Diss. (sammanfattning) Umeå : Umeå universitet, 2005. / Härtill 4 uppsatser.

Stuttgart, Univ., Diss., 2007.

Thesis (Ph. D.)--University of Texas Southwestern Medical Center at Dallas, 2008. / Vita. Includes bibliographical references (p. 116-135).

University, Diss., 2002--Stuttgart. / Gedr. Ausg. im Inst. für Technische Biochemie der Univ. Stuttgart.

abstract: Background: Evidence about the purported hypoglycemic and hypolipidemic effects of nopales (prickly pear cactus pads) is limited. Objective: To evaluate the efficacy of nopales for improving cardiometabolic risk factors and oxidative stress, compared to control, in adults with hypercholesterolemia. Design: In a randomized crossover trial, participants were assigned to a 2-wk intervention with 2 cups/day of nopales or cucumbers (control), with a 2 to 3-wk washout period. The study included 16 adults (5 male; 46±14 y; BMI = 31.4±5.7 kg/m2) with moderate hypercholesterolemia (low density lipoprotein cholesterol [LDL-c] = 137±21 mg/dL), but otherwise healthy. Main outcomes measured included: dietary intake (energy, macronutrients and micronutrients), cardiometabolic risk markers (total cholesterol, LDL-c, high density lipoprotein cholesterol [HDL-c], triglycerides, cholesterol distribution in LDL and HDL subfractions, glucose, insulin, homeostasis model assessment, and C-reactive protein), and oxidative stress markers (vitamin C, total antioxidant capacity, oxidized LDL, and LDL susceptibility to oxidation). Effects of treatment, time, or interactions were assessed using repeated measures ANOVA. Results: There was no significant treatment-by-time effect for any dietary composition data, lipid profile, cardiometabolic outcomes, or oxidative stress markers. A significant time effect was observed for energy, which was decreased in both treatments (cucumber, -8.3%; nopales, -10.1%; pTime=0.026) mostly due to lower mono and polyunsaturated fatty acids intake (pTime=0.023 and pTime=0.003, respectively). Both treatments significantly increased triglyceride concentrations (cucumber, 14.8%; nopales, 15.2%; pTime=0.020). Despite the lack of significant treatment-by-time effects, great individual response variability was observed for all outcomes. After the cucumber and nopales phases, a decrease in LDL-c was observed in 44% and 63% of the participants respectively. On average LDL-c was decreased by 2.0 mg/dL (-1.4%) after the cucumber phase and 3.9 mg/dL (-2.9%) after the nopales phase (pTime=0.176). Pro-atherogenic changes in HDL subfractions were observed in both interventions over time, by decreasing the proportion of HDL-c in large HDL (cucumber, -5.1%; nopales, -5.9%; pTime=0.021) and increasing the proportion in small HDL (cucumber, 4.1%; nopales, 7.9%; pTime=0.002). Conclusions: These data do not support the purported benefits of nopales at doses of 2 cups/day for 2-wk on markers of lipoprotein profile, cardiometabolic risk, and oxidative stress in hypercholesterolemic adults. / Dissertation/Thesis / Ph.D. Nutrition 2013

The production of very low density lipoprotein and high density lipoprotein particles by the liver is a tightly regulated process, which begins with synthesis and assembly of core protein components in the rough endoplasmic reticulum. Factors influencing the production and metabolism of these particles are of immediate medical relevance, as their malfunction or hyperactivity can lead to an assortment of disease states. Hepatic lipase is a secreted liver enzyme, with many previously described roles in the metabolism and clearance of both high and low density lipoproteins. Increased production and assembly of this enzyme is an indicator of metabolic dysfunction, while its absence or insufficiency leads to pre-mature atherosclerosis and death. The present study shows that this enzyme’s role in lipoprotein metabolism is not confined to the degradation and clearance of these particles after they have been secreted. Experiments using co-immunoprecipitation targeted at hepatic lipase demonstrate that this protein interacts with ApoA1 and ApoB100, the core protein components of HDL and VLDL respectively, at the ER level in hepatocytes, as part of an enormous multi-subunit protein complex. This interaction with ApoA1 leads to decreased competence of hepatocytes to secrete HDL, which confers a pro-atherogenic phenotype. Analysis of ER to Golgi VLDL transport vesicles, produced with a cell-free in vitro budding assay, has revealed that hepatic lipase is co-secreted between these compartments with immature VLDL particles. Further analysis of cytosol isolated from hepatocytes demonstrates an interaction between hepatic lipase and the LDL-receptor related protein in a post-Golgi vesicle; the significance of which will be investigated in future studies.

No description available.

The high density lipoprotein (HDL) receptor Scavenger Receptor, Class B, Type I (SRBI) is a 509 amino acid integral membrane protein which has been shown to have an important role in HDL-mediated reverse cholesterol transport. SR-BI has been shown to mediate selective uptake of cholesterol, and also mediates efflux of cholesterol to HDL as seen in in vitro cell culture studies. SR-BI is abundant in the liver and steroidogenic tissues, and is also present in macrophages, which play an important role in the initial stages of atherosclerotic development. SR-BI has been shown to be protective against atherosclerosis by way of overexpression and knockout (KO) studies in murine atherosclerosis models, including low density lipoprotein receptor (LDLR) knockout mice, apolipoprotein E (ApoE) knockout mice, and human apolipoprotein B (ApoB) transgenic mice. SR-BI/LDLR double knockout (dKO) mice show a 6-fold increase in diet-induced atherosclerosis compared to LDLR single KO controls, and SR-BI/ApoE dKO mice show severe coronary occlusion, myocardial infarction, and premature death on a normal chow diet. In both, plasma total cholesterol levels are significantly elevated, and associated with abnormally large HDL particles. The majority ofSR-BI's atheroprotective effect has been shown to result from plasma cholesterol clearance by way of selective uptake in the liver. Recently, Covey et al showed that elimination of SRBI expression in macrophages of LDLR KO mice resulted in increased diet-induced atherosclerosis. To see if SR-BI in macrophages contributes to the overall atheroprotective effect of SR-BI in ApoE KO mice, presumably by mediating cellular cholesterol efflux to HDL, selective deletion ofSR-BI was induced in bone marrow derived cells of ApoE KO mice using bone marrow transplantation. Female ApoE -/recipient mice were transplanted with either SR-BI +/+ ApoE -/-or SR-BI -/- ApoE -/bone marrow from male donor mice, and fed a high fat diet for 12 weeks. This resulted in significantly increased atherosclerosis in mice transplanted with SR-BI -/- ApoE -/-bone marrow, with a concomitant decrease in cholesterol associated with HDL-sized lipoproteins. No significant differences were seen in plasma total cholesterol levels or levels of cholesterol associated with non-HDL lipoproteins. These data suggest that SRBI in macrophages contributes to SR-BI's overall protective effect against atherosclerosis, and also plays a role in the regulation ofHDL cholesterol, in ApoE deficient mice. / Thesis / Master of Science (MSc)

No / Streptococcus equi is the causative agent of strangles, a prevalent and highly contagious disease of horses. Despite the animal suffering and economic burden associated with strangles, little is known about the molecular basis of S. equi virulence. Here we have investigated the contributions of a specific lipoprotein and the general lipoprotein processing pathway to the abilities of S. equi to colonize equine epithelial tissues in vitro and to cause disease in both a mouse model and the natural host in vivo. Colonization of air interface organ cultures after they were inoculated with a mutant strain deficient in the maturase lipoprotein ( prtM138-213, with a deletion of nucleotides 138 to 213) was significantly less than that for cultures infected with wild-type S. equi strain 4047 or a mutant strain that was unable to lipidate preprolipoproteins ( lgt190-685). Moreover, mucus production was significantly greater in both wild-type-infected and lgt190-685-infected organ cultures. Both mutants were significantly attenuated compared with the wild-type strain in a mouse model of strangles, although 2 of 30 mice infected with the lgt190-685 mutant did still exhibit signs of disease. In contrast, only the prtM138-213 mutant was significantly attenuated in a pony infection study, with 0 of 5 infected ponies exhibiting pathological signs of strangles compared with 4 of 4 infected with the wild-type and 3 of 5 infected with the lgt190-685 mutant. We believe that this is the first study to evaluate the contribution of lipoproteins to the virulence of a gram-positive pathogen in its natural host. These data suggest that the PrtM lipoprotein is a potential vaccine candidate, and further investigation of its activity and its substrate(s) are warranted.

Submitted by Angela Maria de Oliveira (amolivei@uepg.br) on 2018-12-19T13:31:11Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Alceu de Oliveira Toledo Junior.pdf: 3822777 bytes, checksum: 8621dbda843628c32379a4d6c54e0ac2 (MD5) / Made available in DSpace on 2018-12-19T13:31:11Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Alceu de Oliveira Toledo Junior.pdf: 3822777 bytes, checksum: 8621dbda843628c32379a4d6c54e0ac2 (MD5) Previous issue date: 2018-12-17 / Este estudo tem como objetivo avaliar comparativamente perfis de marcadores bioquímicos que melhor caracterizem e/ou associem-se às dislipidemias, na modalidade diagnóstica por ampliar a estratificação do risco cardiovascular ou no seu monitoramento para melhor condução. Para isso avaliamos o perfil lipídico composto por colesterol total, triglicérides, colesterol da lipoproteína de alta densidade e da lipoproteína de baixa densidade; esta com a fórmula de Martin, e ainda o colesterol em conteúdo que não faz parte das lipoproteínas de alta densidade, correlacionando-os com os marcadores: lipoproteína a, apoproteína B e colesterol da lipoproteína de baixa densidade; com uso do método homogêneo. Foram selecionados 1012 pacientes, segmentados por faixas etárias, sexo e condição de uso ou não de inibidores de produção hepática do colesterol. Para ampliar o poder dessa análise agrupada os exames realizados foram separados em subgrupos, considerando-se valores obtidos e metodologias utilizadas; correlacionando-se os resultados. A pesquisa foi realizada com variáveis qualitativas e quantitativas, procedendo-se ao uso de testes estatísticos não paramétricos para sua compreensão, distribuição e análise agrupada. Nossos resultados mostraram evidências que o risco cardiovascular não se associa apenas ao colesterol da lipoproteína de baixa densidade obtido pela fórmula de Martin, mas a outras variáveis, sob associação às seguintes análises comparativas: que o uso da apoproteína B amplia o diagnóstico de inclusão das dislipidemias em 43% usando valores referenciais sexo-independentes e com uma nova faixa de monitoramento em 84 mg/dL. Que o colesterol da lipoproteína de baixa densidade obtido pelo método homogêneo apresenta discordância analítica em +3,5% e tendo estratificação diagnóstica 48% superior. E que a lipoproteína a apresenta-se superior a 30 mg/dL em 26% dos pacientes, porém com prevalência e segmentação específicas nas mulheres entre 51 a 60 anos, sendo necessária sua análise numa aparente discordância, superior a 10 mg/dL, quando da comparação de resultados entre a fórmula de Martin e o método homogêneo. / This study aims to comparatively evaluate the profiles of biochemical markers that best characterize and / or associate with dyslipidemias, in the diagnostic modality by increasing the stratification of cardiovascular risk or its monitoring for better conduction. For this, we evaluated the lipid profile composed of total cholesterol, triglycerides, high density lipoprotein cholesterol and low density lipoprotein; and the cholesterol in non-high density lipoprotein content, correlating them with the markers: lipoprotein A, apoprotein B and low density lipoprotein cholesterol; using the homogeneous method. A total of 1012 patients were selected, segmented by age, sex and condition of use or inhibition of hepatic cholesterol production. In order to increase the power of this group analysis the exams were separated into subgroups, considering the obtained values and methodologies used; correlating the results. The research was carried out with qualitative and quantitative variables, using nonparametric statistical tests for their comprehension, distribution and grouped analysis. Our results showed evidence that cardiovascular risk is not only associated with the low density lipoprotein cholesterol obtained by Martin's formula, but other variables, in association with the following comparative analyzes: that the use of apoprotein B expands the diagnosis of inclusion of dyslipidemias in 43 % using genderindependent baseline values and with a new monitoring range of 84 mg/dL. That the low density lipoprotein cholesterol obtained by the homogeneous method presents an analytical disagreement at + 3.5% and having a 48% higher diagnostic stratification. In addition, lipoprotein a levels were higher than 30 mg/dL in 26% of the patients, but with a specific prevalence and segmentation in women between the ages of 51 and 60 years, with an apparent disagreement of more than 10 mg/dL when of the comparison of results between the Martin formula and the homogeneous method.