Thesis (Ph. D.)--Ohio State University, 2006. / Title from first page of PDF file. Includes bibliographical references (p. 211-219).

The synthesis and characterization of simple mimics of pore forming antibiotics such as amphotericin B were explored. A sub-unit approach to the synthesis was employed which allowed for construction of a set of candidate structures. The targets are assembled by joining two "wall" units via a "linkage" unit with subsequent addition of polar head groups to either end of the structure. The wall units are macrocyclic diene tetraesters derived from maleic anhydride prepared by either acid catalyzed ester formation from diols or carboxylate substitution of dihalides (compounds 14, 15, 22, 23, 24, 30, 31, 34). Either set of reaction conditions limit the range of functionality possible in the starting diol or dihalide. Macrocycles 22, 23, and 24 were linked with m-xylylene dithiol via a 2:1 Michael addition reaction to give bis-macrocyclic alkene precursors. Alternatively, macrocycles 22 and 23 reacted with 3-thio-1-propanol and the mono-alcohol products were converted to iodides which were linked with 2R,3R-(+)-tartaric acid. Three types of polar head groups--neutral (1-thio-β-D-glucose and 3-thio-1-propanol), cationic (2-aminoethanethiol), and anionic (2-thioacetic acid)--were added to the bis-macrocyclic alkene precursors via Michael addition reactions. A total of fourteen candidate structures were prepared for transport evaluation. The activity of the fourteen mimics synthesized were determined by the pH-stat technique in which the transport of alkali metal cations across large unilamellar lipid bilayer vesicles were monitored by the collapse of a proton gradient. All the active compounds showed a zero order decay in proton gradient. Of the fourteen mimics surveyed, three had activities comparable to amphotericin B (compounds 51, 52, and 59). The other eleven compounds were not sufficiently active for further characterization. The "add back" experiments, the kinetic orders, and the alkali metal ion selectivity studies are consistent with the proposal that the mimics behave as pore formers. / Graduate

A produção brasileira de alimentos cresce em ritmo vertiginoso, havendo previsão de expansão nos próximos anos. Nota-se, porém, que o modelo atual empregado ao controle de doenças e pragas agrícolas, tem causado diversos problemas de ordem ambiental, social e econômica. Uma alternativa à redução de tais impactos, tem sido a implementação do controle biológico no modelo de manejo. Neste trabalho, avaliou-se o controle biológico do fungo fitopatogênico Botrytis cinerea por compostos produzidos pela linhagem ASBV-1T. Os screenings \"in vitro\" demonstraram que a linhagem produz quitinases e metabólitos secundários ativos, conhecidamente descritos como fatores importantes ao controle de fitopatógenos. A caracterização parcial do complexo enzimático, indicou que as quitinases produzidas pela linhagem ASBV-1T apresentam maior atividade em meio alcalino (pH 6.8-10.0), temperatura de 30°C e possuem estimativa de peso molecular superior a 100 kDa. Os ensaios \"in vivo\", realizados em morangos comerciais (cv. Oso Grande) demonstraram a efetividade dos subprodutos bioativos de caráter ionóforos (monactina, dinactina, trinactina, tetranactina e valinomicina) em controlar a infestação de B. cinerea, durante a fase de pós-colheita, em condições de armazenamento. Por meio da suplementação do meio de cultivo por sais inorgânicos, a via biossintética responsável pela expressão dos compostos de interesse pode ser ativada. A adição de MgS04 resultou em um aumento de 400% na produção de macrotetralídeos e 20% de valinomicina. Contudo, a expressão dos macrotetralídeos foi completamente inibida pela adição de ZnSO4. dobrando a produção de valinomicina. De acordo com os estudos de taxonomia polifasica, o isolado ASBV-1T, apresenta caracteristicas quimiotaxonômicos e moleculares pertinentes ao gênero Streptomyces, formando uma nova linha filética, no subclado das espécies S. albolongus, S. cavourensis subsp. cavourensis e S. celluloflavus. Diante do supra citado, propõem-se que o isolado seja reconhecido como a linhagem tipo de Streptomyces araujoniae sp. nov. Os resultados obtidos neste trabalho, permitem afirmar que a linhagem S. araujoniae sp. nov. apresenta potencial de ação contra o fitopatógeno B. cinerea, podendo auxiliar no controle desta doença durante a fase de pós-colheita da cultura de morangos. Ainda resta, para estudos futuros, o desenvolvimento de formulação específica para o emprego destes compostos no manejo da cultura, bem como ensaios toxicológicos, assegurando a viabilidade de aplicação de tais compostos. / The Brazilian food production has been growing fast in recent years and is expected to expand even more. However, the models used for the control of pests and diseases in agriculture has been widely questioned because they cause problems of environmental, social and economic. To reducing the use of chemical agents, has been the implementation of biological control to the management model to reduce this problematic. In this study, we evaluated the biological control of fungal pathogen Botrytis cinera of active compounds produced by strain ASBV-1T. In vitro assays indicated the presence of chitinase and antifungal metabolites in compounds produced by strain ASBV-1T and may been contributed to the antagonistic activity againts the fungal pathogenic. Partial characterization of the enzymatic complex showed the highest production of chitinase under alkalines conditions at pH (6.8-10.0), 30°C and has estimated molecular weight above 100 kDa. The test in vivo, preformed in commercial strawberries (cv. Oso Grande) demonstrated the effectiveness of bioactive products of character ionophores (monoactin, dinactin, trinactin, tetranactin and valinomycin) controlling the infestation of B. cinerea during the post-harvest, in store conditions. The biosynthetic pathway responsible for the expression of the compounds of interest can be activated by supplementations of the culture medium by inorganic salts mainly with MgSO4 resulted in increse of 400% in the production of macrotetralides and 20% valinomycin. However, the expression of the macrotetralides was inhibited when added ZnSO4, bending the production of valinomycin. According to polyphasic taxonomic studies, the isolated ASBV-1T has chemotaxonomic and molecular characteristics of the genus Streptomyces, which formed a new phyletic line, in subcalde of the S. albolongus, S. cavourensis subsp. cavourensis e S. celluloflavus species. Then propose that the isolate is recognized as the type strain of Streptomyces araujoniae sp. nov. The results obtained in this study revealed that S. araujoniae sp. nov. has action potential against the pathogen B. cinerea, can help control this disease during the post-harvest strawberries. Remains for future studies, the development of specific formulation of the employment of such compounds to crop management and toxicological tests, ensuring the feasibility of using such compounds.

Improvements to broiler production can be made through the means of nutrition and preventative health care. Formulating diets based on a digestible amino acid (AA) basis decreases feed cost and improves bird performance by providing a more accurate diet based on the bird’s specific production or age nutrient requirements. The apparent ileal amino acid digestibility (AIAAD) assay utilized in Experiment 1 demonstrated inconsistent results for age effects on AIAAD of an animal by-product blends for specific AA or age. Increasing pathogenic resistance and consumer’s push on the market, has caused integrators to incorporate alternative medications or inclusion strategies to coccidiosis management. Experiment 2 demonstrated diets containing virginiamycin, with an inclusion of salinomycin during d 14-28 only, decreased lesion scores and improved performance of birds receiving an increased dose of live coccidiosis vaccine. In Experiment 3, birds fed diets utilizing an ionophore regimen and additional algal beta-glucan demonstrated improved live performance.

No description available.

Three experiments were conducted to examine the effects of an ionophore, monensin sodium, on digestion in sheep. The first experiment was concerning alterations induced by long-term supplementation and subsequent withdrawal of the ionophore. The diet was a pelleted mixture of 43% native prairie hay, 34% corn grain, and 21% lupin grain plus 100 g wheat straw. Monensin (33 ppm) was added to the diet of four wethers, and four other animals served as controls and consumed an identical diet. without monensin. Monensin supplementation increased (P <.05) ruminal propionate while decreasing (P <.05) acetate levels throughout the 146-d experiment. Withdrawal caused acetate to return to control levels but decreased (P <.05) propionate. During ionophore supplementation, the digestibilities of organic matter (OM) and dry matter (DM) were increased (P <.05) by an average of 8 and 9%, respectively. Apparent digestibility ' of N was increased from 75 to 77% after 19 d of supplementation. There was an augmentation (P <.05) in the flow of bacterial N at the duodenum after 96 d of supplementation. This effect disappeared with ionophore withdrawal. In a second experiment, the effect of monensin on postruminal digestion was examined in three trials with six wethers. There were three treatments: control, dietary monensin, and monensin infused into the duodenum. The diets were the same as in the previous experiment. Dietary monensin caused the same changes in ruminal VFA as in the previous experiment. Infused monensin had no effect on VFA. Dietary monensin increased (P <.05) trypsin activity at the ileum. Dietary ionophore did not alter nutrient digestibilities, but shifted (P <.O5) the site of OM and DM digestion from the cecum to before the terminal ileum by 14 and 10%, respectively. In an in vitro experiment rumen contents from monensin-adapted and nonadapted sheep were compared with and without additional ionophore in a 6 h incubation system. Rumen contents from adapted sheep did not differ from contents of nonadapted sheep in the quantity of microbial N synthesized. With monensin addition to the incubation, microbial synthesis dropped by 49% in nonadapted microorganisms. In adapted contents, the decrease in synthesis was only 9%. Monensin-adapted microbes degraded (P <.O1) more protein substrate than those which were not adapted. / Ph. D. / incomplete_metadata

L’objectif de cette thèse, réalisée en collaboration avec la société Mérial, concerne la santé animale et s’oriente vers la synthèse de molécules actives à visée préventive ou thérapeutique. Deux sujets distincts sont abordés. Dans un premier temps, le but recherché est la synthèse d’une série de molécules présentant une activité anti-coccidienne pour le traitement préventif des poulets. Quarante-trois composés originaux, issus d’une synthèse courte à deux ou trois étapes, ont été préparés par hémi-synthèse de la monensine. Quinze molécules ont été testées in vitro et trois d’entre elles montrent une activité importante vis-à-vis du parasite Eimeria tenella. Dans un second temps, nous nous sommes intéressés à la synthèse de nouveaux répulsifs pour un large panel d’insectes. Après avoir fait une étude bibliographique approfondie, nos recherches se sont concentrées sur la réactivité de la coumarine. Environ soixante-dix molécules ont été synthétisées par modifications fonctionnelles des 4-, 6- et 7- hydroxycoumarines et de la coumarine. La grande majorité a été testée en présence de drosophiles. Six molécules présentant une activité répulsive équivalente à celle du DEET, produit de référence, ont été identifiées / This thesis was completed in collaboration with the Animal Health Company Merial. The objective of the thesis is the synthesis of preventive and therapeutic bioactive molecules. Two separate subjects were treated. First, the aim was the synthesis of a series of molecules having an anticoccidial activity for the preventive treatment of chickens. Forty-three original compounds, issued from a short synthesis with two or three steps, were prepared from monensin by hemi-synthesis. Among them, fifteen were tested in vitro and three of them showed a significant activity against Eimeria tenella. Thereafter, we have worked on the synthesis of new repellents for a wide range of insects. After a comprehensive bibliographic study, our research was focused on the coumarin reactivity. More than seventy molecules were synthesized by structural modifications of 4-, 6- and 7-hydroxycoumarins and of coumarin. Almost all the compounds were tested in the presence of drosophila. Six molecules showing a repellent activity equivalent to DEET, used as a reference product, were identified

A series of bicyclic peptides have been designed and synthesized to provide ammonium ion complexation sites via hydrogen bonding in a tetrahedral geometry. Molecular modeling dynamics and electrostatics studies indicate that target compounds 1d-6d may provide better selectivity for ammonium ions over potassium ions than the ammonium ionophore currently used for blood analysis applications, nonactin. Attempts to synthesize 1d, cyclo(L-Glu1�D-Val2�L-Ala3�D-Lys4�D-Val5�L-Val6)-cyclo-(1ã-4å), were unsuccessful due to poor solubility of the synthetic intermediates. This led to the design of 2d-6d in which specific amino acid residues were chosen to provide higher solubility. Compound 2d, cyclo(L-Glu1�D-Ala2�D-Ala3�L-Lys4�D-Ala5�L-Ala6)-cyclo-(1ã-4å), was successfully synthesized, but was also too insoluble for characterization or testing in an ion selective electrode (ISE) sensor format. Compound 6d, cyclo(L-Glu1�D-Leu2�Aib3�L-Lys4�D-Leu5�D-Ala6)-cyclo-(1ã-4å), was successfully synthesized and characterized. When 6d was incorporated into an ISE sensor and tested as an ammonium ionophore, results indicated that the bicyclic peptide lacked solubility in the ISE membrane. A 13C-NMR study has been initiated in order to evaluate selectivity of 6d for ammonium over potassium and sodium cations in solution. Preliminary results with the potassium ionophore valinomycin as a control have been completed.

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No. of bitstreams: 2 Tese - Barbara Juliana Martins Lemos - 2016.pdf: 959267 bytes, checksum: 9f20cc6866e6ccdd38204d892b61882f (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2016-03-09 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The objective of this study was evaluate the effects of antimicrobial feed additives and inclusion of pelleted sugarcane crop residue (SCR) as a fiber source in whole shelled corn (WSC)-based finishing diets (85% WSC + 15% pelleted concentrate, DM basis) on growth performance, nutrients digestibility, rumen fermentation and eating behavior of zebu cattle. Growth performance trials were conducted in randomized block design, and metabolical trials were conducted in Latin Square design using ruminally fistulated steers. In the antimicrobial feed additives studies, 100 bulls were fed for 101 d in Exp. 1 to evaluate the treatments M30 (30 mg of monensin [M]/kg DM), V25 (25 mg of virginiamycin [V]/kg DM), M20V25 (M 20 mg/kg DM + V 25 mg/kg DM), F4 (4.4 mg of flavomycin [F]/kg DM), and M20F2 (M 20 mg/kg DM + F 2.2 mg/kg DM); and in the Exp. 2 (Latin Square 7 × 7) were evaluate the same 5 treatments of Exp. 1 plus 2 additional treatments: M30V25 (M 30 mg/kg DM + V25 mg/kg DM) and M20F4 (M 20 mg/kg DM + F 4.4 mg/kg DM). In the SCR studies, 80 bulls were fed diets with 0, 3, 6, and 9% SCR (DM basis; SCR-0, SCR-3, SCR-6, and SCR-9, respectively) for 103 d in Exp. 1; and in the Exp. 2 (5 × 5 Latin Square) were evaluated the inclusion of 0, 3, 6, 9 and 12% of SCR (DM basis; SCR-0, SCR-3, SCR-6, SCR-9, and SCR-12, respectively). In the antimicrobial feed additives studies growth performance (final BW, ADG in live weight basis, DMI, and G:F), carcass characteristics (HCW, ADG in carcass basis, carcass transfer, dressing percent, and 12th-rib-fat), apparent total tract DM, OM, CP, and NDF digestibility were similar among treatments. There were no treatment effects and no interaction of treatment × time in rumen fermentation responses (ruminal pH, rumen ammonia nitrogen, number of protozoa, and VFA). In the WSC study, inclusion of SCR linearly increased daily DMI up to 25% (P = 0.01). Dry matter intake, as percentage of BW, increased (P = 0.01) 0.06 percentage units with each 1% inclusion of SCR. Over the entire finishing period (d 0 to 103), there were trends for linearly increase final BW up to 3.3% (P = 0.10), and ADG up to 10.7% (P = 0.07) in response to dietary SCR levels, consequentially G:F tended (P = 0.07) to linearly decrease up to 10.2% with inclusion of SCR compared with CTL diet. Apparent total tract digestibility linearly decreased (P < 0.01) 30% for DM, 28% for OM, 45% for CP, and 61% for NDF, from CTL for SCR-12. No treatment effect and no interaction of treatment × time were observed on ruminal pH, concentrations of rumen ammonia nitrogen and VFA. Time spent eating, eating rate, and meal frequency were not affected by inclusion of SCR up to 12%. There was a quadratic response on meal size (P = 0.04). In summary, feeding isolated or combined antimicrobial feed additives to zebu cattle resulted in similar responses. Pelleted SCR seemed to be low fermentable and non-effective to stimulate rumination by cattle fed WSC-based finishing diet. / Objetivou-se avaliar os efeitos de aditivos antimicrobianos e a inclusão do resíduo peletizado da cultura de cana de açúcar (SCR) como fonte de fibra em dietas com milho grão inteiro (WSC; 85% WSC + 15% concentrado peletizado) sobre o desempenho, digestibilidade dos nutrientes, fermentação ruminal e comportamento ingestivo de novilhos zebuínos. Os experimentos de desempenho foram conduzidos em delineamento de blocos cazualizados e experimentos de metabolismo foram conduzidos em delineamento em Quadrado Latino usando novilhos castrados fistulados no rúmen. No estudo de aditivos antimicrobianos, no Exp. 1 foram utilizados 100 novilhos não castrados alimentados durante 101 dias para avaliar os tratamentos M30 (30 mg de monensina [M]/kg de DM), V25 (25 mg de virginiamicina [V]/kg de DM), M20V25 (M 20 mg/kg DM + V 25 mg/kg DM), F4 (4.4 mg de flavomicina [F] /kg de DM), e M20F2 (M 20 mg/kg DM + F 2.2 mg/kg DM); no Exp. 2 (Quadrado Latino 7 × 7) foram estudados os mesmos 5 tratamentos do Exp. 1 mais 2 tratamentos adicionais: M30V25 (M 30 mg/kg DM + V25 mg/kg DM) e M20F4 (M 20 mg/kg DM + F 4.4 mg/kg DM). Nos estudos com SCR, 80 novilhos não castrados foram alimentados com dietas contendo 0, 3, 6 e 9% de SCR (base de DM; SCR-0, SCR-3, SCR-6 e SCR-9, respectivamente) durante 103 dias; no Exp. 2 (Quadrado Latino 5 × 5) foram avaliadas inclusões de 0, 3, 6, 9 e 12% de SCR (base de DM; SCR-0, SCR-3, SCR-6, SCR-9 e SCR-12, respectivamente). Nos estudos com aditivos antimicrobianos, o desempenho (final BW, ADG em peso corporal, DMI e G:F), as características de carcaça dos novilhos (HCW, ADG em carcaça, rendimento do ganho em carcaça, rendimento de carcaça e espessura de gordura na 12ª costela), a digestibilidade aparente da DM, OM, CP e NDF no trato total foram similares entre os tratamentos. Não houve efeito de tratamento e interações de tratamento × tempo nas características da fermentação ruminal (pH ruminal, nitrogênio amoniacal, contagem de protozoários e VFA). No estudo da SCR, a DMI aumentou linearmente em até 25% (P = 0.01). O consumo de DM calculado como % do BW aumentou (P = 0.01) 0.06 unidades percentuais a cada 1% de inclusão de SCR. Ao longo de todo o período de confinamento (dia 0 ao dia 103) foram observadas tendências de aumento linear de até 3.3% do BW final (P = 0.10) e 10.7% do ADG (P = 0.07), consequentemente houve tendência de reduzir linearmente a G:F em até 10.2% (P = 0.07) com a inclusão da SCR em comparação à dieta CTL. A digestibilidade aparente dos nutrientes diminuiu linearmente (P < 0.01) em até 30% para DM, 28% para OM, 45% para CP e 61% para o NDF, do CTL para SCR-12. Não foram observados efeitos de tratamento e interação tratamento × tempo no pH ruminal, concentração de nitrogênio amoniacal e VFA. Tempo gasto alimentando, taxa e frequencia de alimentação não foram afetados pela inclusão de até 12% de SCR. Houve uma resposta quadrática no tamanho da refeição (P = 0.04). Em conclusão, o fornecimento de aditivos antimicrobianos isolados ou combinados para novilhos zebuínos resultaram em respostas similares. A SCR peletizada teve baixa digestibilidade e não foi efetiva para estimular a ruminação do gado alimentado com dieta de milho grão inteiro.

Call number: LD2668 .T4 1986 T39 / Master of Science / Animal Sciences and Industry