Environmental pollution has been a serious concern worldwide. Many degradation methods have been developed to clean sites contaminated with pollutants. More knowledge and better understanding in this field will help to protect our environment. The goal of the research in this thesis is to gain a better understanding of the mechanism of organic pollutant degradation in Fenton reactions and sonochemical reactions. Fenton degradation uses hydroxyl radical to oxidize organic compounds. The radical is produced by catalytic decomposition of hydrogen peroxide with Fe(II). Further research has found that addition of cyclodextrins can enhance degradation efficiency of hydrophobic organic pollutants. To study the mechanism of the enhancement, pollutant-cyclodextrin-Fe(II) aqueous systems were studied by fluorescence and NMR techniques. The results indicated the formation of pollutant/carboxymethyl-â-cyclodextrin/Fe(II) ternary complexes in the solution. With the ternary complex, the catalyst Fe(II) becomes closer to the pollutant, therefore leading to more efficient hydroxyl radical attack on the pollutant. Additional studies showed that hydropropyl-â- cyclodextrin, â-cyclodextrin and á-cyclodextrin bound pollutant well, but bound Fe(II) poorly. Sulfated-â-cyclodextrin did not bind well with pollutant although it bound Fe(II) well. Sonochemical degradation is another important pollutant treatment method in practice. It was found that phenol sonolysis can be enhanced by volatile hydrogen atom scavengers such as carbon tetrachloride and perfluorohexane. The non-volatile hydrogen atom scavenger iodate did not enhance phenol degradation. The first order rate constant for aqueous phenol degradation increased by about 2.2-2.8 times in the presence of 150 ìM carbon tetrachloride. In the presence of less than 1.5 ìM perfluorohexane the first order rate constant increased by about 2.3 times. Hydroquinone was the major observed reaction intermediate both in the presence and absence of hydrogen atom scavengers. Hydroquinone yields were substantially higher in the presence of hydrogen atom scavengers, suggesting that hydroxyl radical pathways for phenol degradation were enhanced by the hydrogen atom scavengers. The additives investigated in this study have potential to improve pollutant degradation efficiency. Other fields may also benefit from the information gained in this study. For example the improvement could be achieved in synthetic processes that rely on hydroxyl radical as a key intermediate.

The E2A-PBX1 fusion gene results from the t(1;19) chromosomal translocation that is found in 25% of pre-B-cell cases of acute lymphoblastic leukemia (ALL). The resulting encoded product contains the transactivation domains of E2A, a Class I basic helix-loop-helix transcription factor, and most of PBX1. PBX1 is a major cofactor for most members of the HOX family of homeodomain proteins and is necessary for regulating the essential role that HOX proteins play in development and tissue homeostasis. We have identified an interaction between the E2A-encoded portion of E2A-PBX1 and the CREB-binding domain (KIX) of the transcriptional coactivator CBP and demonstrated a requirement for this interaction in leukemia induction. Others have shown that HOX proteins and CBP also interact directly, with resulting inhibitory effects on the DNA-binding ability of HOX proteins and on the acetylation of substrate proteins by CBP. Several publications have also identified the interaction of HOX proteins with the PBX1 portion of E2A-PBX1 and the result is a potent transcriptional activator at PBX1/HOX target sequences. In an attempt to develop a molecular model for the induction of ALL by E2A-PBX1, we hypothesize that the addition of CBP interactive peptide elements encoded by E2A to PBX1 allows E2A-PBX1 to stabilize a ternary complex involving E2A-PBX1, HOX, and CBP resulting in the deregulated expression of critical PBX1 or HOX target genes. I demonstrate using in vitro protein-protein interactions that this ternary complex involving E2A-PBX1, HOXB4 (chosen as a representative member of the HOX family), and CBP does form. This direct interaction appears to reduce transcriptional activation by E2A-PBX1/HOXB4 heterodimers from PBX1/HOX enhancer elements. I also show that this suppression of transactivation appears to involve CBP antagonism of DNA binding by E2A-PBX1/HOXB4 heterodimers. My results are consistent with the idea that E2A-PBX1 contributes to ALL induction by promoting the redistribution of CBP away from DNA sites bound by E2A-PBX1/HOXB4 heterodimers and in favour of those sites bound by E2A-PBX1 homodimers. / Thesis (Master, Pathology & Molecular Medicine) -- Queen's University, 2008-09-29 13:57:25.324

A f1ourometric procedure for the analysis of free cyanide is described. The method is based on the dissociation of a ternary complex of si1ver-1, 10-phenanthro1ine-tetrabromof1uorescein by cyanide to produce a fluorescent product. The fluorescence intensity is found to be directly proportional to the cyanide concentration. The method can reliably detect 0.02 μg/mL cyanide.

No description available.

京都大学 / 0048 / 新制・課程博士 / 博士(薬科学) / 甲第18918号 / 薬科博第32号 / 新制||薬||4(附属図書館) / 31869 / 京都大学大学院薬学研究科薬科学専攻 / (主査)教授 松﨑 勝巳, 教授 加藤 博章, 教授 石濱 泰 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DGAM

JLP (JNK associated Leucine zipper protein) is a scaffolding protein that has been shown to interact with and activate the JNK/p38MAPK pathway. Its interaction with various signaling proteins is associated with coordinated regulation of cellular processes such as endocytosis, motility, neurite outgrowth, cell proliferation and apoptosis. Here, we undertook a mass spectrometric approach to identify novel interaction partners of JLP and identified the mitotic Ser/Thr kinase, Polo like Kinase 1 (PLK1) and the Fox transcription factor, Forkhead box protein K1 (FoxK1), as proteins that interact with and form a ternary complex with JLP during mitosis. Domain mapping studies showed that the N-terminal domain of JLP interacts with the polo-box domain (PBD) of PLK1 in a phosphorylation-dependent manner. Our results indicate that, JLP is phospho-primed on Thr351, which is recognized by the PBD of PLK1 and leads to phosphorylation of JLP at additional sites. Moreover, treatment of cells with the PLK1 inhibitor BI2536 affects this interaction, demonstrating the importance of PLK1 kinase activity in this process. Because JLP is a scaffolding protein that recruits proteins to mediate specific cell signaling events, the interaction of JLP with PLK1 likely results in the recruitment of other proteins to this complex. To test this hypothesis, we carried out SILAC labeling of proteins in mitotic cells in the presence or absence of BI2536. Through mass-spectrometry, we identified the FoxK1 transcription factor as a PLK1-dependent JLP-interacting protein. Furthermore, we show that JLP, PLK1 and FoxK1 form a ternary complex that is present only during mitosis. Knockdown of PLK1 and not JLP affected the interaction between JLP and FoxK1, indicating that the formation of the ternary complex is PLK1-dependent. FoxK1 is a known transcriptional repressor of the cyclin dependent kinase inhibitor, p21/WAF1. Knockdown of JLP in U2OS cells resulted in increased FoxK1 protein levels and a reduction of p21 expression. Moreover, immunofluorescence studies in asynchronous cells showed that FoxK1 is excluded from the nucleus during mitosis and that a fraction of FoxK1 localizes to the midbody region during cytokinesis. Analysis of FoxK1 protein in cells exiting S-phase suggests that FoxK1 is post-translationally modified during mitosis. In this study we characterized the ternary complex formed between JLP, PLK1 and FoxK1 during mitosis. Based on our observations, we propose that formation of the JLP/PLK1/FoxK1 ternary complex regulates the stability and/or transcriptional activity of FoxK1. / Molecular Biology and Genetics

It has been observed that confusion exists in literature concerning the meaning and use of the term efficacy. Confusion is worsened by the use of the term as a general term describing agonist activity. The meaning of the terms intrinsic activity, efficacy and intrinsic efficacy as used in theoretical models of drug action was investigated. The classical occupation model, the two-state model, the ternary complex model (including conformational change and ideas surrounding G-proteins) and the operational model were studied in order to understand the historical and current usage of these terms. Although efficacy estimates are often reported as a molecular property, it was shown that agonist activity is tissue dependent and cannot be fully portrayed by an efficacy estimate. It was found that efficacy has a different definition in each model. This is not always recognized in literature. It was suggested that the term efficacy should only be used in the context of a specific model / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2007.

It has been observed that confusion exists in literature concerning the meaning and use of the term efficacy. Confusion is worsened by the use of the term as a general term describing agonist activity. The meaning of the terms intrinsic activity, efficacy and intrinsic efficacy as used in theoretical models of drug action was investigated. The classical occupation model, the two-state model, the ternary complex model (including conformational change and ideas surrounding G-proteins) and the operational model were studied in order to understand the historical and current usage of these terms. Although efficacy estimates are often reported as a molecular property, it was shown that agonist activity is tissue dependent and cannot be fully portrayed by an efficacy estimate. It was found that efficacy has a different definition in each model. This is not always recognized in literature. It was suggested that the term efficacy should only be used in the context of a specific model / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2007.

O presente trabalho é composto por 4 capítulos distintos. No primeiro intitulado \"Ciclodextrinas: tecnologia para melhoria da solubilidade de fármacos pouco solúveis\" aborda-se uma revisão das ciclodextrinas e de seus derivados, como também a formação dos complexos de inclusão. No segundo capítulo, \"Obtenção e caracterização de complexos ternários de saquinavir, β-ciclodextrina e polivinilpirrolidona\", foram avaliadas condições que poderiam influenciar na obtenção dos complexos, tais como: tempo de agitação na formação dos complexos, proporção equimolar de fármaco e ciclodextrina, solvente para solubilização do fármaco e porcentagem de polímero hidrossolúvel, concluindo-se que as melhores condições para obtenção dos complexos são 48 horas de agitação, razão equimolar 1:2 e 1:4, água para solubilização do fármaco e acréscimo de1% de polímero ao sistema. O terceiro capítulo, \"Influência do método de secagem na obtenção de complexos ternários de saquinavir\", teve o objetivo de obter e caracterizar complexos ternários de saquinavir, β-ciclodextrina e polivinilpirrolidona pelos métodos de secagem em estufa e liofilização, bem como, comparar a influência dos métodos de obtenção na solubilidade do fármaco, chegando-se ao aumento de 44 vezes da solubilidade do fármaco quando na forma de complexo SAQ:βCD:PVP de proporção equimolar 1:2 obtido por liofilização. O quarto, \"Perfil de dissolução de cápsulas e comprimidos contendo complexos ternários de saquinavir, ciclodextrina e polivinilpirrolidona\", teve o objetivo de comparar o perfil de dissolução de cápsulas de gelatina dura e comprimidos contendo sistemas ternários SAQ:βCD:PVP, obtidos pelos métodos de secagem em estufa e liofilização e o produto referência (Fortovase®). Os resultados indicam que os perfis de dissolução das formas farmacêuticas contendo complexos liofilizados apresentaram melhores resultados de eficiência de dissolução e que as cápsulas liberam mais prontamente o ativo que os comprimidos. / The present study has 4 captions. The first is called \"Cyclodextrins: Technology to improve the solubility of the little soluble drugs\" show a review of the cyclodextrins and its derivates, as well the formations of inclusion complexes. At the second caption, \"Preparation and characterization of the ternary complexes of the saquinavir, &#946-cyclodextrin and polyvinylpyrrolidone\", were evaluated some conditions that could influence in an obtention of the complexes like stirring time at the formation of the complexes, equimolar ratio of the drug and cyclodextrin, solvent for the solubility of the drug and percentage of the hydrosoluble polymer concluding that the best conditions for the formation of the complexes are: 48 hours of the stirring, equimolar ratio 1:2 and 1:4, water to solubilize the drug and addition of 1% of the polymer in the system. The third caption, \"Influence of the drying method at the formation of the ternary complexes of the saquinavir\", had the aim to prepare and characterize ternary complexes of the saquinavir, &#946-cyclodextrin and polyvinylpyrrolidone by the method of drying in equipment and lyophilization, as well to compare the influence of the methods of the obtention at the solubility of the drug, reaching the increasing of 44 times the solubility of the drug when at the form of the ternary inclusion complex (SAQ:βCD:PVP) at the equimolar ratio 1:2 obtained by lyophilization. The fourth and the last caption, \"Dissolution rate of the capsules and tablets of ternary complex of the saquinavir, cyclodextrin and polyvinylpyrrolidone, had the aim to compare the dissolution profile of capsules of the hard gelatine and tablets of ternary complexes SAQ:βCD:PVP obtained by the method of drying in equipment and lyophilization and the reference product (Fortovase®). The results indicate that the dissolution profiles of the pharmaceutical forms of lyophilized complexes show better results of the efficience of the dissolution and that the capsules liberate more efficient the active than the tablets.

O presente trabalho é composto por 4 capítulos distintos. No primeiro intitulado \"Ciclodextrinas: tecnologia para melhoria da solubilidade de fármacos pouco solúveis\" aborda-se uma revisão das ciclodextrinas e de seus derivados, como também a formação dos complexos de inclusão. No segundo capítulo, \"Obtenção e caracterização de complexos ternários de saquinavir, β-ciclodextrina e polivinilpirrolidona\", foram avaliadas condições que poderiam influenciar na obtenção dos complexos, tais como: tempo de agitação na formação dos complexos, proporção equimolar de fármaco e ciclodextrina, solvente para solubilização do fármaco e porcentagem de polímero hidrossolúvel, concluindo-se que as melhores condições para obtenção dos complexos são 48 horas de agitação, razão equimolar 1:2 e 1:4, água para solubilização do fármaco e acréscimo de1% de polímero ao sistema. O terceiro capítulo, \"Influência do método de secagem na obtenção de complexos ternários de saquinavir\", teve o objetivo de obter e caracterizar complexos ternários de saquinavir, β-ciclodextrina e polivinilpirrolidona pelos métodos de secagem em estufa e liofilização, bem como, comparar a influência dos métodos de obtenção na solubilidade do fármaco, chegando-se ao aumento de 44 vezes da solubilidade do fármaco quando na forma de complexo SAQ:βCD:PVP de proporção equimolar 1:2 obtido por liofilização. O quarto, \"Perfil de dissolução de cápsulas e comprimidos contendo complexos ternários de saquinavir, ciclodextrina e polivinilpirrolidona\", teve o objetivo de comparar o perfil de dissolução de cápsulas de gelatina dura e comprimidos contendo sistemas ternários SAQ:βCD:PVP, obtidos pelos métodos de secagem em estufa e liofilização e o produto referência (Fortovase®). Os resultados indicam que os perfis de dissolução das formas farmacêuticas contendo complexos liofilizados apresentaram melhores resultados de eficiência de dissolução e que as cápsulas liberam mais prontamente o ativo que os comprimidos. / The present study has 4 captions. The first is called \"Cyclodextrins: Technology to improve the solubility of the little soluble drugs\" show a review of the cyclodextrins and its derivates, as well the formations of inclusion complexes. At the second caption, \"Preparation and characterization of the ternary complexes of the saquinavir, &#946-cyclodextrin and polyvinylpyrrolidone\", were evaluated some conditions that could influence in an obtention of the complexes like stirring time at the formation of the complexes, equimolar ratio of the drug and cyclodextrin, solvent for the solubility of the drug and percentage of the hydrosoluble polymer concluding that the best conditions for the formation of the complexes are: 48 hours of the stirring, equimolar ratio 1:2 and 1:4, water to solubilize the drug and addition of 1% of the polymer in the system. The third caption, \"Influence of the drying method at the formation of the ternary complexes of the saquinavir\", had the aim to prepare and characterize ternary complexes of the saquinavir, &#946-cyclodextrin and polyvinylpyrrolidone by the method of drying in equipment and lyophilization, as well to compare the influence of the methods of the obtention at the solubility of the drug, reaching the increasing of 44 times the solubility of the drug when at the form of the ternary inclusion complex (SAQ:βCD:PVP) at the equimolar ratio 1:2 obtained by lyophilization. The fourth and the last caption, \"Dissolution rate of the capsules and tablets of ternary complex of the saquinavir, cyclodextrin and polyvinylpyrrolidone, had the aim to compare the dissolution profile of capsules of the hard gelatine and tablets of ternary complexes SAQ:βCD:PVP obtained by the method of drying in equipment and lyophilization and the reference product (Fortovase®). The results indicate that the dissolution profiles of the pharmaceutical forms of lyophilized complexes show better results of the efficience of the dissolution and that the capsules liberate more efficient the active than the tablets.