Doctor of Philosophy / Department of Animal Sciences and Industry / Cassandra K. Jones / Porcine epidemic diarrhea virus (PEDV) is a heat-sensitive virus that devastated the United States swine industry. Because of its heat sensitivity, it was hypothesized that a pellet mill mimicking commercial thermal processing may mitigate PEDV infectivity. From the results, it was determined that a conditioning time of 30 sec or greater and temperatures above 54.4°C were effective point-in-time kill steps to inactive PEDV in a research setting. However, this does not prevent subsequent recontamination after pelleting as it is a point-in-time mitigation step. To further explore this, various mitigation additives were evaluated to prevent or mitigate PEDV post-pellet contamination in swine feed and ingredients. Various additives were examined across 3 experiments and included mitigation additives of medium chain fatty acids (MCFA), organic acids (OA), essential oils (OA), formaldehyde based products, and sodium bisulfate. From Exp. 1, formaldehyde, medium chain fatty acids (MCFA), essential oils (EO), and organic acid (OA) each decreased detectable PEDV RNA compared to the control (P<0.05). Additionally, PEDV stability over time was influenced by matrix as the meat and bone meal and spray-dried animal plasma resulted in a greater (P<0.05) quantity of detectable PEDV RNA over 42 days compared to that of the swine diet and blood meal. In Exp. 2, the 1% MCFA inclusion was equally effective at mitigating PEDV as a commercially available formaldehyde product in the complete swine diet. To further explore the effects of MCFA against PEDV, Exp. 3 was conducted to evaluate lower inclusion levels of MCFA and fat sources containing MCFA. It was noted that formaldehyde, 1% MCFA (1:1:1: of caproic, caprylic, and capric acids), 0.66% caproic, 0.66% caprylic, and 0.66% capric acids enhance the RNA degradation of PEDV in swine feed as determined by a bioassay. The MCFA were also evaluated against Salmonella Typhimurium, Generic Escherichia coli, Enterotoxigenic Escherichia coli, and Campylobacter coli. It was noted that the efficacy of the MCFA varied between each bacteria species with caproic and caprylic being the most effective. Commercial developmental products were also tested and determined that Product A and B provided the lowest MIC values across Salmonella Typhimurium, Generic Escherichia coli, and Enterotoxigenic Escherichia coli (P < 0.05). Product A and B were further tested in an animal disease trial utilizing a strain of enterotoxigenic Escherichia. coli O149:K91: K88. From d 7 to 14, chlortetracycline, 1:1:1 blend, and Product B, all improved G:F compared to the control (P<0.05). This also led to chlortetracycline and Product B having an improvement (P<0.05) over the control diet from d 0 to 14. A treatment × day interaction for the enterotoxigenic E. coli plate scores was observed (P < 0.05), which occurred because of the decrease (P<0.05) in plate scores for Product B from d 1 to d 14 and an increase (P<0.05) in chlortetracycline from d 7 to 14. A decrease (P<0.05) in plasma urea nitrogen and haptoglobin was observed as time increased from d -2 to 14. In summary MCFA have shown to be an effect interventional mitigation strategy against PEDV and various bacteria.

No description available.

The potential for enhancing oleic acid (cis-18:1) and linoleic acid (18:2) content and lowering medium chain fatty acid (MCFA) content of bovine milk was investigated by abomasal infusion or dietary supplementation of oils. In experiment 1, olive oil, sesame oil, sunflower oil, or fish oil was abomasally infused (155 to 219 g/d) into Jersey cows during the last 6 d of each of four 14-d periods. In experiment 2, canola oil, olive oil, high-oleic sunflower oil, or distilled water (control) was abomasally infused (342 to 371 g/d) into three Holsteins and three Jerseys during the last 5 d of each of four 10-d periods. The intestinal digestibility and concentration of cis-18:1 and 18:2 in milk were proportional to flow of these fatty acids to the duodenum. Also, greater concentration of cis-18:1 in milk was associated with lowered yield of MCFA. During olive oil or sesame oil infusion in experiment 1, for each 100 g of cis-18:1 infused into the abomasum, milk cis-18:1 yield was increased by an average of 47 g, and MCFA yield was reduced by 42 g. The yield of 18:2 in milk was increased by approximately 46 g for each 100 g of infused 18:2 during olive oil or sesame oil infusion. Milk produced during sesame oil infusion, however, had an off-flavor when evaluated by a taste panel. In experiment 2, each 100 g of cis-18:1 infused daily increased milk cis-18:1 yield in Holsteins and Jerseys by 41 and 39 g/d, respectively, whereas recovery of infused 18:2 was 34 g/d for Jerseys and 42 g/d for Holsteins. In experiment 3, 22 Jersey cows were fed a basal diet, or the basal diet supplemented with 3.5% high-oleic canola oil, 3.5% soybean oil, or 1.75% high-oleic canola oil plus 1.75% soybean oil for 5 wk. Dietary canola oil supplementation increased conjugated linoleic acid (CLA) percentage in milk to a moderate level without raising trans-18:1 percentage, whereas feeding either supplement containing soybean oil raised both CLA and trans-18:1 percentages. Concentrations of trans-18:1 and CLA in milk apparently reflected the extent of unsaturated fatty acid biohydrogenation in the rumen. Dietary supplementation with canola oil increased yield of cis-18:1 in milk by 21 g for each 100 g of supplemental cis-18:1 intake. Yield of 18:2 in milk was raised by 3 g for each 100 g of supplemental 18:2 intake by cows fed soybean oil. Using abomasal infusion as an indicator of the maximum potential for apparent recovery of cis-18:1 in milk (39 to 49%), cis-18:1 recovery in response to supplemental cis-18:1 in the diet was approximately half of the potential response due to partial biohydrogenation in the rumen. The apparent recovery of dietary 18:2 in milk was reduced to only one-tenth of the potential yield (31 to 47%) indicated by abomasal infusion of seed oils. Results indicated that the fatty acid profile of bovine milk was altered in a manner that would be beneficial to human health when cows were fed supplemental oleic acid, but further research should focus on safe and economical methods to protect dietary unsaturated fatty acids from biohydrogenation. / Ph. D.

Receptores ativados da proliferação de peroxissomos (PPAR) são receptores nucleares que regulam o metabolismo de gordura e glicose, adipogênese e polarização de macrófagos, e são os mediadores da ação de uma grande classe de fármacos usada no tratamento de diabetes tipo 2, as tiazolidinadionas (TZD). Enquanto as TZDs reduzem a glicose do sangue e aumentam efetivamente a sensibilidade à insulina, elas podem também apresentar efeitos colaterais como aumento do risco de complicações cardiovasculares, ganho de peso, retenção de fluido e toxicidade hepática. Por causa disso, novos fármacos que possuem respostas mais favoráveis devem ser desenvolvidos, e o mecanismo de ativação do PPAR por ligantes vem sendo intensamente examinado. Para entender a relação entre a ligação de agonistas ao PPAR e a ativação transcricional, pretendíamos primeiramente obter cristais de PPAR-LBD (domínio de ligação ao ligante) humano na forma apo. Porém, surpreendentemente, a análise do sítio de ligação ao ligante revelou a presença de três pequenas moléculas, identificadas como ácidos nonanoicos e octanoicos. Este trabalho reporta a análise da estrutura cristalográfica do PPAR LBD complexado simultaneamente com três ácidos graxos de cadeia média (AGCM), provindos de bactérias (organismo de expressão), localizados no sítio de ligação ao ligante. A análise estrutural e funcional sugere que os AGCM são agonistas parciais que estabilizam a conformação do LBD do PPAR por mecanismo independente da hélice 12. / PPARs (peroxisome proliferator activated receptors) are nuclear receptors that regulate glucose and fat metabolism, adipogenesis and macrophage polarization and mediate actions of a major class of drugs that are used to treat type 2 diabetes, the thiazolidinediones. While TZDs reduce blood glucose and improve insulin sensitivity effectively, they can also exhibit deleterious side effects such as increased cardiovascular risk, weight gain, fluid retention and liver toxicity. Because it is desirable to develop new PPAR drugs with more favorable spectrums of response, mechanisms of PPAR ligand activation have come under intense scrutiny. To understand relationships between PPAR ligand binding and transcriptional activation, we sought to obtain apo human PPAR-LBD (ligand binding domain) crystals that diffract to high resolution. More surprisingly, close analysis of the ligand binding pocket revealed the presence of three small molecules, identified as nonanoic acid and octanoic acid. Here, we report the X-ray structural analysis of the PPAR LBD complexed with three bacterial (expression organism) medium chain fatty acids (MCFAs) that simultaneously occupy the buried ligand binding pocket (LBP). Structural and functional analysis suggests that MCFAs are partial agonists that stabilize PPAR LBD conformation, through a helix 12 independent mechanism.

Receptores ativados da proliferação de peroxissomos (PPAR) são receptores nucleares que regulam o metabolismo de gordura e glicose, adipogênese e polarização de macrófagos, e são os mediadores da ação de uma grande classe de fármacos usada no tratamento de diabetes tipo 2, as tiazolidinadionas (TZD). Enquanto as TZDs reduzem a glicose do sangue e aumentam efetivamente a sensibilidade à insulina, elas podem também apresentar efeitos colaterais como aumento do risco de complicações cardiovasculares, ganho de peso, retenção de fluido e toxicidade hepática. Por causa disso, novos fármacos que possuem respostas mais favoráveis devem ser desenvolvidos, e o mecanismo de ativação do PPAR por ligantes vem sendo intensamente examinado. Para entender a relação entre a ligação de agonistas ao PPAR e a ativação transcricional, pretendíamos primeiramente obter cristais de PPAR-LBD (domínio de ligação ao ligante) humano na forma apo. Porém, surpreendentemente, a análise do sítio de ligação ao ligante revelou a presença de três pequenas moléculas, identificadas como ácidos nonanoicos e octanoicos. Este trabalho reporta a análise da estrutura cristalográfica do PPAR LBD complexado simultaneamente com três ácidos graxos de cadeia média (AGCM), provindos de bactérias (organismo de expressão), localizados no sítio de ligação ao ligante. A análise estrutural e funcional sugere que os AGCM são agonistas parciais que estabilizam a conformação do LBD do PPAR por mecanismo independente da hélice 12. / PPARs (peroxisome proliferator activated receptors) are nuclear receptors that regulate glucose and fat metabolism, adipogenesis and macrophage polarization and mediate actions of a major class of drugs that are used to treat type 2 diabetes, the thiazolidinediones. While TZDs reduce blood glucose and improve insulin sensitivity effectively, they can also exhibit deleterious side effects such as increased cardiovascular risk, weight gain, fluid retention and liver toxicity. Because it is desirable to develop new PPAR drugs with more favorable spectrums of response, mechanisms of PPAR ligand activation have come under intense scrutiny. To understand relationships between PPAR ligand binding and transcriptional activation, we sought to obtain apo human PPAR-LBD (ligand binding domain) crystals that diffract to high resolution. More surprisingly, close analysis of the ligand binding pocket revealed the presence of three small molecules, identified as nonanoic acid and octanoic acid. Here, we report the X-ray structural analysis of the PPAR LBD complexed with three bacterial (expression organism) medium chain fatty acids (MCFAs) that simultaneously occupy the buried ligand binding pocket (LBP). Structural and functional analysis suggests that MCFAs are partial agonists that stabilize PPAR LBD conformation, through a helix 12 independent mechanism.

Cardiovascular disease (CVD) represents the principal cause of mortality in this country and the prevalence is increasing amongst the lower socioeconomic classes. Modifiable risk factors, that can be removed or controlled by means of changes of lifestyle, are distinguished amongst the variables related to this occurence. Of these factors, tobacco smoking, sedentary behavior and bad eating habits, are significant. The diet, in this case, can exert a protecting or promoting influence on CVD. Amongst the dietary factors, saturated fat has important deleterious effects on the health of the heart. However,even though they belong to the same category of lipids, some triglycerides present metabolic behavior differentiated by virtue of their structural characteristics, particularly the size of the hydrocarbon chain. Thus, it is possible that medium chain triglycerides (MCT) do not represent a cardiovascular risk factor and, on the contrary, can even exert a protective effect. The coconut is a product widespread in the northeast of Brazil, and its oil, rich in MCT, is widely used in the food industry, however it has been poorly accepted for use in the domestic diet, possibly in view of the belief that, without scientific foundation, it is a possible hypercholesterolemic agent. The objective of this study was to ascertain the effect of the consumption of coconut oil on the cardiovascular risk factors and body composition of obese women. This dissertation consists of two articles, one being a literature study and the other presenting the results of an investigation conducted on a sample of 40 women (aged 20 to 40) that were overweight (25 < BMI > 35 kg/m2) and with a waist circumference (WC) > 88cm, randomly allocated into 2 groups, for the consumption of soya oil (S) or coconut oil (C). Anthropometric and biochemical evaluations were performed before (T1) and after 12 weeks (T2) of the lipid supplements. The groups consumed 30ml of oil daily, respectively of soya or coconut, divided amongst the three principal meals. The results demonstrated that the groups presented similar BMI in T1 (31.1 ± 3.3 vs 31.0 ± 3.6). In T2 it had been significantly reduced intra-group but not inter-group (30.7 ± 3.4 vs 30.5 ± 3.6). There was a significant reduction in WC in group C (98.8 ± 6.7 vs 97.4 ± 7.0; p = 0.004) but not in group S (97.1 ± 6.1vs 97.4 ± 5.35; p = 0.48). There was a reduction in the level of HDL in group S. All the other biochemical parameters remained unaltered in all the groups (glycemia, HOMA S, HOMA % &#946;, insulin, triglycerides, total cholesterol, fibrinogen). Therefore it was concluded that the daily consumption of 30g of coconut oil, in this population for a period of 3 months, did not cause dyslipidemia and promoted a reduction in WC. / As doenças cardiovasculares (DCV) representam a principal causa de mortalidade em nosso país e vem apresentando aumento de prevalência nas classes de menor nível socioeconômico. Entre as variáveis relacionadas à sua ocorrência, destacam-se os chamados fatores de risco modificáveis, os quais podem ser removidos ou controlados mediante mudanças no estilo de vida. Entre esses fatores destacam-se o tabagismo, o sedentarismo e os maus hábitos alimentares. A dieta, dessa forma, pode exercer um papel de proteção ou promoção das DCV, sendo a gordura saturada, dentre os fatores dietéticos, um importante agente deletério à saúde do coração. Todavia, mesmo pertencendo a esta categoria de lipídios, alguns triglicerídeos apresentam comportamento metabólico diferenciado em virtude de suas características estruturais, especialmente, o tamanho da cadeia hidrocarbonada. Assim, é possível que os triglicerídeos de cadeia média (TCM) não representem um fator de risco cardiovascular e, ao contrário, possam até exercer um efeito protetor. O coco é um produto bastante difundido no Nordeste brasileiro e seu óleo, rico em TCM, é amplamente utilizado pelas indústrias alimentícias, porém pouco aceito para uso dietético domiciliar, possivelmente em virtude da crença, sem fundamentação científica, de ser um possível agente hipercolesterolêmico. Desta forma objetivou-se verificar o efeito do consumo de óleo de coco sobre os fatores de risco cardiovascular e composição corporal de mulheres obesas. Esta dissertação aborda essa temática por meio de dois artigos, sendo um deles de revisão da literatura e o outro apresentando os resultados de uma investigação conduzida em uma amostra de 40 mulheres (20 a 40 anos) portadoras de sobrepeso (25< IMC < 35 Kg/m2) e circunferência da cintura (CC) > 88cm, aleatoriamente alocadas em 2 grupos, segundo o consumo de óleo de soja (S) ou óleo de coco (C). Procederam-se avaliações antropométricas e bioquímicas antes (T1) e após 12 semanas (T2) de suplementação lipídica. Os grupos consumiam diariamente 30 ml de óleo, respectivamente, de soja ou de coco, racionados nas três principais refeições. Os resultados demonstraram que os grupos apresentaram IMC semelhantes em T1 (31,1 ± 3,3 vs. 31,0 ± 3,6). Em T2 houve redução significativa intragrupo mas não inter grupo (30,7 ± 3,4 vs. 30,5 ± 3,6). Houve redução significativa na CC no grupo C (98,8 ± 6,7 vs. 97,4±7,0; p=0,004) mas não no grupo S (97,1 ± 6,9 e 96,3 ± 5,35; p=0,48). Houve redução do nível de HDL no grupo S. Todos os demais parâmetros bioquímicos permaneceram inalterados em ambos os grupos (glicemia, HOMA S, HOMA % &#946;, insulina, triglicerídeos, colesterol total, fibrinogênio). Desta forma concluiu-se que o consumo diário de 30 g de óleo de coco nesta população por um período de 3 meses não causou dislipidemia e promoveu redução na CC.

No description available.

Ulcerative colitis (UC) is a chronic disease of the colon or large intestine that causes inflammation and ulceration of the inner lining of the colon and rectum. In patients with ulcerative colitis, the body’s immune system overreacts and the body mistakes food, bacteria or other internal materials in the colon for an invading substance. The immune system attacks the material, thus irritating the colon. Limited knowledge of inflammatory conditions coupled with a narrow range of therapeutic options necessitates investigating the role of natural products. This study describes the effect of natural coconut oil on chemically-induced acute and chronic disease in mice. Ulcerative colitis was induced in four groups (5 mice per group) of 10-week-old female C57BL/6 mice by exposing them to 2.5-3% dextran sulfate sodium (DSS) for 5 and 29 days in the acute and chronic models, respectively. Coconut oil treatment was given via food containing 5% coconut oil to three diseased groups in three different regimens: one, preventive group receiving treatment prior to disease induction (14 d in acute; 28 d in chronic); two, simultaneous group receiving treatment simultaneous to disease induction; and three, regular treatment group receiving treatment after the disease induction –until termination of the experiment (14 d in acute; 60 d in chronic). Coconut food was replaced by the regular chow in the disease and water control groups. Clinical symptoms (diarrhea, occult blood, anal bleeding and body weight change) and the size of the isolated colon were recorded for comparison between experimental and control groups. Groups receiving coconut food displayed remissions in clinical markers of the disease. Improvements in clinical symptoms, histopathology, as well as cytokine activities were observed in both models, but the effects were more significant on the basis of standard error in the chronic model.