Thesis (M.Sc. (Zoology & Entomology)) - Rhodes University, 2007.

Orientador: Alexandre Nunes Ponezi / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Civil, Arquitetura e Urbanismo / Made available in DSpace on 2018-08-13T11:10:42Z (GMT). No. of bitstreams: 1 Caminada_SuzeteMariaLenzi_M.pdf: 5250587 bytes, checksum: 52265efd2c8ae0079d610af85e15b3b3 (MD5) Previous issue date: 2008 / Resumo: A Comissão da União Européia e o comitê científico de toxicologia, ecotoxicologia e ambiente, identificaram, a necessidade da obtenção de dados sobre os efeitos dos fármacos no ambiente. Estes compostos e seus metabólitos são introduzidos no ambiente, pelo esgoto em quantidades que superam 100 toneladas/ano. A literatura científica comenta que a presença de fármacos no ambiente é, geralmente, pequena quando comparada a outros produtos químicos. No entanto, a alta persistência de vários destes compostos e sua contínua reposição aumentam o risco de exposição crônica para os organismos aquáticos, como também para os humanos. Um destes compostos, Hidrocloridrato de Fluoxetina, medicamento bastante utilizado no tratamento da ansiedade e distúrbios de comportamento, obesidade e bulemia nervosa, tem sido reportado como um causador de distúrbios em organismos aquáticos. Os resultados demonstram que o fármaco em estudo foi parcialmente degradado pelos organismos no sistema teste com uma remoção de 27%. Os ensaios ecotoxicológicos indicaram que os fármacos apresentam toxicidades diferentes entre as formulações estudadas. As avaliações da toxicidade das amostras geradas pelo sistema de respirometria apresentaram uma redução na toxicidade. Os ensaios indicam uma possível acumulação ambiental com conseqüências prejudiciais aos organismos aquáticos. / Abstract: The Commission of the European Union and the scientific committee of toxicology, ecotoxicology and environment 1990, identified, the need of the obtaining of data on the effects of the drugs in the environment. These composed and they metabolics are, introduced in the environment, through the wastewater sanitary, in larger proportions than 100 ton/year. The scientific literature comments that the drugs presences in the environment are generally, small when compared the other chemical products. However the high persistence of several of these composed and its continuous replacement increases the risk of chronic exhibition for the aquatic organisms as well as for the humans. One of these substance, Hidrocloridrate of Fluoxetine, medication quite used in the treatment of the anxiety and disturbances of behavior, obesity and nervous bulemy, it has been reported as a caused of disturbances in aquatic organisms. The results demonstrate that the drug in study was degraded partially by the organisms in test system with a maximum removal of approximately 27%. The toxicological rehearsals indicated that the drugs presents show different toxicicity among the studied formulations. The evaluation of the toxicicity of the samples generated by the system presented a reduction in the toxicicity. The rehearsals indicate a possible environmental accumulation with harmful consequences to the aquatic organisms. / Mestrado / Saneamento e Ambiente / Mestre em Engenharia Civil

Many severe clinical conditions encountered in Africa involve the effects of iron overload on diseases (AIDS, TB etc) and vital organs (e.g., liver). To intervene successfully in the HIV pandemic, knowledge of AIDS pathogenesis and factors that stimulate or inhibit viral replication are crucial. Iron overload is believed to cause serious damage during HIV infection. Indeed, it is believed that the metal is required by infected cells to synthesize viral particles. The consequences of excess iron in vivo include the stimulation of microorganism growth, an increase in oxidative stress and an impairment of immune system function. Iron chelation have been reported to modulate some of these effects. In a project designed to assess the effect of in vitro iron overload (also synonymously referred to as iron loading) on HIV infection, cells (HIV-infected and controls) were directly loaded with iron and desferrioxamine (DFO, an iron chelator) respectively or combined. We then performed experiments to investigate the effects of these chemicals on host cell defenses and viral replication. Effective iron loading of all cell lines used was confirmed by emission spectroscopy. Through viability assays using tetrazolium salts, flow cytometric analysis of apoptosis and necrosis using Annexin-V, and specialised ELISAS; the effect of iron loading on host cell viability, survival or death and cytokine production was studied. The effect of iron loading on virus infectivity was also investigated by looking at core protein (p24) levels and reverse transcriptase (RT) activity. Prior to the start of the bioassays, several dyes were compared during identical procedures to find an effective and consistently functional dye assay for the assessment of cell growth/viability or proliferation. Viability assays provided a qualitative picture of events while flow cytometric analysis allowed us to compare viability with specific types of cell death (apoptosis/necrosis). Excess iron in the form of 500ƒÝM FeSO4-7H2O in addition to serum iron was found to be non-toxic to cells alone but detrimental to HIV-infected cells. Equimolar amounts of DFO inhibited cell growth, cytokine production and viral replication. Our results indicate that Fe loading stimulates viral replication. Iron chelation on the other hand decreased HIV replication suggesting a possible area for further therapy research using iron chelators in situations of iron loading in the presence of HIV/AIDS. / Dr. Debra Meyer

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Nanoparticles (particles less than 100 nm in at least one dimension) exhibit chemical properties that differ from their bulk counterparts. Furthermore, they exhibit increased potential for systemic toxicities due to their deposition deep within pulmonary tissue upon inhalation. Thus, standard regulatory assays alone may not always be appropriate for evaluation of their full spectrum of toxicity. Systems biology (e.g., the study of molecular processes to describe a system as a whole) has emerged as a powerful platform proposed to provide insight in potential hazard, mode of action and human disease relevance. This work makes use of systems biology to characterize carbon black nanoparticle-induced toxicities in pulmonary and extra-pulmonary tissues (i.e., liver and heart) in mice over dose and time. This includes investigations of gene expression profiles, microRNA expression profiles, tissue-specific phenotypes and plasma proteins. The data are discussed in the context of potential use in human health risk assessment. In general, the work provides an example of how toxicogenomics can be used to support human health risk assessment.

Short-term toxicity tests utilizing mitochondrial and microsomal metabolism were developed and applied to a series of eight quinones. In the mitochondrial assay, the degree to which test compounds inhibited mitochondrial respiration varied from an EC50 of 9 μM to l25 μM. In the microsomal assay, the maximum percent increase over control oxygen consumption rates elicited by the quinones ranged from eight percent to 837 percent. The ability of the compounds to stimulate microsomal oxygen uptake reflects their capability to redox cycle and form reactive oxygen species. Experiments were conducted to evaluate the relationship between the rate of quinone redox cycling and the extent of microsomal lipid peroxidation, a possible toxic insult associated with reactive oxygen species. Results of the mitochondrial and microsomal assays were statistically correlated with several quinone physicochemical parameters and qualitatively compared to reduction potential. The biological response observed in both test systems appeared to be most strongly influenced by the reduction potential of the quinone and biomechanisms of action were suggested based on this relationship. To assess the ability of the mitochondrial and microsomal assays to indicate toxicity of the quinonoid compounds, results were statistically correlated with literature-derived toxicity data. It was concluded that the mitochondrial assay appears to be a valid indicator of acute toxicity, while the microsomal assay better portends the potential for chronic toxicity. / Master of Science

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Currently, protocols for investigating the effects of chemical pollutants on periphyton communities under natural conditions are statistically flawed and/or potentially harmful to the ecosystems in which the studies are conducted. Toxicant-releasing substrates have been proposed to allow the delivery of different levels of chemical pollutants to replicate microbial communities in situ while minimizing the amount of toxicant released into the aquatic ecosystems under investigation. The purpose of this research was to compare the copper-induced responses of laboratory periphyton communities in artificial streams to those generated using standard, laboratory toxicity testing protocols during a summer and winter experiment. Chemical-releasing substrates were successfully used to deliver copper to periphyton communities in a predictable manner, over a broad range of doses, and at fairly constant rates during one week exposure periods. / Master of Science

Single species toxicity tests are widely used to assess the potential effects of a toxicant on aquatic life. Increasingly, it is necessary to understand how the results of these tests relate to toxicant effects in natural communities. This dissertation presents the methodology and validation for a community level toxicity test that bridges the gap between single species tests and natural community responses. The research involved control of environmental parameters, improvement of feeding regimes and testing of the final community. The results are presented as four separate papers. The first paper addresses the development and validation of a standardized reconstituted water for culturing and toxicity testing of algae, cladocerans, a rotifer and two fish species. The next two papers address the substitution of the food source currently used in the fathead minnow survival-growth impairment test (<i>Artemia</i>) with a freshwater food source (the rotiter, <i>Brachionus calyciflorus</i>). Along with the alga <i>Chlorella vulgaris</i> (producer), B. calyciflorus (primary consumer) and the fathead minnow larvae (secondary consumer) comprise a three level food chain that was used to address trophic level interactions (feeding reduction and growth impairment) in the final phase of this research. The end result is an experimental procedure in which environmental parameters (water quality, temperature, etc.) and trophic structure parameters (Le. producer and primary consumer density) can be controlled well enough to insure that any shifts in community structure can be attributed to toxicant related effects. / Ph. D.