No description available.

abstract / Biochemistry / Doctoral / Doctor of Philosophy

published_or_final_version / Biochemistry / Master / Master of Philosophy

Thesis (Ph. D.)--Auburn University, 2008. / Abstract. Vita. Includes bibliographical references (p. 145-153).

In order to search for bioactive compounds, we have studied the chemical constituents from the organic extracts of soft coral Klyxum molle. In this study, fifteen eunicellin-type diterpenoids, including eleven new compounds, klymollins K¡VU (1¡V11), along with four known compounds 12¡V15 were isolated. Compounds 16 and 17 were prepared by chemical synthesis. The structures of all compounds were established by spectroscopic methods and comparing the spectral data with known compounds. Compound 5 represents the first eunicellin-type compound with phenylacetyl group. The cytotoxicity of compounds 1¡V17 against K562 (human erythro myeloblastoid leukemia), Molt-4 (human acute lymphoblastic leukemia), and T47D (human breast earcinoma) were determined. Compounds 1, 2, and 3 exhibited weak cytotoxicity against Molt-4 (with ED50 11.52 ¡Ó 2.75, 20.41 ¡Ó 2.92, and 13.11 ¡Ó 3.87 £gg/mL). Compound 5 was found to exhibt significant cytotoxicity toward K562, Molt-4, and T47D (with ED50 4.32 ¡Ó 1.38, 2.36 ¡Ó 0.34, and 4.65 ¡Ó 0.93 £gg/mL). Compound 5 also displayed significant inhibitory effects on superoxide anion generation and elastase release by human neutrophils at 10 £gg/mL (with Inh % 81.56 ¡Ó 3.23, and 89.16 ¡Ó 5.77).

published_or_final_version / abstract / toc / Biochemistry / Master / Master of Philosophy

Thesis (Ph. D.)--University of Washington, 2004. / Vita. Includes bibliographical references (leaves 74-80).

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13084号 / 論医博第2125号 / 新制||医||1021(附属図書館) / (主査)教授 山下 潤, 教授 柳田 素子, 教授 篠原 隆司 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

O uso de modelos murinos de enfisema pulmonar é importante para testar diferentes estratégias terapêuticas. Dependendo do grau de dano pulmonar, algumas terapias resultam em diferentes efeitos. O objetivo deste estudo foi desenvolver um modelo murino de enfisema induzido por diferentes doses de elastase a fim de produzir diferentes graus de severidade. Foram testadas três diferentes doses de elastase (0,1U, 0,15U e 0,2U), administradas uma vez por semana durante quatro semanas, por via intratraqueal. Foram medidas mecânica pulmonar (pletismografia), diâmetro alveolar médio e fração de área ocupada por fibras colágenas e elásticas em camundongos fêmeas C57BL/6. Este estudo foi realizado no Centro de Pesquisa Experimental do Hospital de Clínicas de Porto Alegre. Observamos aumento na resistência pulmonar com maior dose de elastase (0,2U) [2,02(1,67; 2,34) cmH2O.s/ml; p=0,008]. . No mesmo grupo, volume corrente e ventilação minuto reduziram. O pico de fluxo expiratório aumentou significativamente nos grupos tratados com 0,15U e 0,2U. Nenhuma alteração significativa foi observada na complacência pulmonar dinâmica. O diâmetro alveolar médio foi maior nos grupos com 0,15U e 0,2U de elastase demonstrando a destruição dos espaços alveolares [E15: 30,31(26,65;43,13)μm and E20: 49,49(31,67;57,71)μm; p<0,0001). . A fração de área ocupada por fibras colágenas e fibras elásticas foi menor nos animais que receberam 0,2U de elastase. Concluímos que quatro instilações intratraqueais de 0,2U de elastase, uma vez por semana induzem alterações na função pulmonar e na histologia, sugerindo um modelo experimental de enfisema pulmonar severo, enquanto que doses menores resultam somente em modificações histológicas. / The use of murine models of emphysema is important to test different therapeutic strategies. Depending on the degree of lung damage some therapies result in different effects. The aim of this study was to develop a murine model of emphysema induced by different doses of elastase in order to produce different degrees severity. We tested three doses of elastase (0.1 U, 0.15 U and 0.2 U) administered once a week for four weeks intratracheally. Lung mechanics (plethysmography), mean linear intercept and the fraction area occupied by collagen and elastic fibers were measured in female C57BL/6 mice. This study was conducted at the Experimental Research Center, Hospital de Clínicas de Porto Alegre. We observed an increase in lung resistance with higher dose of elastase (0.2 U) [2.02(1.67; 2.34) cmH2O.s/ml; p=0.008]. In the same group, tidal volume and minute ventilation reduced. Peak expiratory flow increased significantly in groups treated with 0.15 U and 0.2 U. No significant changes in dynamic lung compliance were observed. Mean linear intercept was higher with 0.15 U and 0.2 U elastase, demonstrating the destruction of the alveolar spaces [E15: 30.31(26.65;43.13)μm and E20: 49.49(31.67;57.71)μm; p<0.0001). The fraction area occupied by collagen and elastic fibers was lower in the animals that received 0.2 U elastase. We concluded that four intratracheal instillations with 0.2 U elastase, once a week induced changes in lung function and in histology, suggesting an experimental model of severe pulmonary emphysema whereas lower doses resulted in only histological modifications.