Overproduction of intestinal chylomicrons (CM) has been proposed to contribute to fasting and post-prandial (PP) dyslipidemia and may accelerate the development of cardiovascular disease (CVD) during obesity, insulin resistance (IR) and diabetes. However, the impact of morphological changes in intestinal mucosa structure have not been investigated during IR and intestinal dyslipidemia. The first objective of this thesis was to characterize intestinal villi morphology and to determine whether a morphological relationship exists with enterocytic apoB48 (a marker of CM), and intestinal lymph secretion of apoB48 in the obese and IR JCR:LA-cp rat. The second objective was to assess the impact of n-3 PUFA supplementation on PP dyslipidemia in the JCR:LA-cp rat. Intestinal hypertrophy was observed in IR rats, corresponding to an increase in intestinal and lymphatic apoB48 expression. Further, a dietary intervention of n-3 PUFA showed lower PP plasma concentrations of apoB48 and PP plasma inflammatory markers. We conclude that intestinal hypertrophy may contribute to intestinal CM overproduction during obesity and IR. Additionally, dietary n-3 PUFA improves PP lipemia and the associated PP inflammatory response in the JCR:LA-cp rat model. / Nutrition and Metabolism

A new variant of human apolipoprotein B has been identified in a subject with decreased low density lipoprotein cholesterol and apolipoprotein B concentrations. Although no clinical signs of fat malabsorption were observed the subject was diagnosed, on the basis of his low cholesterol and apolipoprotein B level, as having hypobetalipoproteinaemia. The variant of apolipoprotein B was first identified by Western blot analysis. The analysis revealed an abnormal low molecular weight form of apolipoprotein B as well as normal apolipoprotein B-100 indicating that the subject was heterozygous for a truncated form of apolipoprotein B. The new variant (apo B-32) was a result of a C→T transition at nucleotide 4548 in exon 26 of the apolipoprotein B gene. This mutation changes a CAG codon which codes for glutamine into a TAG stop codon resulting in translation of a truncated apolipoprotein B protein approximately 32% the length of normal apolipoprotein B-100. Although only 32% of the length of apolipoprotein B-100, apo B-32 was still capable of forming lipoprotein particles as indicated by its presence in both the low density and high density lipoprotein fractions. This density distribution is unique since apo B-32 is the shortest known truncated apolipoprotein B to be found in the low density lipoprotein fraction. This finding clearly indicates that the region of apo B-32 is important in the lipid binding characteristics of apolipoprotein B-100. The binding of apo B-32 to heparin confirmed three heparin binding sites previously predicted to be in the amino-terminal 30% of apolipoprotein B-100. Isolated lipoproteins formed from apo B-32 appeared to be similar to high density lipoproteins in size and composition. However, unlike high density lipoproteins, the apo B-32 lipoproteins in plasma were partially precipitated by polyanionlcation reagents normally used to precipitate very low density and low density lipoproteins. The presence of both apolipoproteins Al and E on the apo B-32 lipoproteins suggested that apolipoprotein Al or E may mediate the metabolism of apo B-32 since apo B-32 does not posses the receptor binding region for the low density lipoprotein receptor. Four further subjects were identified as having reduced low density lipoprotein and apolipoprotein B concentrations. However a lack of any truncated apolipoprotein B in their plasma made it difficult to link their hypobetalipoproteinaemia with the apolipoprotein B gene. The cause of the hypobetalipoproteinaemia in these subjects remains uncharacterised although future linkage analysis studies in these individuals and family members will at least establish whether their hypobetalipoproteinaemia is related to the apo B gene.

[Truncated abstract] The metabolic syndrome is characterized by cardiovascular risk factors including dyslipidemia, insulin resistance, visceral obesity, hypertension and diabetes. The dyslipidemia of the metabolic syndrome includes elevated plasma triglyceride and apolipoprotein (apo) B levels, accumulation of small, dense low-density lipoprotein (LDL) particles and low high-density lipoprotein (HDL) cholesterol concentration. However, the precise mechanisms for this dyslipoproteinemia, specifically low plasma HDL cholesterol, are not well understood. This thesis therefore, focuses on HDL, its structure, function and metabolism. However, lipoprotein metabolism is a complex interconnected system, which includes forward and reverse cholesterol transport pathways. Hence, this thesis also examines and discusses the metabolism of apoB-containing lipoproteins. This thesis tests the general hypothesis that apolipoprotein kinetics are altered in the metabolic syndrome, and that lipid regulating therapies can improve these kinetic abnormalities. The aims were first, to compare and establish the clinical, metabolic and kinetic differences between metabolic syndrome and lean subjects; and second, to determine the regulatory effects of statin therapy, specifically, rosuvastatin on lipoprotein transport in the metabolic syndrome. Five observation statements were derived from the general hypothesis and examined in the studies described below. The findings are presented separately as a series of original publications. Study 1 Twelve men with the metabolic syndrome and ten lean men were studied in a case-control setting. ... These findings explain the HDL raising effects of rosuvastatin in the metabolic syndrome. Collectively, these studies suggest that the dyslipidemia of the metabolic syndrome results from increased production rates of VLDL and LDL particles, reduced fractional catabolic rates of these lipoproteins, together with accelerated catabolism of HDL particles. Treatment with rosuvastatin increases the catabolic rates of all apoB-containing lipoproteins and at a higher dose, decreases LDL apoB production. These effects are consistent with inhibition of cholesterol synthesis leading to an upregulation of LDL receptors. Rosuvastatin decreases the fractional catabolism of HDL particles. The effects of rosuvastatin on HDL kinetics may be related to a reduction in triglyceride concentration and cholesterol ester transfer protein activity. These findings are consistent with the general hypothesis that apolipoprotein kinetics are altered in the metabolic syndrome, and that statin therapy improves these kinetic abnormalities.

Diss. (sammanfattning) Umeå : Univ., 2004. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Washington, 1997. / Vita. Includes bibliographical references (leaves [83]-113).

BACKGROUND & AIMS - Metabolic syndrome (MetS), characterized by abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, and insulin resistance is a major public health concern in the United States. The effect of Apolipoprotein E (Apo E) polymorphism has been relatively well studied in relation to cardiovascular disease; however, its effects on MetS are not well established. METHODS - We conducted a cross-sectional study consisting of 1,551 participants from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study to assess the relation of Apo E polymorphism with the prevalence of MetS. Information on the different Apo E genotypes was extracted from the database and we defined MetS according to the AHA-NHLBI-IDF-WHO Harmonized Criteria. We used generalized estimating equations to estimate adjusted odds ratios for prevalent MetS and the Bonferroni correction to account for multiple testing in the secondary analysis. RESULTS – Our study population had a mean age (SD) of 56.5 (11.0) years and 49.7% had MetS. There was no association between the Apo E genotypes and MetS. The multivariable adjusted ORs (95% CI) were 1.00 (reference), 1.26 (0.31-5.21), 0.89 (0.62- 1.29), 1.13 (0.61-2.10), 1.13 (0.88-1.47) and 1.87 (0.91-3.85) for the *e3/e3, *e2/e2, *e2/e3, *e2/e4, *e3/e4 and *e4/e4 genotype respectively. In a secondary analysis, the *e2/e3 genotype was associated with lower HDL levels, with the multivariable adjusted ORs (95% CI) of 0.59 (0.36-0.95) when compared to the reference *e3/e3 genotype. CONCLUSIONS - Our findings do not support an association between Apo E polymorphism and MetS in a multi-center population based study of predominantly white US men and women. The *e2/e3 genotype was associated with lower HDL levels as compared to the *e3/e3 genotype. KEY WORDS: Apolipoprotein E (Apo E) polymorphism, metabolic syndrome, blood pressure, glucose, waist circumference, triglycerides, high-density lipoprotein cholesterol

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2013-10-18T17:05:09Z No. of bitstreams: 1 Marcos Soares Vieira.Atividades das paraoxanase... 2013.pdf: 1230050 bytes, checksum: 912c1ef5707ad9fba3fa861c29a41e7e (MD5) / Made available in DSpace on 2013-10-18T17:05:09Z (GMT). No. of bitstreams: 1 Marcos Soares Vieira.Atividades das paraoxanase... 2013.pdf: 1230050 bytes, checksum: 912c1ef5707ad9fba3fa861c29a41e7e (MD5) Previous issue date: 2013 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Doenças cardiovasculares (DCV) são as principais causas de morbidade e mortalidade do ocidente, aparecendo como causa mais frequente de óbitos nos países desenvolvidos e em desenvolvimento. Alterações no metabolismo das lipoproteínas estão diretamente relacionadas ao aumento do risco de DCV. Objetivos: Avaliar o remodelamento da partícula HDL determinando a capacidade de incorporação de fosfolipídeos na HDL, a atividade da paraoxonase/aril-esterase (PON), dentre outros marcadores plasmáticos relacionados ao metabolismo da HDL, além da influência da hipertrigliceridemia neste processo. Casuística e Métodos: Estudo de corte transversal, com amostragem por conveniência. Foram avaliados ambulatorialmente 66 indivíduos do sexo masculino, idade entre 32 e 75 anos (média: 51,1), distribuídos em dois grupos, não-hipertrigliceridêmicos (NHipTRI) e hipertrigliceridêmicos (HipTRI), estes últimos estratificados em dois níveis, HipTRI HDL-C≥40 e HipTRI HDL-C<40. Foram realizados testes estatísticos paramétricos e não-paramétricos, utilizando o software GraphPad Prism 5.01 (USA), e as diferenças foram consideradas significantes quando p<0,05 para intervalo de confiança de 95%. Resultados: Não foram observadas diferenças nas prevalências dos fatores de risco para DCV, como sedentarismo, etilismo, hipertensão, diabetes e tabagismo, entre os grupos. A atividade da PON e a incorporação de fosfolipídeos foram similares nos três grupos estudados. O tamanho estimado da partícula HDL foi maior no grupo NHipTRI (0,29±0,05), do que nos grupos hipertrigliceridemicos: HipTRI HDL ≥40 (0,26±0,03), e HipTRI HDL<40 (0,24±0,05). No grupo NHipTRI foi encontrada correlação linear positiva entre a atividade da PON e apoA (r=0,3908, p=0,0484, Pearson). Já no grupo HipTRI HDL≥40 houve correlação positiva entre PON e apoB (r=0,5678, p=0,0342, Pearson). Por outro lado, no grupo HipTRI HDL<40 houve correlação linear negativa entre apoB e incorporação de fosfolipídeos na HDL (r=-0,5144, p=0,0290, Pearson). Conclusão: Desta forma, os resultados sugerem que a hipertrigliceridemia interfere não só no remodelamento da HDL, como também sua capacidade antioxidante. / Cardiovascular diseases (CVD) are the leading causes of morbidity and mortality in the western world and is the major cause of death in developed and developing countries. Lipoprotein metabolism is directly related to the risk of developing CVD. Objectives: this study aimed to evaluate HDL particle remodeling, determining HDL ability to incorporate phospholipids, paraoxonase (PON) activity, among others plasma markers related to HDL metabolism, besides the influence of hypertriglyceridemia in this process. Casuistic and Methods: a cross-sectional study with convenience sampling, were carried out with 66 subjects outpatient males, aged between 32 and 75 years old (mean: 51.1), into nonhypertriglyceridemic (NHipTRI) and hypertriglyceridemic (HipTRI) groups, the HipTRI group were stratified in HipTRI com HDL-C ≥ 40 mg/dL and HipTRI com HDL-C <40 mg/dL. Parametric and non-parametric statistic tests were performed in GraphPad Prism 5.01 (USA), and differences were considered significant when p <0.05 to C.I of 95%. Results: there were no differences in the prevalence of CVD risk factors, such as sedentarism, alcohol drinkers, hypertension, diabetes, and tobacco users in the groups. PON activity and phospholipids incorporation were similar in the three groups. The estimated size of HDL particles was greater in NHipTRI (0.29 ± 0.05) when compared to hypertriglyceridemic groups: HipTRI HDL≥40 mg/dL (0.26 ± 0.03) and HipTRI HDL>40 mg/dL (0.24 ± 0.05). In NHipTRI group positive linear correlation was found between PON activity and apoA (r = 0.3908, p = 0.0484, Pearson). In HipTRI HDL≥40 mg/dL group, positive correlation were found between PON and apoB (r = 0.5678, p = 0.0342, Pearson). On the other hand, HipTRI HDL<40 mg/dL shows a negative linear correlation between apoB and phospholipids incorporation into HDL (r = -0.5144, p = 0.0290, Pearson). Conclusion: the results suggest that hypertriglyceridemia can affect both remodeling of particles HDL, as their antioxidant capacity.

Em trabalhos anteriores, mostrou-se que uma nanoemulsão lipídica denomi-nada LDE após injeção endovenosa, em pacientes com carcinoma mamário e outros tumores sólidos concentra-se nos tecidos neoplásicos e pode direcionar especificamente agentes quimioterápicos ao tumor. Estudos clínicos mostraram que a LDE diminui acentuadamente os efeitos tóxicos desses agentes e em estudos com animais de experimentação não reduz seus efeitos antitumorais. No presente estudo, testamos a hipótese de a LDE injetada por via locorregional poderia concentrar-se no tumor de mama e nos linfonodos axilares da mama comprometida, visando futuras aplica-ções do sistema na quimioterapia neoadjuvante desse tumor. Três técnicas de injeção da LDE foram testadas em pacientes com carcinoma de mama avançado com tratamento cirúrgico pré-programado. A LDE marcada com colesterol radioativo foi injetada 12 horas antes da cirurgia, nas pacientes divididas em três grupos: Grupo 1 (G1, n=4): LDE injetada no parênquima mamário, a 5 cm da lesão ; Grupo 2 (G2, n=4): LDE injetada na região peri-tumoral; e Grupo 3 (G3 n=6): LDE injetada em região intratumoral. Este grupo foi subdividido em 2: em 2 pacientes realizaram cirurgia 2hs após a injeção da LDE e nas outras 4, 12hs após a injeção da LDE. Quantificou-se a capta-ção da LDE nos fragmentos de tecido tumoral e mamário normal e do linfonodo axilar retirados durante a cirurgia por contagem de radioatividade após extração lipídica dos tecidos. Os resultados evidenciaram que, em G1, houve maior captação da LDE em tecido normal, sugerindo se tratar de metodologia ina-dequada. Em G2, a captação da LDE foi quatro vezes maior no tecido tumo-ral do que no tecido normal, próximo, portanto, dos valores encontrados em estudos anteriores que utilizaram a injeção da LDE por via hematológica. Em G3, o valor médio de captação da LDE foi 53 vezes maior no tecido tumoral (>75%), com mínima captação pelo tecido mamário normal (<8%). A injeção intratumoral da LDE mostrou-se, portanto, metodologia ainda superior à inje-ção da LDE por via endovenosa para a utilização efetiva dessa nanoemulsão como terapia-alvo em tumores primários de mama. / In previous work had showed that a lipidic nanoemulsion called LDE after intravenous injection in patients with breast carcinoma and others solid tumors focuses in the neoplasic tissue and can target especially chemotherapist agents to the tumors. Clinical studies showed that LDE decreases the toxic effects of those agents and in studies with experimental animals don\'t reduce yours antitumoral effects. In the present study, we had test the hypothesis of the LDE injected by locoregional could focuses in the breast tumor and in the axillary lymph node of the compromised breast, targeting future applications of the system in the neoadjuvant chemotherapy of this tumor. Three techniques of injection of the LDE had test in patients with advanced breast carcinoma with sirurgic treatment pre-programmed. The LDE marked with radioactive cholesterol was injected 12 hours before the surgery, in patients divided in three groups: Group 1 (G1, n=4): LDE injected in the breast parenchyma, about 5 cm of the lesion; Group 2 (G2, n=4): LDE injected in the peritumoral region; and Group 3 (G3, n=6): LDE injected in the intratumoral region. This group was subdivided in 2: in 2 patients had realized surgery 2 hs after the injection of LDE and in the others 4 patients 12hs after the injection of LDE. It had quantified the capture of LDE in the fragments of the tumoral and breast tissue and of the axillary lymph node withdrawn during the surgery by counting of radioactive after lipidic extraction of this tissue. The results showed that, in G1, there was greater capture of LDE in normal tissue, suggesting it is an inappropriate methodology. In G2, the capture of LDE was four times higher in the tumoral tissue than in the normal tissue, closer, therefore, of the values found in previous studies that used the injection of LDE by hematology. In G3, the medium value of capture of LDE was 53 times higher in the tumoral tissue (> 75%), with minimum capture by the normal breast tissue (< 8%). The intratumoral injection of LDE showed, therefore, methodology still higher than the intravenous injection of LDE by intravenous for the effective use of this nanoemulsion as therapy target in primary tumors of breast.

Introdução: As dislipidemias representam um dos principais fatores de risco para as doenças cardiovasculares e, particularmente, para a aterosclerose. Portanto, todos os fatores nutricionais capazes de reduzir a sua incidência ou melhorar seu quadro clínico, representam ferramentas importantes para sua prevenção ou tratamento. Além das dislipidemias, as modificações oxidativas da lipoproteína de baixa densidade (LDL) têm relação direta com o processo aterosclerótico. Objetivos: O objetivo deste estudo foi avaliar a possível influência dos Parâmetros Nutricional (alimentar e antropométrico) e Bioquímicos sobre a geração de LDL- em indivíduos com diferentes níveis de risco cardiovascular Métodos: Para a consecução destes objetivos foram avaliados indivíduos com hipercolesterolemia associada à LDL com (n = 10) ou sem (n = 33) aterosclerose, quando comparados aos indivíduos normocolesterolêmicos (n = 30). A partir desta amostra avaliou-se o hábito alimentar (questionário quantitativo de freqüência alimentar), a antropometria (peso, altura, circunferência da cintura, % de gordura corporal e % de massa magra), o perfil lipídico (colesterol e triacilgliceróis), o conteúdo de LDL- (plasma, LDL total e sub-frações de LDL) e os auto-anticorpos anti-LDL- no plasma. O diagnóstico de aterosclerose foi feito através da pesquisa dos prontuários e da avaliação do índice tornozelo-braço (ITB). Resultados: A análise do perfil lipídico indicou que a concentração de colesterol plasmático no grupo Controle (180,5 ± 19,6 mg/dL) foi menor que a observada nos grupos Hipercolesterolêmico – Hiper (-) (243,5 ± 29,7 mg/dL) e Hipercolesterolêmico com aterosclerose – Hiper (+) (221,1 ± 19,6 mg/dL), sendo a dislipidemia observada resultante do acúmulo de colesterol na LDL. O monitoramento da LDL- no plasma e de seus auto-anticorpos não apresentou diferença significativa entre os grupos. Entretanto, quando se analisou a LDL- na LDL total verificamos que o grupo Controle apresentou conteúdo inferior (850,2 ± 337,8 DO) aos grupos Hiper (-) (1253,1 ± 340,9 DO) e Hiper (+) (1258,5 ± 207,4 DO). Em relação ao hábito alimentar, o grupo Controle apresentou menor consumo de carboidratos e vitamina C, quando comparado ao grupo Hiper (+), e este consumo inferior de ácido graxo monoinsaturado (AGM), ácido graxo poliinsaturado (AGP) e ácido linoléico que o grupo Hiper (-). Não observamos diferença significativa nos parâmetros antropométricos. Considerando que o conteúdo de LDL- no plasma e na LDL (+) densa apresentou correlação positiva, além das correlações positivas entre LDL- isolada e normalizada pelas proteínas e colesterol tanto no plasma, quanto na LDL total e nas sub-frações de LDL, estabelecemos correlações entre estas variáveis e os parâmetros clínicos, de consumo, de composição corporal e bioquímicos. Neste sentido, observamos que houve correlação da pressão arterial sistólica com LDL- no plasma (r = 0,26 e p = 0,03) e escore de risco de Framingham com LDL- na LDL (r = 0,36 e p = 0,01). Em relação ao consumo alimentar, houve correlação entre o consumo de gordura e colesterol com o conteúdo de LDL- no plasma (r = 0,27 e p = 0,02; r = 0,27 e p = 0,02, respectivamente). Verificamos também correlação entre LDL- presente na sub-fração menos densa da LDL com o consumo de AGM (r = -0,27 e p = 0,02), AGP (r = -0,23 e p = 0,05), ácido oléico (r = -0,23 e p = 0,05), ácido linoléico (r = -0,31 e p = 0,01) e vitamina A (r = -0,25 e p = 0,03). As variáveis antropométricas e de composição corporal não apresentaram correlação significativa com a geração de LDL- no plasma, na LDL total e nas sub-frações de LDL, nem com seus auto-anticorpos. Quando avaliamos o perfil lipídico e a LDL- na LDL, observamos correlação positiva com colesterol total (r = 0,52 e p &#8804; 0,001), colesterol associado à LDL, pela equação de Friedewald e analisado na lipoproteína isolada (r = 0,59 e p &#8804; 0,001; r = 0,75 e p &#8804; 0,001, respectivamente), as relações colesterol total/HDL (r= 0,45, p &#8804; 0,001) e LDL/HDL (r= 0,47, p &#8804; 0,001) e colesterol não HDL (r= 0,74, p &#8804; 0,001). Conclusões: Os resultados obtidos mostram que a LDL-, sobretudo quando analisada na LDL, é um importante e sensível parâmetro bioquímico associado ao perfil lipídico, a outros parâmetros de risco cardiovascular e ao consumo alimentar. Portanto, sugere-se que o monitoramento da LDL- faça parte dos protocolos clínicos, visto que este marcador sofre variação em função de fatores exógenos, clínicos e bioquímicos. / Introduction: The dyslipidemias is very important to coronary artery disease (CAD) development, specially in atherosclerosis. Therefore, all nutritional factors able to decrease its incidence represent important tools in the prevent or treatment. In this respect, oxidized low-density lipoprotein (LDL) has been associated to atherosclerotic process. Objectives: Our goal was to evaluate the influence of the Nutritional (intake and anthropometria) and Biochemical Parameters in generation of LDL- in subjects with different levels of cardiovascular risk. Methods: Subjects with hypercholesterolemia associated to LDL with (n = 10) or without (n = 33) atherosclerosis and normocholesterolemic (n = 30) were selected. Habitual food intake (quantitative food frequency questionnaire), anthropometric parameters (weight, heath, waist circumference, % body fat and % mass muscular) were evaluated. In plasma we evaluated lipid profile (cholesterol and triglycerides), LDL- content (plasma, LDL and LDL subfractions) and auto-antibodies anti-LDL-. Atherosclerosis was confirmed by register and ankle-brachial blood pressure index (ABI). Results: The plasma cholesterol in group Control (180.5 ± 19.6 mg/dL) was lower than compared to Hiper (-) group (243.5 ± 29.7 mg/dL) and Hiper (+) group (221.0 ± 19.6 mg/dL). This dyslipidemia was associated to high levels of LDL-cholesterol. The content of LDL- in plasma and its autoantibodies against did not have any significant difference between groups. However, when LDL- content was analyzed in total LDL we verified that Control group showed menas lower (850.2 ± 337.8 DO) than Hiper (-) (1253.1 ± 340.9 DO) and Hiper (+) (1258.5 ± 207.4 DO) groups. Carbohydrate and vitamin C intake in Control group was lower than Hiper (+) group. Monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA) and acid linoleic intake in Hiper (+) was higher than Hiper (-) group. No significant differences in anthropometric parameters were observed when all groups were evaluated. When we analyzed the possible association between variables, we verified positive correlation between blood pressure arterial systolic with LDL- plasma (r = 0.26 and p = 0.03) and Framingham risk score with LDL- in LDL (r = 0.36 and p = 0.01). Total fat and cholesterol intake was correlated to LDL- plasma (r = 0.27 and p = 0.02; r = 0.27 and p = 0.02, respectively). In addition we observed a correlation between LDL- in dense low LDL subfraction with MUFA (r = -0.27 and p = 0.02), PUFA (r = -0.23 and p = 0.05), acid oleic (r = -0.23 and p = 0.05), acid linoleic (r = -0.31 and p = 0.01) and vitamin A (r = -0.25 and p = 0.03). The anthropometric parameters did not show any significant correlation with the LDL- content and its autoantibodies. LDL- in LDL had positive correlation with total cholesterol (r = 0.52 and p &#8804; 0.001), cholesterol associated LDL as calculated by Friedewald equation and crude analysis (r = 0.59 and p &#8804; 0.001; r = 0.75 and p &#8804; 0.001, respectively), TC/HDL ratio (r= 0.45 and p &#8804; 0.001), LDL/HDL ratio (r= 0.47 and p &#8804; 0.001) and non cholesterol HDL (r= 0.74 and p &#8804; 0.001). Conclusion: These results showed that certain component diet could modulate LDL- generation. Furthermore, this particle was correlated with the lipid profile and some of the factors that predispose for cardiovascular desiase.

O efeito do fotossensibilizador na estrutura biológica não é apenas influenciado por suas propriedades fotofísicas, mas também por sua interação específica com biosistemas.Além disso, a localização do fotossensibilizador no tecido tumoral é um importante fator que resulta em diferentes mecanismos de destruição do tumor. Muitos fotossensibilizadores, após administração sistêmica, se ligam às proteínas plasmáticas e com isso são distribuídos em diferentes sítios no organismo. Os fotossensibilizadores hidrofílicos são largamente transportados por albuminas e globilinas e se acumulam preferencialmente no estroma vascular dos tumores. Entretanto, fotossensibilizadores mais hidrofóbicos se ligam às lipoproteínas, principalmente LDL, que promove a entrada do FS na célula através de endocitose mediado por receptor. Sendo assim, a localização do FS depende de sua ligação com as deferentes proteínas plasmáticas, sua farmacocinética e também é influenciada pela diferença entre o tecido normal e tumoral. O tecido tumoral tem pH mais baixo e maior expressão de receptores de LDL do que os tecidos normais, aumentando a seletividade dos FSs as células tumorais. A incorporação de FS hidrofóbicos em lipossomas para a administração sistêmica pode realçar ao transporte deste pelas lipoproteínas. No presente trabalho estudou-se a influência do pH na interação de fotossensibilizadores com lipossomas de DMPC e LDL. Os fotossensibilizadores utilizados nesse estudo foram Photofrin®, Photogem® e Photosan® que são derivados de hematoporfirinas. A metodologia empregada constitui de variação das concentrações de DMPC e LDL para os seguintes valores de pHs 5,0; 7,4 e 9,0, esse último pH utilizou-se somente para DMPC. O complexo FS - DMPC foi obtido por incubação dos FSs na concentração de 10 micro g.mL-1 com diferentes concentrações de DMPC (0 a 400 micro M) por trinta minutos no escuro. Isolou-se o LDL do plasma humano por ultracentrifugação por gradiente de densidade. Após a separação, o complexo FS - LDL foi obtido por incubação (12 horas no escuro) do FS na concentração 10 micro g.mL-1 com diferentes concentrações de LDL (0 a 0,04 micro M). O comportamento desses complexos foi analisado por espectroscopia de absorção ótica e por espectroscopia de fluorescência. / The effect of a photosensitizing compound on biological structures is governed not only by its photophysical properties but also by the specificity of its interaction with biosystems. Moreover, localization of the photosensitizer in the tumor tissue is an important factor affecting the outcome as well as mechanism leading to tumor destruction. Following administration, most photosensitizers are bound to blood components and delivered to different sites in the organism. It is generally accepted that hydrophilic photosensitizers are largely transported by albumins and globulins and mainly accumulate in the vascular stroma of tumors. More hydrophobic sensitizers are bound to lipoproteins, which promote drug internalization by cells through endocytosis of the lipoprotein carrier. In this way, uptake and localization depend on the initial plasma binding and the plasma pharmacokinetics of the drug. However, the selective localization of some photosensitizers are influence for the difference between malignant and normal tissues. Notably, the lower pH of the microenvironment usually found in the tumor tissue and the expression of greater number of LDL receptors on the surface of the tumor cells might influence cellular uptake. Delivery to lipoproteins or target tissues may be facilitated and enhanced by the incorporation of lipophilic photosensitizers into liposomes for systemic administration. In the present work we have studied the pH-dependence of the interaction of photosensitizers with DMPC liposomes and low density lipoprotein (LDL). The photosensitizers used in this study are Photofrin®, Photogem® and Photosan®, which are hematoporphyrin derivates. The methodology used to this work, constitute of various concentrations of DMPC liposomes and LDL at different pH values. It were used the 5,0; 7,4 and 9,0 pH values. The DMPC-drug complexes were obtained by incubation of the photosensitizers 10 _g.mL-1 with differents DMPC concentrations for 30 min in the dark. The LDL was isolated from human plasma by sequential density gradient ultracentrifugation. The LDL-drug complexes were obtained by incubation of the photosensitizers 10 _g.mL-1 with differents LDL concentrations. The incubation was performed in a water bath at 20_C for 12 hours in the dark. The comportment of the complexes was analyzed by fluorescence spectroscopy and UV-visible spectroscopy.