmo tratamento de G1 acrescido de 3 minutos de exposição à luz LED gerada pelo aparelho Whitening Lase Light (DMC) em cada ciclo de aplicação do gel. O grupo 3 recebeu o mesmo tratamento de G2, porém o aparelho emissor de luz estava regulado no modo LED/Laser. Todos os espécimes permaneceram armazenados em água destilada sobre refrigeração em um recipiente que não permitia a passagem de luz, durante todo o tempo de duração desse estudo. Uma tomada fotográfica digital em ambiente com iluminação controlada foi realizada antes e cinco dias após a sessão de tratamento. A cor dos espécimes foi determinada no espaço de cor L*a*b* (CIE) utilizando-se o software de análise de imagens Photoshop (Adobe). Os resultados foram submetidos a análise estatística, por meio de técnicas de comparação de médias entre amostras dependentes, independentes e análise de variância, utilizando-se e os testes estatísticos não paramétricos de Wilcoxon, Mann-Whitney e Kruskal-Wallis no software SPSS 12.0. Foi observado que houveram diferenças estatisticamente significantes em todos os eixos (L*, a* e b*) depois do tratamento, evidenciando o clareamento em ambos os lados dos espécimes para todos os grupos, com exceção do eixo L* do lado A do G3. O lado tratado diferiu estatisticamente do lado não tratado em todos os eixos, para todos os grupos, com exceção do eixo L* do G1. Quando se comparou o efeito clareador de cada técnica usada, observou-se que só houveram diferenças significantes no eixo b*, com redução do amarelo, onde G2 e G3 não diferiram entre si, mas sim de G1. Para variação total de cor ΔE, apenas G2 diferiu dos demais grupos, com resultados clareadores estatisticamente superiores. Concluiu-se que o meio de armazenamento dos espécimes no pós-tratamento contribuiu positivamente para o aumento do grau de clareamento. As três técnicas clareadoras usadas são efetivas e apenas a união do agente clareador com a luz LED apresentou melhoras no efeito clareador proporcionado pelo gel de peróxido de hidrogênio a 35% nos parâmetros usados neste estudo. / The aim of this study was evaluate the changes that can be seem in the color of the tooth after using the Bleaching of Vital Technique with variant kinds of the catalyzed light. Eighteen embedded third molar tooth were extracted and mesion distal direction halved and the vestibular share of them were prepared to assume the rectangle shape of 7mm length and 5mm width sustained by dentin. The specimens were fixed of an acrylic abutment by the denth and the cavity was prepared in a oclusal cervical sense and restored with composite rein to be used as a barrier t divide the specimens in the middle, control side (A) and treatment side (B). The specimens were random distributered in three groups (n = 6). Group one (G1) was treated with hydrogen peroxide gel at 35% (Lase Peroxide DMC) about 69 minutes in 06 cycles of 10 minutes each. Group two has received the same treatment as group one increased of 3 minutes in light exposure (LED produced by Whitening Lase Light (DMC) appliance in each cycle of gel apply. Group three has received the same treatment as group two whatever the light emitter appliance was regulated on LED/Laser mode. All specimens were stored in distilled water in a cooler inside of a recipient that didnt allow light crossing during the whole time of this study. A digital photograph session in an environment with controlled illumination was realized before and 5 days after the treatment meeting. The specimens color was determined by the color of space L*a*b (CIE) using the software of analysis and images Photoshop (Adobe). The results were static analysed using comparison and average techniques between dependents and independents samples and variant analysis using the SPSS 12,0 softtware and the Wilcoxon, Mann-Whithney and Krustal Wallis. It was observed that statistically significance differences happened in all axles (L*a e b*) after treatment, proving the bleaching in both sides of the specimens for all groups, exception of axle L* in A side of G3. The treated side statistically differed in all axles for all groups exception of axle L* of G1, if compared with the non treated side. When was compared the bleaching effect of every technique could be observed that significance changes only happened in axle b* with yellow reduction where G2 and G3 differed of G1 but not between both of them. To total color ΔE variation only G2 differed of the other groups with statistically superior bleaching results. Concluded that the specimens storage manner during post treatment had contribute in a positive way for increase bleaching degree and the three bleaching techniques are effectives and that just the bleaching agent with the LED light union has presented bleaching effect improvement proportioned by hydrogen peroxide gel by 35% at the parameter used in this study.

The aims of this study were to assess the hematological response, erythrocyte membrane lipoperoxidation, antioxidant status and the mineral interaction in lambs supplemented with iron. In the first study, the oxidative profile, erythrogram, and the mineral interaction were assessed in lambs with anemia due to worm infection. For doing it, 27 lambs with anemia due to worm infection were used and they were divided in three groups: Control Group (GC) n=9, Ferrous Sulphate Group (G2) n=9 and Ferric Sulphate Group (G3) n=9. The animals of G2 received 200 mg of iron in the ferrous form (Fe+2) orally daily, the animals of G3 received 200 mg of iron in the ferric form (Fe+3) orally daily, whereas the GC received no treatment. There was no statistic difference in the serum iron values and erythrogram7. Serum copper and zinc values were lower in the G2 and G3 on days 21 and 28 of the experiments, whereas faecal copper, iron and zinc excretion were higher in the same groups. The SOD levels were lower in the G2 and G3 on day 28 whereas the NPTH measurement showed a decrease on days 21 and 28. In relation to TBARS, there was an increase. It was concluded that oral supplementation with 200 mg of iron, irrespective of its form does not increase the erythrocyte response in lambs. As well as, it has antagonist action on copper and zinc, reducing its serum concentrations and increasing the faecal excretion of these minerals. Moreover, the decrease of the serum copper and zinc concentrations causes a decrease in activity of superoxide dismutase, causing an oxidative stress situation. In turn, the second experiment assessed the hematological parameters, weight gain and hepatic function in anemic lambs. It was used 27 lambs with anemia due to worm infection divided in three experimental groups: Control Group (GC) n=9, Ferrous Sulphate Group (G2) n=9 and Iron Dextran Group (G3) n=9. The animals of G2 received 200 mg of iron in the ferrous form (Fe+2) orally daily, the animals of G3 received two intramuscular injections of 25 mg/kg/body weight of iron dextran at 7-day interval, the first one on day zero of the experiment, whereas the GC received no treatment. The serum iron levels in the G3 were higher than GC and G2 on days 7 and 14 (P>0,05). In relation to erythrogram, the G3 showed a significant improvement (P>0,05) compared to GC and G2 on days 7, 14 and 21. The hepatic iron levels in the G3 were higher than GC and G2, without changing the measurement of hepatic function. OPG and leucocytes levels showed no statistic difference among the groups. It was concluded that the administration of two doses of iron dextran increases serum and hepatic concentration of this mineral, however without damage to this organ and increases erythropoiesis whereas daily oral administration of 200 mg has no influence over red blood cell serie, neither serum and hepatic levels of this mineral. Both of them do not influence leucocytes. / O objetivo deste estudo foi avaliar a resposta hematológica, lipoperoxidação da membrana do eritrócito, status antioxidante e a interação mineral em cordeiros suplementados com ferro. No primeiro estudo avaliaram-se o perfil oxidativo, eritrograma e interação mineral em cordeiros com anemia verminótica. Para isto, utilizou-se 27 cordeiros com anemia verminótica divididos em três grupos; Grupo controle (GC) n= 9, Grupo Sulfato ferroso (G2) n= 9 e Grupo Sulfato férrico (G3) n= 9. Os animais do G2 receberam via oral diariamente 200mg de ferro na forma ferrosa (Fe+2), os animais do G3 receberam via oral diariamente 200mg de ferro na forma férrica (Fe+3), enquanto que o GC não recebeu tratamento. Não houve diferença estatística nos valores de ferro sérico e eritrograma. Valores de cobre e zinco sérico foram inferiores nos G2 e G3 nos dias 21 e 28 do experimento, enquanto que a excreção fecal de cobre, ferro e zinco foram superiores nesses mesmos grupos. Os níveis de SOD foram inferiores nos G2 e G3 no dia 28 enquanto que a mensuração dos NPTH demonstrou diminuição nos dias 21 e 28. Em relação ao TBARS, houve um aumento no dia 28 nos G2 e G3. Conclui-se que a suplementação oral de 200mg de ferro, independente da sua forma, não aumenta a resposta eritrocitária em cordeiros. Bem como, tem ação antagonista sobre cobre e zinco, diminuindo suas concentrações séricas e aumentando a excreção fecal destes minerais. Além disso, pela diminuição das concentrações séricas de cobre e zinco causa uma diminuição da atividade da superóxido dismutase, ocasionando uma situação de estresse oxidativo. Por sua vez, o segundo trabalho avaliou os parâmetros hematológicos, ganho de peso e função hepática em cordeiros anêmicos. Foram utilizados 27 cordeiros com anemia verminótica alocados em três grupos experimentais; Grupo controle (GC) n= 9, Grupo Sulfato ferroso (G2) n= 9 e Grupo Ferro Dextrano (G3) n= 9. Os animais do G2 receberam via oral diariamente 200mg de ferro na forma ferrosa (Fe+2), os animais do G3 receberam duas aplicações de 25mg/kg/p.v. de ferro dextrano IM com intervalo de sete dias, a primeira no dia zero do experimento, enquanto que o GC não recebeu tratamento. Os níveis de ferro sérico no G3 foram superiores quando comparado aos GC e G2 nos dias 7 e 14 (P<0,05). Em relação ao eritrograma, o G3 apresentou uma melhora significativa (P<0,05) em comparação aos GC e G2 nos dias 7, 14 e 21. Os níveis de ferro hepático no G3 foram superiores em relação aos GC e G2, sem alterar a mensuração de parâmetros de função hepática. Os níveis de OPG e leucócitos não apresentaram diferença estatística entre os grupos. Conclui-se que a administração de duas doses de ferro dextrano eleva as concentrações séricas e hepáticas deste mineral, entretanto sem causar danos a este órgão e, aumenta a eritropoiese, enquanto que a administração oral diária de 200mg não tem influência sobre a série vermelha do sangue bem como sobre níveis séricos e hepáticos deste mineral. Ambos não exercem influência sobre leucócitos.