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Synthesis of Bioactive Nitrogen Heterocycles and Functionalized Nanomaterials for Biological and Catalytic ApplicationsKrishnan, Anand 15 January 2015 (has links)
Submitted in fulfillment of the requirements of the Degree of Doctor of Technology: Chemistry,Durban University of Technology, 2014. / Aromatic heterocycles are highly important structural units found in a large number of biologically active natural compounds, pharmaceuticals and catalytic compounds. They have a crucial role in organic syntheses, which results in the generation of high value products. Among heterocycles, those containing nitrogen are the most indispensable structural motifs and are widely used against dreaded diseases such as Malaria, TB, HIV/AIDS and Cancer. The inclusion of highly electronegative atoms such as fluorine in these organic molecules render them very reactive towards proteins. Furthermore these molecules exhibit strong interactions with surfaces of quantum range particles of elemental gold. Various approaches for the synthesis of novel gold nanoparticles linked to potent bioactive molecules are documented and their application as drug delivery systems are of immense value to human health. Also many chemical and physical methods are available for the synthesis of gold, silver and palladium nanoparticles however these methods are usually laborious and produce toxic by-products. The green approach is to use plant extracts to synthesise various size and shape nanoparticles which could be used in biological and catalytic systems.
A simple one-pot two component and three component reaction using formyl quinoline, 2-aminothiophenol, thiosemicarbazone and trifluoromethylbenzaldehyde as a reactant to synthesise quinoline, pyridine and pyran based bioactive small molecules; these products are a quinoline type bearing a benzothiazole moiety, quinoline thio semicarbazone ligand, fluorine substituted dihydro pyridine, fluorine substituted dihydropyran and fluorine substituted pyridine derivatives. In total, fifteen compounds were synthesized eleven of which were novel; all compounds were characterized by spectroscopic techniques. In vitro anti-bacterial activities of the synthesized compounds were investigated against a representative panel of pathogenic strains. Compounds 6, 7, 8, 11 and 13 exhibited excellent anti-bacterial activity compared with first line drugs. Potent p53–MDM2 interaction inhibitors 2-thio-1,2-dihydroquinoline-3-carbaldehyde thiosemicarbazone and fluorine substituted new pyridine scaffold were successfully identified by structure-based design.
An efficient one-pot four component route to the synthesis of trifluorinated pyrrolophenanthroline and fluoroquinoline pyrrolophenanthrolines was designed. In this reaction 1-butyl-2,3-dimethylimidazolium tetrafluoroborate ionic liquid (DMTIL) was used as a reaction medium; no catalyst was required. The structure of the pyrrolophenanthrolines was deduced by IR and NMR analysis. These compounds were studied with Bovine Serum Albumin (BSA) through molecular docking. Hydrophopic, electrostatic and hydrogen bonding interaction played a crucial role in the binding to sub domain of BSA. Interaction studies of DMTIL with BSA by emission, absorption, synchronous fluorescence, circular dichroism (CD) and three dimensional emission (3D) spectroscopic techniques were under taken. The results from emission titration experiments revealed the existence of a strong interaction between BSA and DMTIL ionic liquid. It showed that compounds with lesser number of hydrogen bonds are found to be more active which is attributed to hydrophobic interaction and electrostatic interaction which also played a vital role in DMTIL binding to sub domain IB of BSA.
A novel copper-loaded boron nitride nanosheet (Cu/BN) catalyst was prepared and fully characterized. It was used as an efficient and chemoselective catalysts for the synthesis of α-aminophosphonates by the Kabachnik-Fields reaction; twenty one α-aminophosphonates were synthesised. The enhanced catalytic activity and product yield was attributed to the increase of surface acidity. Overall, this methodology offered competitive advantages such as recyclability of the catalyst without further purification or without using additives or cofactors, low catalyst loading, broad substrate applicability and high yields. The application of this new nanocatalyst in organic synthesis will provide a novel pathway for the synthesis of pharmaceutically important compounds.
Gold nanoparticle surfaces were modified with self-assembled monolayers of important thiol and disulfide bioactive molecules since considerable interest is due to their potential application as anti-cancer agents. Herein, a carbazole was conjugated to lipoic acid by using an amide coupling catalyst HBTU and DIEA reaction. The structure of the carbazole thio octanic acid (CTN) was identified by IR and NMR. CTN was attached to the gold nanoparticles surface and the capping behaviour was characterized by UV-vis spectroscopy, TEM, DLS and FTIR. The cytotoxicity of CTNAuNPs on A549 cell lines was determined using the MTT assay. The results suggest CTN and CTNAuNPs possess anti-proliferative properties in the cancerous A549 cells.
Furthermore a dual thiol ligand was synthesized by using equimolar 4-aminothiophenol (4-ATP) and amino oxadiazole thiol (AXT). This dual ligand was attached to the gold nanoparticles surface (DTAu) and the capping behaviour was characterized by UV-vis spectroscopy, TEM, DLS and FTIR. The cytotoxicity of DTAu on A549 cell lines was determined using the MTT assay. The results suggest dual ligands (4-ATP, AXT) and DTAu possess anti-proliferative properties in the cancerous A549 cells.
South African indigenous plants and agroforestry waste were also used in the synthesis of silver, gold and palladium nanoparticles (NPs). Green protocols such as the use of environmentally benign solvents and non-hazardous reagents were an added advantage to physical and chemical means. Furthermore these reactions were rapid and the size and shape of the NPs could be manipulated by choosing the correct medium. The formulation of natural medicinal compounds capped onto NPs was assessed for their anti-cancer activity, in A549 lung cancer line, and catalytic reduction of dyes and nitrobenzene derivatives were studied. These NPs displayed:
Significant cytotoxicity to lung cancer cells with minimal effect on normal healthy cells.
Outstanding catalytic reduction of pharmaceutical and textile waste effluents such as dyes and nitro aromatic compounds.
In addition, palladium nanoparticles containing capped Moringa olifera compounds were used effectively in the Suzuki coupling reaction of iodobenzene and phenylboronic acid. The reaction was rapid and was conducted in an aqueous medium.
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The Study of Electronegative Gases for Time Projection ChambersDion, Michael P. January 2009 (has links)
This work presents results on the study of mechanisms and performance of negative ion drift and gas gain in gas-filled radiation detectors with electronegative fill gases. Negative ions drift with slow drift velocity and the lowest possible (thermal limit) diffusion, which leads to relaxed requirements for readout electronics without sacrificing accuracy. Slow drift velocity and low diffusion are the bases for this work because these characteristics are highly desirable for space-based detectors and for low pressure Time Projection Chambers (TPCs) used to make direction sensitive searches for Galactic Dark Matter. The present work led to two major successes: (1) Nitromethane (CH3NO2) was discovered as a new electronegative fill gas for TPCs. Nitromethane anions drift even slower (mobility = 0.032 m2·T/V ·s) than the only other known capture agent, carbon disulfide (CS2, mobility = 0.036 m2·T/V ·s), and the measured longitudinal diffusion remains at the thermodynamic (lower) limit for fields up to 7 V/cmT. Nitromethane is of particular interest for X-ray photoelectric polarimeters
in the 2-10 keV energy range because of its low atomic number (Z). (2) Using a Diethorn plot, the mechanism which initiates electron avalanches in electronegative gas mixtures was accounted for. The Diethorn plot parameter Emin, is the minimum field needed to start avalanche gain in a proportional counter. Electronegative gases were found to
have extremely large pressure-reduced starting fields (10-50 times larger
than electron gases) which are themselves approximately independent
of pressure. This can only be accounted for by a collisional ionization
mechanism leading to the release of electrons from the ions and subsequent development of gain through a normal Townsend avalanche.
The collision cross-section (σc) calculated from drift velocity data allows an estimate of Emin to be made which agrees with the experimental
findings (5 - 25 % difference).
The light output from Townsend avalanches has been proposed as an
alternative readout mechanism for TPCs. The light output from negative
ion avalanches was investigated using a Negative Ion Drift Chamber (NIDC)
with a Gaseous Electron Multiplier (GEM)-like device as the amplification
structure, viewed through a quartz window by a photomultiplier tube. This study allowed an upper limit of light output to be assigned to several negative
ion gas mixtures.
Finally, a Micromegas NIDC was assembled to test the performance of
negative ion mixtures in this gain device. The detector was stable and
operated at gas gains of ∼ 104
in an electron gas mixture (argon-isobutane).
However, with the two negative ion gases studied, CS2 and CH3NO2, high
voltage breakdown and microphonic noise developed before appreciable gain
was obtained. / Physics
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AROMATICITY RULES IN THE DEVELOPMENT OF NEGATIVE IONSChild, Brandon 28 April 2014 (has links)
Organic molecules are known for their stability due to aromaticity. Superhalogens, on the other hand, are highly reactive anions, whose electron affinity is larger than that of chlorine. This thesis, using first principles calculations, explores possible methods for creation of superhalogen aromatic molecules while attempting to also develop a fundamental understanding of the physical properties behind their creation. The first method studied uses anionic cyclopentadienyl and enhances its electron affinity through ligand substitution or ring annulation in combination with core substitutions. The second method studies the possibilities of using benzene, which has a negative electron affinity (EA), as a core to attain similar results. These cases resulted in EAs of 5.59 eV and 5.87 eV respectively, showing that aromaticity rule can be used to create strong anionic organic molecules. These studies will hopefully lead to new advances in the development of organic based technology.
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Influência da obesidade sobre a concentração das adipocitocinas e a LDL(-) em adolescentes / Influence of obesity on the concentration of adipocytokines and electronegative LDL in adolescentsSampaio, Ticiana Machado 23 March 2011 (has links)
Introdução: O sobrepeso e a obesidade representam um grave problema de Saúde Pública, tendo seu desenvolvimento associado à adolescência, impacto negativo na fase adulta, sobretudo, devido suas complicações metabólicas. Considerando que o caráter crônico e inflamatório de baixa intensidade presente na obesidade estimula a geração de radicais livres, torna-se relevante avaliar a relação entre as adipocitocinas e a oxidação das lipoproteínas. Objetivos: Avaliar a possível influência da obesidade sobre a LDL(-) e adipocitocinas. Material e Métodos: Foram recrutados 156 adolescentes de ambos os sexos, com faixa etária de 10 a 19 anos e regularmente matriculados em escolas públicas da cidade de São Paulo. Os adolescentes foram distribuídos em três grupos: Eutrófico, Sobrepeso e Obeso, segundo COLE et al. (2000). Após jejum (12-15h) foi coletada uma amostra de sangue e a partir do plasma realizamos as seguintes análises: perfil lipídico, glicose e insulina (kits comerciais), LDL(-) e seus auto-anticorpos (ELISA), leptina, resistina e adiponectina (ELISA). O perfil sócio-econômico e clínico dos adolescentes foi investigado por meio de questionários estruturados. Foram coletadas informações antropométricas (peso, altura, circunferência da cintura, porcentagem de gordura) e dados de consumo alimentar (3 x R24h). O consumo alimentar foi estimado por meio do programa NutWin®. As diferenças entre as variáveis qualitativas foram determinadas pelo teste c2. As variáveis quantitativas foram ajustadas pela idade por meio do General Linear Model, sendo as diferenças entre os grupos estabelecidas pelo teste post-hoc de Bonferroni (SPSS®, versão 15.0). Resultados: Dos 156 adolescentes incluídos no estudo, 76 (48,7 por cento ) foram meninos e 80 (51,3 por cento ) meninas, com idade média de 14,5 ± 2,3 anos. Os adolescentes foram distribuídos em três grupos: Eutrófico (n = 52 adolescentes; 33,3 por cento ), Sobrepeso (n = 53 adolescentes; 34,0 por cento ) e Obeso (n = 51 adolescentes; 32,7 por cento ). Estes grupos foram pareados quanto ao sexo, escolaridade da mãe, renda, maturação sexual e antecedentes familiares de doenças. Como previsto pelo critério de estratificação dos grupos, os valores médios de IMC foram diferentes entre os grupos, sendo confirmados pela CC e porcentagem de gordura. Em relação ao hábito alimentar, a análise dos dados brutos e ajustados pela energia e variabilidade intrapessoal não apresentou diferença entre 4 os grupos. As análises da glicemia de jejum, colesterol total, triacilgliceróis e LDL-C não apresentaram diferenças entre os grupos. A insulina plasmática no grupo Obeso apresentou valores superiores aos grupos Eutrófico (p< 0,001) e Sobrepeso (p< 0,001), e o índice HOMA-IR no grupo Obeso apresentou valores superiores aos grupos Eutrófico (p< 0,001) e Sobrepeso (p< 0,001), enquanto o HDL-C apresentou valores maiores no grupo Eutrófico, quando comparado ao Obeso (p=0,012). A LDL(-) e seus autoanticorpos apresentaram diferentes concentrações entre os grupos (p= 0,040; p= 0,026, respectivamente). A leptina no grupo Eutrófico apresentou valores menores que os grupos Sobrepeso (p< 0,001) e Obeso (p< 0,001), assim como o grupo Sobrepeso apresentou valores inferiores ao grupo Obeso (p< 0,001). Perfil inverso foi observado em relação à concentração de adiponectina, A resistina apresentou valores maiores no grupo Obeso (p= 0,006), que no grupo Eutrófico. A leptina apresentou correlações positivas com percentual de gordura (r= 0,540; p= 0,001), circunferência da cintura (r= 0,679; p= 0,003) e IMC (r= 0,670; p< 0,001). Em relação ao metabolismo de carboidratos, a leptina se correlacionou positivamente com a insulina (r= 0,578; p< 0,001) e o HOMA-IR (r= 0,570; p= 0,001), enquanto a adiponectina se correlacionou negativamente com insulina (r= -0,255; p= 0,001) e o HOMA-IR (r= -0,246; p=0,002). Em relação ao perfil lipídico, a leptina correlacionou-se com colesterol total (r= 0,496; p= 0,003), triacilgliceróis (r= 0,409; p= 0,016) e LDL-C (r= 0,416; p= 0,014), assim como a adiponectina correlacionou-se com LDL(-) (r= -0,428; p= 0,012) e a resistina com HDL-C (r= -0,337; p= 0,050). Portanto, os resultados obtidos demonstram que adolescentes com excesso de peso, mesmo ainda considerados clinicamente saudáveis, apresentam diversos parâmetros antropométricos e bioquímicos alterados, que sugerem a presença de um elevado número de fatores de risco cardiometabólico nessa população / Introduction: Overweight and obesity represent a serious Public Health issue. Their development associated with adolescence, generate a negative impact in adulthood, mainly because of metabolic complications. As the low and chronic inflammatory state present in obesity stimulates the generation of free radicals, it becomes relevant to assess the relationship between adipocytokines and the oxidation of lipoproteins. Objective: Evaluate the possible influence of overweight and obesity on the electronegative LDL and adipocytokines (leptin, adiponectin and resistin). Materials and Methods: Adolescents of both genders, aged 10 to 19 years old and regularly registered in public schools at the city of São Paulo were recruited for this research. They were divided into three groups: Healthy weight, Overweight and Obese, according to Cole et al. (2000), by gender and age. After fasting (12-15h) a blood sample was collected and the following tests were performed on each samples plasma: total lipid profile, glucose and insulin (commercial kits), leptin, resistin, adiponectin (ELISA), LDL(-) (ELISA) and its autoantibodies (ELISA). The socio-economic and health profiles of the adolescents were determined by structured questionnaires. Anthropometric (weight, height, waist circumference - WC, percentage of body fat) and food consumption data (3 x 24-hour recall) were collected. The 24-hour recall data was analyzed by the NutWin® software. Differences between qualitative variables were determined by c2 test. Quantitative variables were adjusted for age by means of General Linear Model, being the differences between the groups established by post-hoc Bonferroni test (SPSS ®, version 15.0). Results: Of the 156 eligible individuals, 76 (48.7 per cent ) were boys and 80 (51.3 per cent ) girls, with the average age being of 14.5 ± 2.3 years. The adolescents were divided into three groups: Healthy weight, n = 52 adolescents (33.3 per cent ), Overweight, n = 53 adolescents (34.0 per cent ) and Obese, n = 51 adolescents (32.7 per cent ). These groups were matched up by gender, mother\'s education, income, sexual maturation, and current medical history. As expected by the group inclusion criteria, there were statistical differences in BMI and this profile was confirmed by WC and body fat. Opposite profile was showed for lean body mass. In relation to food consumption, the analysis of crude data adjusted for energy and intrapersonal variability did 6 not differ between the groups. Analyses of fasting glucose, total cholesterol, triglycerides and LDL-C did not differ between the groups. There were higher levels of plasma insulin and HOMA-IR in the obese group than in the healthy weight (p <0.001; p <0.001) and the overweight (p <0.001; p < 0.001) groups. HDL-C in the healthy weight group showed increased values in comparison to Obese one (p = 0.012). The LDL (-) in plasma and its autoantibodies indicated different concentrations between the groups (p = 0.040, p= 0.026, respectively). There were lower values of leptin both in the healthy weight group in comparison with the overweight (p <0.001) and the obese (p <0.001) groups, as well as in the Overweight group in comparison with the Obese group (p <0.001). Opposite profile was observed for adiponectin levels, between the healthy weight group and the overweight (p = 0.019) and obese (p = 0.000) groups. Resistin showed higher values in the obese group (p = 0.006) than in the healthy weight group. Leptin showed positive correlations with body fat percentage (r= 0.540 and p= 0.001), waist circumference (r= 0.679 and p= 0.003) and BMI (r= 0.670 and p <0.001). In relation to carbohydrate metabolism, leptin correlated positively with insulin (r= 0.578 and p <0.001) and HOMA-IR (r= 0.570 and p= 0.001), and opposite profile was showed for adiponectin (Insulin: r= -0.255, p= 0.001; HOMA-IR: r= -0.246, p= 0.002, respectively). Regarding the lipid profile, leptin correlated with total cholesterol (r= 0.496 and p= 0.003), triglycerides (r= 0.409 and p= 0.016) and LDL-C (r= 0.416 and p= 0.014); adiponectin correlated with LDL (-) (r= -0.428, p= 0.012); and resistin with HDL-C (r= -0.337, p= 0.050). Therefore, the results show that overweight and obese adolescents, even those who are still considered clinically healthy, showed several anthropometric and biochemical changes, which suggest increased number of cardiometabolic risk factors in this population
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Estudo da interação de peptídeos mimotopos da LDL eletronegativa com células endoteliais e macrófagos / Study of the interaction between mimotope peptides of electronegative LDL with endothelial cells and macrophages.Tripodi, Gustavo Luis 15 December 2016 (has links)
Introdução: Dentre as diversas formas modificadas da lipoproteína de baixa densidade (LDL), a LDL eletronegativa, LDL (-), contribui para o processo aterosclerótico, promovendo o recrutamento leucocitário para a intima arterial e modulando a resposta inflamatória. Mimotopos são moléculas que podem se ligar à porção variável de um anticorpo, a enzimas ou a receptores. Os peptídeos mimotopos da LDL (-) são moléculas capazes de mimetizar a conformação de epítopos expostos apenas quando a LDL sofre modificações in vivo. Objetivo: Avaliar os efeitos de peptídeos mimotopos da LDL(-), previamente selecionados pela técnica de phage display e denominados p1A3 e p2C7, em células endoteliais e macrófagos. Metodologia: Avaliou-se a atividade dos peptídeos mimotopos sobre a expressão de RNAm de genes relacionados tanto à ativação quanto à disfunção endotelial, assim como a atividade citotóxica e a captação dos peptídeos por células endoteliais (HUVEC, HAEC e EA.Hy 926). Verificou-se também a atividade pró-inflamatória dos peptídeos em cultura primária de macrófagos murinos derivados da medula óssea (BMDM), investigando-se a ativação do complexo proteico inflamassoma, assim como a internalização dos peptídeos por essas células, utilizando citometria de fluxo e microscopia confocal. Resultados: As células endoteliais e os macrófagos internalizaram os peptídeos mimotopos p1A3 e p2C7. Nos macrófagos houve inibição (50%) da internalização dos peptídeos p1A3 e p2C7 na presença de brefeldina A, indicando que esses peptídeos são majoritariamente captados por endocitose independente de clatrina. Nas células HAEC, observou-se 25% de inibição da captação de ambos os peptídeos se bloqueando o receptor scavenger LOX-1 com anticorpo anti-LOX-1. Quanto à atividade citotóxica, observou-se acentuada redução na atividade mitocondrial das células endoteliais EA.Hy 926 e HAEC apenas com o peptídeo p1A3, não sendo observada citotoxicidade para os macrófagos tanto para p1A3 quanto p2C7 nas concentrações estudadas (12,5 a 200 ug/mL). Nos macrófagos, o peptídeo p2C7 induziu o aumento da expressão de RNAm de genes relacionados com a polarização para o fenótipo M1 (iNOS, TNF-α, IL-1α) e da produção de •NO, assim como, a ativação do sinal 1 (transcricional) do complexo proteico inflamassoma, o que também se observou para a LDL (-). O peptídeo p1A3 modulou a expressão gênica da linhagem HAEC, diminuindo a expressão de RNAm dos genes relacionados à proliferação celular (VEGFr1 e 2, TGFβ, PDGFβ e eNOS). Conclusão: Os peptídeos mimotopos p1A3 e p2C7 interagem com as células endoteliais e macrófagos de maneiras distintas. O p2C7 induz uma resposta pró-inflamatória em macrófagos, mimetizando a LDL (-), sugerindo assim, que esse peptídeo possa atuar como um DAMP (padrão molecular associado ao perigo) importante para o processo inflamatório da placa aterosclerótica. / Introduction: Among the different subtypes of modified low-density lipoprotein (LDL), the electronegative LDL [LDL (-)] contributes to the progression of atherosclerosis, promoting leukocyte recruitment into the arterial intima and modulating the inflammatory response. Mimotopes are molecules capable of binding to the variable portion of an antibody, to enzymes or receptors. The mimotope peptides of LDL (-) are molecules mimicking the conformation of epitopes exposed only when LDL undergoes in vivo changes. Objective: To evaluate the effects of two mimotope peptides of LDL (-), previously selected the by phage display and called p1A3 and p2C7, on endothelial cells and macrophages. Methodology: We evaluated the activity of the mimotope peptides on gene mRNA expression related to both the activation and endothelial dysfunction as well as the cytotoxic activity and uptake of peptides by endothelial cells (HUVEC, HAEC and EA.Hy 926). It was also investigated the pro-inflammatory activity of the peptides on murine primary macrophage derived from bone marrow (BMDM), evaluating the activation of the protein complex inflammasome, as well as the internalization of peptides by these cells by flow cytometry and confocal microscopy. Results: The endothelial cells and macrophages internalized both peptides. In macrophages, brefeldin A inhibited the internalization of p1A3 and p2C7 around 50%, indicating that these peptides are mostly taken up by clathrin-independent bulk endocytosis. In HAEC it was observed a 25 % inhibition of the uptake of both peptides by blocking the LOX scavenger receptor with an anti-LOX-1 antibody. In relation to cytotoxicity, a reduction on mitochondrial activity was induced by p1A3 peptide only in endothelial cells (EA.Hy 926 and HAEC). No cytotoxic activity was observed for p2C7 peptide in macrophages or endothelial cells at the studied concentration range (12.5 to 200 µg/mL). In macrophages, the p2C7 peptide increased mRNA expression of genes related to the polarization to M1 phenotype (iNOS, TNF-α and IL-1α) and of •NO production, as well as, protein complex signal 1 activation (transcriptional) what was also observed for LDL (-). The p1A3 peptide modulated the expression of genes related with cell proliferation (VEGFr1 e 2, TGF?β, PDGFβ and eNOS) in HAEC. Conclusion: The mimotope peptides p2C7 and p1A3 interact with the endothelial cells and macrophages by different ways. The p2C7 induces a pro-inflammatory response in macrophages, mimicking LDL (-), thus suggesting that this peptide can act as a DAMP (Damage-associated molecular pattern) important in the inflammatory process of atherosclerotic plaque.
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Lipoproteína de baixa densidade eletronegativa (LDL-) em indivíduos com diferentes níveis de risco cardiovascular: parâmetros nutricionais e bioquímicos / Electronegative low density lipoprotein (LDL-) in subjects with different levels of cardiovascular risk: nutritional and biochemical parametersMello, Ana Paula de Queiroz 31 May 2007 (has links)
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 ≤ 0,001), colesterol associado à LDL, pela equação de Friedewald e analisado na lipoproteína isolada (r = 0,59 e p ≤ 0,001; r = 0,75 e p ≤ 0,001, respectivamente), as relações colesterol total/HDL (r= 0,45, p ≤ 0,001) e LDL/HDL (r= 0,47, p ≤ 0,001) e colesterol não HDL (r= 0,74, p ≤ 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 ≤ 0.001), cholesterol associated LDL as calculated by Friedewald equation and crude analysis (r = 0.59 and p ≤ 0.001; r = 0.75 and p ≤ 0.001, respectively), TC/HDL ratio (r= 0.45 and p ≤ 0.001), LDL/HDL ratio (r= 0.47 and p ≤ 0.001) and non cholesterol HDL (r= 0.74 and p ≤ 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.
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Lipoproteína de baixa densidade oxidada (LDLox) versus lipoproteína de baixa densidade eletronegativa [LDL(-)] de adolescentes: análise comparativa / Oxidized low-density lipoprotein (oxLDL) versus electronegative low density lipoprotein [LDL (-)] of adolescents: a comparative analysisCohen, Danielle 19 August 2013 (has links)
A obesidade é considerada uma doença crônica e multifatorial, onde eventos como a inflamação de baixa intensidade e as modificações oxidativas estão presentes. A elevada prevalência de obesidade tem impacto direto no desenvolvimento precoce de diabetes mellitus, hipertensão e outros fatores de risco cardiovasculares. Esse perfil tem motivado a identificação de biomarcadores precoces, sendo o monitoramento da lipoproteína de baixa densidade oxidada (LDLox) e lipoproteína de baixa densidade eletronegativa [LDL(-)] potenciais candidatos. Diante do exposto, o objetivo deste estudo foi realizar a análise comparativa e de correlação entre o conteúdo de LDLox e [LDL(-)] em adolescentes. Foram selecionados 137 adolescentes de ambos sexos, com faixa etária de 10 a 19 anos e regularmente em matriculados em escolas públicas da cidade de São Paulo. O peso, altura e circunferência da cintura (CC) foram avaliados. Após jejum (12h-15h) foi coletada uma amostra de sangue e, a partir do plasma, foram realizadas as seguintes análises: glicose, insulina, perfil lipídico, apolipoproteína (AI e B), ácidos graxos não esterificados, tamanho de HDL, atividade da CETP e LDL(-) e LDLox. Os resultados encontrados foram analisados por meio do programa SPSS 15.0, considerando valor de significância de p< 0,05. Os 137 adolescentes foram distribuídos em dois grupos: 71 no Eutrófico (51,82%) e 66 no Obeso (48,18%), segundo a classificação do IMC. 48 (35,04%) dos adolescentes eram do sexo masculino e 89 (64,96%) do sexo feminino, com idade média de 14,2 (2,3) anos. Em relação à CC, observou-se que essa confirmou a classificação feita pelo IMC. Observou-se também uma maior prevalência de hipertensão (65% p = 0,011) e obesidade (64,7% p=0,041) nos antecedentes familiares do grupo Obeso quando comparado ao grupo Eutrófico. Os adolescentes obesos apresentaram maiores valores de triglicerídeos, HDL, APO B, CETP, insulina e LDL(-) e LDLox, quando comparados aos eutróficos. Perfil inverso foi observado para Apo AI. O conteúdo de LDLox e LD(-) variou significativamente em função do IMC. Entretanto, essas partículas de LDLs não se correlacionaram entre si, embora tenham apresentado associação com outros parâmetros cardiometabólicos. Os resultados obtidos confirmam o impacto negativo da obesidade sobre os parâmetros cardiometabólicos de adolescentes e, apesar do conteúdo de LDLox e LDL(-) ter aumentado em função do IMC, essas partículas parecem ser estruturalmente distintas. Essa possibilidade foi reforçada pelas diferentes associações dessas partículas com outros marcadores bioquímicos. / Obesity is considered a chronic and multifactorial disease, where events such as low intensity inflammation and oxidative modifications are present. The high prevalence of obesity has a direct impact on the early development of diabetes mellitus, hypertension and other cardiovascular risk factors. This profile has motivated the identification of early biomarkers, and monitoring the oxidized low density lipoprotein (oxLDL) and electronegative low-density lipoprotein [LDL (-)] are potential markers. The aim of this study was to conduct a comparative analysis and correlation between the content of oxLDL and [LDL (-)] in adolescents. We selected 137 adolescents of both sexes, aged 10-19 years, enrolled in public schools in the city of São Paulo. The weight, height, waist circumference (WC) were assessed. After fasting (12-15h) samples of blood were collected and from plasma were performed the following analyzes: glucose, insulin, lipid profile, apolipoprotein (AI and B), NEFA, HDL size, CETP activity and LDL (-) and oxLDL. The results were analyzed by using SPSS 15.0 considering significant value of p <0.05. The 137 adolescents were divided into two groups: 71 Normal Weight (51.82%) and 66 Obese (48.18%), according to BMI classification. 48 (35.04%) of the adolescents were male and 89 (64.96%) females with a mean age of 14.2 (2.3) years. Regarding the CC observed, it confirmed the classification made by BMI. There was a higher prevalence of hypertension (65% p = 0.011) and obesity (64.7% p = 0.041) in the family history group Obese when compared to normal weight. Obese adolescents had higher triglyceride, HDL, APO B, CETP, insulin and LDL (-) and oxLDL, compared to normal weight. Reverse profile was observed for Apo AI. The content of oxLDL and LDL (-) varied significantly according to BMI. However, these LDL particles were not correlated with each other, although they showed cardiometabolic combination with other parameters. The results confirm the negative impact of obesity on cardiometabolic parameters of teenagers and although the content of oxLDL and LDL (-) increased as a function of BMI, these particles appear to be structurally distinct. This possibility was reinforced by different associations of these particles with other biochemical markers.
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Influência da obesidade sobre a concentração das adipocitocinas e a LDL(-) em adolescentes / Influence of obesity on the concentration of adipocytokines and electronegative LDL in adolescentsTiciana Machado Sampaio 23 March 2011 (has links)
Introdução: O sobrepeso e a obesidade representam um grave problema de Saúde Pública, tendo seu desenvolvimento associado à adolescência, impacto negativo na fase adulta, sobretudo, devido suas complicações metabólicas. Considerando que o caráter crônico e inflamatório de baixa intensidade presente na obesidade estimula a geração de radicais livres, torna-se relevante avaliar a relação entre as adipocitocinas e a oxidação das lipoproteínas. Objetivos: Avaliar a possível influência da obesidade sobre a LDL(-) e adipocitocinas. Material e Métodos: Foram recrutados 156 adolescentes de ambos os sexos, com faixa etária de 10 a 19 anos e regularmente matriculados em escolas públicas da cidade de São Paulo. Os adolescentes foram distribuídos em três grupos: Eutrófico, Sobrepeso e Obeso, segundo COLE et al. (2000). Após jejum (12-15h) foi coletada uma amostra de sangue e a partir do plasma realizamos as seguintes análises: perfil lipídico, glicose e insulina (kits comerciais), LDL(-) e seus auto-anticorpos (ELISA), leptina, resistina e adiponectina (ELISA). O perfil sócio-econômico e clínico dos adolescentes foi investigado por meio de questionários estruturados. Foram coletadas informações antropométricas (peso, altura, circunferência da cintura, porcentagem de gordura) e dados de consumo alimentar (3 x R24h). O consumo alimentar foi estimado por meio do programa NutWin®. As diferenças entre as variáveis qualitativas foram determinadas pelo teste c2. As variáveis quantitativas foram ajustadas pela idade por meio do General Linear Model, sendo as diferenças entre os grupos estabelecidas pelo teste post-hoc de Bonferroni (SPSS®, versão 15.0). Resultados: Dos 156 adolescentes incluídos no estudo, 76 (48,7 por cento ) foram meninos e 80 (51,3 por cento ) meninas, com idade média de 14,5 ± 2,3 anos. Os adolescentes foram distribuídos em três grupos: Eutrófico (n = 52 adolescentes; 33,3 por cento ), Sobrepeso (n = 53 adolescentes; 34,0 por cento ) e Obeso (n = 51 adolescentes; 32,7 por cento ). Estes grupos foram pareados quanto ao sexo, escolaridade da mãe, renda, maturação sexual e antecedentes familiares de doenças. Como previsto pelo critério de estratificação dos grupos, os valores médios de IMC foram diferentes entre os grupos, sendo confirmados pela CC e porcentagem de gordura. Em relação ao hábito alimentar, a análise dos dados brutos e ajustados pela energia e variabilidade intrapessoal não apresentou diferença entre 4 os grupos. As análises da glicemia de jejum, colesterol total, triacilgliceróis e LDL-C não apresentaram diferenças entre os grupos. A insulina plasmática no grupo Obeso apresentou valores superiores aos grupos Eutrófico (p< 0,001) e Sobrepeso (p< 0,001), e o índice HOMA-IR no grupo Obeso apresentou valores superiores aos grupos Eutrófico (p< 0,001) e Sobrepeso (p< 0,001), enquanto o HDL-C apresentou valores maiores no grupo Eutrófico, quando comparado ao Obeso (p=0,012). A LDL(-) e seus autoanticorpos apresentaram diferentes concentrações entre os grupos (p= 0,040; p= 0,026, respectivamente). A leptina no grupo Eutrófico apresentou valores menores que os grupos Sobrepeso (p< 0,001) e Obeso (p< 0,001), assim como o grupo Sobrepeso apresentou valores inferiores ao grupo Obeso (p< 0,001). Perfil inverso foi observado em relação à concentração de adiponectina, A resistina apresentou valores maiores no grupo Obeso (p= 0,006), que no grupo Eutrófico. A leptina apresentou correlações positivas com percentual de gordura (r= 0,540; p= 0,001), circunferência da cintura (r= 0,679; p= 0,003) e IMC (r= 0,670; p< 0,001). Em relação ao metabolismo de carboidratos, a leptina se correlacionou positivamente com a insulina (r= 0,578; p< 0,001) e o HOMA-IR (r= 0,570; p= 0,001), enquanto a adiponectina se correlacionou negativamente com insulina (r= -0,255; p= 0,001) e o HOMA-IR (r= -0,246; p=0,002). Em relação ao perfil lipídico, a leptina correlacionou-se com colesterol total (r= 0,496; p= 0,003), triacilgliceróis (r= 0,409; p= 0,016) e LDL-C (r= 0,416; p= 0,014), assim como a adiponectina correlacionou-se com LDL(-) (r= -0,428; p= 0,012) e a resistina com HDL-C (r= -0,337; p= 0,050). Portanto, os resultados obtidos demonstram que adolescentes com excesso de peso, mesmo ainda considerados clinicamente saudáveis, apresentam diversos parâmetros antropométricos e bioquímicos alterados, que sugerem a presença de um elevado número de fatores de risco cardiometabólico nessa população / Introduction: Overweight and obesity represent a serious Public Health issue. Their development associated with adolescence, generate a negative impact in adulthood, mainly because of metabolic complications. As the low and chronic inflammatory state present in obesity stimulates the generation of free radicals, it becomes relevant to assess the relationship between adipocytokines and the oxidation of lipoproteins. Objective: Evaluate the possible influence of overweight and obesity on the electronegative LDL and adipocytokines (leptin, adiponectin and resistin). Materials and Methods: Adolescents of both genders, aged 10 to 19 years old and regularly registered in public schools at the city of São Paulo were recruited for this research. They were divided into three groups: Healthy weight, Overweight and Obese, according to Cole et al. (2000), by gender and age. After fasting (12-15h) a blood sample was collected and the following tests were performed on each samples plasma: total lipid profile, glucose and insulin (commercial kits), leptin, resistin, adiponectin (ELISA), LDL(-) (ELISA) and its autoantibodies (ELISA). The socio-economic and health profiles of the adolescents were determined by structured questionnaires. Anthropometric (weight, height, waist circumference - WC, percentage of body fat) and food consumption data (3 x 24-hour recall) were collected. The 24-hour recall data was analyzed by the NutWin® software. Differences between qualitative variables were determined by c2 test. Quantitative variables were adjusted for age by means of General Linear Model, being the differences between the groups established by post-hoc Bonferroni test (SPSS ®, version 15.0). Results: Of the 156 eligible individuals, 76 (48.7 per cent ) were boys and 80 (51.3 per cent ) girls, with the average age being of 14.5 ± 2.3 years. The adolescents were divided into three groups: Healthy weight, n = 52 adolescents (33.3 per cent ), Overweight, n = 53 adolescents (34.0 per cent ) and Obese, n = 51 adolescents (32.7 per cent ). These groups were matched up by gender, mother\'s education, income, sexual maturation, and current medical history. As expected by the group inclusion criteria, there were statistical differences in BMI and this profile was confirmed by WC and body fat. Opposite profile was showed for lean body mass. In relation to food consumption, the analysis of crude data adjusted for energy and intrapersonal variability did 6 not differ between the groups. Analyses of fasting glucose, total cholesterol, triglycerides and LDL-C did not differ between the groups. There were higher levels of plasma insulin and HOMA-IR in the obese group than in the healthy weight (p <0.001; p <0.001) and the overweight (p <0.001; p < 0.001) groups. HDL-C in the healthy weight group showed increased values in comparison to Obese one (p = 0.012). The LDL (-) in plasma and its autoantibodies indicated different concentrations between the groups (p = 0.040, p= 0.026, respectively). There were lower values of leptin both in the healthy weight group in comparison with the overweight (p <0.001) and the obese (p <0.001) groups, as well as in the Overweight group in comparison with the Obese group (p <0.001). Opposite profile was observed for adiponectin levels, between the healthy weight group and the overweight (p = 0.019) and obese (p = 0.000) groups. Resistin showed higher values in the obese group (p = 0.006) than in the healthy weight group. Leptin showed positive correlations with body fat percentage (r= 0.540 and p= 0.001), waist circumference (r= 0.679 and p= 0.003) and BMI (r= 0.670 and p <0.001). In relation to carbohydrate metabolism, leptin correlated positively with insulin (r= 0.578 and p <0.001) and HOMA-IR (r= 0.570 and p= 0.001), and opposite profile was showed for adiponectin (Insulin: r= -0.255, p= 0.001; HOMA-IR: r= -0.246, p= 0.002, respectively). Regarding the lipid profile, leptin correlated with total cholesterol (r= 0.496 and p= 0.003), triglycerides (r= 0.409 and p= 0.016) and LDL-C (r= 0.416 and p= 0.014); adiponectin correlated with LDL (-) (r= -0.428, p= 0.012); and resistin with HDL-C (r= -0.337, p= 0.050). Therefore, the results show that overweight and obese adolescents, even those who are still considered clinically healthy, showed several anthropometric and biochemical changes, which suggest increased number of cardiometabolic risk factors in this population
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Influência do ω-3 sobre a lipoproteína de baixa densidade eletronegativa [LDL(-)], anticorpos LDL(-) e tamanho das partículas de LDL em indivíduos com síndrome metabólica / Influence of ω-3 over electronegative low density lipoprotein [LDL(-)] plasma concentrations, antiLDL(-) and LDL particles in individuals with metabolic syndromeEstevez Fernandez, Diana Gabriela 23 March 2015 (has links)
Introdução A Síndrome Metabólica (SM) representa um conjunto de fatores que determinam maior risco para Doença Cardiovascular (DCV), devido principalmente à Resistência à Insulina (RI) e ao estado inflamatório promovido pelo tecido adiposo branco hipertrofiado. Nesse contexto, a condição de dislipidemia favorece o desenvolvimento da aterosclerose, devido a que maiores concentrações de lipoproteína de baixa densidade (LDL) no plasma podem propiciar modificações nessas partículas. Essas modificações podem ter origem oxidativa ou não oxidativa e impactar nas características aterogênicas da LDL. O ômega três tem mostrado efeitos hipolipemiantes e anti-inflamatórios, que podem reduzir o risco cardiovascular de indivíduos com SM. Objetivo:: avaliar o efeito da suplementação de 3g de ω-3 por um período de oito semanas sobre a concentração plasmática das partículas de LDL eletronegativas [LDL(-)] e seus anticorpos, assim como monitorar possíveis mudanças nas concentrações das subfrações das LDL. Metodologia: Foram incluídos 115 participantes de ambos os sexos, entre 30 e 74 anos, com SM, separados nos grupos de intervenção com ω-3 (n=58) e controle com ω-9 (n=57). Foram realizadas análises de perfil lipídico e por meio de ELISA foram avaliadas a concentração de LDL(-) e de antiLDL(-) no plasma dos participantes. O tamanho das subfrações de LDL foi realizado no sistema Lipoprint. O efeito do tempo e das intervenções foi testado por meio do programa SPSS versão 20.0, adotando-se o concentração de significância de p<0,05. Resultados: A suplementação de ω-3 teve efeito significativo na redução do % de massa grassa (%MG) e na pressão arterial sistólica (4%) e diastólica (5%). Em relação ao perfil lipídico, ambas intervenções tiveram efeitos significativos de redução de colesterol total (CT), LDL-c, não HDL (nHDL) e triacilglicerois (TG). As concentrações plasmáticas de LDL(-) dos participantes que tomaram ômega 3 apresentaram redução de 21%, enquanto que os que tomaram ômega 9 tiveram redução de 1%. Tal redução foi significativa em relação ao tempo de intervenção (p<0,05), mas não quando o efeito da internveção foi avaliado. Perfil semelhante foi observado para a razão LDL(-)/antiLDL(-), observou-se redução de 22% no grupo ômega 3 e redução de somente 3% no grupo ômega 9. Conclusão: A intervenção com ômega 3 promoveu redução na concentração plasmática de LDL(-), porém não modificou a concentração do anticorpo antiLDL(-) nem o tamanho das subfrações da LDL. / Introduction: The Metabolic Syndrome (MetS) is a combination of factors that determine increased risk for Cardiovascular Diseases (CVD), mainly because of Insulin Resistance (IR) and the inflammatory state promoted by the hypertrophied white adipose tissue. Under this background, the dyslipidemic condition goes together with the developing of atherosclerosis, meaning that higher concentrations of low density lipoprotein (LDL) in plasma promote modifications from different sources in these particles and may have an impact over LDL subfractions, turning them more atherogenic. Omega three has proved hypolipidemic and anti-inflammatory effects, which may reduce cardiovascular risk in MetS individuals. Objetive: evaluate the effect of 3g of fish oil supplementation, 60% EPA and DHA during an eight week period over plasma concentrations of electronegative LDL particles [LDL(-)] and its antibodies, as well as monitoring possible changes in LDL subfractions. Methods: A total number of 115 participants, both sexes, between 30 and 74 years of age, with MetS, were included and separated in the intervention group receiving omega 3 (n=58) and the placebo group with omega 9 (n=57). Biochemical analyses were carried out using ELISA for LDL(-) and antiLDL(-) in plasma. Particle sizes were measured using the Lipoprint system. The effects of time and intervention were analyzed using the statistical program SPSS 20.0, assuming p<0.05 as significant. Results: Omega 3 supplementation had a significant effect in the reduction of fat mass percentage (FM%) and blood pressure, showing a 4% decrease for systolic and 5% decrease for diastolic pressures respectively. Considering the lipid profile, both interventions had significant effects reducing total cholesterol (TC), LDL-c, not HDL (nHDL) and tryacylglycerides (TG). LDL(-) plasma concentrations from the omega 3 group showed 21% reduction while the omega 9 group had only 1% reduction. Such difference was significant considering time (p<0,05), but not while comparing the intervention effect. There was also a change in the antiLDL(-) antibodies; reducing 2% in the omega 3 group and increasing 1% in the omega 9 group. However, those differences were not significant. Similar effects were observed in LDL(-)/antiLDL(-) ratio, showing 22% decrease in the omega 3 group and only 3% in the omega 9 group. Conclusion: Omega 3 intervention promoted a significant reduction in plasmatic LDL(-), however, it didn\'t modify LDL subfraction distribution.
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Lipoproteína de baixa densidade oxidada (LDLox) versus lipoproteína de baixa densidade eletronegativa [LDL(-)] de adolescentes: análise comparativa / Oxidized low-density lipoprotein (oxLDL) versus electronegative low density lipoprotein [LDL (-)] of adolescents: a comparative analysisDanielle Cohen 19 August 2013 (has links)
A obesidade é considerada uma doença crônica e multifatorial, onde eventos como a inflamação de baixa intensidade e as modificações oxidativas estão presentes. A elevada prevalência de obesidade tem impacto direto no desenvolvimento precoce de diabetes mellitus, hipertensão e outros fatores de risco cardiovasculares. Esse perfil tem motivado a identificação de biomarcadores precoces, sendo o monitoramento da lipoproteína de baixa densidade oxidada (LDLox) e lipoproteína de baixa densidade eletronegativa [LDL(-)] potenciais candidatos. Diante do exposto, o objetivo deste estudo foi realizar a análise comparativa e de correlação entre o conteúdo de LDLox e [LDL(-)] em adolescentes. Foram selecionados 137 adolescentes de ambos sexos, com faixa etária de 10 a 19 anos e regularmente em matriculados em escolas públicas da cidade de São Paulo. O peso, altura e circunferência da cintura (CC) foram avaliados. Após jejum (12h-15h) foi coletada uma amostra de sangue e, a partir do plasma, foram realizadas as seguintes análises: glicose, insulina, perfil lipídico, apolipoproteína (AI e B), ácidos graxos não esterificados, tamanho de HDL, atividade da CETP e LDL(-) e LDLox. Os resultados encontrados foram analisados por meio do programa SPSS 15.0, considerando valor de significância de p< 0,05. Os 137 adolescentes foram distribuídos em dois grupos: 71 no Eutrófico (51,82%) e 66 no Obeso (48,18%), segundo a classificação do IMC. 48 (35,04%) dos adolescentes eram do sexo masculino e 89 (64,96%) do sexo feminino, com idade média de 14,2 (2,3) anos. Em relação à CC, observou-se que essa confirmou a classificação feita pelo IMC. Observou-se também uma maior prevalência de hipertensão (65% p = 0,011) e obesidade (64,7% p=0,041) nos antecedentes familiares do grupo Obeso quando comparado ao grupo Eutrófico. Os adolescentes obesos apresentaram maiores valores de triglicerídeos, HDL, APO B, CETP, insulina e LDL(-) e LDLox, quando comparados aos eutróficos. Perfil inverso foi observado para Apo AI. O conteúdo de LDLox e LD(-) variou significativamente em função do IMC. Entretanto, essas partículas de LDLs não se correlacionaram entre si, embora tenham apresentado associação com outros parâmetros cardiometabólicos. Os resultados obtidos confirmam o impacto negativo da obesidade sobre os parâmetros cardiometabólicos de adolescentes e, apesar do conteúdo de LDLox e LDL(-) ter aumentado em função do IMC, essas partículas parecem ser estruturalmente distintas. Essa possibilidade foi reforçada pelas diferentes associações dessas partículas com outros marcadores bioquímicos. / Obesity is considered a chronic and multifactorial disease, where events such as low intensity inflammation and oxidative modifications are present. The high prevalence of obesity has a direct impact on the early development of diabetes mellitus, hypertension and other cardiovascular risk factors. This profile has motivated the identification of early biomarkers, and monitoring the oxidized low density lipoprotein (oxLDL) and electronegative low-density lipoprotein [LDL (-)] are potential markers. The aim of this study was to conduct a comparative analysis and correlation between the content of oxLDL and [LDL (-)] in adolescents. We selected 137 adolescents of both sexes, aged 10-19 years, enrolled in public schools in the city of São Paulo. The weight, height, waist circumference (WC) were assessed. After fasting (12-15h) samples of blood were collected and from plasma were performed the following analyzes: glucose, insulin, lipid profile, apolipoprotein (AI and B), NEFA, HDL size, CETP activity and LDL (-) and oxLDL. The results were analyzed by using SPSS 15.0 considering significant value of p <0.05. The 137 adolescents were divided into two groups: 71 Normal Weight (51.82%) and 66 Obese (48.18%), according to BMI classification. 48 (35.04%) of the adolescents were male and 89 (64.96%) females with a mean age of 14.2 (2.3) years. Regarding the CC observed, it confirmed the classification made by BMI. There was a higher prevalence of hypertension (65% p = 0.011) and obesity (64.7% p = 0.041) in the family history group Obese when compared to normal weight. Obese adolescents had higher triglyceride, HDL, APO B, CETP, insulin and LDL (-) and oxLDL, compared to normal weight. Reverse profile was observed for Apo AI. The content of oxLDL and LDL (-) varied significantly according to BMI. However, these LDL particles were not correlated with each other, although they showed cardiometabolic combination with other parameters. The results confirm the negative impact of obesity on cardiometabolic parameters of teenagers and although the content of oxLDL and LDL (-) increased as a function of BMI, these particles appear to be structurally distinct. This possibility was reinforced by different associations of these particles with other biochemical markers.
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