Magnetic Resonance Spectroscopy (MRS) for the evaluation of in vivo cerebral metabolite ratios is a relatively new radiological modality, which permits the detection and evaluation of specific metabolites within the human body. As with all imaging modalities, the accuracy of the equipment to perform its given task is paramount and the effect of introduction of elements and/or contrast agents to a study, must be understood before a diagnosis or prognosis can be made with any degree of certainty. The following chapters describe the development and testing of a phantom, the development and testing of metabolite simulating solutions and the experiments conducted to determine the spatial localisation accuracy of a MRS imaging system. This thesis begins with a description of the steps undertaken to investigate a clinical MRS system's capacity to reliably produce spectra over both the long and short term. Validation of the phantom construction, metabolite simulating solutions and spatial localisation accuracy is presented in detail. The construction of the localisation phantom resulted in a two compartment perspex phantom and the development of the aqueous metabolite solutions produced two solutions with distinct and separate metabolite peaks with comparable peak amplitudes and sufficient line width separation to prevent possible metabolite resonance cross contamination but without illustrating any significant susceptibility artefacts. Development of the metabolite simulating solutions was a major part of the work conducted. Short and long term (1 year) reproducibility of the measured metabolite peak amplitudes were assessed for four different pulse sequences. Of these, the most reproducible results were obtained with a TE 270ms PRESS sequence (coefficient of variation < 0.6% (short term) and < 3% (long term)). The spatial localisation experiments illustrated a disturbing error in the placement of the user prescribed volume of interest (VOI) with respect to the actual VOI acquisition with a difference between the two volumes of interest of up to 3 mm or 15% of the VOI size in two axes. Possible effects of magnetic resonance imaging contrast agents, specifically Gd-DTPA were also investigated. Fifty patients were included in this study. The metabolic peak amplitudes were measured pre and post-administration of the contrast agent for each subject. A paired t-test demonstrated that there was no significant difference between the mean peak heights pre- and post- administration (0.07 < p < 0.9 for the various peak amplitudes measured).

This thesis describes the in vivo evaluation of orally administered extracts of Echinacea species, and fractions obtained from Echinacea purpurea for specific immunostimulatory function induced in Balb/c mice by immunization with microbial vaccines. Two vaccines were used for this purpose in this study. The first vaccine used consisted of whole-cell formalin-killed Salmonella typhimurium vaccine, which is known to induce production of specific antibodies but no delayed-type hypersensitivity response considered as an indicator of the cell-mediated immune response. The second vaccine was a commercial acellular pertussis vaccine (DTaP) consisting of inactivated diphtheria and tetanus toxoids and native or inactivated virulence factors of Bordetella pertussis (the etiological agent of whooping cough) which is known to induce a humoral immune response but with controversial reports about performance in the induction of cell-mediated immunity. Both vaccines were administered intraperitoneally, whereas the herbal extracts and fractions were administered by oral gavage. The phytochemical profile of the ethanolic extracts of Echinacea purpurea, Echinacea pallida, Echinacea angustifolia and one commercial product "Echinacea Triplex" and three fractions prepared from Echinacea purpurea, namely polysaccharides, phenolics and alkylamides, was determined by thin-layer chromatography, high-performance liquid chromatography and/or by chemical analytical techniques. Statistically significant increases in specific anti-Salmonella typhimurium serum antibody were obtained for the Echinacea purpurea, Echinacea angustifolia and Echinacea Triplex [Trade Mark] treatment groups, and also for groups receiving treatment with fractions obtained from Echinacea purpurea, namely, polysaccharide, alkylamide and phenolic fractions. Statistically significant increases in the anti-B pertussis serum antibodies were also obtained in the young Echinacea Triplex [Trade Mark] group vaccinated with the DTaP vaccine. Significant enhancement of serum interleukin-12 titres was observed in the Echinacea Triplex [Trade Mark] as well as the phenolic fraction treatment groups which were vaccinated with killed Salmonella typhimurium vaccine. Of the groups vaccinated with the DTaP vaccine, only Echinacea Triplex [Trade Mark] displayed statistically significant increases in mean interleukin-12 titre compared to the placebo in both young and old groups, however Echinacea purpurea, and Echinacea angustifolia both displayed significant increases in mean interleukin-12 titre in the young treatment mice. Increases in interferon-gamma levels in mice orally dosed with phenolic, polysaccharide or alkylamide fractions of Echinacea purpurea and vaccinated with the killed Salmonella typhimurium vaccine were also observed, however these need to be repeated for confirmation, and statistical analysis.

Thesis (D.Min.)--South Florida Center for Theological Studies, 1999. / Includes bibliographical references.

Universiẗat, Diss.--Marburg, 1994.

Konstanz, Univ., Diplomarb., 2005.

Tierärztl. Hochsch., Diss., 2007--Hannover.

University, Diss., 2006--Würzburg. / Erscheinungsjahr an der Haupttitelstelle: 2005.

Submitted by Nathália Faria da Silva (nathaliafsilva.ufv@gmail.com) on 2017-07-06T19:24:07Z No. of bitstreams: 1 texto completo.pdf: 389525 bytes, checksum: 6cc14febae6fb28130546ca7e2a6a4e7 (MD5) / Made available in DSpace on 2017-07-06T19:24:07Z (GMT). No. of bitstreams: 1 texto completo.pdf: 389525 bytes, checksum: 6cc14febae6fb28130546ca7e2a6a4e7 (MD5) Previous issue date: 2002-02-28 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / O presente trabalho teve os seguintes objetivos: (1) determinar as alterações na composição químico-bromatológica e nas frações protéicas e de carboidratos, determinar as taxas de digestão das frações de carboidratos e avaliar o valor nutricional de silagens de milho e de sorgo, com diferentes proporções de grãos e panículas, respectivamente, por meio da técnica de produção de gases e da digestibilidade in vitro da matéria seca e, estimar o teor em nutrientes digestíveis totais (NDT); (2) determinar o consumo e a digestibilidade aparente total e parcial dos nutrientes em bovinos alimentados com dietas à base de silagens de milho e de capim-elefante e feno de capim tifton-85; (3) determinar a eficiência microbiana e parâmetros ruminais em bovinos alimentados com dietas à base de silagens de milho e de capim-elefante e feno de capim tifton-85; (4) determinar as taxas de digestão das frações protéicas e de carboidratos para as silagens de milho e de capim-elefante, o feno de capim tifton-85 e o farelo de soja; (5) validar as estimativas relativas à digestão total da matéria seca, à digestão ruminal dos carboidratos totais, digestão total e ruminal dos carboidratos fibrosos e do fluxo de compostos nitrogenados (N) microbianos no abomaso pela utilização da técnica de produção de gases e (6) determinar a digestibilidade e a excreção fecal em bovinos por intermédio de indicadores internos e externos. As silagens de milho e de sorgo foram confeccionadas em silos de PVC com proporções de zero, 15, 30, 45 e 60% de grãos e, zero, 20, 40, 60, 80 e 100% de panículas, respectivamente. Foram determinados nas silagens de milho e sorgo, bem como nos alimentos avaliados na experimentação in vivo, os teores de matéria seca (MS), proteína bruta (PB), extrato etéreo (EE), matéria mineral (MM), carboidratos totais (CT), fibra em detergente neutro (FDN), FDN corrigida para cinzas e proteínas (FDNcp), lignina, compostos nitrogenados não protéicos (NNP), proteína solúvel em detergente neutro (B1+B2), nitrogênio insolúvel nos detergentes neutro (NIDN) e ácido (NIDA), carboidratos não fibrosos (CNF), FDN potencialmente digestível (fração B2) e indigestível (fração C). As taxas de digestão das frações dos carboidratos foram estimadas por intermédio da técnica de produção de gás in vitro, a digestibilidade in vitro da matéria seca por meio da técnica de dois estágios, o NDT por meio das equações do NRC (2001) e, as taxas de digestão das frações protéicas dos alimentos utilizados na experimentação in vivo foram estimadas pela incubação com proteases ruminais. A experimentação in vivo foi realizada por meio da utilização de seis bovinos, fistulados no rúmen e abomaso, distribuídos em delineamento em quadrado latino 3x3 duplo, para avaliação de dietas à base de silagens de silagem de milho e de capim-elefante e feno de capim tifton-85, as quais foram suplementadas com 10% de farelo de soja. Cada período experimental constou de 18 dias, sendo os 10 primeiros destinados à adaptação dos animais às dietas, seis dias para determinação do consumo e digestibilidade aparente total e parcial dos nutrientes, onde foram coletadas amostras de sobras, digesta abomasal e de fezes; no 17 0 dia foi determinado pH ruminal e coletadas amostras de fluido ruminal antes da alimentação e 2, 4 e 8 horas após, para a determinação da concentração N-NH 3 ; e no último dia de cada período, foi coletado conteúdo ruminal para isolamento e determinação da composição microbiana. A excreção fecal e o fluxo de matéria seca no abomaso foram determinados pela utilização da FDN indigestível (FDNI) como indicador, a qual foi determinada nas amostras dos alimentos, sobras, fezes e de digesta abomasal e, o fluxo de compostos microbianos no abomaso foi determinado pela utilização das bases purinas como indicador microbiano. Para avaliação da FDN indigestível (FDNI), da fibra em detergente ácido indigestível (FDAI) e do cromo como indicadores da excreção fecal e da digestibilidade aparente, a FDNI e a FDAI foram determinadas in vitro após 144 horas de incubação, tendo como referência, a coleta total, realizada durante três dias nos dois últimos períodos do experimento. Os dados relativos às silagens de milho e sorgo com diferentes proporções de grãos e panículas, respectivamente, foram avaliados por meio de análise de regressão; os dados de consumo, digestibilidade aparente total e parcial dos nutrientes e eficiência microbiana foram avaliados por meio de análise de variância; os dados relativos ao pH e à concentração de N-NH 3 ruminal foram analisados pelo esquema de parcelas subdivididas, tendo nas subparcelas o tempo de coleta; a validação das predições relativas à degradação ruminal dos carboidratos totais, da digestão total da matéria seca, da digestão total e ruminal dos carboidratos fibrosos e do fluxo de compostos nitrogenados microbianos no abomaso, obtidos por intermédio das estimativas oriundas da técnica de produção de gases, foi feita pela regressão dos valores preditos sobre os observados, sendo as estimativas dos parâmetros da regressão β 0 e β 1 testados de modo a identificar se as estimativas foram subestimadas ou superestimadas, por intermédio de análise de regressão linear simples; a comparação dos indicadores foi feita por meio de análise de regressão dos valores preditos sobre os observados e análise de variância pelo teste de Dunnett. O acréscimo de grãos à silagem de milho aumentou linearmente a MST, PB e CNF e, reduziu a MM, FDN, FDA e lignina. O NNP e as frações B 3 e C da PB da silagem de milho variaram de 34,04 a 54,62%, de 6,63 a 2,61 e de 7,83 a 1,32% da PB. Os teores dos CNF e das frações B 2 e C dos carboidratos totais foram influenciados linearmente pela adição de grãos à silagem de milho, as quais variaram de 153,55 a 585,10, 489,57 a 203,29 e de 233,50 a 85,51 g/kg de MS, respectivamente. As taxas de digestão dos CNF e da fração B 2 foram quadraticamente afetadas, apresentando valores máximos de 0,2723 e 0,02771 h - , para as silagens com 40,08 e 14,57% de grãos, respectivamente. O volume final de gás, a DIVMS e o NDT aumentaram linearmente em função da porcentagem de grãos à silagem de milho, os quais variaram de de 20,03 a 28,47 ximL, de 62,19 a 83,21% e de 56,08 a 81,40%, respectivamente. O acréscimo de panículas à silagem de sorgo aumentou linearmente os teores de MS, PB, CNF, EE e lignina e reduziu os teores de MM e FDN. O NNP e as frações B1+B2, B 3 e C variaram de 9,19 a 21,24, de 67,63 a 75,98, de 3,85 a 6,09 e de 5,09 a 10,98% do N total. Os teores dos CNF aumentaram linearmente e da fração B 2 dos carboidratos totais foram reduzidos pela adição de panículas à silagem de sorgo, os quais variaram de 208,18 a 564,07 e de 381,29 a zero g/kg de MS, respectivamente. As taxas de digestão dos CNF e da fração B 2 variaram de 0,1358 a 0,1563h- 1 e de 0,0247 a 0,0294 h- 1 . O volume final de gás não foi influenciado pela adição de panículas, variando de 23,09 a 25,26 mL e, a DIVMS máxima de 69,52% foi obtida com 60,10% de panículas. Embora o NDT estimado tenha aumentado linearmente com o acréscimo de panículas, considerando a não alteração da produção de gás e o comportamento quadrático da DIVMS, pode-se inferir que a utilização destas estimativas não parecem ser adequadas. Na experimentação in vivo, embora as dietas à base de silagem de milho e de feno de capim tifton-85 não tenham apresentando diferenças quanto à ingestão de matéria seca, a primeira permitiu maior ingestão de nutrientes digestíveis totais. A dieta de feno de capim tifton-85 apresentou maior consumo de FDN (4,52 kg/dia), enquanto a dieta de silagem de milho resultou em maior ingestão de carboidratos não fibrosos (1,95 kg/dia). A dieta de silagem de milho apresentou maior digestão aparente total da matéria seca (66,3%), da matéria orgânica (68,9%), da fibra em detergente neutro (55,7%) e dos carboidratos totais (68,2%). O rúmen foi o principal local de digestão dos carboidratos totais e da FDN para todas as dietas. Foi verificada uma relação inversa entre a digestibilidade total da matéria seca e a ingestão de FDNI e, desta forma, pode-se inferir que essa fração possa ser utilizada na estimação da digestibilidade de gramíneas tropicais. As dietas à base de silagem de milho e feno de capim tifton- 85 proporcionaram maior fluxo de compostos nitrogenados no abomaso. As bactérias isoladas do rúmen apresentaram em média 8,89% de N total e 18,40 para a relação N-RNA:N-total. A dieta à base de silagem de milho proporcionou maior degradação ruminal da matéria orgânica (2,96 kg/dia) e dos carboidratos totais (3,07 kg/dia) e maior fluxo de massa microbiana no abomaso (788,28 g/dia). As dietas à base de feno de capim tifton-85 e de silagem de capim- elefante apresentaram maior eficiência microbiana, cujos valores foram 28,10 e 30,39 g de N microbiano/kg de carboidratos degradados no rúmen. A dieta à base de silagem de milho proporcionou menores concentrações de N-NH 3 e pH ruminal em função do tempo após a alimentação o que, possivelmente, afetou negativamente a eficiência microbiana. As silagens de milho e de capim-elefante destacaram-se pela maior proporção dos seus compostos nitrogenados (N) na forma de NNP, o feno de capim tifton-85 destacou-se pela elevada proporção de PSDN e de fração B3 e, o farelo de soja pela elevada proporção de PSDN (B1+B2). Quanto às frações dos carboidratos (% dos CT), a silagem de milho e o farelo de soja destacaram-se pela elevada proporção de CNF (37,05 e 75,75%), e o feno de capim tifton-85 e a silagem de capim-elefante pelo elevado teor das frações B2 (51,20 e 51,70%) e C (41,77 e 33,56%). As taxas de digestão das frações PSDN (B1+B2) e B3 da PB variaram de 0,0469 a 0,1512 h -1 para o farelo de soja e silagem de capim-elefante e de 0,0081 a 0,0757 h -1 para o feno de capim tifton-85 e silagem de capim-elefante, respectivamente. As taxas de digestão estimadas para os CNF e a fração B2 variaram de 0,1294 a 0,1905 h -1 e de 0,0254 a 0,0300 h -1 para o feno de capim tifton-85 e a silagem de milho, respectivamente. As estimativas foram acuradas na predição da digestão ruminal dos carboidratos totais, da digestão total e ruminal dos carboidratos fibrosos e do fluxo de N microbiano no abomaso. A digestão aparente total da matéria seca também foi acuradamente predita pela diferença entre o gás da dieta e das fezes. A excreção fecal e a digestibilidade aparente da matéria seca foram acuradamente preditas a partir do cromo e da FDNI, entretanto, com a utilização da FDAI, houve subestimação da digestibilidade e superestimação da excreção fecal para a dieta contendo feno de capim tifton-85. / The present work had the following objectives: (1) to determine the chemical composition and protein and carbohydrates fractions alteration, to determine the digestion rate of carbohydrate fractions and to evaluate the nutritional value of corn and sorghum silages with different grains and steam+leaf/head proportions, respectively, by in vitro gas production technique and in vitro dry matter digestibility and to estimate the content of total digestible nutrients (TDN); (2) to determine the intake and the total apparent and partial digestibility of nutrients in cattle fed diets based on corn silage, tifton-85 bermudagrass hay and elephant-grass silage; (3) to determine the microbial efficiency and ruminal parameters of cattle fed diets based with corn silage, tifton-85 bermudagrass hay and elephant-grass silage; (4) to determine the digestion rates of protein and carbohydrates fractions for the corn silage, the tifton-85 bermudagrass hay, elephant-grass silage and soybean meal; (5) to validate the estimates of total dry matter digestion, ruminal digestion of total carbohydrate, total and ruminal digestion of fiber carbohydrates and microbial nitrogen compounds in the abomasum by the gas production technique and (6) to determine the digestibility and faecal excretion in cattle by internal and external markers. The corn and sorghum silages were done in silos of PVC with zero, 15, xiv30, 45 and 60% of grains and zero, 20, 40, 60, 80 and 100% of steam+leaf/head, respectively. The content of dry matter (DM), crude protein (CP), ether extract (EE), ash, total carbohydrates (TC), neutral detergent fiber (NDF), NDF corrected for ash and protein (NDFcp), lignin, non-protein nitrogen compounds (NPN), neutral detergent soluble protein (NDSP), neutral and acid detergent insoluble protein (NDIN and ADIN), non fiber carbohydrates, potentialy digestible (B2) and indigestible (C) NDF were determined in corn and sorghum silages, as well in the feeds evaluated in in vivo experimentation. The digestion rate of carbohydrate fractions were estimated by in vitro gas production technique, the in vitro dry matter digestibility (IVDMD) by two-stage technique, the TDN by NRC (2001) equations and the digestion rate of protein fractions of feeds utilized in the in vivo experimentation by ruminal proteases incubation. The in vivo experimentation was realized by utilization of six rumen and abomasum fistulated cattle arranged in a double 3x3 latin square, in order to evaluate diets based on corn silage, tifton-85 bermudagrass hay and elephant-grass silage supplemented with 10% of soybean meal (in dry matter). Each experimental period had duration of 18 days, in which the 10 first days were destinated for animal adaptation to the diets, the next six days for determination of intake and apparent total and partial digestibilities of nutrients by collection of orts, abomasal digesta and faecal samples; in 17th day for determination of ruminal pH and samples collection of ruminal fluid before and 2, 4 and 8 hours after feeding for N-NH 3 concentration determination; and in the 18th day of each period for collection of ruminal content for isolation and microbial composition determination. The fecal excretion and the dry matter flow in the abomasum were determined by the utilization of indigestible NDF (INDF) as marker, being determined in samples of feeds, orts, faeces and abomasal digesta, and the microbial compounds flow in the abomasum was determined by utilization of purinas as microbial marker. For evaluation of INDF, IADF and chrome as markers of faecal excretion and apparent digestibility, the INDF and IADF were determined in vitro after 144 hours of incubation, having as reference the total collection, realized during three days in the last two periods. The data related to xvcorn and sorghum silage with different grains and steam+leaf/proportions were evaluated by regression analysis; the intake, total apparent and partial digestibilities of nutrients and microbial efficiency were evaluated by variance analysis; the data related to pH and ruminal N-NH 3 concentration were evaluated by split plot design, with time of sampling as subplot; the validation of preditions related to total carbohydrates ruminal degradation, total dry matter digestion, total and ruminal digestion of fiber carbohydrates and microbial nitrogen compounds flow in the abomasum obtained by estimatives from in vitro gas production technique was realized by regression of predicted values over the observed values. The estimative of the regression parameters β 0 and β 1 were tested for identifying if the estimatives were under or overestimated by analysis of simple linear regression. The comparation of markers was realized by regression analysis of predicted values over the observed values and by variance analysis using Dunnett test. The addition of grains in the corn silage increased linearly the total DM, CP and NFC and reduced the ash, NDF, ADF and lignin. The NPN and the B3 and C protein fractions of corn silage ranged from 34.04 to 54.62%, from 6.63 to 2.61 and from 7.83 to 1.32% of CP. The content of NFC and of B2 and C fractions of TC were linearly influenced by grains addition in the corn silage, that ranged from 153.55 to 585.10, from 489.57 to 203.29 and from 233.50 to 85.51g/kg of DM, respectively, for silage with zero and 60% of grains. The digestion rates of NFC and B2 fraction of TC were quadraticaly affected, presenting maximum values of 0.2723 and 0.02771 h -1 , for corn silage with 40.08 and 14.57% of grains, respectively. The total gas production, IVDMD and estimated TDN linearly increased in function of grains porcentage in the corn silage, that ranged from 20.03 to 28.47 mL, from 62.19 to 83.21% and from 56.08 to 81.40%, respectively. The addition of steam+leaf/head in the sorghum silage increased linearly the amounts of DM, CP, NFC, EE and lignin and reduced the ash and NDF. The NPN and B1+B2, B3 and C nitrogen fractions ranged from 9.19 to 21.24, from 67.63 to 75.98, from 3.85 to 6.09 and from 5.09 to 10.98% of total N. The contents of NFC increased linearly and of B 2 fraction of total carbohydrates reduced by addition of steam+leaf/head in sorghum silage, xvithat ranged from 208.18 to 564.07 and from 381.29 to zero g/kg of DM, respectively. The digestion rates of NFC and of B 2 fraction ranged from 0.1358 to 0.1563h- 1 and from 0.0247 to 0.0294 h- 1 . The total gas production was not affected by steam+leaf/head addition ranging from 23.09 to 25.26 mL, and the maximum IVDMD from 69.52% was obtained with 60.10% of steam+leaf/head. Even though he estimated TDN had increased linearly with the steam+leaf/head addition, considering the non alteration in total gas production and the quadratical behaviour for IVDMD, it can be infered that the utilization of these estimatives are not correct. In the in vivo experimentation, despite of the corn silage and tifton-85 bermudagrass hay diets had not presented differences for the dry matter intake, the first allowed higher intake of total digestive nutrients. The tifton-85 bermudagrass hay diet presented the highest NDF intake (4.52 kg/day), while corn silage diet resulted in the highest NFC intake (1.95 kg/day). The corn silage diet presented the highest total apparent digestibility of dry matter (66.3%), organic matter (68.9%), NDF (55.7%) and total carbohydrates (68.2%). The rumen was the main site of digestion of total carbohydrates and NDF for all diets. It was verified a inverse relationship between the total dry matter digestibility and the INDF intake, and therefore, it can be infered that this fraction may be utilized in the digestibility estimation of tropical grasses. The corn silage and tifton-85 bermudagrass hay diets provided the highest nitrogen compounds flow in the abomasum. The isolated rumen bacteria presented average of 8.89% of total N and 18.40 for the N-RNA:N-total relation. The corn silage diet provided the highest ruminal degradation of organic matter (2.96 kg/day) and total carbohydrate (3.07 kg/day) and the highest microbial mass flow in the abomasum (788.28 g/day). The tifton-85 bermudagrass hay and elephant- grass silage diets presented the highest microbial efficiency, with values of 28.10 and 30.39 g of microbial N/kg of rumen degraded carbohydrate. The corn silage diet provided the smallest N-NH 3 concentration and ruminal pH in function of time after feeding, possible affecting negatively the microbial efficiency. The corn silage and the elephant-grass silage presented the highest NPN proportions in the CP, the tifton-85 bermudagrass hay presented the highest NDSP proportion xviiand B3 fraction and the soybean meal the highest NDSP proportion. For the carbohydrate fractions, the corn silage and the soybean meal presented the largest NFC proportion, whose values were 37.05 and 75.75%, and the tifton-85 bermudagrass hay and the elephant-grass silage presented the highest content of B2 and C fractions, whose values were 51.20 and 51.70% and 41.77 and 33.56%, respectively. The digestion rates of NDSP and of B3 fraction of CP ranged from 0.0469 to 0.1512 h -1 for the soybean meal and elephant-grass silage and from 0.0081 to 0.0757 h -1 for the tifton-85 bermudagrass hay and elephant-grass silage, respectively. The estimated digestion rate of NFC and B2 fraction of TC ranged from 0.1294 to 0.1905 h -1 and from 0.0254 to 0.0300 h -1 for the tifton-85 bermudagrass hay and corn silage, respectively. The estimates were accurate in predition of ruminal digestion of total carbohydrates, total and ruminal digestion of fiber carbohydrates and microbial nitrogen flow in the abomasum. The total apparent dry matter digestion also was predicted accurately by difference between diet and faeces gas production. The fecal excretion and the apparent digestibility of dry matter were predicted accurately by chrome and INDF, however, with the IADF utilization, there was underestimation of digestibility and overestimation of faecal excretion for the tifton-85 bermudagrass hay diet.

Apesar da introdução do controle da qualidade individual nas técnicas complexas de tratamentos, tem-se comprovado que, mesmo assim, é possível a ocorrência de erros na aplicação da dose no momento da aplicação. No entanto, ainda não estão bem estabelecidas as ferramentas de redundância a fim de controlar a dose no momento da terapêutica, além do que, as técnicas mais modernas de tratamento radioterápico desenvolvem as aplicações com feixes rotacionais e os dosímetros tradicionalmente utilizados em controle da qualidade oferecem limitações angulares. Assim, este trabalho vem contribuir para o desenvolvimento de uma metodologia de controle da qualidade de transmissão in vivo utilizando filmes radiocrômicos acoplados ao cabeçote do acelerador linear, durante aplicações radioterápicas nas técnicas de tratamento conformacional e IMRT. A metodologia de controle da qualidade desenvolvida neste trabalho baseia-se na obtenção da distribuição de dose in vivo de tratamentos radioterápicos com um filme radiocrômico EBT2 posicionado em um suporte acrílico, semelhante a uma bandeja, a uma distância fonte-superfície de 56,8 cm, acoplado ao acessório holder do acelerador linear durante a aplicação de todo o tratamento teleterápico. Posteriormente, foi realizada uma análise gama para comparação da distribuição de dose medida pelo filme com a esperada pelo sistema de planejamento, obtida no plano coronal e central de um objeto simulador, com dimensões semelhantes ao suporte acrílico, posicionado à distância de 100 cm, como resultado da transferência do plano em questão. Com os resultados encontrados na seção conformacional, avaliando tanto a simulação Monte Carlo quanto as irradiações, pode-se concluir que a diferença entre a distribuição de dose do sistema de planejamento, na distância foco detector de 100 cm, e do filme, na distância de 56,8 cm, é diminuta e, desta forma, é viável criar uma metodologia para verificação dosimétrica de transmissão utilizando o filme radiocrômico acoplado ao cabeçote do acelerador. O controle da qualidade proposto na técnica de IMRT concordou com o esperado em 24 das 25 situações testadas, apresentando apenas um resultado diferente, ou seja, uma concordância de 96% com o esperado. As avaliações in vivo concordaram com 98% dos controles avaliados. Desta forma, pode-se concluir que a metodologia proposta neste trabalho é factível para o controle da qualidade de transmissão in vivo, em tratamentos radioterápicos que usam a técnica de tratamento conformacional e IMRT e, como ela não oferece dificuldades para o deslocamento angular do gantry, ela poderá ser aplicada em técnicas teleterápicas mais modernas. / Even with the introduction of the individual quality control in the complex techniques of radiation therapy treatments, the occurrence of errors in the release of the dose at the time of application is possible. However, in order to monitor the dose at the time of therapy, redundancy tools are not yet well established, Besides that, the most modern techniques of radiation treatment use rotational beams to deliver the desired dose distributions and the dosimeters traditionally used in quality control of radiation therapy suffer angular limitations. In this way, this work aims to contribute to the development of a methodology of transmission quality control in vivo presenting a dose control technique using radiochromic film coupled to the headstock linear accelerator for radiotherapy applications to monitor conformational techniques and IMRT treatment. The quality control methodology developed in this work is based on obtaining the in vivo dose distribution of radiotherapy treatments with a radiochromic film EBT2, positioned on an acrylic stand, similar to a tray at a source-surface distance of 56.8 cm, coupled to the linear accelerator accessory holder during application of any treatment. It was subsequently performed a gama analysis for comparison of the dose distribution measured by the film with the expected dose distribution by the treatment planning system. The expected dose distribution was obtained in the coronal and central plane of a phantom, with similar dimensions to the acrylic stand and positioned on a source-surface distance of 100 cm as a result of the transfer of the plan in question. Based on the results presented in the conformational section, evaluating both, Monte Carlo simulation and irradiation results, it can be concluded that the difference between the distribution of the dose planning system, focus distance 100 cm detector, and the film, on distance of 56.8 cm, are small, and in this way it is feasible to create a methodology for dosimetry verification using radiochromic film coupled to the head of the accelerator. The proposed quality control in IMRT technique agreed with expected in 24 simulations of the 25 situations tested, showing only one different result, i.e., there was a 96% concordance with the expected. In this way, it can be concluded that the methodology proposed in this work is feasible for the in vivo quality control of radiation therapy treatments that use the conformational and IMRT treatment techniques, and also can be applied to the most modern radiotherapy techniques since, it does not offer difficulties with the angular displacement of the gantry.

Sibutramine hydrochloride monohydrate is a weight loss agent banned from most global markets due to reports of serious adverse events including death. It is classified as a serotonin-norepinephrine reuptake inhibitor and acts within the central nervous system by inhibiting the reuptake of these neurotransmitters essentially influencing satiety and also energy expenditure. Despite its ban, sibutramine is still available for use in some countries and is often an unlisted ingredient in herbal or natural weight loss products. This leads to the oblivious and unintentional consumption of this compound which is of great concern especially if used by pregnant women. The aim of this study was to investigate the possible toxic and teratogenic effects of sibutramine by using a Spraque Dawley rat and an in ovo chick embryo model. The Sprague Dawley rat was used as in vivo model and animals were divided into three experimental groups, each consisting of 12 animals (6 males, 6 females). Rats were administered sibutramine over a 28 day period according to their assigned experimental groups namely control (C; sterile H2O), Low dose (LD; 1.32 mg/kg) and High Dose (HD; 13.2 mg/kg). On the day of termination blood was collected for various analyses which included biochemical tests for liver and kidney function, hormonal changes as well as the investigation of coagulation profiles. Brain, heart, lung, kidney and liver tissue of each animal was harvested for investigation of tissue and cellular structure. Rats were weighed daily and this data suggested that sibutramine was well tolerated by all animals, with only the female rats in the HD group showing a significant 8.2% decrease in their rate of weight gain. Biochemical data of liver and kidney function in all groups were normal. Thyroid hormone levels were comparable to control values though cortisol levels were lowered in the HD female group, a finding which correlates with the observed weight loss. Investigations of the ultrastructural morphology of the platelets and fibrin networks revealed differences between the experimental groups that are consistent with changes associated with a procoagulable state. Brain, kidney and liver tissue morphology appeared normal upon investigation, the latter confirming the biochemical findings. Examination of cardiac tissue revealed a slight increase in collagen deposition between the muscle fibers and ultrastructural analysis of lung tissue showed thickening of the alveolar walls, decreased intra-alveolar space and drastic increases in collagen deposition in the sibutramine-exposed groups. These findings were dosage dependant. The in ovo model was implemented with ephedrine, a known teratogen, as positive control. Three control groups were included to ensure the efficacy of the method. Eight experimental groups, each containing sixteen eggs, were exposed to four different concentrations of each drug (i.e. 0.5, 2.5, 5.0, 10.0 μmol). The brain, heart, liver and kidneys were harvested on embryonic day thirteen for morphological analysis. Macroscopic evaluation revealed that both drugs caused congenital abnormalities which included ventral wall and limb defects as well as growth retardation and increased mortality. Sibutramine was found to have a greater teratogenic potential than ephedrine. Histological investigation of kidney and brain samples of embryos revealed no morphological differences between the various experimental groups. Livers and hearts of embryos exposed were severely affected by both compounds in a dose dependant manner. Replacement of myocardium with adipose and connective tissue was observed in cardiac tissue, which is characteristic of muscular dystrophy. Severe liver steatosis was also evident. In conclusion, results from this animal-based study show that, at concentrations which are not toxic to the liver or kidneys, sibutramine administration led to increased coagulation, moderate cardiac and excessive lung fibrosis within the Sprague Dawley rat model. This indicates significant toxicity with the cardiac and respiratory system being more susceptible targets. In addition sibutramine was shown to possess greater teratogenic effects than ephedrine. Both drugs caused cardiac dystrophy and liver steatosis resulting in extensive liver and heart damage. Understanding the underlying mechanisms involved in the pathogenesis of these findings strongly emphasize an important area for future research. / Dissertation (MSc)--University of Pretoria, 2014. / tm2015 / Anatomy / MSc / Unrestricted