Thesis (Ph.D.)--University of Alberta, 2009. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Department of Cell Biology. Title from pdf file main screen (viewed on October 18, 2009). Accompanied by four supplementary video recording files. Includes bibliographical references.

Thesis (Ph. D.)--Florida State University, 2006. / Advisor: R. J. Moffatt, Florida State University, College of Human Sciences, Dept. of Nutrition, Food, and Exercise Sciences. Title and description from dissertation home page (viewed June 12, 2006). Document formatted into pages; contains xi, 140 pages. Includes bibliographical references.

Made available in DSpace on 2015-07-22T20:49:55Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-04-29. Added 1 bitstream(s) on 2015-08-11T03:26:25Z : No. of bitstreams: 1 Publico-256.pdf: 245625 bytes, checksum: 61276128685f362be02ff3b4eea05dbc (MD5) / A presente pesquisa visa estudar as repercussões materno-fetais da natação, na glicemia, triglicérides, ganho de peso e ingesta alimentar materna, além do número e peso dos filhotes ao nascimento. Foram utilizadas 24 ratas fêmeas Wistar adultas, com peso inicial de 235 gramas, sendo distribuídas em 4 grupos: controle grávida sedentária (CGS) (n=6), controle grávida treinada (CGT) (n=6), experimental grávida sedentária (EGS) (n=6), e experimental grávida treinada (EGT) (n=6). Foi utilizada a streptozotocina para a obtenção do diabetes no grupo experimental, e colocado as ratas para cópula, sendo a confirmação feita pela presença de espermatozóide no esfregaço. O controle da glicemia e triglicérides foram feitos nos quatro grupos, iniciando no dia zero de gestação (coleta 1), seguido do 7º (coleta 2), 14º (coleta 3) e 19º dia (coleta 4). O treinamento físico (natação) foi realizado cinco vezes por semana, por um período de 60 minutos, durante três semanas consecutivas até o dia do parto espontâneo. Foi realizado o controle do peso e ingestão alimentar materna diariamente, e após o nascimento, os filhotes foram contados e pesados. Observamos que, o exercício físico (natação) de moderada intensidade foi capaz de diminuir significantemente os valores glicêmicos, principalmente nas ratas prenhas diabéticas, apresentando também, benefícios no perfil dos triglicérides, além de não promover alterações sobre o feto. / This research aims to study the materno-fetal repercussion of the swimming on the glucose, triglycerides levels, weight gain and maternal food intake, and also the number and weight of offspring at birth. We used 24 Wistar adult female rats, with 235 g of initial weight, distributed into 4 groups: sedentary pregnant control (CGS) (n=6), trained pregnant control (CGT) (n=6), sedentary pregnant experimental (EGS ) (n=6) and trained pregnant experimental (EGT) (n=6). It was used streptozotocin-induceddiabetes in the experimental group, and the rats were paired for copulation, and the confirmation by the presence of sperm in the smear. The control of glucose and triglycerides levels were made in the four groups, starting from day zero of gestation (collection 1), followed by the 7th (collection 2), 14th (collection 3) and 19th days (collecting 4). The physical training (swimming) was performed five times a week (60 minutes), for three consecutive weeks until the day of spontaneous delivery. The maternal weight and food intake were daily controled, and after birth, the offsprings were counted and weighed. Therefore, physical exercise (swimming) of moderate intensity was able to significantly reduce the glycemic values, especially in pregnant diabetic rats, also, benefits in the profile of triglycerides, and not to promote change on the fetus. / TEDE / BV UNIFESP: Teses e dissertações

O nonilfenol etoxilado (NPE) é um desregulador endócrino que está presente no meio ambiente devido ao seu uso como detergente nos processos de limpeza de efluentes industriais. O objetivo deste trabalho foi avaliar a influência do NPE sobre o sistema imune adaptativo em ratos Wistar machos. Nestes animais foram avaliados o efeito do NPE sobre as células linfocitárias periféricas através da realização de hemograma e do perfil linfocitário adaptativo, analisando os marcadores de superfície CD4, CD8, CD28 e CD45 RA. Foi também avaliado o efeito do tratamento sobre o fígado e baço, bem como sobre o metabolismo intermediário, através das análises de glicemia, triglicerídeos e colesterol. Os dados não demonstraram diferenças significativas em relação ao índice hepático e esplênico. O nível de triglicerídeos apresentou um aumento de 50% nos grupos tratados, na avaliação dos níveis de colesterol e glicose não foi demonstrado diferenças significativas entre os grupos. Os resultados indicaram que o número de linfócitos e monócitos dos grupos tratados tiveram uma queda significativa de aproximadamente 25% e 50% em relação ao grupo controle. Foi demonstrado que o número de células fortemente marcadas quanto à presença da proteína CD45RA High na superfície celular dos linfócitos é maior nas células dos ratos do grupo tratado e que o tratamento aumenta a relação entre as células CD45RA High/Dim. Esses resultados levantam a hipótese que as células aumentadas nos grupos tratados apresentam fenótipo de membrana compatível com células T terminalmente diferenciadas (TEMRA). Este estudo forneceu dados novos sobre a ação do NPE, até onde se tem conhecimento, é a primeira pesquisa a constatar a presença elevada de células TEMRA em animais tratados com NPE, contribuindo com um novo foco para futuras pesquisas dessa substância. / Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq / Ethoxylated nonylphenol (NPE) is an endocrine disruptor that is present in the environment because of its use as a detergent in the industrial effluent cleaning processes. The objective of this work was to evaluate the influence of ethoxylated nonylphenol (NPE) on the adaptive immune system in male Wistar rats. In these animals, the effect of NPE on peripheral lymphocyte cells was evaluate by performing hemogram and adaptive lymphocytic profile, analyzing CD4, CD8, CD28 and CD45 RA surface markers. The effect of treatment on the liver and spleen, as well as on the intermediate metabolism, was also evaluate through glycemic, triglyceride and cholesterol analyzes. The data did not show significant differences in relation to the hepatic and splenic index. The level of triglycerides presented a 50% increase in the treated groups; in the evaluation of cholesterol and glucose levels, no significant differences between the groups were demonstrate. The results indicated that both, the number of lymphocytes and monocytes of the treated groups had a significant decrease of approximately 25% and 50% relative to the control group. The number of strongly labeled cells for the presence of the CD45RA High protein on the cell surface of the lymphocytes showed to be higher in the cells of the mice in the treated group and that the treatment increases the ratio between the CD45RA High/Dim cells. These results raise the hypothesis that enlarged cells in the treated groups exhibit terminally differentiated T cell (TEMRA). This study provided new data on the action of NPE, to the best of our knowledge, is the first research to verify the elevated presence of TEMRA cells in animals treated with NPE. In addition, these findings contribute a new focus for future research on this substance.

Orientador: Gabriel Hessel / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-09T01:55:34Z (GMT). No. of bitstreams: 1 Banin_MarciaRegina_M.pdf: 2211563 bytes, checksum: e16e20135efbf828907adc92ed40ba6b (MD5) Previous issue date: 2007 / Resumo: Racional - As doenças de depósito de glicogênio compreendem um grupo de doenças geneticamente determinadas e classificadas em 11 tipos, de acordo com as deficiências enzimáticas identificadas. Há pouca informação sobre a evolução dessas doenças. Objetivos - Descrever as características clínicas e laboratoriais, na admissão e evolução, de pacientes com doença de depósito de glicogênio. Pacientes e métodos ¿ Participaram do estudo 22 pacientes com diagnóstico de glicogenose hepática, sendo 11 (50%) do sexo feminino. O estudo foi descritivo e longitudinal. A ficha de coleta de dados constituiu-se de informações iniciais de: quadro clínico, peso, estatura, índice de massa corporal (IMC) e resultados dos exames laboratoriais (hemograma, enzimas hepáticas, colesterol total e frações, triglicérides, glicemia, ácido úrico, uréia e creatinina). Selecionou-se os momentos 1 (admissão), 3 (12 meses de evolução) e 7 (36 meses de evolução) para coleta dos seguintes dados: peso, estatura, IMC, ácido úrico, glicemia, colesterol e triglicérides. Também, foram comparados os resultados de antropometria e exames bioquímicos dos pacientes em dois momentos: admissão e última consulta. Para as variáveis peso e estatura, calculou-se o Z escore sendo considerado déficit quando o valor se situava abaixo do segundo desvio padrão. A velocidade de crescimento foi calculada a partir da 2ª e 1ª consulta (V1) e a partir da última e penúltima consulta (V2). A taxa de aderência foi determinada pela porcentagem de absenteísmo das consultas da seguinte forma: boa: se absenteísmo menor que 20%; regular: se absenteísmo entre 20% e 40% e ruim: se absenteísmo maior que 40%. Utilizou-se como teste estatístico a análise de variância e os testes de Kruskal-Wallis, Mann-Whintney e Wilcoxon, sendo o nível de significância adotado de 5%. Resultados - A média da idade de início dos sintomas foi de 10,7 meses e do diagnóstico de 28,18 meses. O tempo médio de seguimento foi de 105 meses. As manifestações clínicas iniciais mais freqüentes foram: hepatomegalia em 21 (95%), abdômen protuberante em 19 (86%), face de boneca em 14 (64%), diarréia em 10 (45%) e história de hipoglicemia em 8(36%). Nos exames laboratoriais, observou-se, na maioria dos casos, aumento das enzimas hepáticas, hipercolesterolemia, hipertrigliceridemia e hipoglicemia. Na admissão, o déficit de peso/idade foi de 26% (5/19) e de estatura/idade foi de 35% (7/20). Não houve diferença estatística na comparação do Z escore de peso/idade, estatura/idade, índice de massa corporal e exames laboratoriais na admissão, com 12 e 36 meses. Entre a admissão e a última consulta, observou-se diferença significativa no índice de massa corporal, enzimas hepáticas, glicemia e triglicérides, o que não aconteceu com Z escore de peso/idade, estatura/idade e os exames de ácido úrico e colesterol. A taxa de aderência foi considerada boa em 64% dos pacientes. Na comparação da velocidade de crescimento, observou-se tendência de aumento comparando V1 com V2. Conclusões ¿ Houve demora no encaminhamento ao centro de referência para o diagnóstico das glicogenoses. As manifestações clínicas mais freqüentes foram abdômen protuberante e hepatomegalia e as alterações laboratoriais mais significativas foram a elevação dos triglicérides, colesterol e diminuição da glicemia. Na evolução, não houve diferença nos parâmetros antropométricos, mas uma tendência de melhora de velocidade de crescimento. O tratamento melhorou o desarranjo metabólico / Abstract: Background ¿ Glycogen storage diseases comprise a group of genetic diseases determined and classified into 11 types, according to the identified enzymatic deficiency. There is little information regarding the disease evolution. Aim ¿ Describe clinical and laboratorial characteristics in the admission and evolution of patients with glycogen storage disease. Patients and methods ¿ Twenty-two patients with hepatic glycogen diagnosis participated in the study, 11 (50%) of which were female. The study was descriptive and longitudinal. The collected data file consisted of admission information: clinical features, weight, height, body mass index (BMI) and laboratorial exam results: hemogram, hepatic enzymes, total cholesterol and fractions, triglycerides, glycemia, uric acid, urea and creatin. Afterwards, the following phases were selected: 1 (admission), 3 (12 months of evolution) and 7 (36 months of evolution) for the weight, height, BMI and laboratorial tests: uric acid, glycemia, total cholesterol and triglycerides. The antropometric data, hepatic enzymes and mentioned tests were compared during 2 moments: admission and last appointment of each patient. The score Z was utilized to evaluate the weight and height of patients, considered if the standard deviation was under 2. The growth velocity was calculated among the second and first consult and the last and the penultimate consult. The adherence percentage was determined by the appointment absence percentage: Good: absenteeism minor 20%; regular: absenteeism major 20% and minor 40%; bad: absenteeism major 40%. The statistical tests applied were ANOVA, Kruskal-Wallis, Mann-Whintney, and Wilcoxon. The significance level was 5%. Results - The mean time during the first symptoms was 10,73 months and the mean time up to diagnosis was 28,18 months. The mean time of follow-up was 105 months. The most frequent initial clinical manifestations were: hepatomegaly in 21 (95%), protuberant abdomen in 19 (86%), doll face in 14 (64%), diarrhea in 10 (45%) and history hypoglycemia in 8 (36%). In the admission the deficit of the weight to age was 26% (5/19) and height to age was 35% (7/20), In the initial biochemical tests showed elevation of hepatic enzymes, hypercholesterolemia, hypertriglyceridemia, hypoglycemia. There was no statistical difference among the score Z weight to age, score Z height to age, body mass index and laboratorial tests of admission within 12 and 36 months. Significant differences were observed in BMI, hepatic enzymes, glycemia and triglycerides between the first and the last appointments, opposing to the score Z weight to age, score Z height to age, uric acid and cholesterol exam results. In the comparison of the growth velocity there was elevation tendency between the V1 and V2. There was difference significative of the growth velocity among the first and second versus the penultimate and the last consult. The adherence percentage was considered good in 64%. Conclusions - The patients delayed in seeking the reference center for glycogenosis early diagnosis. The most frequent clinical manifestations were protuberant abdomen, hepatomegaly, elevation of triglycerides and cholesterol, and glycemia reduction. In the evolution, there wasn¿t difference statistic in the antropometric parameters, but there was improvement tendency on the growth velocity. The treatment has improved the metabolic derangement / Mestrado / Saude da Criança e do Adolescente / Mestre em Saude da Criança e do Adolescente

Orientador: Glaucia Maria Pastore / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-15T20:38:55Z (GMT). No. of bitstreams: 1 Credidio_EdsonVelardi_D.pdf: 2059038 bytes, checksum: 19e54e694ea57437cf143cbfdce86ca5 (MD5) Previous issue date: 2010 / Resumo: O consumo regular de abacate Persea gratissima, tipo ¿Avocado¿, frutos que incluem as espécies Fuerte e Hass, foi avaliado em relação ao efeito sobre os lipídeos plasmáticos em humanos. Foi realizado estudo prospectivo, com intervenção. Foram selecionados voluntários militares, da ativa do Batalhão de Policia Militar de São Paulo em Campinas - Unidade de Saúde do CPI - 2 de Campinas, São Paulo. A escolha desta população alvo, foi a possíbilidade da utilização, de dieta e condicionamento físico uniformes e comparáveis. Os indivíduos selecionados, após assinatura Termo de Consentimento Livre e Esclarecido ¿ TCLE tiveram o sangue coletado para dosagem dos níveis de colesterol total e frações e de triglicérides, no início e após o consumo do abacate no término do experimento. Foram estimados os valores de Colesterol plasmático (HDL- LDL- VLDL) e Triglicérides , após a utilização da polpa da fruta do abacate por um período de dois meses tendo a finalidade de determinar o efeito do consumo do abacate nos lipídeos sanguíneos. Foi observado após o tempo de intervenção houve redução dos índices lipemicos com redução dos índices lipêmicos sanguíneos e significativo aumento do Colesterol ¿ HDL em 99% dos militares participantes. O grupo controle foi constituído pelos militares que mantiveram a mesma rotina dos voluntários, porém não ingeriram o abacate. Foram analisadas também a composição da polpa do fruto visando a melhor compreensão dos resultados obtidos na pesquisa / Abstract: The regular use of the Persea gratissima ¿Avocado¿ kind, fruits that include the Fuerte and Hass varieties, was evaluated in relation to the effects on the plasmatic lipids in human. A prospective study was realized with intervention. Soldiery volunteers in active from the battalion of São Paulo military police in Campinas ¿ CPI Health unit of Campinas, São Paulo. The choice of this specific group was the possibility to have an equal and comparable diet and physical condition. After the subscription of the informed consent ¿ IC, the select group had their blood collected for total cholesterol and fraction and triglycerides levels test, In the beginning and after the use of Avocado in the end of the experiment. The plasmatic (HDL ¿ LDL ¿ VLDL) cholesterol and triglycerides were obtained after the use of the pulp of Avocado for two months in order to determine the effect of the Avocado use in the blood lipids levels. It was observed, after intervention period, that there was a reduction of the blood lipemic levels and a significative HDL ¿ Cholesterol increase in 99% of the soldiery group. The control group was formed by soldiery that kept the same routine, but did not eat the Avocado. The nutritional composition of the Avocado pulp was also analyzed for a better understanding of the results, obtained in this work / Doutorado / Doutor em Ciência de Alimentos

Orientador: Maria Elena Guariento / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-20T22:26:50Z (GMT). No. of bitstreams: 1 Peterson_JoseCarlosBellini_D.pdf: 887202 bytes, checksum: 3b69bb83a27c8b2d5522e68aa050dc6d (MD5) Previous issue date: 2012 / Resumo: Fundamento: O hipotireoidismo subclínico é mais prevalente em mulheres idosas e existe uma correlação direta entre esta condição e as dislipidemias, com um conseqüente potencial aterosclerótico para a ocorrência de doenças cardiovasculares. Objetivo: Verificar em mulheres idosas com hipotireoidismo subclínico a ocorrência de variações em seus perfis lipídicos e o consequente risco cardiovascular. Métodos: Foram estudadas 121 mulheres com idade ? 65 anos, 76 delas com hipotireoidismo subclínico (grupo 1), comparadas a um grupo controle de 45 mulheres eutireoideas (grupo 2). Foi estudada a relação entre hipotireoidismo subclínico e valores de colesterol total, suas frações e triglicérides. Os índices de Castelli I e II foram utilizados para avaliar o risco cardiovascular. Foram excluídas outras condições que causem dislipidemia. Resultados: Pacientes com hipotireoidismo subclínico apresentaram valores mais elevados de colesterol total, suas frações (exceto HDL-c) e triglicérides; e os índices de Castelli I e II, quando comparadas ao grupo controle (p < 0,01). No grupo 1 foram identificados dois subgrupos de pacientes, o primeiro com menores valores na elevação TSH e nos Índices Castelli I e II; o segundo com maiores valores na elevação de TSH, e nos Índices de Castelli I e II. Conclusão: O estudo demonstrou uma forte correlação entre dislipidemia e hipotireoidismo subclínico e que quanto mais elevado o TSH, mais alterado o perfil lipídico, e mais elevados os índices de Castelli I e II, com conseqüente aumento do risco cardiovascular / Abstract: Background: Subclinical hypothyroidism is more prevalent in elderly women. There is a direct correlation between this condition and dyslipidemia, with consequent arteriosclerotic potential for the occurrence of cardiovascular diseases. Objective: The objective of this study was to verify in elderly women with subclinical hypothyroidism lipid profile variation, with consequent modification in cardiovascular risk. Methods: There were included 121 female patients with age ? 65 years old, 76 with subclinical hypothyroidism (group 1). They were compared with a 45 group control of euthyroid patients (group 2). Other conditions that lead to dyslipidemia were excluded. The relation between subclinical hypothyroidism and the levels of total cholesterol and its fractions, and triglycerides were studied. Also, indexes of Castelli I and II were used to evaluate cardiovascular risk. Results: Patients with subclinical hypothyroidism presented higher levels of all the fractions of cholesterol (except HDL-c), triglycerides and indexes of Castelli I and II, when compared to control group (p<0.01). In group 1, there were identified two subgroups of patients, being the first one with less elevated levels of TSH e lower levels of Castelli I and II, and the second one with higher levels of TSH and with a higher variation of the indexes of Castelli I and II. Conclusions: This study demonstrated a strong correlation between dyslipidemia and subclinical hypothyroidism in elderly women; in addition, it showed that the higher the TSH, the worse the lipid profile, and the higher indexes of Castelli I and II / Doutorado / Clinica Medica / Doutor em Clínica Médica

L'obésité est classiquement associée à plusieurs anomalies métaboliques comme l'insulinorésistance, la dyslipidémie et l'inflammation de bas grade, aujourd'hui reconnues comme facteurs de risques cardio-métaboliques. C’est également un composant fondamental du syndrome métabolique, un concept développé pour aider à l'identification des patients à haut risque cardio-métabolique. Pourtant, il existe une sous-population d'obèses dite "métaboliquement saine" qui est associée à un moindre risque. Cette sous-population n'est actuellement toujours pas définie de manière consensuelle mais l'insulinorésistance est essentielle dans les critères d'identification de la "santé métabolique". Une plus forte prévalence de l'insulinorésistance est associée à l'obésité abdominale, principal facteur diagnostique du syndrome métabolique, mais pourtant ces 2 phénotypes ne sont pas synonymes. Nous savons donc qu'il existe une hétérogénéité métabolique chez les patients obèses. Mon projet proposait d'identifier les meilleurs déterminants de l'insulinorésistance chez ces patients. Nous avons mis en évidence que l’inflammation de bas grade était associée aux marqueurs d’adiposité plutôt qu’à l’insulinorésistance, puis que les anomalies des métabolismes des glucides et des lipides, plus particulièrement les triglycérides et l’hémoglobine glyquée A1c, étaient les principaux facteurs associés de l’insulinorésistance chez nos patients obèses. Ceci restaure l’intérêt de ces dosages simples qui, associés à l’indice de masse corporelle, pourraient servir d’outils rapides et peu couteux pour aider le clinicien à identifier les individus insulino-résistants, alors que les nombreuses définitions du phénotype « obèse métaboliquement sain » ne font pas encore consensus. / Obesity is classically associated with a constellation of metabolic pattern including insulin-resistance, dyslipidemia and low-grade inflammation, now clustered as cardio-metabolic risk factors. Obesity is also a main component of the metabolic syndrome, which has become one of the major public health challenges in helping identify individuals at high risk of both type 2 diabetes and cardiovascular diseases. However a subgroup of metabolically healthy individuals with obesity (MHO) who might be at lower risk of cardiovascular events has been clinically recognized but no universally accepted criteria exist to define it.Assessment of insulin resistance phenotype is essential, and for most definitions of metabolic health, insulin sensitivity is taken into account. It is well accepted that a higher prevalence of insulin resistance is associated with abdominal obesity measured by waist circumference in routine. Although abdominal adiposity is a major component of the concept of metabolic syndrome, it appears that metabolic syndrome is not synonymous with the insulin resistance phenotype. We can assume that there is heterogeneity in the metabolic status of patients with obesity. Accordingly, the aim of my project was to explore what are the best determinants of insulin resistance in the obesity condition. We showed that inflammation was associated to fat accumulation rather than insulin resistance and that triglycerides and glycated hemoglobin were the factors best correlated to insulin resistance. Finally, a simple blood test as triglycerides and glycated hemoglobin determination could be an easy and available method to help physicians identify obesity related insulin resistance for appropriate prevention.

Background: Clinical management of dyslipidemia is challenging, particularly hypertriglyceridemia in patients with HIV-infection. Changing combined anti-retroviral therapy (CART) and the use of lipid-lowering drugs have proven useful in treating dyslipidemia in HIV infected patients Objective: To assess the efficacy of lipid lowering drugs (LLDs) and/or CART switching, in the management of HIV-associated dyslipidemia Design: A retrospective, longitudinal cohort study Setting: Phidisa HIV research project, 6 sites in South Africa, period April 2008 and April 2011 Patients: HIV positive South African National Defence Force (SANDF) members and their dependents; who are on CART and are 18 years or older. Four hundred and forty eight participants with dyslipidemia had non-fasted, total serum cholesterol ≥ 8.0mmol/l, serum triglyceride levels ≥4.52 mmol/l and naïve to lipid lowering drugs at baseline. Measurements: Mean change over time of total serum cholesterol and serum triglyceride in the following treatment strategies were used: exercise and dietary advice, lipid-lowering drugs (statins or fibrates or both), CART switches separately and combined lipid lowering drug with ART switch was measured using panel data with first–order autoregressive-response and xtabond. Results: The mean age for a total of 448 participants was 39.9 years; males were 87%, females were only 13%. The participants contributed to 1861 follow-up visits. CD4 count was normally distributed with the baseline mean value of 402 cells/mm3 (18.5%). Mean change over time for total serum cholesterol and triglycerides increased by 0.099 mmol/l (p=0.007) and 0.248 mmol/l (p=0.018) respectively, with an increase in body mass index while an increase in CD4 cell percent decreased mean over time for total serum cholesterol by 0.045 mmol/l (p=0.002). Our hypothesis was confirmed when lipid lowering drugs and ART switch combined treatment strategy even more decrease in the mean total serum cholesterol and triglycerides levels over time by 0.754 mmol/l (p<0.001) and 2.073 mmol/l (p<0.001) respectively compared to the exercise and dietary advice treatment strategy. Our findings showed that combined treatment strategy maintained a decrease in both the mean total serum cholesterol and triglycerides levels over time of 0.283 mmol/l (p=0.038) and 0.941 mmol/l (p=0.016) respectively, when compared to lipid lowering drugs; the mean serum triglycerides over time were also reduced by 0.486 mmol/l (p=0.048) when the combined treatment strategy was compared to CART switch only. Furthermore combined treatment strategy of lipid lowering drugs with ART switch showed significant virological suppression by decreasing log of viral load, 0.486 (p<0.001) when compared to the exercise and dietary advice group. Conclusions: Combining lipid lowering drugs and ART switching as a treatment strategy in the management of HIV-associated dyslipidemia is effective in lowering the mean over time of both total serum cholesterol and triglycerides when compared to exercise and dietary advice strategy, while maintaining virological suppression. / Dissertation (MSc)--University of Pretoria, 2015. / tm2015 / School of Health Systems and Public Health (SHSPH) / MSc / Unrestricted

Background: Obstructive sleep apnea (OSA) consists of repeated, involuntary breathing suspension during sleep. These events induce rapid depletion/repletion of blood/tissue oxygen content, a phenomenon known as intermittent hypoxia. Aside from causing daytime sleepiness, the most important health consequence of OSA is a 2-fold increase in cardiovascular (CVD) risk. Animal studies provide evidence that intermittent hypoxia, a simulating model of OSA, causes important rise in plasma TG, especially in the postprandial state. However, the underpinning mechanisms linking intermittent hypoxia to altered postprandial TG levels remain unknown. As such, the objective of this study was to characterize the effects of acute intermittent hypoxia on postprandial TG levels in 2 distinct lipoprotein subtypes in humans: chylomicrons which are secreted by the intestine and carry dietary lipids, and denser TG carriers (mainly VLDL) which are secreted by the liver and carry endogenous lipids. Methods: The research consisted of a randomized crossover design. In collaboration with the Sleep laboratory at Montfort Hospital, 7 individuals diagnosed with moderate sleep apnea were recruited through phone calls as well as 8 healthy individuals without OSA from the University of Ottawa. While lying on a bed, participants were given a meal after which they were exposed for 6 hours to normoxia or intermittent hypoxia corresponding to moderate OSA, e.g. 15 hypoxic events per hour. Blood lipid levels were measured hourly.  Results: Plasma TG levels increased over time in both experimental conditions and tended to be greater under 6-h exposure to intermittent hypoxia (p=0.093, effect size ηp2= 0.383.). This trend toward higher total plasma TG under intermittent hypoxia was attributable to increased levels in denser TG carrying lipoproteins such as VLDL and CM remnants (p= 0.009, ηp2 = 0.173).  Conclusion: Acute intermittent hypoxia, a simulating model of obstructive sleep apnea, tends to negatively affect postprandial TG levels, which is attributable to an increase in denser TG carrying lipoprotein levels such as VLDL and CM remnants. These results lend support to the increase in blood lipid levels in animal studies observing the effect of acute hypoxia in mice.  Contribution to advancement of knowledge: This proposed research will allow a better understanding of the mechanisms by which obstructive sleep apnea may alter blood lipid profile. This information will be beneficial to the treatment of obstructive sleep apnea related dyslipidemia and contribute to reduce CVD risk in the large proportion of obstructive sleep apnea patients who are reluctant to current treatment avenues.