Thesis (Ph. D.)--University of Missouri-Columbia, 1997. / Typescript. Vita. Includes bibliographical references. Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 1997. / Typescript. Vita. Includes bibliographical references. Also available on the Internet.

Made available in DSpace on 2014-06-11T19:24:15Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-06-28Bitstream added on 2014-06-13T19:51:40Z : No. of bitstreams: 1 arruda_cm_me_botfm.pdf: 2320697 bytes, checksum: 36d804ba3cd19d52297e0d01b3162ada (MD5) / Atualmente a Aids é considerada doença crônica controlada com baixa morbidade e mortalidade. A terapia com antiretrovirais têm sido eficaz, porém associada com sérios efeitos metabólicos colaterais, dentre eles a hipertrigliceridemia..Ensaios epidemiológicos demonstram correlação entre níveis elevados de triglicérides, alterações de adipocitocinas e doença arterial coronariana.O uso do acido graxo omega-3( w-3) tem sido preconisado para a hipertrigliceridemia embora sem consenso. Avaliar o efeito do acido graxo ômega-3 em pacientes com HIV em tratamento antiretroviral (HAART) com níveis de triglicérides entre 200 e 400 mg/dl, correlacionando com os níveis de adipocitocinas. Foram estudados 17 pacientes de ambos os sexos com HIV/Aids em uso de antiretrovirais, no Serviço de Ambulatórios Especializados de Infectologia Domingos Alves Meira- UNESP, divididos em 2 grupos (G 1 e G 2)em dois momentos ( início e após 4 meses) todos com a mesma orientação alimentar e prática de atividade física. Ômega-3 foi preconizado no G1 . Em ambos os grupos foram avaliados: perfil antropométrico, hematimétrico, lipídico e imunológico. Dos 17 estudados , 7 eram do Grupo 1, 43% do sexo feminino,46,1±19,1 anos de idade, e o Grupo 2 foi composto por 10 pacientes, 40% do sexo feminino, 54,5± 25,4 anos de idade . Sobrepeso ocorreu em ambos os grupos, com tendência a melhora não muito significativa no Grupo 1 após 4 meses, e no Grupo 2 um leve aumento do peso no M2. Circunferência da cintura (CC), massa magra, gordura corporal, água corporal, perfil hematimétrico, imunológico não mostraram diferenças significativas nos dois grupos. Colesterol total e Triglicérides revelaram uma tendência a diminuir no M2 nos dois Grupos, o LDL teve um leve aumento no Grupo 1 no M2. As adipocitocinas mostraram... / Currently, AIDS is considered a chronic disease controlled with low morbidity and mortality. The antiretroviral therapy has been effective, but associated with serious metabolic side effects, including hypertriglyceridemia. Epidemiological trials demonstrate correlation between elevated triglyceride levels, changes in adipocytokines and arterial coronary disease. The use of omega-3 fatty acid (w -3) has been recommended to hipertrigliceridemia, although no agreement. Evaluating the effect of omega-3 fatty acid in patients with HIV on antiretroviral therapy (HAART) with triglyceride levels between 200 and 400 mg / dl, correlating with the levels of adipocytokines. We studied 17 patients of both sexes with HIV / AIDS on antiretroviral use in Specialized Outpatient Service of Infectious Diseases “Domingos Alves Meira” - UNESP, divided into two groups (G1 and G2) on two occasions (beginning and after four months) all with the same nutritional guidance and physical activity. Omega-3 has been recommended in G1. Both groups were evaluated: anthropometric profile, erythrocyte, lipid and immune systems. From the 17 studies, 7 were in Group 1, 43% were female, 46.1 ± 19.1 year-age; Group 2 comprised ten patients, 40% were female, 54.5 ± 25, 4 year-age. Overweight occurred in both groups, with a trend towards improvement not very significant in Group 1 after four months, and in Group 2, there was a slight weight increase in M2. Waist circumference (WC), lean mass, body fat, body water, erythrocyte and immune profiles showed no significant differences in the two groups. Total cholesterol and triglycerides showed a tendency to decrease in M2 in both groups, LDL increased slightly in Group 1 in M2. The adipocytokines showed a tendency to... (Complete abstract click electronic access below)

Orientador: Paulo Câmara Marques Pereira / Banca: Sueli Aparecida Calvi / Banca: Rita Cristina Chaim / Resumo: Atualmente a Aids é considerada doença crônica controlada com baixa morbidade e mortalidade. A terapia com antiretrovirais têm sido eficaz, porém associada com sérios efeitos metabólicos colaterais, dentre eles a hipertrigliceridemia..Ensaios epidemiológicos demonstram correlação entre níveis elevados de triglicérides, alterações de adipocitocinas e doença arterial coronariana.O uso do acido graxo omega-3( w-3) tem sido preconisado para a hipertrigliceridemia embora sem consenso. Avaliar o efeito do acido graxo ômega-3 em pacientes com HIV em tratamento antiretroviral (HAART) com níveis de triglicérides entre 200 e 400 mg/dl, correlacionando com os níveis de adipocitocinas. Foram estudados 17 pacientes de ambos os sexos com HIV/Aids em uso de antiretrovirais, no Serviço de Ambulatórios Especializados de Infectologia Domingos Alves Meira- UNESP, divididos em 2 grupos (G 1 e G 2)em dois momentos ( início e após 4 meses) todos com a mesma orientação alimentar e prática de atividade física. Ômega-3 foi preconizado no G1 . Em ambos os grupos foram avaliados: perfil antropométrico, hematimétrico, lipídico e imunológico. Dos 17 estudados , 7 eram do Grupo 1, 43% do sexo feminino,46,1±19,1 anos de idade, e o Grupo 2 foi composto por 10 pacientes, 40% do sexo feminino, 54,5± 25,4 anos de idade . Sobrepeso ocorreu em ambos os grupos, com tendência a melhora não muito significativa no Grupo 1 após 4 meses, e no Grupo 2 um leve aumento do peso no M2. Circunferência da cintura (CC), massa magra, gordura corporal, água corporal, perfil hematimétrico, imunológico não mostraram diferenças significativas nos dois grupos. Colesterol total e Triglicérides revelaram uma tendência a diminuir no M2 nos dois Grupos, o LDL teve um leve aumento no Grupo 1 no M2. As adipocitocinas mostraram... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Currently, AIDS is considered a chronic disease controlled with low morbidity and mortality. The antiretroviral therapy has been effective, but associated with serious metabolic side effects, including hypertriglyceridemia. Epidemiological trials demonstrate correlation between elevated triglyceride levels, changes in adipocytokines and arterial coronary disease. The use of omega-3 fatty acid (w -3) has been recommended to hipertrigliceridemia, although no agreement. Evaluating the effect of omega-3 fatty acid in patients with HIV on antiretroviral therapy (HAART) with triglyceride levels between 200 and 400 mg / dl, correlating with the levels of adipocytokines. We studied 17 patients of both sexes with HIV / AIDS on antiretroviral use in Specialized Outpatient Service of Infectious Diseases "Domingos Alves Meira" - UNESP, divided into two groups (G1 and G2) on two occasions (beginning and after four months) all with the same nutritional guidance and physical activity. Omega-3 has been recommended in G1. Both groups were evaluated: anthropometric profile, erythrocyte, lipid and immune systems. From the 17 studies, 7 were in Group 1, 43% were female, 46.1 ± 19.1 year-age; Group 2 comprised ten patients, 40% were female, 54.5 ± 25, 4 year-age. Overweight occurred in both groups, with a trend towards improvement not very significant in Group 1 after four months, and in Group 2, there was a slight weight increase in M2. Waist circumference (WC), lean mass, body fat, body water, erythrocyte and immune profiles showed no significant differences in the two groups. Total cholesterol and triglycerides showed a tendency to decrease in M2 in both groups, LDL increased slightly in Group 1 in M2. The adipocytokines showed a tendency to... (Complete abstract click electronic access below) / Mestre

Proprotein convertase subtilisin / kexin type 9 (PCSK9) is a negative regulator of the low-density lipoprotein receptor, and PCSK9 inhibition has become an important cholesterol-lowering therapeutic strategy. PCSK9 also associates with LDL particles, and evidence suggests that the activity of PCSK9 may be regulated by LDL binding. We have investigated the biochemistry of the interaction between PCSK9 and lipoproteins. Through mutagenesis and in-vitro binding assays, we found conserved motifs in the PCSK9 N-terminus that play a role in LDL binding. Through secondary structure studies using circular dichroism and computational modelling, we determined that the N-terminal region of the PCSK9 prodomain undergoes an environment-dependent structural shift that affects the ability of PCSK9 to bind LDL. We also found that the commonly found loss-of-function polymorphism R46L is capable of modulating this structural shift. Importantly, we found a surface-exposed region of the PCSK9 prodomain that maps a cluster of gain-of-function mutations (L108R, S127R, and D129G) that severely disrupt LDL binding. Through gel shift assays and density gradient centrifugation, we observed that PCSK9 shows remodeling-dependent ability to bind different classes of lipoprotein particles in vitro, binding strongly to LDL and IDL but showing barely detectable association to VLDL. Further, in human plasma, we found that lipoprotein-bound populations of PCSK9 shifted in response to differences in lipoprotein profiles between normolipidemic and hypercholesterolemic or hypertriglyceridemic subjects. Overall, elucidation of how lipoproteins regulate PCSK9 activity will reveal new targets for designing cholesterol-lowering therapeutics.

O jejum ou anorexia podem resultar em diversos distúrbios metabólicos prejudicais ao organismo. Este estudo objetivou avaliar e comparar os efeitos do jejum no perfil hematológico, de bioquímica sérica e na cicatrização de feridas cutâneas induzidas em equinos. Os animais foram distribuídos aleatoriamente em quatro grupos experimentais, sendo eles: DT12, representado por quatro equinos que permaneceram 12 horas em jejum e receberam dieta total na reintrodução alimentar; DC12, representado por quatro equinos que permaneceram 12 horas em jejum e receberam dieta convencional na reintrodução alimentar; DT72, representado por quatro equinos que permaneceram 72 horas em jejum e receberam dieta total na reintrodução alimentar; e DC72, representado por quatro equinos que permaneceram 72 horas em jejum e receberam dieta convencional na reintrodução alimentar. A dieta total e a dieta convencional possuíam a mesma composição bromatológica, porém, a dieta total era composta por um único produto triturado (volumoso e concentrado) e misturado, enquanto a dieta convencional era composta por volumoso e concentrado fornecidos separadamente. No dia de início do jejum, foi induzida ferida de pele no flanco de todos os animais experimentais. O experimento foi desenvolvido em duas etapas, sendo utilizados os mesmos animais, respeitando-se um intervalo de 15 dias e realizando-se a ferida cutânea no flanco contralateral. Foram realizadas análises laboratoriais comparadas de hemograma, bioquímica sérica e avaliação macro e microscópica da cicatrização das feridas de pele, assim como avaliação de alterações em peso, escore corporal, consumo hídrico, aceitação e tempo de consumo das dietas e consistência das fezes. Os animais dos grupos DT72 e DC72 apresentaram hipertrigliceridemia, hiperbilirrubinemia, redução de leucócitos, aumento dos valores de ureia, AST, colesterol e redução no peso em até 6% (p≤0,05). Após a inclusão da alimentação, foi observada elevação dos valores de lactato. Nos grupos DT12 e DC12 não foram observadas alterações hematológicas e de bioquímica sérica, assim como não houve influência do tipo de dieta. A cicatrização das feridas cutâneas não foi influenciada pelo jejum ou pelo tipo de dieta, embora observações macroscópicas sugiram melhor cicatrização nos animais que permaneceram 12 horas de jejum. Conclui-se que 12 horas de jejum não apresentam alterações hematológicas e de bioquímica sérica, enquanto 72 horas de jejum acarretam distúrbios metabólicos e perda de peso. / Fasting or anorexia can result in various metabolic disturbances detrimental to the body. This study aimed to evaluate and compare the effects of fasting on the hematological profile, serum biochemistry and healing of induced skin wounds in horses. The animals were randomly assigned to four experimental groups: DT12, represented by four horses that remained 12 hours in fasting and received a total diet in the food reintroduction; DC12, represented by four equines that stayed 12 hours fasting and received conventional diet in the food reintroduction; DT72, represented by four horses that remained 72 hours in fasting and received total diet in the food reintroduction; and DC72, represented by four equines that remained 72 hours in fasting and received conventional diet in the alimentary reintroduction. The total diet and the conventional diet had the same bromatological composition, but the total diet consisted of a single product crushed (bulky and concentrated) and mixed, while the conventional diet was composed of bulky and concentrated supplied separately. On the day of onset of fasting, a skin wound was induced on the flank of all experimental animals. The experiment was carried out in two stages, using the same animals, respecting an interval of 15 days and performing the cutaneous wound on the contralateral flank. Laboratory tests were performed comparing hemogram, serum biochemistry and macro and microscopic evaluation of skin wound healing, as well as evaluation of changes in weight, body score, water consumption, acceptance and time of diet consumption and feces consistency. The animals of the DT72 and DC72 groups showed hypertriglyceridemia, hyperbilirubinemia, leukocyte reduction, increased urea, AST, cholesterol and weight reduction by up to 6% (p≤0,05). After inclusion of the diet, elevation of lactate values was observed. In the DT12 and DC12 groups, no hematological and serum biochemical changes were observed, nor was there any influence of diet type. Healing of skin wounds was not influenced by fasting or type of diet, although macroscopic observations suggest better healing in animals that remained 12 hours fast. It is concluded that 12 hours of fasting do not present hematological alterations and serum biochemistry, while 72 hours of fasting lead to metabolic disorders and weight loss.

The relationship between hyperlipidemia and pancreatitis remains obscure in dogs. The aim of the present study was to investigate any possible association between hyperlipidemia and pancreatitis in dogs. In the first part of the study, Miniature Schnauzers with hypertriglyceridemia were found to have significantly higher serum cPLI concentrations than Miniature Schnauzers with normal serum triglyceride concentrations (P=0.0001). Also, Miniature Schnauzers with severe hypertriglyceridemia (>862 mg/dL) had 4.5 times higher odds (P=0.0343) for having a serum cPLI concentration consistent with pancreatitis. In the second part of the study, 17 Miniature Schnauzers prospectively enrolled with a history of pancreatitis were significantly more likely to have hypertriglyceridemia (71 percent) after resolution of pancreatitis than 34 age-matched Miniature Schnauzers without a history of pancreatitis (33 percent; odds ratio=5.02; P=0.0163). For the third part of the study, assessment of the feasibility and usefulness of a novel density gradient ultracentrifugation method using NaBiEDTA for lipoprotein profiling in dogs was attempted. Density gradient ultracentrifugation using NaBiEDTA was found to be useful for the study of lipoprotein profiles in dogs. Significant differences were detected in the lipoprotein profiles (mainly involving TRL and specific LDL fractions) among healthy Miniature Schnauzers, dogs of various other breeds, and hypertriglyceridemic Miniature Schnauzers. In the fourth part of the study, the effect of a commercially available low-fat diet on serum lipid and pancreas-specific lipase (Spec cPL) concentrations and lipoprotein profiles in Miniature Schnauzers with primary hypertriglyceridemia was evaluated. The study diet was found to be effective in significantly reducing serum triglyceride and cholesterol concentrations and changing the lipoprotein profiles of the dogs studied within 2 months. However, there was no significant effect of the study diet on serum Spec cPL concentrations. In the last part of the study, serum triglyceride and cholesterol concentrations and lipoprotein profiles were compared between dogs with naturally occurring pancreatitis and healthy dogs. The majority of dogs with naturally occurring pancreatitis had normal serum triglyceride and cholesterol concentrations. Important differences were identified in lipoprotein profiles between dogs with pancreatitis (higher LDL2, LDL3, and LDL4 fractions and lower TRL, HDL2a, and HDL3c fractions) and healthy control dogs.

Postprandial hypertriglyceridemia (PPHT), an independent risk factor for atherosclerosis (Smyth and Heron 2006; Nordestgaard, Benn et al. 2007), is strongly associated with metabolic syndrome and cardiovascular diseases (CVD) (Kolovou, Anagnostopoulou et al. 2005). It has been proposed that elevated triglycerides after a high-fat meal may be a postprandial phenomenon (Zilversmit 1979). PPHT are commonly concurrent with sedentary behaviors, such as extended sitting, which amplify PPHT (Levine, Vander Weg et al. 2006). The purpose of this study was to examine the effects of prolonged sitting with or without a balanced caloric diet and walking with a balanced diet on postprandial triglycerides (PPTG). Seven healthy, young men (age, 25.6 ± 3.7 y; height, 174 ± 5 cm; weight, 71.4 ± 6.2kg; VO2max, 49.3 ± 7.7 ml/kg/min) were recruited from a college and from within the Austin community. After 2 days of food and activity control (D1and D2), subjects performed one of three trials in a randomized, cross-over design for 2 days (D3 and D4); (1) active walking with a balanced diet (WB), (2) prolonged sitting with a hyper-caloric diet (SH), and (3) prolonged sitting with a balanced diet (SB). High fat tolerance tests (HFTT) were conducted on the following day, (D5), after 13 hour over-night fasting. Blood samples were obtained in the fasting state and every hour for 6 hours after subjects had eaten a high fat test meal consisting of 1.2 g fat, 1.1 g CHO, 0.2 g protein/kg body mass. All food was provided during the 5-day duration of the study. Body postures, heart rate, and daily steps were monitored. In both sit trials (SH and SB), subjects sat ~320 minutes longer and took 10 times fewer steps than WB. In WB, the total area under the curves for plasma triglycerides (AUC[subscript T] TG) was lower, compared to SH by 21.3% (p<0.001) and to SB by 19.7% (N.S.; p = 0.055), respectively. In WB, the incremental AUC TG (AUC[subscript I] TG), an index of postprandial response, was lower than both SH by 17.4% (p <0.005) and SB by 20.1% (p <0.05), respectively. Postprandial plasma insulin concentration was lower in WB, compared to SH by 19.4% (p <0.005) in AUC[scubscript T] and 18.8 % (p < 0.05) in AUC[subscript I]. No differences were shown in the metabolic responses between SB and SH despite the diet modifications. These findings indicate that two days of prolonged sitting significantly amplifies PPTG and suppresses insulin action. / text

No description available.

Trans-11 vaccenic acid (VA) is the predominant trans fatty acid in dairy fat and is the major precursor to endogenous synthesis of cis9,trans11-conjugated linoleic acid (CLA) in humans and animals. Epidemiological studies have shown the positive association between trans fat intake and incidence of coronary heart disease. Nevertheless, CLA, categorized as a group of trans fatty acids, has been shown to possess anti-carcinogenic, hypolipidemic and anti-diabetic benefits in several animal models as well as certain human populations, possibly via activating peroxisome proliferator-activated receptor (PPAR) related metabolic pathways. The subsequent effort in enriching CLA in dairy products (e.g. butter) has led to a concomitant increase in VA, whose bioactivity and health implications were not fully appreciated. Interestingly, VA is the major natural trans fat found in the diet. Therefore, the objectives of this thesis were to assess the effect of dietary supplementation of synthetic VA on lipid metabolism especially during conditions of dyslipidemia and metabolic syndrome, and to delineate the intestinal and hepatic metabolic pathways potentially modulated by VA. The JCR:LA-cp rat model, when homozygous for the cp trait (cp/cp), develop leptin receptor deficiency which leads to symptoms of metabolic syndrome and pre-diabetes including obesity, insulin resistance, hepatic steatosis, hypertriglyceridemia and exacerbated production of hepatic very low-density lipoproteins and intestinal chylomicrons (CM). Gas chromatography analysis on nascent lymph shows that VA was effectively absorbed into the intestine. In addition, VA from natural source (i.e. beef fat) showed higher intestinal bioavailability compared to synthetic VA. Dietary supplementation of 1.0% (w/w) synthetic VA to JCR:LA-cp rats (but not lean healthy controls) demonstrated a profound reduction in plasma triglyceride, total cholesterol, low-density lipoprotein-cholesterol, non-esterified fatty acid and haptoglobin concentrations (51%, p<0.001; 40%, p<0.001; 50%, p<0.05; 20%, p<0.05 and 50%, p<0.001; respectively), as well as improvement in hepatic steatosis and postprandial lipaemia. Gastric infusion of VA also resulted in an acute reduction in CM secretion in response to a fat load (p<0.05). We also found that the overall hypolipidemic benefits of VA might be partially contributed by suppression of hepatic de novo lipogenesis, activation of PPAR- activity as well as up-regulation of PPAR- and PPAR- expression in the intestine. In conclusion, VA as a natural trans fat, possesses beneficial properties in a rat model of dyslipidemia and metabolic syndrome, suggesting potential for the prevention of cardiovascular disease risk. / Nutrition and Metabolism