The research undertaken in this study is an attempt to determine the influence of farm advisory services, socio-economic factors, and physical factors on the aggregate toxicity of pesticides used by cotton and peanut farmers in the Albemarle-Pamlico Watershed of Virginia and North Carolina. An aggregate toxicity index is developed for all pesticides used on each farm site. Four different types of farm advisors are considered in this study, namely, hired staff, university and state extension agents, chemical dealers, and scouting personnel. Regression analysis is used to estimate how the aggregate toxicity index and the aggregate pesticide expenditures were affected by farmers' choice of the most important farm advisory services; the farmer's age, education, and farming experience; productivity of the soil; soil erosion index; distance of farm from nearest water source; and the state in which the farm was located. The results of this study indicate that hired staff, scouting personnel, and extension agents are associated with higher aggregate toxicity of pesticides on cotton farms, while scouting personnel and chemical dealers are associated with higher aggregate toxicity of pesticides on peanut farms. More years of farming experience is associated with a slight decrease in aggregate toxicity on cotton farms. Increasing age of farmers is associated with a slight increase in aggregate toxicity on peanut farms. Training of farm advisors should include information about potential environmental damage from alternative pesticides. Advisors should be informed about the effects of soil physical characteristics on potential for environmental damage from pesticide use. Farm advisors should also be trained in methods to disseminate information to farmers on pesticide toxicity to the environment. More information on pesticide toxicity could also be publicized on pesticide packages. Continued research on less toxic pesticides and alternative pesticides is also an important strategy to reduce pesticide toxicity. / Master of Science

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The aim of this study was to evaluate the effect of cadusafos and Fluensulfone nematicides applied at three different depths and positions in the soybean planting in furrow, in order to control Meloidogyne javanica, Pratylenchus brachyurus end Heterodera glycines. The experiments were cared out in the field naturally infested by nematodes, Júlio de Castilhos city - RS. It was nine treatments and five replications in a randomized block design, totaling 45 experimental units per experiment. The treatments were: 1 check treatment; 2 - position 1 (nozzle installed on the upper furrower); 3 - Position 2 (nozzle installed at the bottom of the open furrow); 4 - Position 3 (nozzle installed in the distribution disc of seeds); 5 - Positions 1 and 2 associates; 6 - The positions 2 and 3 associates; 7 - Positions 1 and 3 associates; 8 Full seed treatment by Avicta completo (abamectin (30 g ai.ha-1) + thiamethoxam (42 g ai.ha-1) + fludioxonil (1.5 g ai.ha-1) + metalaxyl-M (1.2 g ai.ha-1 ) + thiabendazole (9 g ai.ha-1) and 9 - position 1 and Avicta completo treatment seeds associated. The variables measured in the experiment were: number of nematodes in the soil, number of nematodes on the roots, shoot dry weight, plant height (pre-harvest); number of pods per plant and Yield. The results showed significant reduction in the population of nematodes in the both soil and the roots, regardless of the nematicide. For the deposition positions in soil, the responses were vary according to the species of nematodes in the soil. / O objetivo do presente trabalho foi avaliar o efeito dos nematicidas Fluensulfone e Cadusafós aplicados no sulco de semeadura da soja, em três diferentes profundidades no solo para o controle de Meloidogyne javanica, Pratylenchus brachyurus e Heterodera glycines. Os experimentos foram conduzidos a campo, no município de Júlio de Castilhos RS, em área comercial de soja naturalmente infestada. Os tratamentos foram dispostos no delineamento de blocos ao acaso, contendo nove tratamentos e cinco repetições, totalizando 45 unidades experimentais por experimentos. Os tratamentos foram: 1 - Testemunha sem produto; 2 - Posição 1 (Ponta instalada na parte superior do sulcador); 3 - Posição 2 (Ponta instalada na parte inferior do sulcador); 4 - Posição 3 (Ponta instalada na haste do disco de distribuição das sementes) 5 - As pontas 1 e 2 associadas; 6 - As pontas 2 e 3 associadas; 7 - As pontas 1 e 3 associadas; 8 - Tratamento de semente com Avicta completo (abamectina + tiametoxam + fludioxonil + metalaxil-M + tiabendazol - 30 + 42 + 1,5 + 1,2 + 9 g de i.a./ha) e 9 - A ponta 1 associada ao tratamento de semente com Avicta completo. As variáveis resposta medidas no experimento foram: número de nematoides presentes no solo, aos 30 dias após a emergência (D.A.E.); número de nematoides nas raízes (30 D.A.E.); massa seca de parte aérea (MSPA), aos 30 DAE; estatura de plantas (Pré-colheita); número de legumes por planta e produtividade. Os resultados mostraram que houve redução significativa na população dos nematoides, tanto no solo quanto nas raízes, independente do nematicida aplicado. No entanto, foram observadas diferentes respostas de controle em função dos pontos de deposição dos nematicidas no solo.

A epilepsia é uma patologia que afeta 50 milhões de pessoas, sendo que cerca de 30% dos pacientes apresentam epilepsia refratária, ou seja, não respondem a terapia medicamentosa disponível. Portanto, é necessária a busca contínua de novos fármacos. Os complexos organometálicos vêm ao encontro a esta necessidade conjugando moléculas já aplicadas na terapia (como o ácido valproico), a metais essenciais e outros ligantes a fim de aprimorar os efeitos farmacológicos. Neste trabalho foram testados quatro complexos derivados do ácido valproico: [Cu(Valp)2Fen] , [Cu(Valp)2Bipi], [Zn(Valp)2Fen] e [Zn(Valp)2Bipi], através do screening toxicológico embrionário e atividade anticonvulsivante em zebrafish induzidos por pentilenotetrazol (PTZ). O complexo [Cu(Valp)2Bipi] apresentou maior toxicidade embrionária (CL50=0.12 μM), seguido pelo [Zn(Valp)2Bipi] (CL50 = 10μM). Estes mesmo complexos nas doses de 10 mM/Kg, 30 mM/Kg e 100 mM/Kg para derivado contendo zinco a intensidade das convulsões em relação ao valproato de sódio (175 mM/Kg) em peixes adultos, demonstrando ação superior ao fármaco tradicional. Devido a baixa toxicidade aliada a ação anticonvulsivante evidente selecionamos o derivado [Zn(Valp)2Bipi] para estudos futuros em modelos complexos de epilepsia. / Submitted by Ana Guimarães Pereira (agpereir@ucs.br) on 2016-04-29T13:43:16Z No. of bitstreams: 1 Dissertacao Lauren Dockhorn Grunspan.pdf: 2281256 bytes, checksum: 5ed8d708e6f55d2418086df48fc4f6ac (MD5) / Made available in DSpace on 2016-04-29T13:43:16Z (GMT). No. of bitstreams: 1 Dissertacao Lauren Dockhorn Grunspan.pdf: 2281256 bytes, checksum: 5ed8d708e6f55d2418086df48fc4f6ac (MD5) Previous issue date: 2016-04-27 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES / The most important determinant of quality of life in patients with epilepsy is complete seizure control, and therefore this should be the ultimate goal of pharmacological therapy. Unfortunately, around 30% of epileptic patients still suffer with refractory epilepsy. Metal ions have been frequently incorporated into pharmaceuticals for therapeutic or diagnostic purposes and the research. In this study, we access the embryo toxicity and anticonvulsant activity of 4 novel metallodrugs, with Zn+2 and Cu+2, derivative with valproic acid and the N-donor ligand in adult zebrafish pentylenetetrazole epileptic seizure model. [Cu(Valp)2Bipy] LC50 in 48 Hours Post Fertilization (hpf) was 0.22 μM and 0.12 μM in 96 hpf followed by [Zn(Valp)2Bipy] (LC50 = 10 μM). This same metallodrugs ([CuValp)2Bipi] 10 mM/Kg and [Zn(Valp)2Bipi] 30 mM and 100 mM/Kg) displayed a superior activity reducing the seizure intensity compared to Sodium Valproate (175 mM/Kg). As conclusion, among all, the [Cu(Valp)2Bipi] showed the best anticonvulsant effects, but due to its toxic effects on embryos and larvae, the [Zn(Valp)2Bipi] should be considered the most promising for future studies as anticonvulsant drug.

A epilepsia é uma patologia que afeta 50 milhões de pessoas, sendo que cerca de 30% dos pacientes apresentam epilepsia refratária, ou seja, não respondem a terapia medicamentosa disponível. Portanto, é necessária a busca contínua de novos fármacos. Os complexos organometálicos vêm ao encontro a esta necessidade conjugando moléculas já aplicadas na terapia (como o ácido valproico), a metais essenciais e outros ligantes a fim de aprimorar os efeitos farmacológicos. Neste trabalho foram testados quatro complexos derivados do ácido valproico: [Cu(Valp)2Fen] , [Cu(Valp)2Bipi], [Zn(Valp)2Fen] e [Zn(Valp)2Bipi], através do screening toxicológico embrionário e atividade anticonvulsivante em zebrafish induzidos por pentilenotetrazol (PTZ). O complexo [Cu(Valp)2Bipi] apresentou maior toxicidade embrionária (CL50=0.12 μM), seguido pelo [Zn(Valp)2Bipi] (CL50 = 10μM). Estes mesmo complexos nas doses de 10 mM/Kg, 30 mM/Kg e 100 mM/Kg para derivado contendo zinco a intensidade das convulsões em relação ao valproato de sódio (175 mM/Kg) em peixes adultos, demonstrando ação superior ao fármaco tradicional. Devido a baixa toxicidade aliada a ação anticonvulsivante evidente selecionamos o derivado [Zn(Valp)2Bipi] para estudos futuros em modelos complexos de epilepsia. / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES / The most important determinant of quality of life in patients with epilepsy is complete seizure control, and therefore this should be the ultimate goal of pharmacological therapy. Unfortunately, around 30% of epileptic patients still suffer with refractory epilepsy. Metal ions have been frequently incorporated into pharmaceuticals for therapeutic or diagnostic purposes and the research. In this study, we access the embryo toxicity and anticonvulsant activity of 4 novel metallodrugs, with Zn+2 and Cu+2, derivative with valproic acid and the N-donor ligand in adult zebrafish pentylenetetrazole epileptic seizure model. [Cu(Valp)2Bipy] LC50 in 48 Hours Post Fertilization (hpf) was 0.22 μM and 0.12 μM in 96 hpf followed by [Zn(Valp)2Bipy] (LC50 = 10 μM). This same metallodrugs ([CuValp)2Bipi] 10 mM/Kg and [Zn(Valp)2Bipi] 30 mM and 100 mM/Kg) displayed a superior activity reducing the seizure intensity compared to Sodium Valproate (175 mM/Kg). As conclusion, among all, the [Cu(Valp)2Bipi] showed the best anticonvulsant effects, but due to its toxic effects on embryos and larvae, the [Zn(Valp)2Bipi] should be considered the most promising for future studies as anticonvulsant drug.

Thesis (M.Pharm. (Pharmacy Practice))---North-West University, Potchefstroom Campus, 2008.

Thesis (M.Pharm. (Pharmacy Practice))---North-West University, Potchefstroom Campus, 2008.

Thesis (M.Pharm. (Pharmacy Practice))---North-West University, Potchefstroom Campus, 2008.

Ces travaux visent à déterminer l‘intérêt de deux types de nanosystèmes (NS) coeur-couronne dans des applications dermatologiques ou cosmétiques. Les nanocapsules lipidiques (LNC) sont obtenues par une méthode déjà décrite dans la littérature. Leur formule est modifiée pour incorporer un actif cosmétique d‘intérêt. Les nanocapsules d‘alginate (ANC) sont développées au moyen de plans d‘expériences. Elles sont composées d‘un coeur huileux et d‘une coque d‘alginate de calcium gélifiée obtenue par gélification ionique de surface d‘une nanoémulsion. Des méthodes basées sur le phénomène de fluorescence nous permettent de mettre en évidence l‘endocytose des ANC par les kératinocytes. Leur contenu est rapidement libéré dans le cytoplasme. Une étude sur différents modèles ex vivo montre que les deux nanosystèmes permettent aux molécules encapsulées d‘atteindre les couches vivantes de l‘épiderme. ANC et LNC sont stables plusieurs mois dispersées dans des formes galéniques semi-solides. Ces deux NS sont donc adaptés à la délivrance de molécules actives dans la peau. / Two types of core-shell nanosystems have been evaluated for dermatological and cosmetic applications. Lipid nanocapsules (LNC) are obtained by a method that has already been described in the literature. Their composition is adapted for incorporation of a specific cosmetic ingredient. Alginate nanocapsules (ANC) are developed with the aid of experimental design. They consist of a triglyceride core with a rigid calcium alginate shell obtained by ionic gelation of the surface of a nanoemulsion. By incorporating fluorophores into these nanosystems, they can be studied by advanced spectral fluorescence imaging methods. We were thus able to show that ANC are first internalized into keratinocytes by endocytosis, and once inside the cells, their contents are rapidly released into the cytoplasm. A study of different ex vivo skin model systems has shown that both nanosystems enable active substances to reach the living epidermis. When incorporated into gels similar to those used as galenic forms for topical administration, LNC and ANC remain stable for months. They can thus be used as vectors for delivering active substances to the skin.

Ce travail a eu pour objectif la conception de nouveau matériaux à base de polysaccharide pour la libération contrôlée de principes actifs et pour d'éventuelles applications environnementales. Pour cela, des gels ont été préparés par réticulation du carboxymethylepullulane CMP et du pullulane interpénétré par l’alginate avec le sodium trimétaphosphate STMP. Les hydrogels obtenus ont été caractérisés et leurs propriétés physico-chimiques et rhéologiques ont été investiguées. La séquestration de principes actifs modèles dans les hydrogels a été réalisée par regonflement des gels dans une solution de bleu de méthylène BM ou par dispersion de la 3- aminopyridine 3AP à l’intérieur des gels. L'’influence des différents paramètres comme la nature du gel, le taux d’agent réticulant et le pH sur la libération des principes actifs a permis de conclure sur la performance des gels comme matrice à libération contrôlée. D'autre part, ces hydrogels de morphologies différentes se sont révélés être des adsorbants prometteurs, les tests sur le BM servant dans ce cas comme polluant modèle ont montré des capacités d'adsorption plus de 1000 mg/g pour les gels à base de CMP et de 500 mg/g pour les gels Pullulane/alginate. Les capacités d'adsorption étaient sensibles à la quantité du STMP, au degré de substitution du CMP et aux variations du pH. Les résultats expérimentaux étaient bien modélisés par une équation cinétique de pseudo-second ordre et l'isotherme de Freundlich décrivait d'une manière satisfaisante le phénomène. / This work has aimed at the design of new polysaccharide-based materials for the controlled release of active ingredients and for possible environmental applications. For this, gels were prepared by crosslinking the carboxymethylpullulan CMP and the pullulan interpenetrated by the alginate with the sodium trimetaphosphate STMP. The hydrogels obtained were characterized and their physicochemical and rheological properties were investigated. The sequestration of model active ingredient in the hydrogels was carried out by re-inflation gels in a solution of BM or dispersion of 3AP within the gels. The influence of the various parameters such as the nature of the gel, the level of crosslinking agent and the pH on the release of the active ingredients made it possible to conclude on the performance of the gels as a controlled-release matrix. On the other hand, these hydrogels of different morphologies have proved to be promising adsorbents, the tests on the BM used in this case as a model pollutant showed an adsorption capacity of more than 1000 mg / g for CMP-based gels and 500 mg / g for Pullulane / alginate gels. Absorption capacities were sensitive to the amount of SMTP, the degree of CMP substitution, and pH changes. The experimental results were well modeled by a pseudo-second order kinetic equation and the Freundlich isotherm satisfactorily described the phenomenon.

<div> <div> <p>Continuous flow chemistry for organic synthesis is an emerging technique in academia and industry because of its exceptional heat and mass transfer ability and, in turn, higher productivity in smaller reactor volumes. Preparative electrospray (ES) is a technique that exploits reactions in charged microdroplets that seeks to accelerate chemical synthesis. In Chapter 2, the flow synthesis of atropine, a drug which is included in the WHO list of essential of medicines and currently in shortage according to the U.S Food and Drug Administration (FDA)is reported.The two steps of atropine synthesis were initially optimized separately and then continuously synthesized using two microfluidic chips under individually optimized condition.The telescoped continuous-flow microfluidics experiment gave a 55% conversion with an average of 34% yield in 8 min residence time. In Chapter 3, a robotic HTE technique to execute reactions in 96-well arrays was coupled with fast MS analysis. Palladium-catalyzed Suzuki-Miyaura (S-M) cross-coupling reactions were screened in this system and a heat map was generated to identify the best reaction condition for downstream scale up in continuous flow. <br></p><p><br></p><p>In Chapter 4, an inexpensive and rapid synthesis of an old anticancer drug, lomustine,was synthesized. Using only four inexpensive commercially available starting materials and a total residence time of 9 min, lomustine was prepared via a linear sequence of two chemical reactions performed separately in two telescoped flow reactors. Sequential offline extraction and filtration resulted in 63% overall yield of pure lomustine at a production rate of 110 mg/h. The primary advantage of this approach lies in the rapid manufacture of lomustine with two telescoped steps to avoid isolation and purification of a labile intermediate, thereby decreasing the production cost significantly. A high throughput reaction screening approach based on desorption electrospray ionization mass spectrometry (DESI-MS) is described in Chapter 4 and 5 for finding the heat-map from a set of reaction conditions. DESI-MS is used to quickly explore a large number of reaction conditions and guide the efficient translation of optimized conditions to continuous flow synthesis that potentially accelerate the process of reaction optimization and discovery. Chapter 5 described HTE ofSNAr reactions using DESI-MS and bulk techniques with 1536 unique reaction conditions explored using both in DESI-MS and bulk reactors. The hotspots from the HTE screening effort were validated using a microfluidic system that confirmed the conditions as true positives or true.<br></p> </div> </div>