Thesis (M.S.)--University of Wisconsin--Madison, 1969. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1959. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 150-155).

Thesis (M.S.)--University of Wisconsin--Madison, 1966. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (M.S.)--University of Wisconsin--Madison, 1961. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves [67]-75).

Zugl.: Berlin, Freie Universiẗat, Diss., 2004. / Dateiformat: zip, Dateien im PDF-Format.

Universiẗat, Diss., 2002--Tübingen.

Thesis (Ph. D.)--University of Iowa, 2007. / Supervisors: Jerrold P. Weiss, William M. Nauseef. Includes bibliographical references (leaves 101-119).

Proefschrift Maastricht. / Met lit. opg. - Met een samenvatting in het Nederlands.

Thesis (Ph.D.)--Boston University / The purpose of this investigation was to concentrate, purify, and assay the enzyme elaborated by certain strains of Micrococcus pyogenes var.aureus (Staphylococcus aureus), whereby these organisms are capable of effecting the lysis of fibrin. These studies included the selection of strains capable of producing filtrates containing potent kinase; the selection of a culture medium which woud support the growth of the organism, and at the same time insure adequate enzyme production; a method of concentration and assay of enzyme activity; and studies of the concentrate for properties characteristic of various pathogenic staphylococci. A review of the literature pertaining to staphylokinase or as it had formerly been designated, staphylococcal fibrinolysin, is presented. Few data are available for the production of staphylokinase specifically; however, it has been generally agreed that coagulase activity, hemolysin and pigment production, as well as kinas activity, are intimately related to the pathogenicity of the organism. Therefore, strains used in these studies of kinase production were selected primarily on the basis of these other criteria. [TRUNCATED]

As naftoquinonas são amplamente distribuídas na natureza e várias destas moléculas tem um papel importante na produção de energia, através da fotossíntese e respiração celular. No entanto, a atividade biológica de naftoquinonas com grupamentos amino é pouco investigada em células procarióticas e eucarióticas. No presente trabalho nós estudamos a atividade biológica da 5-amino-8-hidroxi-1,4- naftoquinona (ANQ) em comparação com a 1,4-naftoquinona (NQ) na bactéria Staphylococcus aureus. ANQ e NQ inibem o crescimento do S. aureus nas concentrações de 50 e 10 μg/mL, respectivamente. O efeito antimicrobiano das naftoquinonas diminui na presença de ascorbato de sódio, por outro lado o ácido 4,5-dihidroxi-1,3-benzeno-sulfônico (Tiron), um antioxidante especifico para o ânion superóxido foi capaz de proteger o S. aureus somente dos efeitos da ANQ. A ANQ e NQ bloqueiam o consumo de oxigênio e com a cadeia respiratória bloqueada com cianeto induzem o consumo de oxigênio. Os ensaios realizados com a presença das naftoquinonas se verificou que estes compostos induzem peroxidação de lipídios, sendo demonstrado pela formação de substancias reativas ao ácido tiobabitúrico. Estes resultados mostram que estes compostos atuam como aceptores de elétrons e induzem a formação de espécies reativas de oxigênio, que são tóxicas para o S. aureus. Com a proposta de elucidar a atividade mutagênica da ANQ e da 5-amino—2,8-dihidroxi- 1,4-naftoquinona (ANQ-OH) em comparação com a NQ, nós utilizamos o ensaio Salmonella/microssoma. A genotoxicidade e o potencial recombinogênico foram analisados nas linhagens haplóide e diplóide da levedura Saccharomyces cerevisiae. No ensaio Salmonella/microssoma a NQ não foi mutagênica, enquanto as aminonaftoquinonas apresentaram uma fraca mutagênese nas linhagens TA98 e TA102. Na linhagem haplóide, somente NQ induziu mutagênese. Na diplóide, as naftoquinonas não induziram eventos recombinacionais. Os resultados sugerem que as aminonaftoquinonas são fracos agentes mutagênicos em células procarióticas. Além disto, a genotoxicidade destes compostos foi determinada utilizando o ensaio Cometa (single cell gel – SCG) e o ensaio Cometa modificado com as enzimas formamidopirimidina DNA-glicosilase (FPG) e endonuclease III (ENDOIII) em células de fibroblasto de pulmão de hamster Chinês (células V79). Em nosso estudo foi demonstrado que ANQ e NQ induzem danos oxidativos no DNA das células V79, como apresentado no ensaio na presença de enzimas. O pós-tratamento com ENDOIII e FPG não reconhecem danos promovidos pela ANQ-OH, quando comparado com o ensaio cometa padrão. Além disso, todas as naftoquinonas apresentaram genotoxicidade nas células V79 em presença de ativação metabólica. Nas células de mamíferos, NQ e ANQ são agentes genotóxicos, enquanto ANQ-OH é genotóxico somente com metabolização. O conjunto destes resultados reforça que ANQ e NQ produzem o radical superóxido e demonstra que o grupamento amino na posição 5 não elimina a capacidade da ANQ em produzir espécies reativas de oxigênio. Por fim, nós podemos afirmar que a citotoxicidade e genotoxicidade destes compostos é pela produção de danos oxidativos em todos os sistemas celulares. / Naphthoquinones are widely distributed in nature and some of these molecules have an important role in the biochemistry of microbial energy production, by means of photosynthesis and respiratory chain. However, the biological activity of naphthoquinones amino derivates on prokaryotic and eukaryotic cells is poorly investigated. In the present work we have studied the biological activity of 5-amino-8-hydroxi-1,4- naphthoquinone (ANQ) on Staphylococcus aureus in comparison with unsubstituted 1,4- naphthoquinone (NQ). Complete inhibition of microbial growth was observed with ANQ and NQ at 50 and 10 μg/mL, respectively. The antibacterial effect of naphthoquinones decrease in presence of sodium ascorbate, but the superoxide scavenger 4,5-dihydroxi-1,3- benzene-disulfonic acid (Tiron) was able to protect S. aureus only from the harmful effect of ANQ. Naphthoquinones blocked oxygen uptake and induced-cyanide insensitive oxygen consumption. Assays in presence of naphthoquinones induced an increase of lipid peroxidation in S. aureus, as determined by thiobarbituric acid reactive substances. These results showed that 1,4-naphthoquinones effectively act as electron acceptor and induced an increase in reactive oxygen species that are toxic to S. aureus cells. In order to elucidate the mutagenic activity of ANQ and 5-amino-2,8-dihydroxy-1,4- naphthoquinone (ANQ-OH) in comparison with the unsubstituted 1,4-naphthoquinone (NQ) we have employed the Salmonella microssoma/assay. The genotoxic and recombinogenic potencial effects were analysed in haploid and diploid yeast Saccharomyces cerevisiae strains. In Salmonella microssoma/assay the NQ was not mutagenic while the aminonaphthoquinones were weakly mutagenic in TA98 and TA102 stains. In haploid yeast, only NQ showed a mutagenic response. In diploid yeast, the naphthoquinones did not induce any recombinogenic events. All these results suggest that aminonaphthoquinones are weak mutagenic agents only in prokaryotic cells. Moreover, the genotoxicity of these compounds was determined using standard Comet assay (single-cell gel – SCG) and modified Comet assay with bacterial enzymes formamidopyrimidine DNAglycosylase (FPG) and endonuclease III (ENDOIII) in V79 Chinese hamster lung fibroblast cells. Our study demonstrated that ANQ and NQ induced oxidative DNA damage in V79 cells as shown in comet assay with the lesion-specific enzymes. Post-treatment with ENDOIII and FPG proteins had not significant effect on ANQ-OH-induced oxidative DNA damage when compared to standard alkaline comet assay. Besides, all naphthoquinones showed genotoxic effect on V79 cells in presence of metabolic activation. In mammalian cells, NQ and ANQ are genotoxic agents and ANQ-OH is genotoxic only in presence of metabolic activation. Taken together these results reinforce that ANQ and NQ produce superoxide radicals and reveal that amino group in position 5 does not abolish the ability of ANQ in producing reactive oxygen species. Finally, we were able to affirm that cytotoxicity and genotoxicity of these compounds is promoted by oxidative damage despite the cell system.