Toxic/mutagenic potentials of Gambierdiscus toxicus (GT) and Prorocentrum lima (PL) methanol extracts (CME) were determined using brine shrimp (Artemia salina), mouse, chicken embryo and Salmonella microsomal assays. PL-CME and GT-CME were toxic to shrimp and mice. Isolation and separation were accomplished using ether/water, hexane/methanol partition and butanol extraction. Toxic fractions were purified using column and thin layer chromatography (TLC). GT-CME showed low levels of mutagenic potential. For GT isolated fractions and PL-CME, no mutagenic effects were observed. Both CMEs showed embryotoxicity, with no teratogenic effects. Ether/methanol and water/butanol fractions showed shrimp toxicity. These fractions were purified by treatment with warm/cold acetone. Acetone insoluble precipitates were obtained. Ether soluble acetone filtrate (ESAF) and butanol soluble acetone precipitate (BSAP) showed shrimp and mouse toxicity. GT-BSAP produced temperature depression in mice. Three toxic isolates were obtained from PL-ESAF, four from GT-ESAF and one from both BSAPs columns. TLC preparative plates showed at least 12 toxic isolates for PL-ESAF, 8 for GT-ESAF and 4 for GT-BSAP.

O monóxido de carbono (CO) constitui sério risco à saúde de indivíduos expostos a este gás. Os efeitos nocivos aparecem como conseqüência de sua combinação com a hemoglobina formando a carboxiemoglobina(COHb). A avaliação da exposição ao CO pela monitorização biológica é realizada, preferencialmente, pela determinação da carboxiemoglobinemia. O método espectrofotométrico proposto, para a determinação de COHb, utiliza a leitura na região Soret (420 e 432 nm) e fatores de calibração do espectrofotômetro. É realizado estudo comparativo entre o uso do CO obtido por reação química e o de cilindro de gás no preparo de solução 100% de COHb. O método apresenta boa precisão (coeficiente de variação de 2 e 6% para 4,98 e 1,01 % de COHb, respectivamente) e sensibilidade (0,50 % de COHb) adequadas à avaliação da exposição ao monóxido de carbono. A quantificação da COHb não é comprometida pelo teor hemoglobínico nem pela opalescência (lipemia) da amostra colhida no período pós-prandial. É apresentada a carboxiemoglobinemia em fumantes (n= 119) e não-fumantes (n= 189) que constituem 4 grupos de indivíduos expostos ocupacionalmente ao CO (n=209) e um grupo controle (n=99); e a análise estatística dos resultados (teste não-paramétrico). / Carbon monoxide (CO) is recognized as a high risk hazard to the health of exposed workers. Combining with hemoglobin it reduces the oxigen carrying capacity of the blood. The individual overall exposure may be assessed through the carboxyhemoglobin (COHb) content of blood samples, as a biological exposure index. A spectrophotometric method is proposed using measurements in the region Soret (420 - 432 nrn) together with calibration factors of the instrument. A comparative study is made between the use of CO from compressed gas cilinders and the CO delivered by a chemical reaction in preparing the saturated COHb solution. The method presents precision (coefficient of variation is 2 and 6% to 4,98 and 1,01% of COHb, respectively) and sensitivity (0,5% of COHb), which are adequate to the purpose. Hemoglobin and lipidic content of samples showed no effect in the COHb measurement. Carboxyhiemoglobin level of four groups of exposed workers (n = 209) and a control group (n = 99) among smokers (n = 115) and non-smokers (n = 189) were determinated using the method. The statistical analysis of the results are presented (non-parametric test).

Large quantities of manufactured nanomaterials (MNM) are released into the environment by human activity each year. The entry of MNM into the terrestrial food webs, which has the potential for far-reaching impacts, begins with the uptake by plant species from the soil. These processes can be affected by MNM physico-chemical properties such as size, chemical composition, surface charge, etc., of which our knowledge is still incomplete. To bridge some of the gaps in our understanding of these processes and, specifically, to determine whether the physico-chemical properties of the MNM are predictive of their behavior in terrestrial food chains, we conducted a series of experiments using different MNM and model organisms. First, we synthesized functionalized CeO2 MNM having different charges and exposed tomato plants (Solanum lycopersicum cv Micro-Tom) to them. We found that plant growth and the rate of root-to-shoot translocation were functions of surface charge and exposure concentration. Mechanisms of entry into roots were examined using recent advances in high-resolution synchrotron X-ray microscopy to show that a combination of apoplastic and symplastic routes was used by the particles to penetrate to the interior of the roots. Our results also illustrate that these particles have drastically different tissue distribution patterns depending on their surface charges. Second, we exposed tomato plants with these CeO2 MNM and fed the leaves to the tobacco hornworm (Manduca sexta). Differential trophic transfer was observed as a function of the surface charge of the particles. An uptake and elimination study was conducted to obtain a time course of Ce dynamics. Despite no observed overall biomagnification across trophic levels, these differentially charged CeO2 MNMs had higher bioaccumulation factors than that of ionic Ce3+. The uptake-elimination dynamics were influenced by the surface charge of the NPs. Positively charged NPs had higher bioaccumulation factors and assimilation efficiencies but lower elimination rate than neutral and negatively charged CeO2 MNMs. Finally, to determine if studies conducted with highly purified, lab synthesized materials, were predictive of behavior of commercial nanopesticide formulations, we studied the dietary uptake of Cu(OH)2 MNMs by hornworms feeding on surface-contaminated tomato leaves. We compared lab-synthesized copper hydroxide (Cu(OH)2) nanowire with the widely used fungicide KOCIDE® 3000, whose active ingredient is nano-needles of copper hydroxide (Cu(OH)2). The difference in their toxicity and accumulation/elimination dynamics was found to correlate with the solubility of the materials. We have shown that the physico-chemical properties of MNM affect the toxicity, bio-distribution and trophic transfer of MNM in terrestrial ecosystems. With the increase of MNM release into the environment as a result of the rapid development of nanotechnology, these results have important implications for the evaluation of environmental risks associated with these MNMs and may help the application of nanotechnology to evolve to be more environmentally friendly.

A model of acute glutamate- and domoate-induced toxicity was developed and characterized in cultured rat cerebellar granule cells (CGCs) using experimental conditions which preserve the voltage-dependency of NMDA receptor function. Glutamate, which is normally non-toxic to CGCs in physiologic media (pH 7.4), was shown to induce a cytotoxic response after 2 hours when the exposure temperature was reduced from 37�� to 22��. Pharmacological characterization of this response demonstrated that cytotoxicity is mediated by the activation of NMDA receptors, while non-NMDA receptors produce a depolarizing stimulus that enhances release of the voltage-dependent Mg����� blockade of NMDA receptor ion channels. Reduced temperature was shown to facilitate NMDA receptor activation by compromising the ability of CGCs to maintain normal electrochemical gradients during glutamate-induced ion flux. When compared to glutamate, the non-NMDA receptor agonist, domoate, demonstrated an acute cytotoxic response in CGCs that was also mediated predominantly by NMDA receptors. NMDA receptor activation was produced secondary to a domoateinduced release of glutamate and aspartate from CGCs; therefore, domoate synergistically potentiates glutamate/aspartate-mediated neurotoxicity. Domoate-induced excitatory amino acid (EAA) release was investigated and found to occur almost exclusively through reversal of the high affinity Na+-coupled glutamate transporter and by osmoregulatory mechanisms. CGCs also responded to domoate-induced depolarization by releasing adenosine which suppresses exocytotic EAA release through A1 receptor activation. The functional and pharmacological characteristics of NMDA receptors were characterized in 12 DIC CGCs using the channel blocking compound [��H]MK-801 (dizocilpine). Kinetic analysis of [��H]MK-801 binding indicated the possible existence of at least two NMDA receptor populations on 12 DIC CGC membranes, and the equilibrium competition binding of MK-801 and other channel blocking compounds was consistent with the presence of high and low affinity binding sites. The neuroprotective potencies of NMDA receptor channel blockers correlated significantly with their affinities for the NMDA receptor derived from equilibrium competition analysis of [��H]MK-801 high-affinity binding. Thus, whereas 12 DIC CGCs express a pharmacologically heterogeneous population of NMDA receptors, it is the high-affinity component of [��H]MK-801 binding that mediates glutamate toxicity. / Graduation date: 1998

Thesis (D.Psych.)--Murdoch University, 2009. / Thesis submitted to the Faculty of Health Sciences. Includes bibliographical references.

Thesis (Ph. D.)--University of Missouri-Columbia, 2003. / Typescript. Vita. Includes bibliographical references (leaves 99-111). Also available on the Internet.

Thesis (Ph. D.)--University of Texas at Austin, 2002. / Vita. Includes bibliographical references. Available also from UMI Company.

Thesis (Ph. D.)--University of Missouri-Columbia, 2003. / Typescript. Vita. Includes bibliographical references (leaves 99-111). Also available on the Internet.

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