Organophosphorus compounds are widely used in agriculture as pesticides and in industry as petroleum additives and modifiers of plastics. Some of these compounds are capable of inducing an irreversible neuropathy developing weeks to months after exposure, yet there is no effective treatment. This may be due in part to the lack of knowledge of how this neuropathy develops. In this dissertation, it is proposed that as a consequence of a triggering event, peripheral nerves may be predisposed to an increase in calcium (Ca⁺⁺) mobilization and the neuronal accumulation of this cation. This increase in Ca could thereby initiate a cascade of events, in both nerve and muscle, that may account for some of the detrimental changes occurring during organophosphorus-induced delayed neuropathy (OPIDN). The involvement of Ca⁺⁺ in the pathogenesis of OPIDN was tested using functional, morphological, and biochemical techniques in the domestic hen, the recognized animal model of OPIDN. The isolated biventer cervicis nerve-muscle preparation was developed for quick assessment of the time course of OPIDN deficits and validated by comparison to in vivo preparations. This preparation proved more sensitive by functional and morphological evaluation indicating early damage at 4 days following exposure and before appearance of clinical signs. Regeneration was detected after 21 days. OPIDN was modified by using Ca⁺⁺ channel blockers, nifedipine, and verapamil, in the presence of phenyl saligenin phosphate, an active neurotoxicant. Attenuation of OPIDN by these compounds was revealed by clinical assessment, by changes in nerve excitability denoted by strength-duration relationships in response to electrical stimulation, by denervation hypersensitivity to neurotransmitter, and by morphology. These modifiers attenuated all degenerative responses. Furthermore, it was revealed that the activity of Ca⁺⁺-activated neutral protease (CANP), an enzyme responsible for neurofilament degradation, was increased in OPIDN. Such increases were ameliorated by modifiers of Ca movement. This study strongly suggests that Ca⁺⁺, possibly through activation of CANP, may contribute to functional and morphological deficits of OPIDN. / Ph. D.

"December 2004" / Includes bibliographical references. / 2 v. (various pagings) : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (D.Sc.)--University of Adelaide, School of Chemistry and Physics, Discipline of Chemistry, 2005

The dominant organic phosphorus compound classes were characterized in marine samples using a new, high recovery method for isolating and concentrating bulk dissolved organic matter (DOM) called combined electrodialysis+reverse osmosis (ED/RO). In contrast to earlier studies which use ultrafiltration (UF) to recover only the high molecular weight DOM, ED/RO is capable of isolating both low molecular weight (LMW) and high molecular weight (HMW) DOM. Samples were collected from a broad range of marine environments: along a transect incorporating coastal and offshore waters off the Southeastern United States, in Effingham Inlet, a Pacific fjord located on Vancouver Island, British Columbia and in the Amundsen Sea, Antarctica. Results from phosphorus nuclear magnetic resonance (31P NMR) analysis reveals a similar abundance of P compound classes between samples, phosphate esters (80-85%), phosphonates (5-10%) and polyphosphates (8-13%). These samples contain significantly higher proportions of polyphosphate P and P esters and lower proportions of phosphonates than measured in previous studies using the UF method. The much higher levels of polyphosphate detected in our samples suggests that polyphosphate is present mainly in the LMW DOM fraction. Polyphosphates in DOM may be present as (or derived from) dissolved nucleotides or organismal polyphosphate bodies, or both. Low molecular weight P esters are likely composed of phosphoamino acids and small carbohydrates, like simple sugar phosphates and/or dissolved nucleotides. Phosphonates in DOM are more prevalent as HMW phosphonate compounds, which suggests that LMW phosphonates are more readily utilized in marine ecosystems. Overall, the investigation of DOM across a size spectrum that includes both the HMW and the LMW fractions reveals a new picture of phosphorus distribution, cycling and bioavailability.

Thesis (D.Sc.)--University of Adelaide, School of Chemistry and Physics, Discipline of Chemistry, 2005? / "December 2004" Includes bibliographical references.

CAPES / O agrotóxico organofosforado clorpirifós (CP) é considerado tóxico principalmente devido à inibição da enzima acetilcolinesterase (AChE). Devido à ineficiência de tratamentos biológicos convencionais na degradação do CP e de seus metabólitos, processos avançados de oxidação vêm sendo estudados para possibilitar sua efetiva degradação. Este trabalho avaliou a degradação do CP (200 μg L-1) em água (0,2% de ACN) através da radiação UVC e do processo UV/H2O2, em escala de bancada, bem como a ecotoxicidade após os tratamentos aplicados. A partir das condições de pH e concentração de peróxido de hidrogênio adotados neste estudo (pH 5,2 e 12 mg L-1 H2O2) verificou-se que em ambos os tratamentos, mais de 97% do composto foi degradado após 20 minutos de tratamento por UV/H2O2 e após 60 minutos de tratamento por radiação UVC. Através do estudo cinético, verificou-se que a degradação do CP segue uma reação de pseudo-primeira ordem, sendo o valor da constante k para o processo UV/H2O2 calculada em 0,119 min-1, e 0,053 min-1 para o tratamento UVC, demonstrando que o processo avançado de oxidação é mais rápido na degradação do CP do que apenas a fotólise direta. Embora o CP tenha sido praticamente degradado, ensaios ecotoxicológicos demonstraram que após o tratamento, as soluções tratadas pelo processo UV/H2O2 apresentaram ecotoxicidade aguda maior do que as tratadas por radiação UVC. Em ensaios com Daphnia magna, a toxicidade se manteve em relação à toxicidade inicial da solução de CP para ambos os tratamentos, enquanto que em ensaios com Aedes aegypti, a ecotoxicidade reduziu 95% após tratamento por radiação UVC e 1,7% após tratamento por processo UV/H2O2. Lactuca sativa apresentou fitotoxicidade para as soluções tratadas por ambos os processos. Ensaios realizados com os três organismos com as amostras-controle das soluções (soluções dos reagentes, sem CP) demonstraram que a ecotoxicidade aguda e a fitotoxicidade das amostras tratadas pelo processo UV/H2O2 são provenientes de subprodutos da degradação da acetonitrila formados durante o tratamento. Quanto aos ensaios realizados com Danio rerio, foi observada mortalidade de todos os peixes expostos à amostra tratada por processo UV/H2O2, com e sem o agrotóxico. Solução de CP tratada por radiação UVC foi empregada em ensaio de genotoxicidade, porém não foi observado efeito genotóxico nos organismos expostos. Devido aos resultados obtidos, conclui-se que embora ambos os tratamentos tenham atingindo uma eficiência superior a 97% de degradação, a ecotoxicidade aguda e a fitotoxicidade do efluente tratado manteve-se após degradação por processo UV/H2O2 devido à formação de subprodutos de degradação da acetonitrila, mesmo esta tendo sido aplicada em baixas concentrações (0,2% v/v). / The organophosphate pesticide chlorpyrifos (CP) is considered toxic mostly due to inhibition of the enzyme acetylcholinesterase (AChE) and the genotoxic potential in living organisms, even at low concentrations. Due to the inefficiency of conventional biological treatments in the degradation of CP and its metabolites, advanced oxidation processes have been studied to enable their effective degradation. This study evaluated the degradation of CP (200 μg L-1) in aqueous solution (0,2% de ACN) by direct photolysis (UVC) and homogeneous process UV/H2O2 and the ecotoxicity before and after the treatments are applied. From the conditions of pH and concentration of hydrogen peroxide used in this study (pH 5.2 and 12 mg L-1 H2O2) it was found that in both treatments, over 97% of the compound was deteriorated after 20 minutes of treatment with UV/H2O2 and 60 minutes after UVC radiation. The kinetic study demonstrates that the degradation of CP following a pseudo-first reaction. The rate constants k was calculated in 0.119 min-1 for the UV/H2O2 process and 0,053 min-1 for the UVC radiation. However, bioassays tests showed that after the UV/H2O2 treatment, the solutions was considered more toxic than the solutions treated by UVC radiation. In tests with Daphnia magna, the toxicity has remained relative to the initial toxicity of CP solution for both treatments, while in Aedes aegypti assays the toxicity reduced 95% after treatment with UVC and 1.7% after treatment process by UV/H2O2. Lactuca sativa indicates phytotoxicity for both treatments. Tests carried out with the components of the solutions without CP, showed that acute ecotoxicity of the samples treated by UV/H2O2 process could be explain by the generation of acetonitrile byproducts during treatment, possibly cyanide ions. For the tests performed with zebrafish it was observed mortality of all the organisms exposed to the sample treated by the UV/H2O2process and the blank sample. CP solutions without treatment and after UVC radiation degradation were used in genotoxicity assays, but were not observed genotoxic effects of these samples in the exposed organisms. Due to the results obtained, it was concluded that although both treatments have reached efficiency greater than 97% degradation, acute ecotoxicity of the treated effluent remained after degradation by UV/H2O2 process due to formation of by-products of acetonitrile, even it has been applied in low concentrations (0.2% v/v).

CAPES / O agrotóxico organofosforado clorpirifós (CP) é considerado tóxico principalmente devido à inibição da enzima acetilcolinesterase (AChE). Devido à ineficiência de tratamentos biológicos convencionais na degradação do CP e de seus metabólitos, processos avançados de oxidação vêm sendo estudados para possibilitar sua efetiva degradação. Este trabalho avaliou a degradação do CP (200 μg L-1) em água (0,2% de ACN) através da radiação UVC e do processo UV/H2O2, em escala de bancada, bem como a ecotoxicidade após os tratamentos aplicados. A partir das condições de pH e concentração de peróxido de hidrogênio adotados neste estudo (pH 5,2 e 12 mg L-1 H2O2) verificou-se que em ambos os tratamentos, mais de 97% do composto foi degradado após 20 minutos de tratamento por UV/H2O2 e após 60 minutos de tratamento por radiação UVC. Através do estudo cinético, verificou-se que a degradação do CP segue uma reação de pseudo-primeira ordem, sendo o valor da constante k para o processo UV/H2O2 calculada em 0,119 min-1, e 0,053 min-1 para o tratamento UVC, demonstrando que o processo avançado de oxidação é mais rápido na degradação do CP do que apenas a fotólise direta. Embora o CP tenha sido praticamente degradado, ensaios ecotoxicológicos demonstraram que após o tratamento, as soluções tratadas pelo processo UV/H2O2 apresentaram ecotoxicidade aguda maior do que as tratadas por radiação UVC. Em ensaios com Daphnia magna, a toxicidade se manteve em relação à toxicidade inicial da solução de CP para ambos os tratamentos, enquanto que em ensaios com Aedes aegypti, a ecotoxicidade reduziu 95% após tratamento por radiação UVC e 1,7% após tratamento por processo UV/H2O2. Lactuca sativa apresentou fitotoxicidade para as soluções tratadas por ambos os processos. Ensaios realizados com os três organismos com as amostras-controle das soluções (soluções dos reagentes, sem CP) demonstraram que a ecotoxicidade aguda e a fitotoxicidade das amostras tratadas pelo processo UV/H2O2 são provenientes de subprodutos da degradação da acetonitrila formados durante o tratamento. Quanto aos ensaios realizados com Danio rerio, foi observada mortalidade de todos os peixes expostos à amostra tratada por processo UV/H2O2, com e sem o agrotóxico. Solução de CP tratada por radiação UVC foi empregada em ensaio de genotoxicidade, porém não foi observado efeito genotóxico nos organismos expostos. Devido aos resultados obtidos, conclui-se que embora ambos os tratamentos tenham atingindo uma eficiência superior a 97% de degradação, a ecotoxicidade aguda e a fitotoxicidade do efluente tratado manteve-se após degradação por processo UV/H2O2 devido à formação de subprodutos de degradação da acetonitrila, mesmo esta tendo sido aplicada em baixas concentrações (0,2% v/v). / The organophosphate pesticide chlorpyrifos (CP) is considered toxic mostly due to inhibition of the enzyme acetylcholinesterase (AChE) and the genotoxic potential in living organisms, even at low concentrations. Due to the inefficiency of conventional biological treatments in the degradation of CP and its metabolites, advanced oxidation processes have been studied to enable their effective degradation. This study evaluated the degradation of CP (200 μg L-1) in aqueous solution (0,2% de ACN) by direct photolysis (UVC) and homogeneous process UV/H2O2 and the ecotoxicity before and after the treatments are applied. From the conditions of pH and concentration of hydrogen peroxide used in this study (pH 5.2 and 12 mg L-1 H2O2) it was found that in both treatments, over 97% of the compound was deteriorated after 20 minutes of treatment with UV/H2O2 and 60 minutes after UVC radiation. The kinetic study demonstrates that the degradation of CP following a pseudo-first reaction. The rate constants k was calculated in 0.119 min-1 for the UV/H2O2 process and 0,053 min-1 for the UVC radiation. However, bioassays tests showed that after the UV/H2O2 treatment, the solutions was considered more toxic than the solutions treated by UVC radiation. In tests with Daphnia magna, the toxicity has remained relative to the initial toxicity of CP solution for both treatments, while in Aedes aegypti assays the toxicity reduced 95% after treatment with UVC and 1.7% after treatment process by UV/H2O2. Lactuca sativa indicates phytotoxicity for both treatments. Tests carried out with the components of the solutions without CP, showed that acute ecotoxicity of the samples treated by UV/H2O2 process could be explain by the generation of acetonitrile byproducts during treatment, possibly cyanide ions. For the tests performed with zebrafish it was observed mortality of all the organisms exposed to the sample treated by the UV/H2O2process and the blank sample. CP solutions without treatment and after UVC radiation degradation were used in genotoxicity assays, but were not observed genotoxic effects of these samples in the exposed organisms. Due to the results obtained, it was concluded that although both treatments have reached efficiency greater than 97% degradation, acute ecotoxicity of the treated effluent remained after degradation by UV/H2O2 process due to formation of by-products of acetonitrile, even it has been applied in low concentrations (0.2% v/v).

Orientador: Angelo Pires do Prado / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-05T17:23:06Z (GMT). No. of bitstreams: 1 Mendes_MarciaCristina_D.pdf: 1282171 bytes, checksum: b6fcf8f3ba4709b8f115eb5ced83bcf8 (MD5) Previous issue date: 2005 / Resumo: Entre os ectoparasitos dos animais bovinos, o carrapato ¿ Boophilus microplus (Acari: Ixodidae) - continua sendo uma das principais causas das perdas econômicas na pecuária do Estado de São Paulo. A situação atual do controle do carrapato caracteriza-se por uma crise na produção de novas moléculas de parasiticidas e o desenvolvimento acelerado da resistência dos parasitas aos produtos usados. O presente trabalho teve por objetivo verificar o perfil de sensibilidade do carrapato B. microplus nas fazendas localizadas em alguns municípios do Vale do Ribeira e no município de Pindamonhangaba e propor um sistema de tratamento carrapaticida com base na infestação de paternóginas. Foram realizados testes de larvas - LPT (larval packet test) adotado pela FAO - teste de imersão com a fêmea adulta e o levantamento sobre as práticas de controle adotadas nas duas regiões. Os resultados de resistência para as fazendas de Pindamonhangaba mostraram que, para cipermetrina 15,4% das fazendas foram classificadas como sensível; 7,7% com resistência nível I; 69,2% com resistência nível II e 7,7% com resistência nível III. Para a deltametrina 23% sensível; 38,5% com resistência nível II e 38,5% com resistência nível III. Para o organofosforado clorpirifós 54% mostraram-se sensível; 38,4% com resistência nível I e 7,6% com resistência nível II. A região do Vale do Ribeira apresenta uma média de eficácia inferior a 20% para os piretróides; eficácia entre 49% e 72% para as associações piretróides e organofosforados; 66,83% para o amitraz e acima de 90% para as associações entre os organosfosforados. Para o teste de larvas a cipermetrina apresentou uma porcentagem de 42,85% de amostras sensível; 14,3% com resistência nível I e 42,85% com resistência nível II. Deltametrina, 50% sensível; 25% com resistência nível II e 25% com resistência nível III. O organofosforado clorpirifós mostrou uma porcentagem de 50% de amostras sensível; 25% com resistência nível I e 25% com resistência nível II. Constatouse, para as duas regiões estudadas, a falta de conhecimento dos principais grupos químicos usados no controle dos carrapatos. O produto amitraz é o mais usado e a maioria das fazendas usam o método de pulverização na aplicação dos carrapaticidas. Experimento realizado no ano de 2001 a 2003 num sítio localizado no município de Ibiúna mostrou que a avaliação de infestação de paternóginas do carrapato B. microplus na área do úbere ou escroto e baixo períneo é um critério que pode ser empregado para se determinar a aplicação de carrapaticidas. Quando se realiza a aplicação de carrapaticidas nos animais infestados com bastante paternóginas diminui a infestação de larvas no campo. Testes de bioensaios, usando fêmeas adultas, realizados num intervalo de três meses, e teste de larvas no período de seis meses servem como orientação para o proprietário na avaliação da sensibilidade dos carrapatos aos produtos químicos / Abstract: The cattle tick - Boophilus microplus (Acari: Ixodidae) ¿ is one of the principal causes of economic losses in the cattle farms in São Paulo state. The current situation of the tick control is characterized by a crisis in the production of new molecules with acaricidal properties and by an increasing in the parasites resistance to the products used to control them. The current study aimed to verifying the sensibility profile of tick B. microplus in farms located in the municipalities of Vale do Ribeira and in the region of Pindamonhangaba, and propose a tick control treatment system based on nymph infestation. The resistance diagnosis tests have been carried by the larval bioassay (Larval packet test), adult immersion test and the survey of the tick control practices applied in both regions. The results for the farms at Pindamonhangaba show that to Cypermethrin 15,4% of the farms were classified as sensible, 7,7% resistance level I, 69,2% resistance level II and 7,7% resistance level III. To deltamethrin 23% were considered sensible, 38,5% Resistance level II, and 38,5% resistance level III. To organophosphate chlorpyriphos 54% presented a sensible frame, 38,4% resistance level I and 7,6% resistance level II. The Vale do Ribeira region presents an average efficacy lower than 20% for all pyrethroids; efficacy between 49% and 72% to associations with pyrethroids and organophosphates; 66,83% to amitraz, and over 90% to organophosphates associations. For the larval test, the cypermethrin presented a percentage of 42,85% from samples sensible; 14,3% resistance level I and 42,85% resistance level II. Deltamethrin, 50% sensible; 25% resistance level II and 25% resistance level III. The organophosphate chlorpyriphos presented a percentage of 50% from samples sensible; 25% resistance level I and 25% resistance level II. It has been proved, that for both regions under this study, there is a lack of knowledge concerning the main chemical groups used in the tick control. The amitraz is the most used and most farms apply the pulverization method when performing the tick control. An experiment taken from 2001 to 2003 in a little farm located in the municipality of Ibiúna has shown the evaluation in the infestation of tick B. microplus in the udder area or escrotum and low perineum is a good criteria to be applied in order to determine the application of anti-ticks. When the application of anti-ticks is undertaken on infested animals full of pathenogens, the field larvae infestation is diminished. Bioassay, using engorged female ticks, undertaken at three months intervals and larval packet test undertaken at six months intervals serve as orientation for the owners for the evaluation of ticks¿ sensibility to the chemical products / Doutorado / Entomologia / Doutor em Parasitologia

Le développement d’un système de détection sensible, sélectif, rapide, fiable et portable à coût modéré est devenu une nécessité pour prévenir le risque chimique lors d’attaques operationnelles ou terroristes potentielles. Ainsi, ce projet porte sur l’élaboration d’un capteur pour la détection d’agents chimiques de guerre de type organophosphorés (Sarin, Tabun, Soman, VX). L’utilisation de microleviers comme capteur pour augmenter la sensibilité est une méthode prometteuse. La surface faible des microleviers conventionnels limite, la sensibilité de la méthode. Ainsi, pour augmenter la surface de capture, nous avons crée un réseau de nanotubes de TiO2 verticalement alignés. Cette nanostructuration est réalisée par une anodisation électrochimique d’une couche de titane pour obtenir les nanotubes de TiO2. L’influence des paramètres du dépôt de titane et de l’anodisation a été optimisée sur des surfaces modèles puis les conditions ont été transferées sur les microleviers. Afin d’augmenter la sélectivité des capteurs (mais aussi la sensibilité) une fonctionnalisation a été réalisée avec une famille originale de ligands bifonctionnels capables de promouvoir la reconnaissance moléculaire des composés organophosphorés cibles et adaptés à la liaison avec une surface de TiO2. / The development of a sensitive, selective, fast, reliable, and moderate cost portable detection system has become a necessity to prevent chemical risk during operational or terrorist attacks. Thus, this project is focused on the elaboration of sensor for the detection of chemical warfare agents (Sarin, Tabun, Soman, VX). The use of microcantilevers as sensors is a promising method to increase sensitivity of detection. The low surface area of conventional microcantilevers limits the sensitivity of the method. Thus, to increase the surface of capture, we create a nanotubular titanium oxide structures. This nanostructuration is performed by anodization of titanium layer to obtain titania nanotubes. The influence of Ti deposition and anodization parameters was studied and the synthesis was optimized onto model surfaces, then beeing transferred to the microcantilevers. In order to increase the selectivity (but also sensitivity) of the sensors functionalization has been carried out with an original family of bifunctional ligands able to promote the molecular recognition of target organophosphorus compounds and suitable for the binding with a TiO2 surface.

Advances in computing capabilities have facilitated the application of quantum mechanical methods to increasingly larger and more complex chemical systems, including weakly interacting and biologically relevant species. One such ab initio-based composite methodology, the correlation consistent composite approach (ccCA), has been shown to be reliable for the prediction of enthalpies of formation and reaction energies of main group species in the gas phase to within 1 kcal mol-1, on average, of well-established experiment, without dependence on experimental parameterization or empirical corrections. In this collection of work, ccCA has been utilized to determine the proton affinities of deoxyribonucleosides within an ONIOM framework (ONIOM-ccCA) and to predict accurate enthalpies of formation for organophosphorus compounds. Despite the complexity of these systems, ccCA is shown to result in enthalpies of formation to within ~2 kcal mol-1 of experiment and predict reliable reaction energies for systems with little to no experimental data. New applications for the ccCA method have also been introduced, expanding the utility of ccCA to solvated systems and complexes with significant noncovalent interactions. By incorporating the SMD solvation model into the ccCA formulation, the Solv-ccCA method is able to predict the pKa values of nitrogen systems to within 0.7 pKa unit (less than 1.0 kcal mol-1), overall. A hydrogen bonding constant has also been developed for use with weakly interacting dimers and small cluster compounds, resulting in ccCA interaction energies for water clusters and dimers of the S66 set to within 1.0 kcal mol-1 of well-established theoretical values.

Effects of developmental exposure to chlorpyrifos (CPS) or methyl parathion (MPS) on visuospatial, adaptive fear response, and passive avoidance memory and the signaling mechanisms responsible for these neurocognitive changes were investigated. Using an incremental low dose regimen, rat pups were orally gavaged daily with either corn oil (vehicle), CPS, or MPS from postnatal day 1 (PND1) -PND21. Cholinesterase activity was significantly inhibited with the highest dosages of CPS and MPS for up to 19 days after the last dosages. OP exposure impaired working and reference memory in males whereas in the females, enhancement occurred following CPS exposure. In addition, the adaptive fear response and passive avoidance retention memory was impaired in males whereas differential changes occurred in females. Accordingly, the behavioral deficits observed in males were persistent whereas the enhancement in females was transient. Males were more sensitive to OPs than females in that the medium and high dosages of CPS and MPS produced greater effects in females whereas all dosages of both compounds produced effects in males. Training in the radial arm maze significantly increased protein kinase C gamma (PKC ) expression and activity in the hippocampal membrane fraction of control rats whereas exposure to OPs exhibited a significant decrease in PKC and PKC immunoreactivity in both untrained and trained rats. However, MPS exposed females exhibited a significant increase in PKC expression in the cytosolic fraction but this was not related to improved memory. Reduction of membrane PKC expression and activity and cytosolic PKC expression and activity seemed to be related to visuospatial learning and memory deficits in exposed males but not exposed females. Brain-derived neurotrophic factor (BDNF) gene expression in the hippocampus was significantly increased (60%) in trained control males as compared to untrained control males. In contrast, trained and untrained females exhibited similar levels of BDNF gene expression. However, exposure of both sexes to either CPS or MPS significantly reduced the expression of BDNF in trained rats. In summary, these data indicate that OP exposure induced gender-specific changes in working memory formation and altered PKC isozyme levels/activity and BDNF expression.