Thesis (Ph.D. (Pharmacy))--North-West University, Potchefstroom Campus, 2008.

Thesis (Ph.D. (Pharmacy))--North-West University, Potchefstroom Campus, 2008.

Orientador: Hermes Pretel / Resumo: O objetivo desse estudo foi realizar a caracterização morfo-fisicoquimica e avaliar a resposta histopatológica e a biodegradação de AH indicados para preenchimento dérmico: DMC-Facial 12,5% (D12) e RennovaFill (RF) e aumento volumétrico de tecido: DMC-Facial 15% (D15) e RennovaLift (RL). A caracterização foi realizada por microscopia eletrônica de varredura (MEV), espéctroscopia dispersiva de raios X (EDX) e infra vermelha com transformada de Fourier (FT-IR) e reometria dinâmica oscilatória. Para avaliação da resposta histopatológica e da biodegradação foi implantado 0,1 mL de cada AH no plano sub-dérmico do dorso de 25 ratos Hostsman, aleatóriamente distribuidos em 5 grupos (n=5), de acordo com o tempo de implantação dos AH (7, 14, 30, 60 e 120 dias). Um examinador experiente (HP), calibrado e cego para os AHs utilizados analisou os cortes. Modelo loglinear e teste de quiquadrado (χ2) foram utilizados para avaliar a associação entre os AH e a intensidade da resposta histopatológica e biodegradação para p<0,05. A hipótese nula (H0) foi rejeitada pois tanto na caracterização morfo-fisicoquimica quanto na avaliação da resposta histopatológica e da biodegradação mostraram diferenças signficatica entre os Ahs testados. Pode-se concluir que: 1) AH com a mesma indicação clínica diferem tanto nas características morfo-fisicoquimica com na resposta inflamatória provocada e no padrão de biodegradação. 2) O nível de resposta histopatológica depende do AH utilizado. 3) Uma morfologia es... (Resumo completo, clicar acesso eletrônico abaixo) / The aim of this study was to perform the morpho-physicochemical characterization and to evaluate the histopathological response and biodegradation of AH indicated for dermal filling: DMC-Facial 12.5% (D12) and RennovaFill (RF) and tissue lifting: DMC-Facial 15% (D15) and RennovaLift (RL). The characterization was performed by scanning electron microscopy (SEM), X-ray dispersive (EDX) and Fourier transform infra red spectroscopy (FT-IR) and oscillatory dynamic rheometry. To evaluate the histopathological response and biodegradation, 0.1 mL of each HA was implanted in the dorsal subdermal plane of 25 male Hostsman rats, randomly distributed in 5 groups (n = 5), according to the time of implantation of AH: 7, 14, 30, 60 and 120 days). Slides were analyzed by a experienced examiner (HP), calibrated and blinded for the AH used. Loglinear model and chi-square statistical test (χ2) were used to evaluate the association between AH and the intensity of histopathological response and biodegradation for p <0.05. Results: The null hypothesis (H0) was rejected because both the morpho-physicochemically characterization and the histopathological analysis showed significant differences between the tested AHs. It can be concluded that: 1) AH with the same clinical indication differ in the morpho-physicochemical characteristics, in the inflammatory response and in the biodegradation pattern. 2) The level of histopathological response depends on the AH used. 3) A structural morphology characteristic of D12 and D15, formed by chambers separated by thin septa, with sharp and irregular borders, causes a greater inflammatory response, 4) All HA tested stimulated the fibroblast and collagen neoformation. 5)...(Complete abstract electronic access below) / Mestre

Made available in DSpace on 2014-06-11T19:35:15Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-25Bitstream added on 2014-06-13T21:07:40Z : No. of bitstreams: 1 rotundo_m_dr_ilha.pdf: 1427510 bytes, checksum: fd9f2e2aae52aa3472867b502aa325c9 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Nas últimas décadas a consciência ecológica despertou a atenção de governos e da sociedade para o problema dos resíduos dos pesticidas nos alimentos e no ambiente, onde os amostradores de pragas agrícolas se enquadram dentro de um grupo de risco. A exposição dérmica de amostradores foi avaliada na reentrada em lavoura de algodoeiro após pulverização de três inseticidas. Aos 3 minutos após a aplicação quatro equipes vestiram um conjunto de vestimentas amostradoras (calça, camisa e luvas), entrando e permanecendo nas áreas tratadas por 30 minutos, simulando uma amostragem de pragas. O procedimento foi repetido aos 60 e 300 minutos e aos 1, 3, e 7 dias após a aplicação. As vestimentas amostradoras contaminadas após as exposições foram seccionadas em campo em 6 regiões distintas mais as luvas, embaladas e levadas ao Laboratório. Os inseticidas foram extraídos das vestimentas amostradoras com acetato de etila e a determinação quantitativa foi realizada por meio de cromatografia gasosa. As exposições dérmicas foram extrapoladas para uma jornada de trabalho de oito horas. Para classificar a segurança das condições de trabalho foram estimadas a margem de segurança (MS) e o tempo de trabalho seguro (TTS). O conjunto correspondente aos antebraços/braços/mãos concentrou 35% dos resíduos presentes nas vestimentas amostradoras. Partes correspondentes ao tronco (frente), coxas, pernas e tronco (atrás) alcançaram 19; 19; 10 e 16% dos resíduos, respectivamente. Constatou-se que o intervalo de reentrada estabelecido para os inseticidas comerciais Thiodan 350 CE (endosulfan) e Tamaron 600 BR (metamidofós) estão subestimados, enquanto que para o Marshal 200 SC (carbosulfan) o mesmo está superestimado, em relação aos intervalos de reentrada estabelecidos na legislação em vigor / The objective of this work was to study the dermal exposure of workers to residues of the pesticides, applied in cotton crop. After 3 minutes of application four people dressed a group with cotton clothes (pants, shirt and gloves), entered and stayed in the treated area by 30 minutes, simulating a sampling. The procedure was repeated after 60 and 300 minutes and 1, 3, and 7 days after application. The clothes were cut and put in plastic bags, and stored cold at -18oC until analyses was performed. The analytical method consisted on the extraction of pesticides residues with ethyl acetate and the quantitative determination was done by gas chromatography. Exposure was extrapolated to a work day of 8 hours. To evaluate safety conditions at work was estimated the Working Condition Unsafe (margin of safety – MOS <1) and the estimate of Safe Work Duration (SWD). The corresponding group for the forearms/arms/hands concentrated 35% of present residues in the clothes. The residues found on the clothes, trunk, lame, legs and trunk-back, were 19, 19, 10, and 16%, respectively. Results of carbosulfan amounts trapped on cotton clothes showed that 24h as a reentry interval is overestimated. For methamidophos and endosulfan a reentry interval is underestimated

Orientador: Rosemary Adriana Chiérici Marcantonio / Banca: Joni Augusto Cirelli / Banca: Elton Gonçalves Zenóbio / Resumo: O propósito deste estudo foi analisar histologicamente a utilização da matriz dérmica acelular (AlloDermâ) associada ou não à proteína derivada da matriz do esmalte (Emdogainâ) em recessões gengivais criadas cirurgicamente em cães. Foram criados defeitos periodontais na superfície vestibular dos caninos superiores de seis cães. Estes foram submetidos à indução do acúmulo de placa por oito semanas, e após este período foram divididos e tratados em dois grupos: grupo I: matriz dérmica acelular; grupo II: matriz dérmica acelular associada à proteína derivada da matriz do esmalte, ambos com reposição coronária do retalho. Após três meses os animais foram sacrificados, os dentes retirados em bloco e processados histologicamente. Realizou-se análise histológica descritiva e histométrica, medindo-se a extensão do tecido epitelial, neoformação óssea e cementária, nível gengival, inserção conjuntiva e tamanho do defeito para os grupos I e II. Os resultados demonstraram valores estatisticamente iguais para as médias dos valores de cemento: 0.06 mm e 0.32 mm; osso: -0,75 mm e -0,86 mm; nível gengival: -2,15 mm e -3,11 mm; tamanho do defeito: 4,90 mm e 5,51 mm, respectivamente para os grupos I e II. Foi encontrada diferença estatisticamente significante em relação tecido epitelial, com médias de 2,88 mm e 2,15 mm, respectivamente para os grupos I e II. Não foi encontrada inserção conjuntiva. Com isso, pudemos concluir que o Emdogainâ não trouxe efeitos adicionais quando associado ao AlloDermâ. / Abstract: The purpose of the present study was to histologically evaluate the healing of acellular dermal matrix (AlloDermâ), associated or not, a enamel matrix proteins (Emdogainâ) in gingival recessions defects created in dogs. Recessions defects were surgically created (5X7 mm) on the buccal aspect of the uppercuspids in contralateral jaw quadrants, in 6 mongrel dogs. The defects were exposed to plaque accumulation for 2 months. After they were divided into 2 groups, according to the treatment applied: Group I- acellular dermal matrix and coronally positioned flap; Group II: acellular dermal matrix, enamel matrix proteins and coronally positioned flap. After 3 months, the animals were sacrificed, and the blocks obtained were processed. Histologic and histometric analysis were performed to examine: ephithelium formation, cementum and bone regeneration, connective tissue adaptation, attachment level and defect measure. Results did not show a statistically significant difference in the cementum and bone regeneration, connective tissue adaptation, attachment level and defect measure parameters. The mean values were: 0,06 mm and 0,32 mm for cementum regeneration; -0,75 mm and -0,86 mm for bone regeneration; -2,15mm and -3,11 mm for attachment level; and 4,90 mm and 5,51 mm for defect measure, in the I and II groups, respectively. The ephithelium formation parameter was 2,88 mm and 2,15 mm, in the I and II groups, respectively, with a statistically significant difference. Within limits of this study, it can be concluded that Emdogainâ not brought additional effects when associated with AlloDermâ. / Mestre

Orientador: Geraldo Papa / Banca: Enes Furlani Júnior / Banca: Marineide Rosa Vieira / Banca: Joaquim Gonçalves Machado Neto / Banca: Gilberto Casadei de Baptista / Resumo: Nas últimas décadas a consciência ecológica despertou a atenção de governos e da sociedade para o problema dos resíduos dos pesticidas nos alimentos e no ambiente, onde os amostradores de pragas agrícolas se enquadram dentro de um grupo de risco. A exposição dérmica de amostradores foi avaliada na reentrada em lavoura de algodoeiro após pulverização de três inseticidas. Aos 3 minutos após a aplicação quatro equipes vestiram um conjunto de vestimentas amostradoras (calça, camisa e luvas), entrando e permanecendo nas áreas tratadas por 30 minutos, simulando uma amostragem de pragas. O procedimento foi repetido aos 60 e 300 minutos e aos 1, 3, e 7 dias após a aplicação. As vestimentas amostradoras contaminadas após as exposições foram seccionadas em campo em 6 regiões distintas mais as luvas, embaladas e levadas ao Laboratório. Os inseticidas foram extraídos das vestimentas amostradoras com acetato de etila e a determinação quantitativa foi realizada por meio de cromatografia gasosa. As exposições dérmicas foram extrapoladas para uma jornada de trabalho de oito horas. Para classificar a segurança das condições de trabalho foram estimadas a margem de segurança (MS) e o tempo de trabalho seguro (TTS). O conjunto correspondente aos antebraços/braços/mãos concentrou 35% dos resíduos presentes nas vestimentas amostradoras. Partes correspondentes ao tronco (frente), coxas, pernas e tronco (atrás) alcançaram 19; 19; 10 e 16% dos resíduos, respectivamente. Constatou-se que o intervalo de reentrada estabelecido para os inseticidas comerciais Thiodan 350 CE (endosulfan) e Tamaron 600 BR (metamidofós) estão subestimados, enquanto que para o Marshal 200 SC (carbosulfan) o mesmo está superestimado, em relação aos intervalos de reentrada estabelecidos na legislação em vigor / Abstract: The objective of this work was to study the dermal exposure of workers to residues of the pesticides, applied in cotton crop. After 3 minutes of application four people dressed a group with cotton clothes (pants, shirt and gloves), entered and stayed in the treated area by 30 minutes, simulating a sampling. The procedure was repeated after 60 and 300 minutes and 1, 3, and 7 days after application. The clothes were cut and put in plastic bags, and stored cold at -18oC until analyses was performed. The analytical method consisted on the extraction of pesticides residues with ethyl acetate and the quantitative determination was done by gas chromatography. Exposure was extrapolated to a work day of 8 hours. To evaluate safety conditions at work was estimated the Working Condition Unsafe (margin of safety - MOS <1) and the estimate of Safe Work Duration (SWD). The corresponding group for the forearms/arms/hands concentrated 35% of present residues in the clothes. The residues found on the clothes, trunk, lame, legs and trunk-back, were 19, 19, 10, and 16%, respectively. Results of carbosulfan amounts trapped on cotton clothes showed that 24h as a reentry interval is overestimated. For methamidophos and endosulfan a reentry interval is underestimated / Doutor

Ultraviolet A is a major spectral component of solar electromagnetic energy reaching the surface of the earth. Excessive exposure to solar UVA is a known contributor to skin photoaging and photocarcinogenesis, associated with increased incidence rates and a significant health burden imposed by skin cancer worldwide. However, the molecular mechanisms underlying UVA-induced skin photodamage remain largely undefined. UVA radiation has been shown to cause cutaneous oxidative stress and photosensitization reactions involving the light-driven photochemistry of specific skin chromophores upstream of reactive oxygen species formation, recognized as key players in skin photooxidative damage. Consequently, there has been significant interest in the identification of endogenous compounds that facilitate these reactions serving as endogenous photosensitizers. In my graduate research, we assessed the potential of selected endogenous chromophores, pyridoxal and 6-formylindolo[3,2-b]carbazole (FICZ), to elicit UVA-induced photo- and genotoxicity in relevant models of human skin, and further identified the underlying molecular mechanisms involved. We demonstrated for the first time that the B6-vitamer pyridoxal, previously shown to contain the phototoxic 3-hydroxypyridine moiety, is a micromolar sensitizer of UVA-induced genotoxicity in human primary keratinocytes and human epidermal reconstructs, which may be relevant to human skin exposed to high concentrations of B6-vitamers. Additionally, we have demonstrated that FICZ, a tryptophan photoproduct and endogenous high-affinity aryl hydrocarbon receptor (AhR) agonist, as the most potent endogenous UVA- and visible light-activated photosensitizer identified as of today. FICZ potentiates photooxidative stress, an effect that occurs independent of AhR ligand activity. Given the extraordinary photodynamic potency of FICZ, which surpasses that of any known endogenous photosensitizer, including protoporphyrin IX, and its rapid metabolic turnover, we tested the feasibility of using FICZ for the photodynamic elimination of malignant skin cancer cells in vitro and in vivo. Indeed, light photoactivation of FICZ-induced phototoxidative damage and cytotoxicity in a panel of cultured human malignant skin cells, and furthermore suppressed post-UVB tumorigenic progression in high-risk SKH-1 mice. Based on these pilot studies, follow up experiments will further optimize FICZ-based photodynamic interventions targeting human skin malignancies in relevant model systems. In pursuit of minimizing the need for invasive therapeutic methods, exploitation of stress response pathways has become a topic of interest for interventions aimed at the eradication of skin cancer at early or late progressional stages. Therefore, we tested feasibility of harnessing the cellular metal stress response for the elimination of skin cancer cells using the zinc-ionophore and FDA-approved microbicidal agent zinc pyrithione (ZnPT). Indeed, in a panel of cultured malignant skin cancer cells it was observed that ZnPT treatment caused rapid intracellular zinc overload and redox dysregulation, followed by a loss of genomic integrity and induction of caspase-independent cell death. In a murine photocarcinogenesis model, chronic topical ZnPT-administration post-UV caused epidermal zinc-overload and stress response gene expression with pronounced blockade of tumorigenic progression. These data suggest the feasibility of repurposing a topical OTC-drug for zinc-directed photochemoprevention of solar UV-induced nonmelanoma skin cancer. In summary, these studies contribute to our mechanistic understanding of photosensitizer- and zinc-induced stress responses in human skin, and furthermore provide the molecular basis for innovative therapeutic strategies aimed at the elimination of skin cancer cells.

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京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18178号 / 医博第3898号 / 新制||医||1004(附属図書館) / 31036 / 京都大学大学院医学研究科医学専攻 / (主査)教授 宮地 良樹, 教授 羽賀 博典, 教授 山下 潤 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DGAM

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