Doctor of Philosophy / Department of Animal Sciences and Industry / Barry Bradford / High levels of milk production has been and will continue to be a priority for the global dairy industry. Non-steroidal antiinflammatory drugs administered to dairy cattle following calving can be an effective way of programming higher milk production for the entirety of lactation. When dairy cattle on a commercial dairy received either sodium salicylate or meloxicam following calving, they responded with increased whole-lactation milk production, which was driven by higher daily milk yields following the seventh week of lactation. When dairy cattle at a research dairy received sodium salicylate following calving, they did not show the same increase in milk production but feed intake, feeding behavior, and blood parameters were altered for an extended period of time. The response to treatment was largely dependent on the parity of the animal. In an effort to determine whether re-programming of the rumen environment could explain these findings, sodium salicylate was administered to batch cultures of rumen fluid, and as a result, fermentation was inhibited. When substrate was fermented in rumen fluid from heifers who had been dosed with sodium salicylate, fermentation was inhibited for an extended period of time following sodium salicylate administration. Beyond the use of compounds such as these, other factors can program lactation for higher milk production, including the gender of the calf. Analysis of lactation records from the US has indicated that cows produce more milk following the birth of a heifer calf compared to a bull. With further research, findings such as these can provide farmers with more tools for improving productivity and lead to the sustainability of the dairy industry as a whole.

Doctor of Philosophy / Department of Animal Sciences and Industry / Barry Bradford / High levels of milk production has been and will continue to be a priority for the global dairy industry. Non-steroidal antiinflammatory drugs administered to dairy cattle following calving can be an effective way of programming higher milk production for the entirety of lactation. When dairy cattle on a commercial dairy received either sodium salicylate or meloxicam following calving, they responded with increased whole-lactation milk production, which was driven by higher daily milk yields following the seventh week of lactation. When dairy cattle at a research dairy received sodium salicylate following calving, they did not show the same increase in milk production but feed intake, feeding behavior, and blood parameters were altered for an extended period of time. The response to treatment was largely dependent on the parity of the animal. In an effort to determine whether re-programming of the rumen environment could explain these findings, sodium salicylate was administered to batch cultures of rumen fluid, and as a result, fermentation was inhibited. When substrate was fermented in rumen fluid from heifers who had been dosed with sodium salicylate, fermentation was inhibited for an extended period of time following sodium salicylate administration. Beyond the use of compounds such as these, other factors can program lactation for higher milk production, including the gender of the calf. Analysis of lactation records from the US has indicated that cows produce more milk following the birth of a heifer calf compared to a bull. With further research, findings such as these can provide farmers with more tools for improving productivity and lead to the sustainability of the dairy industry as a whole.

Este trabalho trata do estudo de complexos de rutênio contendo antiinflamatórios não-esteróides, com o objetivo de contribuir para ampliar as pesquisas na área de potenciais metalofármacos antitumorais. A partir de reações do precursor dimetálico [Ru2(O2CCH3)4Cl] com os fármacos carboxílicos sulindaco (HSulin) e diclofenaco de sódio (NaDiclofen) foram isolados, respectivamente, os correspondentes complexos [Ru2(Sulin)4Cl] e [Ru2(Diclofen)4Cl]. A reação entre o monômero [RuCl2(dmso)4] e o meloxicam (H2Melox) deu origem ao derivado misto [Ru(dmso)2(HMelox)2]. Os compostos foram caracterizados por meio de análise elementar, medidas de condutância molar, medidas de susceptibilidade magnética, espectroscopia de absorção eletrônica UV-VIS-IR, espectroscopia vibracional FTIR e Raman, e estudos de análise térmica (TG/DSC/MS). As interações da albumina de soro humana HSA, importante proteína do plasma, com os complexos obtidos, com o análogo [Ru2(IBP)4Cl] (HIBP = ibuprofeno) e também com os fármacos orgânicos não-complexados foram investigadas empregando-se dicroísmo circular, SDS-Page e fluorescência. A atividade antitumoral dos metalofármacos foi avaliada, através de ensaios com MTT, com base nos seus efeitos citotóxicos para a linhagem celular de leucemia humana K562. / This work describes the study of ruthenium complexes containing non-steroidal antiinflammatory drugs with the aim of helping to expand the research in the field of potential anticancer metallodrugs. Reactions of the [Ru2(O2CCH3)4Cl] dimetal complex with sulindac (HSulin) and sodium diclofenac (NaDiclofen) carboxylic drugs gave the correspondent complexes [Ru2(Sulin)4Cl] and [Ru2(Diclofen)4Cl], respectively. The reaction between the [RuCl2(dmso)4] monomer and the meloxicam drug (H2Melox) led to the mixed derivative [Ru(dmso)2(HMelox)2]. The compounds were characterized by elemental analysis, molar conductance measurements, magnetic susceptibility, UV-VIS-IR electronic absorption spectroscopy, Raman and FTIR vibrational spectroscopies and by studies of thermal analysis (TG / DSC / MS). The interactions of human serum albumin (HSA), the major plasma protein, with the obtained complexes, the analogous [Ru2(IBP)4Cl] (= HIBP ibuprofen) and also with the noncoordinated organic drugs have been investigated by circular dichroism, SDS-Page and fluorescence. The antitumor activity of the metallodrugs has been evaluated by MTT assays, on the basis of their cytotoxic effects on K562 human leukemia cell line.

Este trabalho trata do estudo de complexos de rutênio contendo antiinflamatórios não-esteróides, com o objetivo de contribuir para ampliar as pesquisas na área de potenciais metalofármacos antitumorais. A partir de reações do precursor dimetálico [Ru2(O2CCH3)4Cl] com os fármacos carboxílicos sulindaco (HSulin) e diclofenaco de sódio (NaDiclofen) foram isolados, respectivamente, os correspondentes complexos [Ru2(Sulin)4Cl] e [Ru2(Diclofen)4Cl]. A reação entre o monômero [RuCl2(dmso)4] e o meloxicam (H2Melox) deu origem ao derivado misto [Ru(dmso)2(HMelox)2]. Os compostos foram caracterizados por meio de análise elementar, medidas de condutância molar, medidas de susceptibilidade magnética, espectroscopia de absorção eletrônica UV-VIS-IR, espectroscopia vibracional FTIR e Raman, e estudos de análise térmica (TG/DSC/MS). As interações da albumina de soro humana HSA, importante proteína do plasma, com os complexos obtidos, com o análogo [Ru2(IBP)4Cl] (HIBP = ibuprofeno) e também com os fármacos orgânicos não-complexados foram investigadas empregando-se dicroísmo circular, SDS-Page e fluorescência. A atividade antitumoral dos metalofármacos foi avaliada, através de ensaios com MTT, com base nos seus efeitos citotóxicos para a linhagem celular de leucemia humana K562. / This work describes the study of ruthenium complexes containing non-steroidal antiinflammatory drugs with the aim of helping to expand the research in the field of potential anticancer metallodrugs. Reactions of the [Ru2(O2CCH3)4Cl] dimetal complex with sulindac (HSulin) and sodium diclofenac (NaDiclofen) carboxylic drugs gave the correspondent complexes [Ru2(Sulin)4Cl] and [Ru2(Diclofen)4Cl], respectively. The reaction between the [RuCl2(dmso)4] monomer and the meloxicam drug (H2Melox) led to the mixed derivative [Ru(dmso)2(HMelox)2]. The compounds were characterized by elemental analysis, molar conductance measurements, magnetic susceptibility, UV-VIS-IR electronic absorption spectroscopy, Raman and FTIR vibrational spectroscopies and by studies of thermal analysis (TG / DSC / MS). The interactions of human serum albumin (HSA), the major plasma protein, with the obtained complexes, the analogous [Ru2(IBP)4Cl] (= HIBP ibuprofen) and also with the noncoordinated organic drugs have been investigated by circular dichroism, SDS-Page and fluorescence. The antitumor activity of the metallodrugs has been evaluated by MTT assays, on the basis of their cytotoxic effects on K562 human leukemia cell line.