The Application of a Modified d-ROMs Test for Measurement of Oxidative Stress and Oxidized High-Density Lipoprotein

PubMed Central

Ito, Fumiaki; Ito, Tomoyuki; Suzuki, Chinatsu; Yahata, Tomoyo; Ikeda, Kazuyuki; Hamaoka, Kenji

2017-01-01

Reactive oxygen species (ROS) are involved in the initiation and progression of atherosclerosis. ROS-derived hydroperoxides, as an indicator of ROS production, have been measured by using the diacron reactive oxygen metabolites (d-ROMs) test, which requires iron-containing transferrin in the reaction mixture. In this study we developed a modified d-ROMs test, termed the Fe-ROMs test, where iron ions were exogenously added to the reaction mixture. This modification is expected to exclude the assay variation that comes from different blood iron levels in individuals. In addition, this Fe-ROMs test was helpful for determining the class of plasma lipoproteins that are hydroperoxidized. Low-density lipoprotein/very low-density lipoprotein (LDL/VLDL) and high-density lipoprotein (HDL) were purified by use of an LDL/VLDL purification kit and the dextran sulfate-Mg2+ precipitation method, respectively; their hydroperoxide contents were assessed by performing the Fe-ROMs test. The majority of the hydroperoxides were detected only in the HDL fraction, not in the LDL/VLDL. Further detailed analysis of HDLs by size-exclusion high-performance liquid chromatography revealed that the hydroperoxide-containing molecules were small-sized HDLs. Because HDL was shown to be the principal vehicle for the plasma hydroperoxides, this Fe-ROMs test is a beneficial method for the assessment of oxidized-HDL levels. Indeed, Fe-ROMs levels were strongly associated with the levels of oxidized HDL, which were determined by performing the malondialdehyde-modified HDL enzyme immunoassay. In conclusion, the Fe-ROMs test using plasma itself or the HDL fraction after dextran sulfate-Mg2+ precipitation is useful to assess the functionality of HDL, because the oxidation of HDL impairs its antiatherogenic capacity. PMID:28230785

The Application of a Modified d-ROMs Test for Measurement of Oxidative Stress and Oxidized High-Density Lipoprotein.

PubMed

Ito, Fumiaki; Ito, Tomoyuki; Suzuki, Chinatsu; Yahata, Tomoyo; Ikeda, Kazuyuki; Hamaoka, Kenji

2017-02-21

Reactive oxygen species (ROS) are involved in the initiation and progression of atherosclerosis. ROS-derived hydroperoxides, as an indicator of ROS production, have been measured by using the diacron reactive oxygen metabolites (d-ROMs) test, which requires iron-containing transferrin in the reaction mixture. In this study we developed a modified d-ROMs test, termed the Fe-ROMs test, where iron ions were exogenously added to the reaction mixture. This modification is expected to exclude the assay variation that comes from different blood iron levels in individuals. In addition, this Fe-ROMs test was helpful for determining the class of plasma lipoproteins that are hydroperoxidized. Low-density lipoprotein/very low-density lipoprotein (LDL/VLDL) and high-density lipoprotein (HDL) were purified by use of an LDL/VLDL purification kit and the dextran sulfate-Mg 2+ precipitation method, respectively; their hydroperoxide contents were assessed by performing the Fe-ROMs test. The majority of the hydroperoxides were detected only in the HDL fraction, not in the LDL/VLDL. Further detailed analysis of HDLs by size-exclusion high-performance liquid chromatography revealed that the hydroperoxide-containing molecules were small-sized HDLs. Because HDL was shown to be the principal vehicle for the plasma hydroperoxides, this Fe-ROMs test is a beneficial method for the assessment of oxidized-HDL levels. Indeed, Fe-ROMs levels were strongly associated with the levels of oxidized HDL, which were determined by performing the malondialdehyde-modified HDL enzyme immunoassay. In conclusion, the Fe-ROMs test using plasma itself or the HDL fraction after dextran sulfate-Mg 2+ precipitation is useful to assess the functionality of HDL, because the oxidation of HDL impairs its antiatherogenic capacity.

Genetics of Lipid and Lipoprotein Disorders and Traits.

PubMed

Dron, Jacqueline S; Hegele, Robert A

2016-01-01

Plasma lipids, namely cholesterol and triglyceride, and lipoproteins, such as low-density lipoprotein (LDL) and high-density lipoprotein, serve numerous physiological roles. Perturbed levels of these traits underlie monogenic dyslipidemias, a diverse group of multisystem disorders. We are on the verge of having a relatively complete picture of the human dyslipidemias and their components. Recent advances in genetics of plasma lipids and lipoproteins include the following: (1) expanding the range of genes causing monogenic dyslipidemias, particularly elevated LDL cholesterol; (2) appreciating the role of polygenic effects in such traits as familial hypercholesterolemia and combined hyperlipidemia; (3) accumulating a list of common variants that determine plasma lipids and lipoproteins; (4) applying exome sequencing to identify collections of rare variants determining plasma lipids and lipoproteins that via Mendelian randomization have also implicated gene products such as NPC1L1 , APOC3 , LDLR , APOA5 , and ANGPTL4 as causal for atherosclerotic cardiovascular disease; and (5) using naturally occurring genetic variation to identify new drug targets, including inhibitors of apolipoprotein (apo) C-III, apo(a), ANGPTL3, and ANGPTL4. Here, we compile this disparate range of data linking human genetic variation to plasma lipids and lipoproteins, providing a "one stop shop" for the interested reader.

Toward Reliable Lipoprotein Particle Predictions from NMR Spectra of Human Blood: An Interlaboratory Ring Test.

PubMed

Monsonis Centelles, Sandra; Hoefsloot, Huub C J; Khakimov, Bekzod; Ebrahimi, Parvaneh; Lind, Mads V; Kristensen, Mette; de Roo, Niels; Jacobs, Doris M; van Duynhoven, John; Cannet, Claire; Fang, Fang; Humpfer, Eberhard; Schäfer, Hartmut; Spraul, Manfred; Engelsen, Søren B; Smilde, Age K

2017-08-01

Lipoprotein profiling of human blood by 1 H nuclear magnetic resonance (NMR) spectroscopy is a rapid and promising approach to monitor health and disease states in medicine and nutrition. However, lack of standardization of measurement protocols has prevented the use of NMR-based lipoprotein profiling in metastudies. In this study, a standardized NMR measurement protocol was applied in a ring test performed across three different laboratories in Europe on plasma and serum samples from 28 individuals. Data was evaluated in terms of (i) spectral differences, (ii) differences in LPD predictions obtained using an existing prediction model, and (iii) agreement of predictions with cholesterol concentrations in high- and low-density lipoproteins (HDL and LDL) particles measured by standardized clinical assays. ANOVA-simultaneous component analysis (ASCA) of the ring test spectral ensemble that contains methylene and methyl peaks (1.4-0.6 ppm) showed that 97.99% of the variance in the data is related to subject, 1.62% to sample type (serum or plasma), and 0.39% to laboratory. This interlaboratory variation is in fact smaller than the maximum acceptable intralaboratory variation on quality control samples. It is also shown that the reproducibility between laboratories is good enough for the LPD predictions to be exchangeable when the standardized NMR measurement protocol is followed. With the successful implementation of this protocol, which results in reproducible prediction of lipoprotein distributions across laboratories, a step is taken toward bringing NMR more into scope of prognostic and diagnostic biomarkers, reducing the need for less efficient methods such as ultracentrifugation or high-performance liquid chromatography (HPLC).

Lipoprotein particle distribution and skeletal muscle lipoprotein lipase activity after acute exercise.

PubMed

Harrison, Michael; Moyna, Niall M; Zderic, Theodore W; O'Gorman, Donal J; McCaffrey, Noel; Carson, Brian P; Hamilton, Marc T

2012-07-10

Many of the metabolic effects of exercise are due to the most recent exercise session. With recent advances in nuclear magnetic resonance spectroscopy (NMRS), it is possible to gain insight about which lipoprotein particles are responsible for mediating exercise effects. Using a randomized cross-over design, very low density lipoprotein (VLDL) responses were evaluated in eight men on the morning after i) an inactive control trial (CON), ii) exercising vigorously on the prior evening for 100 min followed by fasting overnight to maintain an energy and carbohydrate deficit (EX-DEF), and iii) after the same exercise session followed by carbohydrate intake to restore muscle glycogen and carbohydrate balance (EX-BAL). The intermediate, low and high density lipoprotein particle concentrations did not differ between trials. Fasting triglyceride (TG) determined biochemically, and mean VLDL size were lower in EX-DEF but not in EX-BAL compared to CON, primarily due to a reduction in VLDL-TG in the 70-120 nm (large) particle range. In contrast, VLDL-TG was lower in both EX-DEF and EX-BAL compared to CON in the 43-55 nm (medium) particle range. VLDL-TG in smaller particles (29-43 nm) was unaffected by exercise. Because the majority of VLDL particles were in this smallest size range and resistant to change, total VLDL particle concentration was not different between any of these conditions. Skeletal muscle lipoprotein lipase (LPL) activity was also not different across these 3 trials. However, in CON only, the inter-individual differences in LPL activity were inversely correlated with fasting TG, VLDL-TG, total, large and small VLDL particle concentration and VLDL size, indicating a regulatory role for LPL in the non-exercised state. These findings reveal a high level of differential regulation between different sized triglyceride-rich lipoproteins following exercise and feeding, in the absence of changes in LPL activity.

Mild Oxidation Promotes and Advanced Oxidation Impairs Remodeling of Human High-Density Lipoprotein in vitro

PubMed Central

Gao, Xuan; Jayaraman, Shobini; Gursky, Olga

2008-01-01

SUMMARY High-density lipoproteins (HDL) prevent atherosclerosis by removing cholesterol from macrophages and by exerting anti-oxidant and anti-inflammatory effects. Oxidation is thought to impair HDL functions, yet certain oxidative modifications may be advantageous; thus, mild oxidation reportedly enhances cell cholesterol uptake by HDL whereas extensive oxidation impairs it. To elucidate the underlying energetic and structural basis, we analyzed the effects of copper and hypochlorite (that preferentially oxidize lipids and proteins, respectively) on thermal stability of plasma spherical HDL. Circular dichroism, light scattering, calorimetry, gel electrophoresis and electron microscopy showed that mild oxidation destabilizes HDL and accelerates protein dissociation and lipoprotein fusion, while extensive oxidation inhibits these reactions; this inhibition correlates with massive protein cross-linking and lipolysis. We propose that mild oxidation lowers kinetic barriers for HDL remodeling due to diminished apolipoprotein affinity for lipids resulting from oxidation of methionine and aromatic residues in apolipoproteins A-I and A-II followed by protein cross-linking into dimers and/or trimers. In contrast, advanced oxidation inhibits protein dissociation and HDL fusion due to lipid re-distribution from core to surface upon lipolysis and to massive protein cross-linking. Our results help reconcile the apparent controversy in the studies of oxidized HDL and suggest that mild oxidation may benefit HDL functions. PMID:18190928

Lipoprotein particle distribution and skeletal muscle lipoprotein lipase activity after acute exercise

PubMed Central

2012-01-01

Background Many of the metabolic effects of exercise are due to the most recent exercise session. With recent advances in nuclear magnetic resonance spectroscopy (NMRS), it is possible to gain insight about which lipoprotein particles are responsible for mediating exercise effects. Methods Using a randomized cross-over design, very low density lipoprotein (VLDL) responses were evaluated in eight men on the morning after i) an inactive control trial (CON), ii) exercising vigorously on the prior evening for 100 min followed by fasting overnight to maintain an energy and carbohydrate deficit (EX-DEF), and iii) after the same exercise session followed by carbohydrate intake to restore muscle glycogen and carbohydrate balance (EX-BAL). Results The intermediate, low and high density lipoprotein particle concentrations did not differ between trials. Fasting triglyceride (TG) determined biochemically, and mean VLDL size were lower in EX-DEF but not in EX-BAL compared to CON, primarily due to a reduction in VLDL-TG in the 70–120 nm (large) particle range. In contrast, VLDL-TG was lower in both EX-DEF and EX-BAL compared to CON in the 43–55 nm (medium) particle range. VLDL-TG in smaller particles (29–43 nm) was unaffected by exercise. Because the majority of VLDL particles were in this smallest size range and resistant to change, total VLDL particle concentration was not different between any of these conditions. Skeletal muscle lipoprotein lipase (LPL) activity was also not different across these 3 trials. However, in CON only, the inter-individual differences in LPL activity were inversely correlated with fasting TG, VLDL-TG, total, large and small VLDL particle concentration and VLDL size, indicating a regulatory role for LPL in the non-exercised state. Conclusions These findings reveal a high level of differential regulation between different sized triglyceride-rich lipoproteins following exercise and feeding, in the absence of changes in LPL activity. PMID

Cholesterol efflux from THP-1 macrophages is impaired by the fatty acid component from lipoprotein hydrolysis by lipoprotein lipase.

PubMed

Yang, Yanbo; Thyagarajan, Narmadaa; Coady, Breanne M; Brown, Robert J

2014-09-05

Lipoprotein lipase (LPL) is an extracellular lipase that primarily hydrolyzes triglycerides within circulating lipoproteins. Macrophage LPL contributes to atherogenesis, but the mechanisms behind it are poorly understood. We hypothesized that the products of lipoprotein hydrolysis generated by LPL promote atherogenesis by inhibiting the cholesterol efflux ability by macrophages. To test this hypothesis, we treated human THP-1 macrophages with total lipoproteins that were hydrolyzed by LPL and we found significantly reduced transcript levels for the cholesterol transporters ATP binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor BI. These decreases were likely due to significant reductions for the nuclear receptors liver-X-receptor-α, peroxisome proliferator activated receptor (PPAR)-α, and PPAR-γ. We prepared a mixture of free fatty acids (FFA) that represented the ratios of FFA species within lipoprotein hydrolysis products, and we found that the FFA mixture also significantly reduced cholesterol transporters and nuclear receptors. Finally, we tested the efflux of cholesterol from THP-1 macrophages to apolipoprotein A-I, and we found that the treatment of THP-1 macrophages with the FFA mixture significantly attenuated cholesterol efflux. Overall, these data show that the FFA component of lipoprotein hydrolysis products generated by LPL may promote atherogenesis by inhibiting cholesterol efflux, which partially explains the pro-atherogenic role of macrophage LPL. Copyright © 2014 Elsevier Inc. All rights reserved.

Impaired lipoprotein processing in HIV patients on antiretroviral therapy: aberrant high-density lipoprotein lipids, stability, and function.

PubMed

Gillard, Baiba K; Raya, Joe L; Ruiz-Esponda, Raul; Iyer, Dinakar; Coraza, Ivonne; Balasubramanyam, Ashok; Pownall, Henry J

2013-07-01

HIV patients on antiretroviral therapy (HIV/ART) exhibit a unique atherogenic dyslipidemic profile with hypertriglyceridemia (HTG) and low plasma concentrations of high-density lipoprotein (HDL) cholesterol. In the Heart Positive Study of HIV/ART patients, a hypolipidemic therapy of fenofibrate, niacin, diet, and exercise reduced HTG and plasma non-HDL cholesterol concentrations and raised plasma HDL cholesterol and adiponectin concentrations. We tested the hypothesis that HIV/ART HDL have abnormal structures and properties and are dysfunctional. Hypolipidemic therapy reduced the TG contents of low-density lipoprotein and HDL. At baseline, HIV/ART low-density lipoproteins were more triglyceride (TG)-rich and HDL were more TG- and cholesteryl ester-rich than the corresponding lipoproteins from normolipidemic (NL) subjects. Very-low-density lipoproteins, low-density lipoprotein, and HDL were larger than the corresponding lipoproteins from NL subjects; HIV/ART HDL were less stable than NL HDL. HDL-[(3)H]cholesteryl ester uptake by Huh7 hepatocytes was used to assess HDL functionality. HIV/ART plasma were found to contain significantly less competitive inhibition activity for hepatocyte HDL-cholesteryl ester uptake than NL plasma were found to contain (P<0.001). Compared with NL subjects, lipoproteins from HIV/ART patients are larger and more neutral lipid-rich, and their HDL are less stable and less receptor-competent. On the basis of this work and previous studies of lipase activity in HIV, we present a model in which plasma lipolytic activities or hepatic cholesteryl ester uptake are impaired in HIV/ART patients. These findings provide a rationale to determine whether the distinctive lipoprotein structure, properties, and function of HIV/ART HDL predict atherosclerosis as assessed by carotid artery intimal medial thickness.

Nanocrystal Core Lipoprotein Biomimetics for Imaging of Lipoproteins and Associated Diseases.

PubMed

Fay, Francois; Sanchez-Gaytan, Brenda L; Cormode, David P; Skajaa, Torjus; Fisher, Edward A; Fayad, Zahi A; Mulder, Willem J M

2013-02-01

Lipoproteins are natural nanoparticles composed of phospholipids and apolipoproteins that transport lipids throughout the body. As key effectors of lipid homeostasis, the functions of lipoproteins have been demonstrated to be crucial during the development of cardiovascular diseases. Therefore various strategies have been used to study their biology and detect them in vivo. A recent approach has been the production of lipoprotein biomimetic particles loaded with diagnostically active nanocrystals in their core. These include, but are not limited to: quantum dots, iron oxide or gold nanocrystals. Inclusion of these nanocrystals enables the utilization of lipoproteins as probes for a variety of imaging modalities (computed tomography, magnetic resonance imaging, fluorescence) while preserving their biological activity. Furthermore as some lipoproteins naturally accumulate in atherosclerotic plaque or specific tumor tissues, nanocrystal core lipoprotein biomimetics have been developed as contrast agents for early diagnosis of these diseases.

Nanocrystal Core Lipoprotein Biomimetics for Imaging of Lipoproteins and Associated Diseases

PubMed Central

Fay, Francois; Sanchez-Gaytan, Brenda L.; Cormode, David P.; Skajaa, Torjus; Fisher, Edward A.; Fayad, Zahi A.

2013-01-01

Lipoproteins are natural nanoparticles composed of phospholipids and apolipoproteins that transport lipids throughout the body. As key effectors of lipid homeostasis, the functions of lipoproteins have been demonstrated to be crucial during the development of cardiovascular diseases. Therefore various strategies have been used to study their biology and detect them in vivo. A recent approach has been the production of lipoprotein biomimetic particles loaded with diagnostically active nanocrystals in their core. These include, but are not limited to: quantum dots, iron oxide or gold nanocrystals. Inclusion of these nanocrystals enables the utilization of lipoproteins as probes for a variety of imaging modalities (computed tomography, magnetic resonance imaging, fluorescence) while preserving their biological activity. Furthermore as some lipoproteins naturally accumulate in atherosclerotic plaque or specific tumor tissues, nanocrystal core lipoprotein biomimetics have been developed as contrast agents for early diagnosis of these diseases. PMID:23687557

Native and Reconstituted Plasma Lipoproteins in Nanomedicine: Physicochemical Determinants of Nanoparticle Structure, Stability, and Metabolism

PubMed Central

Pownall, Henry J.; Rosales, Corina; Gillard, Baiba K.; Ferrari, Mauro

2016-01-01

Although many acute and chronic diseases are managed via pharmacological means, challenges remain regarding appropriate drug targeting and maintenance of therapeutic levels within target tissues. Advances in nanotechnology will overcome these challenges through the development of lipidic particles, including liposomes, lipoproteins, and reconstituted high-density lipoproteins (rHDL) that are potential carriers of water-soluble, hydrophobic, and amphiphilic molecules. Herein we summarize the properties of human plasma lipoproteins and rHDL, identify the physicochemical determinants of lipid transfer between phospholipid surfaces, and discuss strategies for increasing the plasma half-life of lipoprotein- and liposome-associated molecules. PMID:27826368

Contribution of lipoproteins and lipoprotein processing to endocarditis virulence in Streptococcus sanguinis.

PubMed

Das, Sankar; Kanamoto, Taisei; Ge, Xiuchun; Xu, Ping; Unoki, Takeshi; Munro, Cindy L; Kitten, Todd

2009-07-01

Streptococcus sanguinis is an important cause of infective endocarditis. Previous studies have identified lipoproteins as virulence determinants in other streptococcal species. Using a bioinformatic approach, we identified 52 putative lipoprotein genes in S. sanguinis strain SK36 as well as genes encoding the lipoprotein-processing enzymes prolipoprotein diacylglyceryl transferase (lgt) and signal peptidase II (lspA). We employed a directed signature-tagged mutagenesis approach to systematically disrupt these genes and screen each mutant for the loss of virulence in an animal model of endocarditis. All mutants were viable. In competitive index assays, mutation of a putative phosphate transporter reduced in vivo competitiveness by 14-fold but also reduced in vitro viability by more than 20-fold. Mutations in lgt, lspA, or an uncharacterized lipoprotein gene reduced competitiveness by two- to threefold in the animal model and in broth culture. Mutation of ssaB, encoding a putative metal transporter, produced a similar effect in culture but reduced in vivo competiveness by >1,000-fold. [(3)H]palmitate labeling and Western blot analysis confirmed that the lgt mutant failed to acylate lipoproteins, that the lspA mutant had a general defect in lipoprotein cleavage, and that SsaB was processed differently in both mutants. These results indicate that the loss of a single lipoprotein, SsaB, dramatically reduces endocarditis virulence, whereas the loss of most other lipoproteins or of normal lipoprotein processing has no more than a minor effect on virulence.

Lipoprotein-Cholesterol Fractions in Marginalized Roma versus Majority Population.

PubMed

Hubková, Beáta; Bódy, Gabriel; Mašlanková, Jana; Birková, Anna; Frišman, Eugen; Kraus, Vladimír; Mareková, Mária

2018-01-06

The trend of modern clinical biochemistry is to emphasize the composition and the quality of lipoproteins over their quantity. The serum lipoprotein fractions and subfractions were analyzed by the Lipoprint Lipoprotein Subfractions Testing System, the parameters of lipid profile, as total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triacylglycerides (TAG) were determined by an automated selective biochemical analyzer. Our results showed a significantly lower concentration of cholesterol in the LDL fractions 1 and 2 and in the HDL fractions 8 to 10 in Roma compared to the majority population. The most significant differences between Roma and the majority population when considering body mass index (BMI), waist-to-hip ratio and the index of central obesity were in very low-density lipoproteins (VLDL), intermediate-density lipoproteins, fraction A (IDL-A) and LDL-2. The last two listed were significantly higher in the majority population. VLDL was significantly higher in overweight or obese Roma men and in Roma men with central obesity compared to men from the majority population, as well as in Roma women with normal weight and physiological waist-to-hip ratio compared to the women from majority population. Our study is among the first describing the distribution of lipoprotein subfractions in different ethnic groups.

Prediction of lipoprotein signal peptides in Gram-negative bacteria.

PubMed

Juncker, Agnieszka S; Willenbrock, Hanni; Von Heijne, Gunnar; Brunak, Søren; Nielsen, Henrik; Krogh, Anders

2003-08-01

A method to predict lipoprotein signal peptides in Gram-negative Eubacteria, LipoP, has been developed. The hidden Markov model (HMM) was able to distinguish between lipoproteins (SPaseII-cleaved proteins), SPaseI-cleaved proteins, cytoplasmic proteins, and transmembrane proteins. This predictor was able to predict 96.8% of the lipoproteins correctly with only 0.3% false positives in a set of SPaseI-cleaved, cytoplasmic, and transmembrane proteins. The results obtained were significantly better than those of previously developed methods. Even though Gram-positive lipoprotein signal peptides differ from Gram-negatives, the HMM was able to identify 92.9% of the lipoproteins included in a Gram-positive test set. A genome search was carried out for 12 Gram-negative genomes and one Gram-positive genome. The results for Escherichia coli K12 were compared with new experimental data, and the predictions by the HMM agree well with the experimentally verified lipoproteins. A neural network-based predictor was developed for comparison, and it gave very similar results. LipoP is available as a Web server at www.cbs.dtu.dk/services/LipoP/.

Contribution of Lipoproteins and Lipoprotein Processing to Endocarditis Virulence in Streptococcus sanguinis▿ §

PubMed Central

Das, Sankar; Kanamoto, Taisei; Ge, Xiuchun; Xu, Ping; Unoki, Takeshi; Munro, Cindy L.; Kitten, Todd

2009-01-01

Streptococcus sanguinis is an important cause of infective endocarditis. Previous studies have identified lipoproteins as virulence determinants in other streptococcal species. Using a bioinformatic approach, we identified 52 putative lipoprotein genes in S. sanguinis strain SK36 as well as genes encoding the lipoprotein-processing enzymes prolipoprotein diacylglyceryl transferase (lgt) and signal peptidase II (lspA). We employed a directed signature-tagged mutagenesis approach to systematically disrupt these genes and screen each mutant for the loss of virulence in an animal model of endocarditis. All mutants were viable. In competitive index assays, mutation of a putative phosphate transporter reduced in vivo competitiveness by 14-fold but also reduced in vitro viability by more than 20-fold. Mutations in lgt, lspA, or an uncharacterized lipoprotein gene reduced competitiveness by two- to threefold in the animal model and in broth culture. Mutation of ssaB, encoding a putative metal transporter, produced a similar effect in culture but reduced in vivo competiveness by >1,000-fold. [3H]palmitate labeling and Western blot analysis confirmed that the lgt mutant failed to acylate lipoproteins, that the lspA mutant had a general defect in lipoprotein cleavage, and that SsaB was processed differently in both mutants. These results indicate that the loss of a single lipoprotein, SsaB, dramatically reduces endocarditis virulence, whereas the loss of most other lipoproteins or of normal lipoprotein processing has no more than a minor effect on virulence. PMID:19395487

Lipoprotein profile, lipoprotein-associated phospholipase A2 and cardiovascular risk in hemodialysis patients.

PubMed

Rolla, Roberta; De Mauri, Andreana; Valsesia, Ambra; Vidali, Matteo; Chiarinotti, Doriana; Bellomo, Giorgio

2015-12-01

Cardiovascular disease is the leading cause of morbidity and mortality in hemodialysis patients; the increased risk of cardiovascular disease is due to accelerated atherosclerosis, inflammation and impaired lipoprotein metabolism. We aimed to evaluate lipoprotein-associated phospholipase A2 (Lp-PLA2) and some pro-inflammatory aspects of the lipoprotein profile in dialyzed patients in order to evaluate the relationship with the accelerated atherosclerosis and vascular accidents. In 102 dialysis patients and 40 non-uremic controls, we investigated the lipoprotein plasma profile, high sensitivity C-reactive protein (CRP), ceruloplasmin and serum amyloid A protein (SAA), and followed patients for 1 year to analyze the risk of acute cardiovascular events. Total cholesterol, low-density lipoprotein and high-density lipoprotein plasma levels were significantly lower in uremic patients than controls, whereas CRP, SAA, ceruloplasmin, Lp-PLA2 and their ratio with apolipoprotein A1 were significantly higher. Patients with Lp-PLA2 levels >194 nmol/min/ml had more acute cardiovascular events than patients with lower values. Our results show that in dialysis subjects: (1) low-density lipoproteins show a more atherogenic phenotype than in the general population; (2) high-density lipoproteins are less anti-inflammatory; (3) Lp-PLA2 could potentially be used to evaluate cardiovascular risk.

Effect of phospholipase A treatment of low density lipoproteins on the dextran sulfate--lipoprotein interaction.

PubMed

Nishida, T

1968-09-01

The effect of phospholipase A on the interaction of low density lipoproteins of the S(f) 0-10 class with dextran sulfate was studied in phosphate buffer of pH 7.4, ionic strength 0.1, by chemical, spectrophotometric, and centrifugal methods. When low density lipoproteins that had been treated with phospholipase A were substituted for untreated lipoproteins, the amount of insoluble dextran sulfate-lipoprotein complex formed was greatly reduced. Hydrolysis of over 20% of the lecithin and phosphatidyl ethanolamine constituents of the lipoproteins prevented the formation of insoluble complex. However, even the lipoproteins in which almost all the phosphoglycerides were hydrolyzed produced soluble complex, which was converted to insoluble complex upon addition of magnesium sulfate. It is apparent that the lipoproteins altered extensively by treatment with phospholipase A retain many characteristic properties of native low density lipoproteins. Fatty acids, but not lysolecithin, released by the action of phospholipase A interfered with the formation of insoluble complex; this interference was due to association of the fatty acids with the lipoproteins. With increases in the concentration of the associated fatty acids, the amounts of magnesium ion required for the conversion of soluble complex to insoluble complex increased progressively. Charge interaction is evidently of paramount importance in the formation of sulfated polysaccharide-lipoprotein complexes.

Titration of Serum Lipoproteins with Lipoprotein Precipitants.

DTIC Science & Technology

1981-12-01

Lipid Res 11:583 (1970). 6. Grove, T. H. Effect of reagent pH on determination of high-density lipo- protein cholesterol by precipitation with sodium ...of choles- terol in the supernate plateaued at 43 mg/dl after the beta and prebeta lipo- proteins had been precipitated . The intensities of the two...AD-A113 370 SCHOOL OF AEROSPACE MEDICINE BROOKS AFS TX F/S 6/1 TITRATION OF SERU’LIPOPROTEINS WITH LIPOPROTEIN PRECIPITANTS .(Ul DEC 81 0 A CLARK. J A

Plasma-Advanced Oxidation Protein Products Are Potent High-Density Lipoprotein Receptor Antagonists In Vivo

PubMed Central

Marsche, Gunther; Frank, Sasa; Hrzenjak, Andelko; Holzer, Michael; Dirnberger, Sabine; Wadsack, Christian; Scharnagl, Hubert; Stojakovic, Tatjana; Heinemann, Akos; Oettl, Karl

2010-01-01

Advanced oxidation protein products (AOPPs) are carried by oxidized plasma proteins, especially albumin and accumulate in subjects with renal disease and coronary artery disease. AOPPs represent an excellent novel marker of oxidative stress and their roles in the development of cardiovascular disease might be of great importance. Here, we show that in vitro–generated AOPP-albumin binds with high affinity to the high-density lipoprotein (HDL) receptor scavenger receptor class B type I (SR-BI). Already an equimolar concentration of AOPP-albumin to HDL blocked HDL association to SR-BI and effectively inhibited SR-BI–mediated cholesterol ester (CE) uptake. Interestingly, albumin extensively modified by advanced glycation end products (AGE-albumin), which is an established SR-BI ligand known to accumulate in renal disease, only weakly interfered with HDL binding to SR-BI. Furthermore, AOPP-albumin administration increased the plasma half-life of [3H]CE-HDL in control mice 1.6-fold (P=0.01) and 8-fold (P=0.0003) in mice infected with adenoviral vectors encoding human SR-BI. Moreover, albumin isolated from hemodialysis patients, but not albumin isolated from healthy controls, markedly inhibited SR-BI–mediated HDL-CE transfer in vitro dependent on the AOPP content of albumin. These results indicate that AOPP-albumin effectively blocks SR-BI in vitro and in vivo. Thus, depressed plasma clearance of HDL-cholesterol may contribute to the abnormal composition of HDL and the high cardiovascular risk observed in patients with chronic renal failure. PMID:19179658

Dietary fatty acids were not independently associated with lipoprotein subclasses in elderly women.

PubMed

Alaghehband, Fatemeh Ramezan; Lankinen, Maria; Värri, Miika; Sirola, Joonas; Kröger, Heikki; Erkkilä, Arja T

2017-07-01

Dietary fatty acids are known to affect serum lipoproteins; however, little is known about the associations between consumption of dietary fatty acids and lipoprotein subclasses. In this study, we hypothesized that there is an association between dietary fatty acids and lipoprotein subclasses and investigated the cross-sectional association of dietary fat intake with subclasses of lipoproteins in elderly women. Altogether, 547 women (aged ≥65 years) who were part of OSTPRE cohort participated. Dietary intake was assessed by 3-day food records, lifestyle, and health information obtained through self-administrated questionnaires, and lipoprotein subclasses were determined by nuclear magnetic resonance spectroscopy. To analyze the associations between fatty acids and lipoprotein subclasses, we used Pearson and Spearman correlation coefficients and the analysis of covariance (ANCOVA) test with, adjustment for physical activity, body mass index, age, smoking status, and intake of lipid-lowering drugs. There were significant correlations between saturated fatty acids (SFA; % of energy) and concentrations of large, medium, and small low-density lipoproteins (LDL); total cholesterol in large, medium, and small LDL; and phospholipids in large, medium, and small LDL, after correction for multiple testing. After adjustment for covariates, the higher intake of SFA was associated with smaller size of LDL particles (P = .04, ANCOVA) and lower amount of triglycerides in small very low-density lipoproteins (P = .046, ANCOVA). However, these associations did not remain significant after correction for multiple testing. In conclusion, high intake of SFA may be associated with the size of LDL particles, but the results do not support significant, independent associations between dietary fatty acids and lipoprotein subclasses. Copyright © 2017 Elsevier Inc. All rights reserved.

Prediction of lipoprotein signal peptides in Gram-negative bacteria

PubMed Central

Juncker, Agnieszka S.; Willenbrock, Hanni; von Heijne, Gunnar; Brunak, Søren; Nielsen, Henrik; Krogh, Anders

2003-01-01

A method to predict lipoprotein signal peptides in Gram-negative Eubacteria, LipoP, has been developed. The hidden Markov model (HMM) was able to distinguish between lipoproteins (SPaseII-cleaved proteins), SPaseI-cleaved proteins, cytoplasmic proteins, and transmembrane proteins. This predictor was able to predict 96.8% of the lipoproteins correctly with only 0.3% false positives in a set of SPaseI-cleaved, cytoplasmic, and transmembrane proteins. The results obtained were significantly better than those of previously developed methods. Even though Gram-positive lipoprotein signal peptides differ from Gram-negatives, the HMM was able to identify 92.9% of the lipoproteins included in a Gram-positive test set. A genome search was carried out for 12 Gram-negative genomes and one Gram-positive genome. The results for Escherichia coli K12 were compared with new experimental data, and the predictions by the HMM agree well with the experimentally verified lipoproteins. A neural network-based predictor was developed for comparison, and it gave very similar results. LipoP is available as a Web server at www.cbs.dtu.dk/services/LipoP/. PMID:12876315

Liver lipase and high-density lipoprotein. Lipoprotein changes after incubation of human serum with rat liver lipase.

PubMed

Groot, P H; Scheek, L M; Jansen, H

1983-05-16

Human sera were incubated with rat liver lipase after inactivation of lecithin:cholesterol acyltransferase, and the changes in serum lipoprotein composition were measured. In the presence of liver lipase serum triacylglycerol and phosphatidylcholine were hydrolyzed. The main changes in the concentrations of these lipids were found in the high-density lipoprotein fraction. Subfractionation of high-density lipoprotein by rate-zonal ultracentrifugation showed a prominent decrease in all constituents of high-density lipoprotein2, a smaller decrease in the 'light' high-density lipoprotein3 and an increase in the 'heavy' high-density lipoprotein3. These data support a concept in which liver lipase is involved in high-density lipoprotein2 phospholipid and triacylglycerol catabolism and suggest that as a result of this action high-density lipoprotein2 is converted into high-density lipoprotein3.

Lipoprotein Uptake by Neuronal Growth Cones in Vitro

NASA Astrophysics Data System (ADS)

Ignatius, Michael J.; Shooter, Eric M.; Pitas, Robert E.; Mahley, Robert W.

1987-05-01

Macrophages that rapidly enter injured peripheral nerve synthesize and secrete large quantities of apolipoprotein E. This protein may be involved in the redistribution of lipid, including cholesterol released during degeneration, to the regenerating axons. To test this postulate, apolipoprotein E-associated lipid particles released from segments of injured rat sciatic nerve and apolipoprotein E-containing lipoproteins from plasma were used to determine whether sprouting neurites, specifically their growth cones, possessed lipoprotein receptors. Pheochromocytoma (PC12) cells, which can be stimulated to produce neurites in vitro, were used as a model system. Apolipoprotein E-containing lipid particles and lipoproteins, which had been labeled with fluorescent dye, were internalized by the neurites and their growth cones; the unmetabolized dye appeared to be localized to the lysosomes. The rapid rate of accumulation in the growth cones precludes the possibility of orthograde transport of the fluorescent particles from the PC12 cell bodies. Thus, receptor-mediated lipoprotein uptake is performed by the apolipoprotein B,E(LDL) (low density lipoprotein) receptors, and in the regenerating peripheral nerve apolipoprotein E may deliver lipids to the neurites and their growth cones for membrane biosynthesis.

The fibrate drug gemfibrozil disrupts lipoprotein metabolism in rainbow trout

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prindiville, John S., E-mail: jprin041@uottawa.ca; Mennigen, Jan A.; Zamora, Jake M.

2011-03-15

Gemfibrozil (GEM) is a fibrate drug consistently found in effluents from sewage treatment plants. This study characterizes the pharmacological effects of GEM on the plasma lipoproteins of rainbow trout (Oncorhynchus mykiss). Our goals were to quantify the impact of the drug on: 1) lipid constituents of lipoproteins (phospholipids (PL), triacylglycerol (TAG), and cholesterol), 2) lipoprotein classes (high, low and very low density lipoproteins), and 3) fatty acid composition of lipoproteins. Potential mechanisms of GEM action were investigated by measuring lipoprotein lipase activity (LPL) and the hepatic gene expression of LPL and of the peroxisome proliferator-activated receptor (PPAR) {alpha}, {beta}, andmore » {gamma} isoforms. GEM treatment resulted in decreased plasma lipoprotein levels (- 29%) and a reduced size of all lipoprotein classes (lower PL:TAG ratios). However, the increase in HDL-cholesterol elicited by GEM in humans failed to be observed in trout. Therefore, HDL-cholesterol cannot be used to assess the impact of the drug on fish. GEM also modified lipoprotein composition by reducing the abundance of long-chain n-3 fatty acids, thereby potentially reducing the nutritional quality of exposed fish. The relative gene expression of LPL was increased, but the activity of the enzyme was not, and we found no evidence for the activation of PPAR pathways. The depressing effects of GEM on fish lipoproteins demonstrated here may be a concern in view of the widespread presence of fibrates in aquatic environments. Work is needed to test whether exposure to environmental concentrations of these drugs jeopardizes the capacity of fish for reproduction, temperature acclimation or migratory behaviors.« less

Smooth muscle cell biglycan overexpression results in increased lipoprotein retention on extracellular matrix: implications for the retention of lipoproteins in atherosclerosis.

PubMed

O'Brien, Kevin D; Lewis, Katherine; Fischer, Jens W; Johnson, Pamela; Hwang, Jin-Yong; Knopp, Eleanor A; Kinsella, Michael G; Barrett, P Hugh R; Chait, Alan; Wight, Thomas N

2004-11-01

Lipoprotein retention on extracellular matrix (ECM) may play a central role in atherogenesis, and a specific extracellular matrix proteoglycan, biglycan, has been implicated in lipoprotein retention in human atherosclerosis. To test whether increased cellular biglycan expression results in increased retention of lipoproteins on ECM, rat aortic smooth muscle cells (SMCs) were transduced with a human biglycan cDNA-containing retroviral vector (LBSN) or with an empty retroviral vector (LXSN). To assess the importance of biglycan's glycosaminoglycan side chains in lipoprotein retention, ECM binding studies were also performed using RASMCs transduced with a retroviral vector encoding for a mutant, glycosaminoglycan-deficient biglycan (LBmutSN). Human biglycan mRNA and protein were confirmed in LBSN and LBmutSN RASMCs by Northern and Western blot analyses. HDL3+E binding to SMC ECM was increased significantly (as determined by 95% confidence intervals for binding curves) for LBSN as compared to either LXSN or LBmutSN cells; the increases for LBSN cell ECM were due primarily to an approximately 50% increase in binding sites (increased Bmax) versus LXSN cell ECM and of approximately 25% versus LBmutSN cell ECM. These results are consistent with the hypothesis that biglycan, through its glycosaminoglycan side chains, may mediate lipoprotein retention on atherosclerotic plaque ECM.

Spirochetal Lipoproteins and Immune Evasion

PubMed Central

Christodoulides, Alexei; Boyadjian, Ani; Kelesidis, Theodoros

2017-01-01

Spirochetes are a major threat to public health. However, the exact pathogenesis of spirochetal diseases remains unclear. Spirochetes express lipoproteins that often determine the cross talk between the host and spirochetes. Lipoproteins are pro-inflammatory, modulatory of immune responses, and enable the spirochetes to evade the immune system. In this article, we review the modulatory effects of spirochetal lipoproteins related to immune evasion. Understanding lipoprotein-induced immunomodulation will aid in elucidating innate pathogenesis processes and subsequent adaptive mechanisms potentially relevant to spirochetal disease vaccine development and treatment. PMID:28424696

Identification of the trypanocidal factor in normal human serum: high density lipoprotein.

PubMed Central

Rifkin, M R

1978-01-01

The differentiation of Trypanosoma brucei from T. rhodesiense, the causative agent of human sleeping sickness, depends on their relative sensitivities to the cytotoxic effects of normal human serum. The molecule responsible for the specific lysis of T. brucei has now been isolated. Serum lipoproteins were fractionated and purified by ultracentrifugal flotation and chromatography on Bio-Gel A-5m. Trypanocidal activity was recovered in the high density lipoprotein fraction (density, 1.063-1.216 g/ml). Contamination by other serum proteins was checked by crossed immunoelectrophoresis and sodium dodecyl sulfate/acrylamide gel electrophoresis. Only a trace of beta-lipoprotein was found. The trypanocidal activity of pure human high density lipoprotein was identical to that of unfractionated serum when the following were tested: (i) time course of in vitro lysis of T. bruceli; (ii) in vivo destruction of T. brucei; (iii) relative resistance of T. rhodesiense to lysis. Rat or rabbit high density lipoprotein had no trypanocidal activity. Identification of the trypanocidal factor as high density lipoprotein was confirmed by the finding that serum from patients with Tangier disease, an autosomal recessive disorder characterized by a severe deficiency of high density lipoprotein, had no trypanocidal activity. Images PMID:210461

Genetics of non-conventional lipoprotein fractions

USDA-ARS?s Scientific Manuscript database

Lipoprotein subclass measures associate with cardiometabolic disease risk. Currently the information that lipoproteins convey on disease risk over that of traditional demographic and lipid measures is minimal, and so their use is clinics is limited. However, lipoprotein subclass perturbations repres...

Effects of hormones on lipids and lipoproteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krauss, R.M.

1991-12-01

Levels of plasma lipids and lipoproteins are strong predictors for the development of atherosclerotic cardiovascular disease in postmenopausal women. In women, as in men, numerous factors contribute to variations in plasma lipoproteins that may affect cardiovascular disease risk. These include age, dietary components, adiposity, genetic traits, and hormonal changes. Each of these factors may operate to varying degrees in determining changes in plasma lipoprotein profiles accompanying menopause- Cross-sectional and longitudinal studies have suggested increases in levels of cholesterol, low density lipoproteins (LDL) and triglyceride-rich lipoproteins associated with menopause. High density lipoproteins (HDL), which are higher in women than men andmore » are thought to contribute to relative protection of premenopausal women from cardiovascular disease, remain relatively constant in the years following menopause, although small, and perhaps transient reductions in the HDL{sub 2} subfraction have been reported in relation to reduced estradiol level following menopause. Despite these associations, it has been difficult to determine the role of endogenous hormones in influencing the plasma lipoproteins of postmenopausal women. In principle, the effects of hormone replacement should act to reverse any alterations in lipoprotein metabolism that are due to postmenopausal hormone changes. While there may be beneficial effects on lipoproteins, hormone treatment does not restore a premenopausal lipoprotein profile. Furthermore, it is not dear to what extent exogenous hormone-induced lipoprotein changes contribute to the reduced incidence of cardiovascular disease with hormone replacement therapy.« less

Regulating intestinal function to reduce atherogenic lipoproteins.

PubMed

Hussain, M Mahmood; Leung, Tung Ming; Zhou, Liye; Abu-Merhi, Sarah

2013-08-01

Significant knowledge regarding different molecules involved in the transport of dietary fat into the circulation has been garnered. Studies point to the possibility that accumulation of intestine-derived lipoproteins in the plasma could contribute to atherosclerosis. This article provides a brief overview of dietary lipid metabolism and studies in mice supporting the hypothesis that intestinal lipoproteins contribute to atherosclerosis. Deficiencies in lipoprotein lipase and Gpihbp1, and overexpression of heparanse in mice, are associated with increases in atherosclerosis, suggesting that defects in catabolism of larger lipoproteins in the plasma contribute to atherosclerosis. Furthermore, inositol-requiring enzyme 1β-deficient mice that produce more intestinal lipoproteins also develop more atherosclerosis. Thus, increases in plasma intestinal lipoproteins due to either overproduction or reduced catabolism result in augmented atherosclerosis. Intestinal lipoproteins tend to adhere strongly to subendothelial proteoglycans, elicit an inflammatory response by endothelial cells and activate macrophages, contributing to the initiation and progression of the disease. Thus, molecules that reduce intestinal lipid absorption can be useful in lowering atherosclerosis.

Ultracentrifugal and electrophoretic characteristics of the plasma lipoproteins of miniature schnauzer dogs with idiopathic hyperlipoproteinemia.

PubMed

Whitney, M S; Boon, G D; Rebar, A H; Story, J A; Bottoms, G D

1993-01-01

To better characterize the idiopathic hyperlipoproteinemia of Miniature Schnauzer dogs, the plasma lipoproteins of 20 Miniature Schnauzers (MS) and 11 dogs of other breeds (DOB) were evaluated by ultracentrifugation, electrophoresis, and biochemical tests. Seventeen MS were healthy; 3 had diabetes mellitus. Plasma from 6 of 17 healthy and all 3 diabetic MS was visibly lipemic. Lipemia was slight to marked in healthy lipemic MS, and marked in diabetic ones. All DOB had clear plasma; 8 were healthy and 3 had diabetes. All healthy lipemic MS and diabetic lipemic MS had hypertriglyceridemia associated with excess very low density lipoproteins. Chylomicronemia was present in 4 of 6 healthy lipemic MS and all 3 diabetic lipemic MS. Lipoproteins with ultracentrifugal and electrophoretic characteristics of normal low density lipoprotein were lacking in 4 of 6 healthy lipemic MS. The lipoprotein patterns of 4 of 11 healthy nonlipemic MS were characterized by mild hypertriglyceridemia associated with increased very low density lipoproteins and a lack of lipoproteins with characteristics of normal low density lipoproteins. Lipoprotein patterns of diabetic DOB closely resembled those of healthy DOB; those of diabetic lipemic MS resembled those of markedly lipemic healthy lipemic MS. In conclusion, the hyperlipoproteinemia of Miniature Schnauzers is characterized by increased very low density lipoproteins with or without accompanying chylomicronemia; some affected dogs may have decreased low density lipoproteins.

Lipoprotein-associated phospholipase A(2) and atherosclerosis.

PubMed

Wilensky, Robert L; Macphee, Colin H

2009-10-01

There is substantial data from over 50 000 patients that increased lipoprotein-associated phospholipase A2 (Lp-PLA2) mass or activity is associated with an increased risk of cardiac death, myocardial infarction, acute coronary syndromes and ischemic stroke. However, only recently have data emerged demonstrating a role of Lp-PLA2 in development of advanced coronary artery disease. Indeed, Lp-PLA2 may be an important link between lipid homeostasis and the vascular inflammatory response. Lp-PLA2, also known as platelet-activating factor acetylhydrolase, rapidly cleaves oxidized phosphatidylcholine molecules produced during the oxidation of LDL and atherogenic lipoprotein Lp(a), generating the soluble proinflammatory and proapoptotic lipid mediators, lyso-phosphatidylcholine and oxidized nonesterified fatty acids. These proinflammatory lipids play an important role in the development of atherosclerotic necrotic cores, the substrate for acute unstable coronary disease by recruiting and activating leukocytes/macrophages, inducing apoptosis and impairing the subsequent removal of dead cells. Selective inhibition of Lp-PLA2 reduces development of necrotic cores and may result in stabilization of atherosclerotic plaques. Recent data have shown that immune pathways play a major role in the development and progression of high-risk atherosclerosis, which leads to ischemic sudden death, myocardial infarction, acute coronary syndromes and ischemic strokes. Persistent and sustained macrophage apoptosis appears to play a major role in the resulting local inflammatory response in part by effects elicited by Lp-PLA2. Selective inhibition of Lp-PLA2 has been postulated to reduce necrotic core progression and the clinical sequelae of advanced, unstable atherosclerosis.

Effects of the Absence of Apolipoprotein E on Lipoproteins, Neurocognitive Function, and Retinal Function

PubMed Central

Mak, Angel C. Y.; Pullinger, Clive R.; Tang, Ling Fung; Wong, Jinny S.; Deo, Rahul C.; Schwarz, Jean-Marc; Gugliucci, Alejandro; Movsesyan, Irina; Ishida, Brian Y.; Chu, Catherine; Poon, Annie; Kim, Phillip; Stock, Eveline O.; Schaefer, Ernst J.; Asztalos, Bela F.; Castellano, Joseph M.; Wyss-Coray, Tony; Duncan, Jacque L.; Miller, Bruce L.; Kane, John P.; Kwok, Pui-Yan; Malloy, Mary J.

2016-01-01

IMPORTANCE The identification of a patient with a rare form of severe dysbetalipoproteinemia allowed the study of the consequences of total absence of apolipoprotein E (apoE). OBJECTIVES To discover the molecular basis of this rare disorder and to determine the effects of complete absence of apoE on neurocognitive and visual function and on lipoprotein metabolism. DESIGN, SETTING, AND PARTICIPANTS Whole-exome sequencing was performed on the patient’s DNA. He underwent detailed neurological and visual function testing and lipoprotein analysis. Lipoprotein analysis was also performed in the Cardiovascular Research Institute, University of California, San Francisco, on blood samples from the proband’s mother, wife, 2 daughters, and normolipidemic control participants. MAIN OUTCOME MEASURES Whole-exome sequencing, lipoprotein analysis, and neurocognitive function. RESULTS The patient was homozygous for an ablative APOE frameshift mutation (c.291del, p.E97fs). No other mutations likely to contribute to the phenotype were discovered, with the possible exception of two, in ABCC2 (p.I670T) and LIPC (p.G137R). Despite complete absence of apoE, he had normal vision, exhibited normal cognitive, neurological, and retinal function, had normal findings on brain magnetic resonance imaging, and had normal cerebrospinal fluid levels of β-amyloid and tau proteins. He had no significant symptoms of cardiovascular disease except a suggestion of myocardial ischemia on treadmill testing and mild atherosclerosis noted on carotid ultrasonography. He had exceptionally high cholesterol content (760 mg/dL; to convert to millimoles per liter, multiply by 0.0259) and a high cholesterol to triglycerides ratio (1.52) in very low-density lipoproteins with elevated levels of small-diameter high-density lipoproteins, including high levels of prebeta-1 high-density lipoprotein. Intermediate-density lipoproteins, low-density lipoproteins, and very low-density lipoproteins contained elevated apo

Advanced Beamline Design for Fermilab's Advanced Superconducting Test Accelerator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prokop, Christopher

2014-01-01

The Advanced Superconducting Test Accelerator (ASTA) at Fermilab is a new electron accelerator currently in the commissioning stage. In addition to testing superconducting accelerating cavities for future accelerators, it is foreseen to support a variety of Advanced Accelerator R&D (AARD) experiments. Producing the required electron bunches with the expected flexibility is challenging. The goal of this dissertation is to explore via numerical simulations new accelerator beamlines that can enable the advanced manipulation of electron bunches. The work especially includes the design of a low-energy bunch compressor and a study of transverse-to-longitudinal phase space exchangers.

Lipoprotein metabolism indicators improve cardiovascular risk prediction

USDA-ARS?s Scientific Manuscript database

Background: Cardiovascular disease risk increases when lipoprotein metabolism is dysfunctional. We have developed a computational model able to derive indicators of lipoprotein production, lipolysis, and uptake processes from a single lipoprotein profile measurement. This is the first study to inves...

Advanced Test Reactor Tour

ScienceCinema

Miley, Don

2017-12-21

The Advanced Test Reactor at Idaho National Laboratory is the foremost nuclear materials test reactor in the world. This virtual tour describes the reactor, how experiments are conducted, and how spent nuclear fuel is handled and stored.

Auto antibodies against oxidized low density lipoprotein in severe preeclampsia.

PubMed

Jain, Meenakshi; Sawhney, Harjeet; Aggarwal, Neelam; Vashistha, Kala; Majumdhar, Siddarth

2004-06-01

To study autoantibody titres against oxidized low density lipoprotein in preeclamsia. Ten millimeters of heparinized blood samples were collected from 20 primigravidae with severe preeclamsia (study group) and 20 gestation-matched normotensive primigravidae (control group). Concentration of malondialdehyde, metabolite of lipid peroxidation were measured in sera by HPLC and autoantibodies against oxidized low density lipoproteins (obtained after oxidation with 2 mm CuSO(4)) were determined by ELISA. Statistical analysis was performed by Student's t-test and chi(2) test. Mean triglyceride levels were significantly (P < 0.001) higher in the study group (193.20 +/- 31.16 mg/dL) compared to the control group (170.60 +/- 23.2 mg/dL). Mean plasma lipid per oxide levels were not significantly different between the study (4.45 +/- 1.28 mmol/mL) and control (3.88 +/- 0.99 mmol/mL) groups. The majority of women in both groups had low antibody titres (<1.32) against low density lipoprotein. Six women (30%) of the study group and four (20%) of the control group had high autoantibody titres (>/=1.32). In preeclamptic women, diastolic blood pressure, the amount of urinary protein excretion and the plasma level of urea were significantly higher (P < 0.05) in patients with higher auto antibody titre. Titres of autoantibodies to oxidized low density lipoprotein were similar in normotensive and preeclamptic women. In preeclamptic women, titres correlated positively with the severity of preeclampsia.

Corn oil intake favorably impacts lipoprotein cholesterol, apolipoprotein and lipoprotein particle levels compared with extra-virgin olive oil.

PubMed

Maki, K C; Lawless, A L; Kelley, K M; Kaden, V N; Geiger, C J; Palacios, O M; Dicklin, M R

2017-01-01

Corn oil (CO) and extra-virgin olive oil (EVOO) are rich sources of unsaturated fatty acids (UFA), but UFA profiles differ among oils, which may affect lipoprotein levels. The objective of this study was to assess the effects of CO versus EVOO intake on fasting lipoprotein and subfraction cholesterol levels, apolipoprotein (apo) A1, apo B, and low-density lipoprotein particle concentrations in men and women. As part of a weight maintenance diet, men and women were provided with food items prepared with 54 g per day of CO or EVOO (21-day treatment, 21-day washout) in a randomized, double-blind, controlled-feeding, crossover trial. Fasting lipoprotein cholesterol and related variables were determined with density gradient ultracentrifugation. Among the 54 completers, CO reduced total cholesterol, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apo B and LDL particle concentration to a greater extent compared with EVOO intake. Changes in LDL-C and VLDL-C contributed to the larger reduction in non-HDL-C with CO compared with EVOO intake (-0.39 mmol/l vs -0.04 mmol/l; P<0.001). The larger reduction in LDL-C by CO intake was attributable to changes (P<0.05) caused by CO vs EVOO in large LDL 1+2 -C (-0.22 mmol/l) and intermediate-density lipoprotein cholesterol (-0.12 mmol/l). HDL-C responses did not differ between treatments, but apo A1 increased more with EVOO compared with CO intake (4.6  versus 0.7 mg/dl, respectively, P=0.016). CO intake reduced atherogenic lipoprotein cholesterol and particle concentrations to a larger extent than did EVOO, which may have implications for cardiovascular disease risk.

Postprandial lipoprotein metabolism; VLDL vs chylomicrons

PubMed Central

Nakajima, Katsuyuki; Nakano, Takamitsu; Tokita, Yoshiharu; Nagamine, Takeaki; Inazu, Akihiro; Kobayashi, Junji; Mabuchi, Hiroshi; Stanhope, Kimber L.; Havel, Peter J.; Okazaki, Mitsuyo; Ai, Masumi; Tanaka, Akira

2012-01-01

Since Zilversmit first proposed postprandial lipemia as the most common risk of cardiovascular disease, chylomicrons (CM) and CM remnants have been thought to be the major lipoproteins which are increased in the postprandial hyperlipidemia. However, it has been shown over the last two decades that the major increase in the postprandial lipoproteins after food intake occurs in the very low density lipoprotein (VLDL) remnants (apoB100 particles), not CM or CM remnants (apoB48 particles). This finding was obtained using the following three analytical methods; isolation of remnant-like lipoprotein particles (RLP) with specific antibodies, separation and detection of lipoprotein subclasses by gel permeation HPLC and determination of apoB48 in fractionated lipoproteins by a specific ELISA. The amount of the apoB48 particles in the postprandial RLP is significantly less than the apoB100 particles, and the particle sizes of apoB48 and apoB100 in RLP are very similar when analyzed by HPLC. Moreover, CM or CM remnants having a large amount of TG were not found in the postprandial RLP. Therefore, the major portion of the TG which is increased in the postprandial state is composed of VLDL remnants, which have been recognized as a significant risk for cardiovascular disease. PMID:21531214

Serum lipoprotein concentrations in cystic fibrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vaughan, W.J.; Lindgren, F.T.; Whalen, J.B.

1978-02-17

Two major classes of lipoproteins, low density and high density, are decreased in the serum of patients with cystic fibrosis; major apoproteins are also decreased. Since essential fatty acids and certain fat-soluble vitamins depend on lipoproteins for transport in the serum, knowledge of lipoprotein levels in cystic fibrosis patients could prove valuable in understanding (i) the basis for the abnormally low serum levels of these fatty acids and vitamins and (ii) the effects of therapies involving these molecules.

Analyzing the molecular mechanism of lipoprotein localization in Brucella

PubMed Central

Goolab, Shivani; Roth, Robyn L.; van Heerden, Henriette; Crampton, Michael C.

2015-01-01

Bacterial lipoproteins possess diverse structure and functionality, ranging from bacterial physiology to pathogenic processes. As such many lipoproteins, originating from Brucella are exploited as potential vaccines to countermeasure brucellosis infection in the host. These membrane proteins are translocated from the cytoplasm to the cell membrane where they are anchored peripherally by a multifaceted targeting mechanism. Although much research has focused on the identification and classification of Brucella lipoproteins and their potential use as vaccine candidates for the treatment of Brucellosis, the underlying route for the translocation of these lipoproteins to the outer surface of the Brucella (and other pathogens) outer membrane (OM) remains mostly unknown. This is partly due to the complexity of the organism and evasive tactics used to escape the host immune system, the variation in biological structure and activity of lipoproteins, combined with the complex nature of the translocation machinery. The biosynthetic pathway of Brucella lipoproteins involves a distinct secretion system aiding translocation from the cytoplasm, where they are modified by lipidation, sorted by the lipoprotein localization machinery pathway and thereafter equipped for export to the OM. Surface localized lipoproteins in Brucella may employ a lipoprotein flippase or the β-barrel assembly complex for translocation. This review provides an overview of the characterized Brucella OM proteins that form part of the OM, including a handful of other characterized bacterial lipoproteins and their mechanisms of translocation. Lipoprotein localization pathways in gram negative bacteria will be used as a model to identify gaps in Brucella lipoprotein localization and infer a potential pathway. Of particular interest are the dual topology lipoproteins identified in Escherichia coli and Haemophilus influenza. The localization and topology of these lipoproteins from other gram negative bacteria

SPEPlip: the detection of signal peptide and lipoprotein cleavage sites.

PubMed

Fariselli, Piero; Finocchiaro, Giacomo; Casadio, Rita

2003-12-12

SPEPlip is a neural network-based method, trained and tested on a set of experimentally derived signal peptides from eukaryotes and prokaryotes. SPEPlip identifies the presence of sorting signals and predicts their cleavage sites. The accuracy in cross-validation is similar to that of other available programs: the rate of false positives is 4 and 6%, for prokaryotes and eukaryotes respectively and that of false negatives is 3% in both cases. When a set of 409 prokaryotic lipoproteins is predicted, SPEPlip predicts 97% of the chains in the signal peptide class. However, by integrating SPEPlip with a regular expression search utility based on the PROSITE pattern, we can successfully discriminate signal peptide-containing chains from lipoproteins. We propose the method for detecting and discriminating signal peptides containing chains and lipoproteins. It can be accessed through the web page at http://gpcr.biocomp.unibo.it/predictors/

Serum Lipoproteins Are Critical for Pulmonary Innate Defense against Staphylococcus aureus Quorum Sensing.

PubMed

Manifold-Wheeler, Brett C; Elmore, Bradley O; Triplett, Kathleen D; Castleman, Moriah J; Otto, Michael; Hall, Pamela R

2016-01-01

Hyperlipidemia has been extensively studied in the context of atherosclerosis, whereas the potential health consequences of the opposite extreme, hypolipidemia, remain largely uninvestigated. Circulating lipoproteins are essential carriers of insoluble lipid molecules and are increasingly recognized as innate immune effectors. Importantly, severe hypolipidemia, which may occur with trauma or critical illness, is clinically associated with bacterial pneumonia. To test the hypothesis that circulating lipoproteins are essential for optimal host innate defense in the lung, we used lipoprotein-deficient mice and a mouse model of Staphylococcus aureus pneumonia in which invasive infection requires virulence factor expression controlled by the accessory gene regulator (agr) operon. Activation of agr and subsequent virulence factor expression is inhibited by apolipoprotein B, the structural protein of low-density lipoprotein, which binds and sequesters the secreted agr-signaling peptide (AIP). In this article, we report that lipoprotein deficiency impairs early pulmonary innate defense against S. aureus quorum-sensing-dependent pathogenesis. Specifically, apolipoprotein B levels in the lung early postinfection are significantly reduced with lipoprotein deficiency, coinciding with impaired host control of S. aureus agr-signaling and increased agr-dependent morbidity (weight loss) and inflammation. Given that lipoproteins also inhibit LTA- and LPS-mediated inflammation, these results suggest that hypolipidemia may broadly impact posttrauma pneumonia susceptibility to both Gram-positive and -negative pathogens. Together with previous reports demonstrating that hyperlipidemia also impairs lung innate defense, these results suggest that maintenance of normal serum lipoprotein levels is necessary for optimal host innate defense in the lung. Copyright © 2015 by The American Association of Immunologists, Inc.

Hemoglobin level and lipoprotein particle size.

PubMed

Hämäläinen, Päivi; Saltevo, Juha; Kautiainen, Hannu; Mäntyselkä, Pekka; Vanhala, Mauno

2018-01-10

Alterations in lipoprotein size are associated with increased cardiovascular disease risk. Higher hemoglobin levels may indicate a higher risk of atherosclerosis and was previously associated with obesity, metabolic syndrome, and insulin resistance. No previous studies have investigated an association between hemoglobin concentration and lipoprotein particle size. We conducted a population-based, cross-sectional study of 766 Caucasian, middle-aged subjects (341 men and 425 women) born in Pieksämäki, Finland, who were categorized into five age groups. The concentrations and sizes of lipoprotein subclass particles were analyzed by high-throughput nuclear magnetic resonance (NMR) spectroscopy. Larger very low density lipoprotein (VLDL) particle diameter was associated with higher hemoglobin concentrations in men (p = 0.003). There was a strong relationship between smaller high density lipoprotein (HDL) particle size and higher hemoglobin concentration in both men and women as well as with smaller low density lipoprotein (LDL) particle size and higher hemoglobin concentration in men and women (p < 0.001; p = 0.009, p = 0.008). VLDL particle concentration had a moderate positive correlation with hemoglobin concentration (r = 0.15; p < 0.001). LDL particle concentration showed a statistical trend suggesting increasing particle concentration with increasing hemoglobin levels (r = 0.08; p = 0.05). Higher hemoglobin levels are associated with larger VLDL, smaller LDL, and smaller HDL particle sizes and increasing amounts of larger VLDL and smaller LDL particles. This suggests that a higher hemoglobin concentration is associated with an unfavorable lipoprotein particle profile that is part of states that increase cardiovascular disease risk like diabetes and metabolic syndrome.

Intimal hyperplasia induced by vascular intervention causes lipoprotein retention and accelerated atherosclerosis.

PubMed

Kijani, Siavash; Vázquez, Ana Maria; Levin, Malin; Borén, Jan; Fogelstrand, Per

2017-07-01

Accelerated atherosclerosis diminishes the long term patency of vascular interventions, such as percutaneous coronary intervention and implantation of saphenous vein grafts. However, the cause of this accelerated atherosclerosis is unclear. In this study, we tested the hypothesis that intimal hyperplasia formed following vascular intervention promotes retention of atherogenic lipoproteins. Intimal hyperplasia was surgically induced in the mouse common carotid artery. The surgery was combined with different mouse models of hypercholesterolemia to obtain different cholesterol levels and to control the onsets of hypercholesterolemia. Three weeks after surgery, samples were immunostained for apoB lipoproteins, smooth muscle cells and leukocytes. Already at mild hypercholesterolemia (193 mg/dL), pronounced apoB lipoprotein retention was found in the extracellular matrix in both intimal hyperplasia and the injured underlying media. In contrast, minimal retention was detected in the uninjured proximal region of the same vessel, or in vessels from mice with normal cholesterol levels (81 mg/dL). Induction of aggravated hypercholesterolemia 3 weeks after surgery, when a mature intimal hyperplasia had been formed, caused a very rapid development of atherosclerotic lesions. Mechanistically, we show that lipoprotein retention was almost exclusively dependent on electrostatic interactions to proteoglycan glycosaminoglycans, and the lipoprotein retention to intimal hyperplasia could be inhibited in vivo using glycosaminoglycan-binding antibodies. Thus, formation of intimal hyperplasia following vascular intervention makes the vessel wall highly susceptible for lipoprotein retention and accelerated atherosclerosis. The increased lipoprotein retention in intimal hyperplasia can be targeted by blocking the interaction between apoB lipoproteins and glycosaminoglycans in the extracellular matrix. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on

Understanding Lipoproteins as Transporters of Cholesterol and Other Lipids

ERIC Educational Resources Information Center

Biggerstaff, Kyle D.; Wooten, Joshua S.

2004-01-01

A clear picture of lipoprotein metabolism is essential for understanding the pathophysiology of atherosclerosis. Many students are taught that low-density lipoprotein-cholesterol is "bad" and high-density lipoprotein-cholesterol is "good." This misconception leads to students thinking that lipoproteins are types of cholesterol rather than…

Lipoproteins during the estrous cycle in swine.

PubMed

Liu, Ying; Rector, R Scott; Thomas, Tom R; Taylor, Julia A; Holiman, Denise A; Henderson, Kyle K; Welshons, Wade V; Sturek, Michael S

2004-02-01

The purpose of this study was to examine lipoprotein values at high versus low 17beta-estradiol (E2) concentrations in Yucatan miniature swine. Estrous cycles were measured by heat checking the female on a daily basis using a boar. All swine were fed a 1,050-g low-fat, standard chow diet (8% kcal from fat) once per day. Fasted (24 hours) blood samples were collected during low (early luteal, day 5) and high (late follicular, day 18) E2 concentrations to determine differences in concentrations of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), high-density lipoprotein cholesterol (HDL-C), and subfractions. Concentrations of E2 differed significantly from day 5 (3.5 +/- 0.7 pg/mL) to day 18 (14.2 +/- 1.8 pg/mL) of the estrous cycle. Except for HDL(3)-C, all lipoprotein parameters examined were significantly elevated during high E2 versus low E2. TC/HDL-C and LDL-C/HDL-C ratios were significantly lower during the high E2 phase. These results suggest that lipoprotein concentrations fluctuate during the estrous cycle of swine, with high E2 concentrations associated with elevated lipoprotein concentrations.

Lipoproteins: When size really matters

PubMed Central

German, J. Bruce; Smilowitz, Jennifer T.; Zivkovic, Angela M.

2010-01-01

The field of nanoscience is extending the applications of physics, chemistry and biology into previously unapproached infinitesimal length scales. Understanding the behavior and manipulating the positions and properties of single atoms and molecules hold great potential to improve areas of science as disparate as medicine and computation, and communication and orbiting satellites. Yet, in the race to develop novel, previously unavailable nanoparticles, there is an opportunity for scientists in this field to digress and to apply their growing understanding of nanoscience and the tools of nanotechnology to one of the most pressing problems in all of human biology—diseases related to lipoproteins. Although not appreciated outside the field of lipoprotein biology, variations in the compositions, structures and properties of these nanoscale-sized, blood-borne particles are responsible for most of the variations in health, morbidity and mortality in the Western world. If the lipoproteins could be understood at the nanometer length scale with precise details of their structures and functions, scientists could understand a wide range of perplexing physiological processes and also address the dysfunctions in normal lipoprotein biology that lead to such diseases as hypercholesterolemia, heart disease, stroke and neurodegenerative diseases. Furthermore, if the capabilities of nanoscience to assemble and manipulate nanometer-sized particles could be recruited to studies of lipoproteins, these biological particles would provide a new dimension to therapeutic agents, and these natural particles could be designed to carry out many specialized beneficial tasks. PMID:20592953

Triglycerides, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol in rats exposed to premium motor spirit fumes.

PubMed

Aberare, Ogbevire L; Okuonghae, Patrick; Mukoro, Nathaniel; Dirisu, John O; Osazuwa, Favour; Odigie, Elvis; Omoregie, Richard

2011-06-01

Deliberate and regular exposure to premium motor spirit fumes is common and could be a risk factor for liver disease in those who are occupationally exposed. A possible association between premium motor spirit fumes and plasma levels of triglyceride, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol using a rodent model could provide new insights in the pathology of diseases where cellular dysfunction is an established risk factor. The aim of this study was to evaluate the possible effect of premium motor spirit fumes on lipids and lipoproteins in workers occupationally exposed to premium motor spirit fumes using rodent model. Twenty-five Wister albino rats (of both sexes) were used for this study between the 4(th) of August and 7(th) of September, 2010. The rats were divided into five groups of five rats each. Group 1 rats were not exposed to premium motor spirit fumes (control group), group 2 rats were exposed for 1 hour daily, group 3 for 3 hours daily, group 4 for 5 hours daily and group 5 for 7 hours daily. The experiment lasted for a period of 4 weeks. Blood samples obtained from all the groups after 4 weeks of exposure were used for the estimation of plasma levels of triglyceride, total cholesterol, high density lipoprotein- cholesterol and low density lipoprotein- cholesterol. Results showed significant increase in means of plasma total cholesterol and low density lipoprotein levels (P<0.05). The mean triglyceride and total body weight were significantly lower (P<0.05) in the exposed group when compared with the unexposed. The plasma level of high density lipoprotein, the ratio of low density lipoprotein to high density lipoprotein and the ratio of total cholesterol to high density lipoprotein did not differ significantly in exposed subjects when compared with the control group. These results showed that frequent exposure to petrol fumes may be highly deleterious to the liver cells.

Serum lipoprotein changes in dogs with renal disease.

PubMed

Behling-Kelly, E

2014-01-01

People with renal disease develop a dyslipidemia that contributes to progression of renal injury and development of cardiovascular disease. Lipoproteins in dogs with renal disease have not been investigated. Dogs with chronic kidney disease (CKD) have dyslipidemia characterized by increased lower density lipoproteins and decreased high-density lipoproteins (HDLs). The degree of dyslipidemia is positively correlated with severity of disease, as reflected by serum creatinine concentration. Prospective study of client-owned dogs presented to the Cornell University Hospital for Animals: 29 dogs with confirmed CKD, 5 dogs with nephrotic syndrome (NS), and 12 healthy control dogs presented for routine vaccinations, dental cleaning, or owned by students. Lipoprotein electrophoresis was used to quantify relative proportions of the 3 main classes of lipoproteins in canine serum: low-density lipoproteins (LDL), very low-density lipoproteins (VLDL), and HDL. Serum cholesterol and creatinine concentrations; urinalysis and urine protein-to-creatinine ratio were measured by standard methods. Dyslipidemia was consistently found in dogs with CKD and NS and was characterized by a decrease in HDL and variable increases in LDL and VLDL. Dogs with NS had a proportionately greater increase in the VLDL fraction, as compared with dogs with CKD. Dyslipidemia similar to that documented in people with renal disease occurs in dogs with CKD, despite serum cholesterol concentrations often being within the reference interval. The contribution of altered lipoproteins to the pathogenesis of renal disease in dogs warrants additional study. Copyright © 2014 by the American College of Veterinary Internal Medicine.

Ion mobility analysis of lipoproteins

DOEpatents

Benner, W Henry [Danville, CA; Krauss, Ronald M [Berkeley, CA; Blanche, Patricia J [Berkeley, CA

2007-08-21

A medical diagnostic method and instrumentation system for analyzing noncovalently bonded agglomerated biological particles is described. The method and system comprises: a method of preparation for the biological particles; an electrospray generator; an alpha particle radiation source; a differential mobility analyzer; a particle counter; and data acquisition and analysis means. The medical device is useful for the assessment of human diseases, such as cardiac disease risk and hyperlipidemia, by rapid quantitative analysis of lipoprotein fraction densities. Initially, purification procedures are described to reduce an initial blood sample to an analytical input to the instrument. The measured sizes from the analytical sample are correlated with densities, resulting in a spectrum of lipoprotein densities. The lipoprotein density distribution can then be used to characterize cardiac and other lipid-related health risks.

Aerosol preparation of intact lipoproteins

DOEpatents

Benner, W Henry [Danville, CA; Krauss, Ronald M [Berkeley, CA; Blanche, Patricia J [Berkeley, CA

2012-01-17

A medical diagnostic method and instrumentation system for analyzing noncovalently bonded agglomerated biological particles is described. The method and system comprises: a method of preparation for the biological particles; an electrospray generator; an alpha particle radiation source; a differential mobility analyzer; a particle counter; and data acquisition and analysis means. The medical device is useful for the assessment of human diseases, such as cardiac disease risk and hyperlipidemia, by rapid quantitative analysis of lipoprotein fraction densities. Initially, purification procedures are described to reduce an initial blood sample to an analytical input to the instrument. The measured sizes from the analytical sample are correlated with densities, resulting in a spectrum of lipoprotein densities. The lipoprotein density distribution can then be used to characterize cardiac and other lipid-related health risks.

Abnormalities of Lipoprotein Levels in Liver Cirrhosis: Clinical Relevance.

PubMed

Privitera, Graziella; Spadaro, Luisa; Marchisello, Simona; Fede, Giuseppe; Purrello, Francesco

2018-01-01

Progressive lipoprotein impairment occurs in liver cirrhosis and is associated with increased morbidity and mortality. The present review aims to summarize the current evidence regarding the prognostic value of lipoprotein abnormalities in liver cirrhosis and to address the need of a better prognostic stratification of patients, including lipoprotein profile assessment. Low levels of lipoproteins are usual in cirrhosis. Much evidence supports the prognostic role of hypolipidemia in cirrhotic patients. In particular, hypocholesterolemia represents an independent predictor of survival in cirrhosis. In cirrhotic patients, lipoprotein impairment is associated with several complications: infections, malnutrition, adrenal function, and spur cell anemia. Alterations of liver function are associated with modifications of circulating lipids. Decreased levels of lipoproteins significantly impact the survival of cirrhotic patients and play an important role in the pathogenesis of some cirrhosis-related complications.

Distribution and Kinetics of Lipoprotein-Bound Lipoteichoic Acid

PubMed Central

Levels, Johannes H. M.; Abraham, Philip R.; van Barreveld, Erik P.; Meijers, Joost C. M.; van Deventer, Sander J. H.

2003-01-01

Lipoteichoic acid (LTA), a major cell wall component of gram-positive bacteria, is an amphipathic anionic glycolipid with structural similarities to lipopolysaccharide (LPS) from gram-negative bacteria. LTA has been implicated as one of the primary immunostimulatory components that may trigger the systemic inflammatory response syndrome. Plasma lipoproteins have been shown to sequester LPS, which results in attenuation of the host response to infection, but little is known about the LTA binding characteristics of plasma lipid particles. In this study, we have examined the LTA binding capacities and association kinetics of the major lipoprotein classes under simulated physiological conditions in human whole blood (ex vivo) by using biologically active, fluorescently labeled LTA and high-performance gel permeation chromatography. The average distribution of an LTA preparation from Staphylococcus aureus in whole blood from 10 human volunteers revealed that >95% of the LTA was associated with total plasma lipoproteins in the following proportions: high-density lipoprotein (HDL), 68% ± 10%; low-density lipoprotein (LDL), 28% ± 8%; and very low density lipoprotein (VLDL), 4% ± 5%. The saturation capacity of lipoproteins for LTA was in excess of 150 μg/ml. The LTA distribution was temperature dependent, with an optimal binding between 22 and 37°C. The binding of LTA by lipoproteins was essentially complete within 10 min and was followed by a subsequent redistribution from HDL and VLDL to LDL. We conclude that HDL has the highest binding capacity for LTA and propose that the loading and redistribution of LTA among plasma lipoproteins is a specific process that closely resembles that previously described for LPS (J. H. M. Levels, P. R. Abraham, A. van den Ende, and S. J. H. van Deventer, Infect. Immun. 68:2821-2828, 2001). PMID:12761109

The Impact of Cardiorespiratory Fitness on Age-Related Lipids and Lipoproteins

PubMed Central

Park, Yong-Moon Mark; Sui, Xuemei; Liu, Junxiu; Zhou, Haiming; Kokkinos, Peter F.; Lavie, Carl J.; Hardin, James W.; Blair, Steven N.

2015-01-01

Background Evidence on the effect of cardiorespiratory fitness (CRF) on age-related longitudinal changes of lipids and lipoproteins is scarce. Objectives This study sought to assess the longitudinal, aging trajectory of lipids and lipoproteins for the life course in adults, and to determine whether CRF modifies the age-associated trajectory of lipids and lipoproteins. Methods Data came from 11,418 men, 20 to 90 years of age, without known high cholesterol, high triglycerides, cardiovascular disease, and cancer at baseline and during follow-up from the Aerobics Center Longitudinal Study. There were 43,821 observations spanning 2 to 25 (mean 3.5) health examinations between 1970 and 2006. CRF was quantified by a maximal treadmill exercise test. Marginal models using generalized estimating equations were applied. Results Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and non-high-density lipoprotein cholesterol (non-HDL-C) presented similar inverted U-shaped quadratic trajectories with aging: gradual increases were noted until the mid-40s to early 50s, with subsequent declines (all p < 0.0001). Compared to men with higher CRF, those with lower CRF developed abnormal values earlier in life: TC (≥200 mg/dl), LDL-C (≥130 mg/dl), non-HDL-C (≥160 mg/dl), and TG/HDL-C ratio (≥3.0). Notably, abnormal values for TC and LDL-C in men with low CRF were observed around 15 years earlier than in those with high CRF. After adjusting for time-varying covariates, a significant interaction was found between age and CRF in each trajectory, indicating that CRF was more strongly associated with the aging trajectories of lipids and lipoproteins in young to middle-aged men than in older men. Conclusions Our investigation reveals a differential trajectory of lipids and lipoproteins with aging according to CRF in healthy men, and suggests that promoting increased CRF levels may help delay the development of dyslipidemia. PMID:25975472

Cigarette smoking and its association with serum lipid/lipoprotein among Chinese nonagenarians/centenarians

PubMed Central

2012-01-01

Objective Cigarette smoking had been confirmed as an increased risk for dyslipidemia, but none of the evidence was from long-lived population. In present study, we detected relationship between cigarette smoking habits and serum lipid/lipoprotein (serum Triglyceride (TG), Total cholesterol (TC), Low-density lipoprotein (LDL) and high-density lipoprotein (HDL)) among Chinese Nonagenarians/Centenarian. Methods The present study analyzed data from the survey that was conducted on all residents aged 90 years or more in a district, there were 2,311,709 inhabitants in 2005. Unpaired Student’s t test, χ2 test, and multiple logistic regression were used to analyze datas. Results The individuals included in the statistical analysis were 216 men and 445 women. Current smokers had lower level of TC (4.05 ± 0.81 vs. 4.21 ± 0.87, t = 2.403, P = 0.017) and lower prevalence of hypercholesteremia (9.62% vs. 15.13%, χ2 = 3.018,P = 0.049) than nonsmokers. Unadjusted and adjusted multiple logistic regressions showed that cigarette smoking was not associated with risk for abnormal serum lipid/lipoprotein. Conclusions In summary, we found that among Chinese nonagenarians/centenarians, cigarette smoking habits were not associated with increased risk for dyslipidemia, which was different from the association of smoking habits with dyslipidemia in general population. PMID:22828289

Practical technique to quantify small, dense low-density lipoprotein cholesterol using dynamic light scattering

NASA Astrophysics Data System (ADS)

Trirongjitmoah, Suchin; Iinaga, Kazuya; Sakurai, Toshihiro; Chiba, Hitoshi; Sriyudthsak, Mana; Shimizu, Koichi

2016-04-01

Quantification of small, dense low-density lipoprotein (sdLDL) cholesterol is clinically significant. We propose a practical technique to estimate the amount of sdLDL cholesterol using dynamic light scattering (DLS). An analytical solution in a closed form has newly been obtained to estimate the weight fraction of one species of scatterers in the DLS measurement of two species of scatterers. Using this solution, we can quantify the sdLDL cholesterol amount from the amounts of the low-density lipoprotein cholesterol and the high-density lipoprotein (HDL) cholesterol, which are commonly obtained through clinical tests. The accuracy of the proposed technique was confirmed experimentally using latex spheres with known size distributions. The applicability of the proposed technique was examined using samples of human blood serum. The possibility of estimating the sdLDL amount using the HDL data was demonstrated. These results suggest that the quantitative estimation of sdLDL amounts using DLS is feasible for point-of-care testing in clinical practice.

Lifestyle and Metformin Treatment Favorably Influence Lipoprotein Subfraction Distribution in the Diabetes Prevention Program

PubMed Central

Temprosa, M.; Otvos, J.; Brunzell, J.; Marcovina, S.; Mather, K.; Arakaki, R.; Watson, K.; Horton, E.; Barrett-Connor, E.

2013-01-01

Context: Although intensive lifestyle change (ILS) and metformin reduce diabetes incidence in subjects with impaired glucose tolerance (IGT), their effects on lipoprotein subfractions have not been studied. Objective: The objective of the study was to characterize the effects of ILS and metformin vs placebo interventions on lipoprotein subfractions in the Diabetes Prevention Program. Design: This was a randomized clinical trial, testing the effects of ILS, metformin, and placebo on diabetes development in subjects with IGT. Participants: Selected individuals with IGT randomized in the Diabetes Prevention Program participated in the study. Interventions: Interventions included randomization to metformin 850 mg or placebo twice daily or ILS aimed at a 7% weight loss using a low-fat diet with increased physical activity. Main Outcome Measures: Lipoprotein subfraction size, density, and concentration measured by magnetic resonance and density gradient ultracentrifugation at baseline and 1 year were measured. Results: ILS decreased large and buoyant very low-density lipoprotein, small and dense low-density lipoprotein (LDL), and small high-density lipoprotein (HDL) and raised large HDL. Metformin modestly reduced small and dense LDL and raised small and large HDL. Change in insulin resistance largely accounted for the intervention-associated decreases in large very low-density lipoprotein, whereas changes in body mass index (BMI) and adiponectin were strongly associated with changes in LDL. Baseline and a change in adiponectin were related to change in large HDL, and BMI change associated with small HDL change. The effect of metformin to increase small HDL was independent of adiponectin, BMI, and insulin resistance. Conclusion: ILS and metformin treatment have favorable effects on lipoprotein subfractions that are primarily mediated by intervention-related changes in insulin resistance, BMI, and adiponectin. Interventions that slow the development of diabetes may also

Advanced expander test bed engine

NASA Technical Reports Server (NTRS)

Mitchell, J. P.

1992-01-01

The Advanced Expander Test Bed (AETB) is a key element in NASA's Space Chemical Engine Technology Program for development and demonstration of expander cycle oxygen/hydrogen engine and advanced component technologies applicable to space engines as well as launch vehicle upper stage engines. The AETB will be used to validate the high pressure expander cycle concept, study system interactions, and conduct studies of advanced mission focused components and new health monitoring techniques in an engine system environment. The split expander cycle AETB will operate at combustion chamber pressures up to 1200 psia with propellant flow rates equivalent to 20,000 lbf vacuum thrust.

Metabolism of cholesteryl esters of rat very low density lipoproteins.

PubMed

Faergeman, O; Havel, R J

1975-06-01

Rat very low density lipoproteins (d smaller than 1.006), biologically labeled in esterified and free cholesterol, were obtained form serum 6 h after intravenous injection of particulate (3-H) cholesterol. When injected into recipient animals, the esterified cholesterol was cleared form plasma with a half-life of 5 min. After 15 min, 71% of the injected esterified (3-H) cholesterol had been taken up by the liver, where it was rapidly hydrolyzed. After 60 min only 3.3% of the amount injected had been transferred, via lipoproteins of intermediate density, to the low density lipoproteins of plasma (d 1.019-1.063). Both uptake in the liver and transfer to low density lipoproteins occurred without change of distribution of 3-H in the various cholesteryl esters. 3-H appearing in esterified cholesterol of high density lipoproteins (d greater than 1.063) was derived from esterification, presumably by lecithin: cholesterol acyltransferase, of simultaneously injected free (3-H) cholesterol. Content of free (3-H) cholesterol in the very low density lipoproteins used for injection could be reduced substantially by incubation with erythrocytes. This procedure, however, increased the rate of clearance of the lipoproteins after injection into recipient rats. These studies show that hepatic removal is the major catabolic pathway for cholesteryl esters of rat very low density lipoproteins and that transfer to low density lipoproteins occurs to only a minor extent.

[A history and review of cholesterol ester transfer protein inhibitors and their contribution to the understanding of the physiology and pathophysiology of high density lipoprotein].

PubMed

Corral, Pablo; Schreier, Laura

2014-01-01

There is irrefutable evidence that statins reduce the risk of cardiovascular events in a magnitude proportional to the intensity of the decrease in cholesterol transport by the low density lipoproteins. Despite this great advance there is still a residual risk of cardiovascular events. For this reason, an increase in the levels of high density lipoprotein is considered in order to boost the main action of this lipoprotein, which is reverse cholesterol transport. Distinct classes of evidence (epidemiological, genetic, and pathophysiological) show that the inhibition and/or modulation of cholesterol ester transfer protein increases plasma high density lipoprotein-cholesterol levels. The main reason for presenting this review is to look at the physiology of cholesterol ester transfer protein, its interrelationship with high density lipoproteins, and to give an update on the development of different cholesterol ester transfer protein inhibitor/modulator molecules. Copyright © 2013 Elsevier España, S.L. y SEA. All rights reserved.

Lipoprotein-cholesterol levels in infertile women with luteal phase deficiency.

PubMed

Hansen, K K; Knopp, R H; Soules, M R

1991-05-01

To determine if reductions in plasma progesterone (P) secretion seen in luteal phase deficiency (LPD) might be because of reduced availability of circulating low-density lipoprotein (LDL) or high-density lipoprotein (HDL), known substrates for corpus luteum P synthesis. We measured plasma lipoproteins in the luteal phase of the menstrual cycle in 39 infertile women. These women were divided into two groups on the basis of endometrial biopsies; the LPD group had biopsies that were greater than or equal to 3 days out-of-phase. All participants were recruited from the Reproductive Endocrinology and Infertility Clinic at the University of Washington, an institutional tertiary care center. Eighteen women had in-phase and 21 had out-of-phase LPD biopsies. Lipoprotein levels were obtained in a fasted state on the day of the luteal phase on which the biopsy was performed. No difference in covariates that affect lipoprotein levels such as obesity, age, and alcohol use were observed between the two groups. No significant differences between groups were found for triglycerides, total cholesterol, very low density lipoprotein, LDL, HDL, HDL2, and HDL3 concentrations. However, LPD was associated with a reduction in the extent to which: age and obesity are associated with higher triglycerides; obesity is associated with a lower HDL2; and alcohol is associated with a higher HDL3-cholesterol. Lipoproteins on average are not different in LPD, suggesting reasons other than a deficient plasma lipoprotein cholesterol source as the explanation for decreased P secretion. A lesser interaction between LDL or HDL and obesity, age, and alcohol in LPD could signify an influence of the altered hormonal milieu of LPD on the way lipoproteins interact with covariates and could lead to differences in lipoproteins between normal and LPD subjects at the extremes of the lipoprotein distribution.

Elevation of small, dense low density lipoprotein cholesterol-a possible antecedent of atherogenic lipoprotein phenotype in type 2 diabetes patients in Jos, North-Central Nigeria.

PubMed

Inaku, Kenneth O; Ogunkeye, Obasola O; Abbiyesuku, Fayeofori M; Chuhwak, Evelyn K; Isichei, Christian O; Imoh, Lucius C; Amadu, Noel O; Abu, Alexander O

2017-01-01

The global prevalence of type 2 diabetes is increasing. Dyslipidaemia is a known complication of diabetes mellitus manifesting frequently as cardiovascular diseases and stoke. Elevation of small, dense low density lipoprotein has been recognised as a component of the atherogenic lipoprotein phenotype associated with cardiovascular complications. We speculate that the elevation of this lipoprotein particle may be the antecedent of the atherogenic lipoprotein phenotype. This study therefore aims to determine the pattern of dyslipidaemia among diabetes mellitus patients in Jos, North-Central Nigeria. One hundred and seventy-six patients with type 2 diabetes and 154 age-matched controls were studied. The patients with diabetes were regular clinic attenders and had stable glycaemic control. None were on lipid-lowering therapy. Anthropometric indices, blood pressure, and lipids (including total cholesterol, high density lipoprotein cholesterol, and triglyceride) were measured by chemical methods using the Hitachi 902 analyzer. Low density lipoprotein cholesterol was calculated using the Friedewald's equation. Small, dense low density lipoprotein cholesterol, -sdLDL-C was measured using the precipitation method by Hirano et al. Means of the different groups were compared using EPI Info and a P -value of <0.05 was accepted as significant difference. Total cholesterol, low density lipoprotein cholesterol, triglyceride and small, dense lipoprotein cholesterol were all significantly higher in diabetes patients than controls except high density lipoprotein cholesterol. The percentage of LDL-C as sdLDL-C among the diabetes versus control group was 45% ± 17.79 v 32.0% ± 15.93. Serum sdLDL-C concentration was determined to be 1.45 ± 0.64 among diabetes patients and 0.8 ± 0.54 among control subjects. 75% of diabetes patients had hypertension and were taking blood pressure lowering medications. The classical atherogenic lipoprotein phenotype was not demonstrated

Interrelationships between postprandial lipoprotein B:CIII particle changes and high-density lipoprotein subpopulation profiles in mixed hyperlipoproteinemia.

PubMed

Saïdi, Y; Sich, D; Camproux, A; Egloff, M; Federspiel, M C; Gautier, V; Raisonnier, A; Turpin, G; Beucler, I

1999-01-01

We studied the relationships postprandially between triglyceride-rich lipoprotein (TRL) and high-density lipoprotein (HDL) in 11 mixed hyperlipoproteinemia (MHL) and 11 hypercholesterolemia (HCL) patients. The high and prolonged postprandial triglyceridemia response observed in MHL but not HCL patients was essentially dependent on very-low-density lipoprotein (VLDL) changes. This abnormal response was related to decreased lipoprotein lipase (LPL) activity (-48.7%, P<.01) in MHL compared with HCL subjects. Cholesteryl ester transfer protein (CETP) activity was postprandially enhanced only in MHL patients, and this elevation persisted in the late period (+19% at 12 hours, P<.05), sustaining the delayed enrichment of VLDL with cholesteryl ester (CE). The late postprandial period in MHL patients was also characterized by high levels of apolipoprotein B (apoB)-containing lipoproteins with apoCIII ([LpB:CIII] +36% at 12 hours, P<.01) and decreased levels of apoCIII contained in HDL ([LpCIII-HDL] -34% at 12 hours, P<.01), reflecting probably a defective return of apoCIII from TRL toward HDL. In MHL compared with HCL patients, decreased HDL2 levels were related to both HDL2b and HDL2a subpopulations (-57% and -49%, respectively, P<.01 for both) and decreased apoA-I levels (-53%, P<.01) were equally linked to decreased HDL2 with apoA-I only (LpA-I) and HDL2 with both apoA-I and apoA-II ([LpA-I:A-II] -55% and -52%, respectively, P<.01 for both). The significant inverse correlations between the postprandial magnitude of LpB:CIII and HDL2-LpA-I and HDL2b levels in MHL patients underline the close TRL-HDL interrelationships. Our findings indicate that TRL and HDL abnormalities evidenced at fasting were postprandially amplified, tightly interrelated, and persistent during the late fed period in mixed hyperlipidemia. Thus, these fasting abnormalities are likely postprandially originated and may constitute proatherogenic lipoprotein disorders additional to the HCL in MHL patients.

Aging, age-related macular degeneration, and the response-to-retention of apolipoprotein B-containing lipoproteins

PubMed Central

Curcio, Christine A.; Johnson, Mark; Huang, Jiahn-Dar; Rudolf, Martin

2015-01-01

The largest risk factor for age-related macular degeneration (ARMD) is advanced age. A prominent age-related change in the human retina is the accumulation of histochemically detectable neutral lipid in normal Bruch’s membrane (BrM) throughout adulthood. This change has the potential to have a major impact on physiology of the retinal pigment epithelium (RPE). It occurs in the same compartment as drusen and basal linear deposit, the pathognomonic extracellular, lipid-containing lesions of ARMD. Here we present evidence from light microscopic histochemistry, ultrastructure, lipid profiling of tissues and isolated lipoproteins, and gene expression analysis that this deposition can be accounted for by esterified cholesterol-rich, apolipoprotein B-containing lipoprotein particles constitutively produced by the RPE. This work collectively allows ARMD lesion formation and its aftermath to be conceptualized as a response to the retention of a sub-endothelial apolipoprotein B lipoprotein, similar to a widely accepted model of atherosclerotic coronary artery disease (CAD) (Tabas et al., 2007). This approach provides a wide knowledge base and sophisticated clinical armamentarium that can be readily exploited for the development of new model systems and the future benefit of ARMD patients. PMID:19698799

Factorial Effects of Evolocumab and Atorvastatin on Lipoprotein Metabolism.

PubMed

Watts, Gerald F; Chan, Dick C; Dent, Ricardo; Somaratne, Ransi; Wasserman, Scott M; Scott, Rob; Burrows, Sally; R Barrett, P Hugh

2017-01-24

Monoclonal antibodies against proprotein convertase subtilisin kexin type 9 (PCSK9), such as evolocumab, lower plasma low-density lipoprotein (LDL)-cholesterol concentrations. Evolocumab is under investigation for its effects on cardiovascular outcomes in statin-treated, high-risk patients. The mechanism of action of PCSK9 monoclonal antibodies on lipoprotein metabolism remains to be fully evaluated. Stable isotope tracer kinetics can effectively elucidate the mode of action of new lipid-regulating pharmacotherapies. We conducted a 2-by-2 factorial trial of the effects of atorvastatin (80 mg daily) and subcutaneous evolocumab (420 mg every 2 weeks) for 8 weeks on the plasma kinetics of very-low-density lipoprotein (VLDL)-apolipoprotein B-100 (apoB), intermediate-density lipoprotein-apoB, and LDL-apoB in 81 healthy, normolipidemic, nonobese men. The kinetics of apoB in these lipoproteins was studied using a stable isotope infusion of D3-leucine, gas chromatography/mass spectrometry, and multicompartmental modeling. Atorvastatin and evolocumab independently accelerated the fractional catabolism of VLDL-apoB (P<0.001 and P.032, respectively), intermediate-density lipoprotein-apoB (P=0.021 and P=.002, respectively), and LDL-apoB (P<0.001, both interventions). Evolocumab but not atorvastatin decreased the production rate of intermediate-density lipoprotein-apoB (P=0.043) and LDL-apoB (P<0.001), which contributed to the reduction in the plasma pool sizes of these lipoprotein particles. The reduction in LDL-apoB and LDL-cholesterol concentrations was significantly greater with combination versus either monotherapy (P<0.001). Whereas evolocumab but not atorvastatin lowered the concentration of free PCSK9, atorvastatin lowered the lathosterol/campesterol ratio (a measure of cholesterol synthesis/absorption) and apoC-III concentration. Both interventions decreased plasma apoE, but neither significantly altered lipoprotein lipase and cholesteryl ester protein mass or measures

Metabolic Characterization of a Rare Genetic Variation Within APOC3 and Its Lipoprotein Lipase-Independent Effects.

PubMed

Drenos, Fotios; Davey Smith, George; Ala-Korpela, Mika; Kettunen, Johannes; Würtz, Peter; Soininen, Pasi; Kangas, Antti J; Dale, Caroline; Lawlor, Debbie A; Gaunt, Tom R; Casas, Juan-Pablo; Timpson, Nicholas J

2016-06-01

Plasma triglyceride levels have been implicated in atherosclerosis and coronary heart disease. Apolipoprotein C-III (APOC3) plays a key role in the hydrolysis of triglyceride-rich lipoproteins to remnant particles by lipoprotein lipase (LPL) and their uptake by the liver. A rare variant in APOC3(rs138326449) has been associated with triglyceride, very low-density lipoprotein, and high-density lipoprotein levels, as well as risk of coronary heart disease. We aimed to characterize the impact of this locus across a broad set of mainly lipids-focused metabolic measures. A high-throughput serum nuclear magnetic resonance metabolomics platform was used to quantify 225 metabolic measures in 13 285 participants from 2 European population cohorts. We analyzed the effect of the APOC3 variant on the metabolic measures and used the common LPL(rs12678919) polymorphism to test for LPL-independent effects. Eighty-one metabolic measures showed evidence of association with APOC3(rs138326449). In addition to previously reported triglyceride and high-density lipoprotein associations, the variant was also associated with very low-density lipoprotein and high-density lipoprotein composition measures, other cholesterol measures, and fatty acids. Comparison of the APOC3 and LPL associations revealed that APOC3 association results for medium and very large very low-density lipoprotein composition are unlikely to be solely predictable by the action of APOC3 through LPL. We characterized the effects of the rare APOC3(rs138326449) loss of function mutation in lipoprotein metabolism, as well as the effects of LPL(rs12678919). Our results improve our understanding of the role of APOC3 in triglyceride metabolism, its LPL independent action, and the complex and correlated nature of human metabolites. © 2016 The Authors.

Metabolic Characterization of a Rare Genetic Variation Within APOC3 and Its Lipoprotein Lipase–Independent Effects

PubMed Central

Davey Smith, George; Ala-Korpela, Mika; Kettunen, Johannes; Würtz, Peter; Soininen, Pasi; Kangas, Antti J.; Dale, Caroline; Lawlor, Debbie A.; Gaunt, Tom R.; Casas, Juan-Pablo

2016-01-01

Background— Plasma triglyceride levels have been implicated in atherosclerosis and coronary heart disease. Apolipoprotein C-III (APOC3) plays a key role in the hydrolysis of triglyceride-rich lipoproteins to remnant particles by lipoprotein lipase (LPL) and their uptake by the liver. A rare variant in APOC3(rs138326449) has been associated with triglyceride, very low–density lipoprotein, and high-density lipoprotein levels, as well as risk of coronary heart disease. We aimed to characterize the impact of this locus across a broad set of mainly lipids-focused metabolic measures. Methods and Results— A high-throughput serum nuclear magnetic resonance metabolomics platform was used to quantify 225 metabolic measures in 13 285 participants from 2 European population cohorts. We analyzed the effect of the APOC3 variant on the metabolic measures and used the common LPL(rs12678919) polymorphism to test for LPL-independent effects. Eighty-one metabolic measures showed evidence of association with APOC3(rs138326449). In addition to previously reported triglyceride and high-density lipoprotein associations, the variant was also associated with very low–density lipoprotein and high-density lipoprotein composition measures, other cholesterol measures, and fatty acids. Comparison of the APOC3 and LPL associations revealed that APOC3 association results for medium and very large very low–density lipoprotein composition are unlikely to be solely predictable by the action of APOC3 through LPL. Conclusions— We characterized the effects of the rare APOC3(rs138326449) loss of function mutation in lipoprotein metabolism, as well as the effects of LPL(rs12678919). Our results improve our understanding of the role of APOC3 in triglyceride metabolism, its LPL independent action, and the complex and correlated nature of human metabolites. PMID:27114411

One precursor, three apolipoproteins: the relationship between two crustacean lipoproteins, the large discoidal lipoprotein and the high density lipoprotein/β-glucan binding protein.

PubMed

Stieb, Stefanie; Roth, Ziv; Dal Magro, Christina; Fischer, Sabine; Butz, Eric; Sagi, Amir; Khalaila, Isam; Lieb, Bernhard; Schenk, Sven; Hoeger, Ulrich

2014-12-01

The novel discoidal lipoprotein (dLp) recently detected in the crayfish, differs from other crustacean lipoproteins in its large size, apoprotein composition and high lipid binding capacity, We identified the dLp sequence by transcriptome analyses of the hepatopancreas and mass spectrometry. Further de novo assembly of the NGS data followed by BLAST searches using the sequence of the high density lipoprotein/1-glucan binding protein (HDL-BGBP) of Astacus leptodactylus as query revealed a putative precursor molecule with an open reading frame of 14.7 kb and a deduced primary structure of 4889 amino acids. The presence of an N-terminal lipid bind- ing domain and a DUF 1943 domain suggests the relationship with the large lipid transfer proteins. Two-putative dibasic furin cleavage sites were identified bordering the sequence of the HDL-BGBP. When subjected to mass spectroscopic analyses, tryptic peptides of the large apoprotein of dLp matched the N-terminal part of the precursor, while the peptides obtained for its small apoprotein matched the C-terminal part. Repeating the analysis in the prawn Macrobrachium rosenbergii revealed a similar protein with identical domain architecture suggesting that our findings do not represent an isolated instance. Our results indicate that the above three apolipoproteins (i.e HDL-BGBP and both the large and the small subunit of dLp) are translated as a large precursor. Cleavage at the furin type sites releases two subunits forming a heterodimeric dLP particle, while the remaining part forms an HDL-BGBP whose relationship with other lipoproteins as well as specific functions are yet to be elucidated.

Advanced Stirling Convertor (ASC-E2) Characterization Testing

NASA Technical Reports Server (NTRS)

Williams, Zachary D.; Oriti, Salvatore M.

2012-01-01

Testing has been conducted on Advanced Stirling Convertors (ASCs)-E2 at NASA Glenn Research Center in support of the Advanced Stirling Radioisotope Generator (ASRG) project. This testing has been conducted to understand sensitivities of convertor parameters due to environmental and operational changes during operation of the ASRG in missions to space. This paper summarizes test results and explains the operation of the ASRG during space missions

Comparison of Lipoprotein Electrophoresis and Apolipoprotein E Genotyping in Investigating Dysbetalipoproteinemia.

PubMed

Ahmed, Farhan; El-Kadiki, Alia; Gibbons, Stephen

2017-06-01

Dysbetalipoproteinemia is often associated with apolipoprotein E2E2 homozygosity; however, lipoprotein electrophoresis may also be used to assist in the diagnosis. The aim of this study was to compare apolipoprotein E (apo E) genotyping and lipoprotein electrophoresis in investigating dysbetalipoproteinemia. Data were collected over a three-year period from a lipid clinic in a tertiary referral centre and reviewed for apo E genotyping and lipoprotein electrophoresis. Sixty-two patients had both apo E genotyping and lipoprotein electrophoresis. Of these, 16 patients showed broad beta band on electrophoresis. However, only 3 of them had apo E2E2 homozygosity on genotyping. Lipoprotein electrophoresis and apo E genotyping results showed poor concordance. This was primarily due to visual interpretation error of lipoprotein electrophoresis which may over diagnose dysbetalipoproteinemia.

Advanced expander test bed program

NASA Technical Reports Server (NTRS)

Masters, A. I.; Mitchell, J. C.

1991-01-01

The Advanced Expander Test Bed (AETB) is a key element in NASA's Chemical Transfer Propulsion Program for development and demonstration of expander cycle oxygen/hydrogen engine technology component technology for the next space engine. The AETB will be used to validate the high-pressure expander cycle concept, investigate system interactions, and conduct investigations of advanced missions focused components and new health monitoring techniques. The split-expander cycle AETB will operate at combustion chamber pressures up to 1200 psia with propellant flow rates equivalent to 20,000 lbf vacuum thrust.

Advanced Instrumentation for Transient Reactor Testing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Corradini, Michael L.; Anderson, Mark; Imel, George

Transient testing involves placing fuel or material into the core of specialized materials test reactors that are capable of simulating a range of design basis accidents, including reactivity insertion accidents, that require the reactor produce short bursts of intense highpower neutron flux and gamma radiation. Testing fuel behavior in a prototypic neutron environment under high-power, accident-simulation conditions is a key step in licensing nuclear fuels for use in existing and future nuclear power plants. Transient testing of nuclear fuels is needed to develop and prove the safety basis for advanced reactors and fuels. In addition, modern fuel development and designmore » increasingly relies on modeling and simulation efforts that must be informed and validated using specially designed material performance separate effects studies. These studies will require experimental facilities that are able to support variable scale, highly instrumented tests providing data that have appropriate spatial and temporal resolution. Finally, there are efforts now underway to develop advanced light water reactor (LWR) fuels with enhanced performance and accident tolerance. These advanced reactor designs will also require new fuel types. These new fuels need to be tested in a controlled environment in order to learn how they respond to accident conditions. For these applications, transient reactor testing is needed to help design fuels with improved performance. In order to maximize the value of transient testing, there is a need for in-situ transient realtime imaging technology (e.g., the neutron detection and imaging system like the hodoscope) to see fuel motion during rapid transient excursions with a higher degree of spatial and temporal resolution and accuracy. There also exists a need for new small, compact local sensors and instrumentation that are capable of collecting data during transients (e.g., local displacements, temperatures, thermal conductivity, neutron flux

Lipoprotein(a) in patients with aortic stenosis: Insights from cardiovascular magnetic resonance

PubMed Central

Vassiliou, Vassilios S.; Flynn, Paul D.; Raphael, Claire E.; Newsome, Simon; Khan, Tina; Ali, Aamir; Halliday, Brian; Studer Bruengger, Annina; Malley, Tamir; Sharma, Pranev; Selvendran, Subothini; Aggarwal, Nikhil; Sri, Anita; Berry, Helen; Donovan, Jackie; Lam, Willis; Auger, Dominique; Cook, Stuart A.; Pennell, Dudley J.; Prasad, Sanjay K.

2017-01-01

Background Aortic stenosis is the most common age-related valvular pathology. Patients with aortic stenosis and myocardial fibrosis have worse outcome but the underlying mechanism is unclear. Lipoprotein(a) is associated with adverse cardiovascular risk and is elevated in patients with aortic stenosis. Although mechanistic pathways could link Lipoprotein(a) with myocardial fibrosis, whether the two are related has not been previously explored. In this study, we investigated whether elevated Lipoprotein(a) was associated with the presence of myocardial replacement fibrosis. Methods A total of 110 patients with mild, moderate and severe aortic stenosis were assessed by late gadolinium enhancement (LGE) cardiovascular magnetic resonance to identify fibrosis. Mann Whitney U tests were used to assess for evidence of an association between Lp(a) and the presence or absence of myocardial fibrosis and aortic stenosis severity and compared to controls. Univariable and multivariable linear regression analysis were undertaken to identify possible predictors of Lp(a). Results Thirty-six patients (32.7%) had no LGE enhancement, 38 (34.6%) had midwall enhancement suggestive of midwall fibrosis and 36 (32.7%) patients had subendocardial myocardial fibrosis, typical of infarction. The aortic stenosis patients had higher Lp(a) values than controls, however, there was no significant difference between the Lp(a) level in mild, moderate or severe aortic stenosis. No association was observed between midwall or infarction pattern fibrosis and Lipoprotein(a), in the mild/moderate stenosis (p = 0.91) or severe stenosis patients (p = 0.42). Conclusion There is no evidence to suggest that higher Lipoprotein(a) leads to increased myocardial midwall or infarction pattern fibrosis in patients with aortic stenosis. PMID:28704465

Advanced Stirling Convertor Testing at GRC

NASA Technical Reports Server (NTRS)

Schifer, Nick; Oriti, Salvatore M.

2013-01-01

NASA Glenn Research Center (GRC) has been supporting development of the Advanced Stirling Radioisotope Generator (ASRG) since 2006. A key element of the ASRG project is providing life, reliability, and performance testing of the Advanced Stirling Convertor (ASC). The latest version of the ASC, deemed ASC-E3, is of a design identical to the forthcoming flight convertors. The first pair of ASC-E3 units was delivered in December 2012. GRC has begun the process of adding these units to the catalog of ongoing Stirling convertor operation. This process includes performance verification, which examines the data from various tests to validate the convertors performance to the product specification.

Advanced traffic technology test-bed.

DOT National Transportation Integrated Search

2004-06-01

The goal of this project was to create a test-bed to allow the University of California to conduct advanced traffic technology research in a designated, non-public, and controlled setting. Caltrans, with its associated research facilities on UC campu...

Familial lipoprotein lipase deficiency

MedlinePlus

... Coronary artery disease References Hegele RA. Lipoprotein and lipid metabolism. In: Rimoin D, Korf B, eds. Emery ... Semenkovich CF, Goldberg AC, Goldberg IJ. Disorders of lipid metabolism. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg ...

Advanced expander test bed program

NASA Technical Reports Server (NTRS)

Riccardi, D. P.; Mitchell, J. C.

1993-01-01

The Advanced Expander Test Bed (AETB) is a key element in NASA's Space Chemical Engine Technology Program for development and demonstration of expander cycle oxygen/hydrogen engine and advanced component technologies applicable to space engines as well as launch vehicle upper stage engines. The AETB will be used to validate the high-pressure expander cycle concept, investigate system interactions, and conduct investigations of advanced mission focused components and new health monitoring techniques in an engine system environment. The split expander cycle AETB will operate at combustion chamber pressures up to 1200 psia with propellant flow rates equivalent to 20,000 lbf vacuum thrust. Contract work began 27 Apr. 1990. During 1992, a major milestone was achieved with the review of the final design of the oxidizer turbopump in Sep. 1992.

Proteomic analysis of electronegative low-density lipoprotein[S

PubMed Central

Bancells, Cristina; Canals, Francesc; Benítez, Sònia; Colomé, Nuria; Julve, Josep; Ordóñez-Llanos, Jordi; Sánchez-Quesada, José Luis

2010-01-01

Low density lipoprotein is a heterogeneous group of lipoproteins that differs in lipid and protein composition. One copy of apolipoprotein (apo)B accounts for over 95% of the LDL protein, but the presence of minor proteins could disturb its biological behavior. Our aim was to study the content of minor proteins in LDL subfractions separated by anion exchange chromatography. Electropositive LDL [LDL(+)] is the native form, whereas electronegative LDL [LDL(−)] is a minor atherogenic fraction present in blood. LC-ESI MS/MS analysis of both LDL fractions identified up to 28 different proteins. Of these, 13 proteins, including apoB, were detected in all the analyzed samples. LDL(−) showed a higher content of most minor proteins. Statistical analysis of proteomic data indicated that the content of apoE, apoA-I, apoC-III, apoA-II, apoD, apoF, and apoJ was higher in LDL(−) than in LDL(+). Immunoturbidimetry, ELISA, or Western blot analysis confirmed these differences. ApoJ and apoF presented the highest difference between LDL(+) and LDL(−) (>15-fold). In summary, the increased content of several apolipoproteins, and specifically of apoF and apoJ, could be related to the physicochemical characteristics of LDL(−), such as apoB misfolding, aggregation, and abnormal lipid composition. PMID:20699421

Lipoprotein Changes in HIV-Infected Antiretroviral-Naïve Individuals after Starting Antiretroviral Therapy: ACTG Study A5152s Stein: Lipoprotein Changes on Antiretroviral Therapy

PubMed Central

Stein, James H.; Komarow, Lauren; Cotter, Bruno R.; Currier, Judith S.; Dubé, Michael P.; Fichtenbaum, Carl J.; Gerschenson, Mariana; Mitchell, Carol K.C.; Murphy, Robert L.; Squires, Kathleen; Parker, Robert A.; Torriani, Francesca J.

2008-01-01

Background Dyslipidemia is a frequent complication of antiretroviral therapy (ART) for patients with human immunodeficiency virus infection (HIV). The effects of ART on lipoproteins are less well-understood, and have not been investigated in a prospective study where assignment to ART is randomized. Objective To evaluate the effects of three class-sparing ART regimens on lipids and lipoproteins. Methods This was a substudy of a prospective, multicenter study treatment-naïve HIV-infected individuals randomly assigned to receive a regimen of nucleoside reverse transcriptase inhibitors (NRTIs) + the non-nucleoside reverse transcriptase inhibitor efavirenz, NRTIs + the protease inhibitor lopinavir/ritonavir, or a NRTI-sparing regimen of efavirenz + lopinavir/ritonavir. Lipoproteins were measured by nuclear magnetic resonance spectroscopy. Results Among the 82 participants, total and small low-density lipoprotein concentrations increased (median, interquartile range) by 152 (-49 - +407, p<0.01) and 130 (-98 - +417, p<0.01) nmol/L, respectively, especially in the arms containing lopinavir/ritonavir (pKW<0.04). Very low-density lipoproteins also increased (p<0.01), with a larger increase in the arms that contained lopinavir/ritonavir (p=0.022). High-density lipoproteins increased by 6.0 nmol/L (2.8 - 10.4, p<0.01), but differences between arms were not significant (pKW=0.069). Changes were not related to changes in markers of insulin/glucose metabolism. Conclusions Total and small low-density lipoprotein concentrations increased, especially in the arms containing lopinavir/ritonavir, as did increases in total very low-density lipoproteins. Adverse changes were especially prominent in the arm with efavirenz + lopinavir/ritonavir. PMID:19956354

Distribution of thiobarbituric acid-reactive substances in lipoproteins and proteins in serum.

PubMed

Bonnefont, D; Legrand, A; Peynet, J; Emerit, J; Delattre, J; Galli, A

1989-10-01

We assessed the distribution of malondialdehyde (MDA) in lipoproteins and proteins in serum after using two procedures to separate the lipoproteins: sequential ultracentrifugation or selective precipitation with a sodium phosphotungstate and magnesium chloride reagent followed by ultracentrifugation of the supernate. MDA concentrations were determined by the thiobarbituric acid reaction and quantified by fluorometry. We found that 43% of the thiobarbituric acid-reactive substances (TBARS) was bound to the lipoproteins--27% to very-low- and low-density lipoproteins (VLDL-LDL) and 16% to high-density lipoproteins (HDL)--and from 11.5% to 15.8% to proteins, depending on the separation procedure. Residual unbound TBARS were located in the ultracentrifugation layers that contained no lipoproteins or proteins. The TBARS concentration in serum lipoproteins containing apolipoprotein B (i.e., VLDL-LDL) was the same after ultracentrifugation or selective precipitation. We therefore consider the precipitation method more suitable for routine TBARS determination in these lipoproteins, because it is easier to handle and faster. However, for determination of TBARS in HDL, selective precipitation requires subsequent ultracentrifugation at a density of 1.21 kg/L.

Preparation and Characterization of Stable α-Synuclein Lipoprotein Particles.

PubMed

Eichmann, Cédric; Campioni, Silvia; Kowal, Julia; Maslennikov, Innokentiy; Gerez, Juan; Liu, Xiaoxia; Verasdonck, Joeri; Nespovitaya, Nadezhda; Choe, Senyon; Meier, Beat H; Picotti, Paola; Rizo, Josep; Stahlberg, Henning; Riek, Roland

2016-04-15

Multiple neurodegenerative diseases are caused by the aggregation of the human α-Synuclein (α-Syn) protein. α-Syn possesses high structural plasticity and the capability of interacting with membranes. Both features are not only essential for its physiological function but also play a role in the aggregation process. Recently it has been proposed that α-Syn is able to form lipid-protein particles reminiscent of high-density lipoproteins. Here, we present a method to obtain a stable and homogeneous population of nanometer-sized particles composed of α-Syn and anionic phospholipids. These particles are called α-Syn lipoprotein (nano)particles to indicate their relationship to high-density lipoproteins formed by human apolipoproteins in vivo and of in vitro self-assembling phospholipid bilayer nanodiscs. Structural investigations of the α-Syn lipoprotein particles by circular dichroism (CD) and magic angle solid-state nuclear magnetic resonance (MAS SS-NMR) spectroscopy establish that α-Syn adopts a helical secondary structure within these particles. Based on cryo-electron microscopy (cryo-EM) and dynamic light scattering (DLS) α-Syn lipoprotein particles have a defined size with a diameter of ∼23 nm. Chemical cross-linking in combination with solution-state NMR and multiangle static light scattering (MALS) of α-Syn particles reveal a high-order protein-lipid entity composed of ∼8-10 α-Syn molecules. The close resemblance in size between cross-linked in vitro-derived α-Syn lipoprotein particles and a cross-linked species of endogenous α-Syn from SH-SY5Y human neuroblastoma cells indicates a potential functional relevance of α-Syn lipoprotein nanoparticles. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Disturbed Laminar Blood Flow Vastly Augments Lipoprotein Retention in the Artery Wall: A Key Mechanism Distinguishing Susceptible From Resistant Sites.

PubMed

Steffensen, Lasse Bach; Mortensen, Martin Bødtker; Kjolby, Mads; Hagensen, Mette Kallestrup; Oxvig, Claus; Bentzon, Jacob Fog

2015-09-01

Atherosclerosis develops initially at branch points and in areas of high vessel curvature. Moreover, experiments in hypercholesterolemic mice have shown that the introduction of disturbed flow in straight, atherosclerosis-resistant arterial segments turns them highly atherosclerosis susceptible. Several biomechanical mechanisms have been proposed, but none has been demonstrated. In the present study, we examined whether a causal link exists between disturbed laminar flow and the ability of the arterial wall to retain lipoproteins. Lipoprotein retention was detected at natural predilection sites of the murine thoracic aorta 18 hours after infusion of fluorescently labeled low-density lipoprotein. To test for causality between blood flow and the ability of these areas to retain lipoproteins, we manipulated blood flow in the straight segment of the common carotid artery using a constrictive collar. Disturbed laminar flow did not affect low-density lipoprotein influx, but increased the ability of the artery wall to bind low-density lipoprotein. Concordantly, disturbed laminar flow led to differential expression of genes associated with phenotypic modulation of vascular smooth muscle cells, increased expression of proteoglycan core proteins associated with lipoprotein retention, and of enzymes responsible for chondroitin sulfate glycosaminoglycan synthesis and sulfation. Blood flow regulates genes associated with vascular smooth muscle cell phenotypic modulation, as well as the expression and post-translational modification of lipoprotein-binding proteoglycan core proteins, and the introduction of disturbed laminar flow vastly augments the ability of a previously resistant, straight arterial segment to retain lipoproteins. © 2015 American Heart Association, Inc.

Social Inclusion Predicts Lower Blood Glucose and Low-Density Lipoproteins in Healthy Adults.

PubMed

Floyd, Kory; Veksler, Alice E; McEwan, Bree; Hesse, Colin; Boren, Justin P; Dinsmore, Dana R; Pavlich, Corey A

2017-08-01

Loneliness has been shown to have direct effects on one's personal well-being. Specifically, a greater feeling of loneliness is associated with negative mental health outcomes, negative health behaviors, and an increased likelihood of premature mortality. Using the neuroendocrine hypothesis, we expected social inclusion to predict decreases in both blood glucose levels and low-density lipoproteins (LDLs) and increases in high-density lipoproteins (HDLs). Fifty-two healthy adults provided self-report data for social inclusion and blood samples for hematological tests. Results indicated that higher social inclusion predicted lower levels of blood glucose and LDL, but had no effect on HDL. Implications for theory and practice are discussed.

NASA Advanced Life Support Technology Testing and Development

NASA Technical Reports Server (NTRS)

Wheeler, Raymond M.

2012-01-01

Prior to 2010, NASA's advanced life support research and development was carried out primarily under the Exploration Life Support Project of NASA's Exploration Systems Mission Directorate. In 2011, the Exploration Life Support Project was merged with other projects covering Fire Prevention/Suppression, Radiation Protection, Advanced Environmental Monitoring and Control, and Thermal Control Systems. This consolidated project was called Life Support and Habitation Systems, which was managed under the Exploration Systems Mission Directorate. In 2012, NASA re-organized major directorates within the agency, which eliminated the Exploration Systems Mission Directorate and created the Office of the Chief Technologist (OCT). Life support research and development is currently conducted within the Office of the Chief Technologist, under the Next Generation Life Support Project, and within the Human Exploration Operation Missions Directorate under several Advanced Exploration System projects. These Advanced Exploration Systems projects include various themes of life support technology testing, including atmospheric management, water management, logistics and waste management, and habitation systems. Food crop testing is currently conducted as part of the Deep Space Habitation (DSH) project within the Advanced Exploration Systems Program. This testing is focused on growing salad crops that could supplement the crew's diet during near term missions.

Cholesterol in serum lipoprotein fractions after spaceflight

NASA Technical Reports Server (NTRS)

Leach, Carolyn S.; Johnson, Philip C., Jr.; Krauhs, Jane M.; Cintron, Nitza M.

1988-01-01

Results are reported from blood-lipid measurements obtained from 125 Space Shuttle crew members before and after space flight. The data are presented in tables and discussed in detail. The main differences noted between preflight and postflight values are a 12.8-percent decrease in high-density lipoproteins on postflight day 1 and significant decreases in total cholesterol and both high- and low-density lipoproteins later in the 23-day postflight period.

The triglyceride to high-density lipoprotein-cholesterol ratio in adolescence and subsequent weight gain predict nuclear magnetic resonance-measured lipoprotein subclasses in adulthood.

PubMed

Weiss, Ram; Otvos, James D; Sinnreich, Ronit; Miserez, Andre R; Kark, Jeremy D

2011-01-01

To assess whether the fasting triglyceride-to-high-density lipoprotein (HDL)-cholesterol (TG/HDL) ratio in adolescence is predictive of a proatherogenic lipid profile in adulthood. A longitudinal follow-up of 770 Israeli adolescents 16 to 17 years of age who participated in the Jerusalem Lipid Research Clinic study and were reevaluated 13 years later. Lipoprotein particle size was assessed at the follow-up with proton nuclear magnetic resonance. The TG/HDL ratio measured in adolescence was strongly associated with low-density lipoprotein, very low-density lipoprotein (VLDL), and HDL mean particle size in young adulthood in both sexes, even after adjustment for baseline body mass index and body mass index change. The TG/HDL ratio measured in adolescence and subsequent weight gain independently predicted atherogenic small low-density lipoprotein and large VLDL particle concentrations (P < .001 in both sexes). Baseline TG/HDL and weight gain interacted to increase large VLDL concentration in men (P < .001). Adolescents with an elevated TG/HDL ratio are prone to express a proatherogenic lipid profile in adulthood. This profile is additionally worsened by weight gain. Copyright © 2011 Mosby, Inc. All rights reserved.

Test model designs for advanced refractory ceramic materials

NASA Technical Reports Server (NTRS)

Tran, Huy Kim

1993-01-01

The next generation of space vehicles will be subjected to severe aerothermal loads and will require an improved thermal protection system (TPS) and other advanced vehicle components. In order to ensure the satisfactory performance system (TPS) and other advanced vehicle materials and components, testing is to be performed in environments similar to space flight. The design and fabrication of the test models should be fairly simple but still accomplish test objectives. In the Advanced Refractory Ceramic Materials test series, the models and model holders will need to withstand the required heat fluxes of 340 to 817 W/sq cm or surface temperatures in the range of 2700 K to 3000 K. The model holders should provide one dimensional (1-D) heat transfer to the samples and the appropriate flow field without compromising the primary test objectives. The optical properties such as the effective emissivity, catalytic efficiency coefficients, thermal properties, and mass loss measurements are also taken into consideration in the design process. Therefore, it is the intent of this paper to demonstrate the design schemes for different models and model holders that would accommodate these test requirements and ensure the safe operation in a typical arc jet facility.

Methylation at CPT1A locus is associated with lipoprotein subfraction profiles

USDA-ARS?s Scientific Manuscript database

Lipoprotein subfractions help discriminate cardiometabolic disease risk. Genetic loci validated as associating with lipoprotein measures do not account for a large proportion of the individual variation in lipoprotein measures. We hypothesized that DNA methylation levels across the genome contribute...

Influence of medium components on the expression of recombinant lipoproteins in Escherichia coli.

PubMed

Tseng, Chi-Ling; Leng, Chih-Hsiang

2012-02-01

Bacterial lipoproteins are crucial antigens for protective immunity against bacterial pathogens. Expression of exogenous lipoproteins in Escherichia coli at high levels is thought to be an extremely difficult endeavor because it frequently results in incomplete or absent lipid modification. Previously, we identified a fusion sequence (D1) from a Neisseria meningitidis lipoprotein that induced a non-lipidated protein, E3 (the domain III of the dengue virus envelope protein), to become lipidated. However, without optimizing the growth conditions, some of the D1-fusion proteins were not lipidated. Here, we report the influence of medium components on the expression of recombinant lipoproteins in E. coli. For high-level expression of mature lipoproteins in the C43 (DE3) strain, M9 medium was better than M63 and the rich medium. Furthermore, we analyzed the influence of other media factors (including nitrogen and carbon sources, phosphate, ferrous ions, calcium, magnesium, and pH) on the levels of lipoprotein expression. The results showed that excess nitrogen sources and phosphate in M9 medium could increase the amount of immature lipoproteins, and glucose was a better carbon source than glycerol for expressing mature lipoproteins. We also found that lipoproteins tended to be completely processed in the alkaline environment, even in the nutrient-rich medium. Additional constructs expressing different immunogens or lipid signal peptides as targets were also utilized, demonstrating that these targets could be expressed as completely mature lipoproteins in the M9 medium but not in the rich medium. Our results provide the useful information for expressing mature exogenous lipoproteins in E. coli.

Random Vibration Testing of Advanced Wet Tantalum Capacitors

NASA Technical Reports Server (NTRS)

Teverovsky, Alexander

2015-01-01

Advanced wet tantalum capacitors allow for improved performance of power supply systems along with substantial reduction of size and weight of the systems that is especially beneficial for space electronics. Due to launch-related stresses, acceptance testing of all space systems includes random vibration test (RVT). However, many types of advanced wet tantalum capacitors cannot pass consistently RVT at conditions specified in MIL-PRF-39006, which impedes their use in space projects. This requires a closer look at the existing requirements, modes and mechanisms of failures, specifics of test conditions, and acceptance criteria. In this work, different lots of advanced wet tantalum capacitors from four manufacturers have been tested at step stress random vibration conditions while their currents were monitored before, during, and after the testing. It has been shown that the robustness of the parts and their reliability are mostly due to effective self-healing processes and limited current spiking or minor scintillations caused by RVT do not increase the risk of failures during operation. A simple model for scintillations events has been used to simulate current spiking during RVT and optimize test conditions. The significance of scintillations and possible effects of gas generation have been discussed and test acceptance criteria for limited current spiking have been suggested.

Advanced Plant Habitat Test Harvest

NASA Image and Video Library

2017-08-24

John "JC" Carver, a payload integration engineer with NASA Kennedy Space Center's Test and Operations Support Contract, opens the door to the growth chamber of the Advanced Plant Habitat (APH) Flight Unit No. 1 for a test harvest of half of the Arabidopsis thaliana plants growing within. The harvest is part of an ongoing verification test of the APH unit, which is located inside the International Space Station Environmental Simulator in Kennedy's Space Station Processing Facility. The APH undergoing testing at Kennedy is identical to one on the station and uses red, green and broad-spectrum white LED lights to grow plants in an environmentally controlled chamber. The seeds grown during the verification test will be grown on the station to help scientists understand how these plants adapt to spaceflight.

Lipid and lipoprotein changes in women following 6 months of exercise training in a worksite fitness program.

PubMed

Grandjean, P W; Oden, G L; Crouse, S F; Brown, J A; Green, J S

1996-03-01

It was the purpose of this investigation to examine the influence of a worksite aerobic training program on serum lipid and lipoproteins and cardiovascular fitness in female employees. Thirty-seven healthy but previously untrained, female employees (Ss) from Westinghouse Corporation, (College Station, Texas) volunteered for the study. Ss were randomly assigned to either an exercise group (Ex) (n = 20) or control group (C) (n = 17). Prior to training (PRE) and following training (POST), all Ss were measured for weight (WT), body composition (%FAT) and tested for maximal oxygen consumption (VO2 max). PRE and POST Lipid analysis included: total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and triglycerides (TG). Following PRE testing, the Ex group aerobically trained by walking, jogging and/or cycling, at least 3 days per wk for 24 wks. Exercise training resulted in an improvement in VO2 max (p < 0.0006) and a 2 kg WT loss in Ex (p < 0.025) with no change in C. Both Ex and C Ss exhibited a loss in %-FAT (p < 0.0001), and a decrease in TC (p < 0.0001) and LDL-C (p < 0.0001). No differences were observed between groups or over the training period for VLDL-C or TG. Although HDL-C increased 6 mg/dl in the Ex group but not in C, this difference did not reach statistical significance (p < 0.0625). These results demonstrate that aerobic training by females in a worksite fitness program significantly improves cardiovascular fitness without altering lipids or lipoproteins.

Advanced Plant Habitat Test Harvest

NASA Image and Video Library

2017-08-24

John "JC" Carver, a payload integration engineer with NASA Kennedy Space Center's Test and Operations Support Contract, places Arabidopsis thaliana plants harvested from the Advanced Plant Habitat (APH) Flight Unit No. 1 into a Mini ColdBag that quickly freezes the plants. The harvest is part of an ongoing verification test of the APH unit, which is located inside the International Space Station Environmental Simulator in Kennedy's Space Station Processing Facility. The APH undergoing testing at Kennedy is identical to one on the station and uses red, green and broad-spectrum white LED lights to grow plants in an environmentally controlled chamber. The seeds grown during the verification test will be grown on the station to help scientists understand how these plants adapt to spaceflight.

Advanced Plant Habitat Test Harvest

NASA Image and Video Library

2017-08-24

John "JC" Carver, a payload integration engineer with NASA Kennedy Space Center's Test and Operations Support Contract, places Arabidopsis thaliana plants harvested from the Advanced Plant Habitat (APH) Flight Unit No. 1 into an Ultra-low Freezer chilled to -150 degrees Celsius. The harvest is part of an ongoing verification test of the APH unit, which is located inside the International Space Station Environmental Simulator in Kennedy's Space Station Processing Facility. The APH undergoing testing at Kennedy is identical to one on the station and uses red, green and broad-spectrum white LED lights to grow plants in an environmentally controlled chamber. The seeds grown during the verification test will be grown on the station to help scientists understand how these plants adapt to spaceflight.

Advanced Plant Habitat Test Harvest

NASA Image and Video Library

2017-08-24

John "JC" Carver, a payload integration engineer with NASA Kennedy Space Center's Test and Operations Support Contract, harvests half the Arabidopsis thaliana plants inside the growth chamber of the Advanced Plant Habitat (APH) Flight Unit No. 1. The harvest is part of an ongoing verification test of the APH unit, which is located inside the International Space Station Environmental Simulator in Kennedy's Space Station Processing Facility. The APH undergoing testing at Kennedy is identical to one on the station and uses red, green and broad-spectrum white LED lights to grow plants in an environmentally controlled chamber. The seeds grown during the verification test will be grown on the station to help scientists understand how these plants adapt to spaceflight.

Z-Scan Analysis: a New Method to Determine the Oxidative State of Low-Density Lipoprotein and Its Association with Multiple Cardiometabolic Biomarkers

NASA Astrophysics Data System (ADS)

de Freitas, Maria Camila Pruper; Figueiredo Neto, Antonio Martins; Giampaoli, Viviane; da Conceição Quintaneiro Aubin, Elisete; de Araújo Lima Barbosa, Milena Maria; Damasceno, Nágila Raquel Teixeira

2016-04-01

The great atherogenic potential of oxidized low-density lipoprotein has been widely described in the literature. The objective of this study was to investigate whether the state of oxidized low-density lipoprotein in human plasma measured by the Z-scan technique has an association with different cardiometabolic biomarkers. Total cholesterol, high-density lipoprotein cholesterol, triacylglycerols, apolipoprotein A-I and apolipoprotein B, paraoxonase-1, and glucose were analyzed using standard commercial kits, and low-density lipoprotein cholesterol was estimated using the Friedewald equation. A sandwich enzyme-linked immunosorbent assay was used to detect electronegative low-density lipoprotein. Low-density lipoprotein and high-density lipoprotein sizes were determined by Lipoprint® system. The Z-scan technique was used to measure the non-linear optical response of low-density lipoprotein solution. Principal component analysis and correlations were used respectively to resize the data from the sample and test association between the θ parameter, measured with the Z-scan technique, and the principal component. A total of 63 individuals, from both sexes, with mean age 52 years (±11), being overweight and having high levels of total cholesterol and low levels of high-density lipoprotein cholesterol, were enrolled in this study. A positive correlation between the θ parameter and more anti-atherogenic pattern for cardiometabolic biomarkers together with a negative correlation for an atherogenic pattern was found. Regarding the parameters related with an atherogenic low-density lipoprotein profile, the θ parameter was negatively correlated with a more atherogenic pattern. By using Z-scan measurements, we were able to find an association between oxidized low-density lipoprotein state and multiple cardiometabolic biomarkers in samples from individuals with different cardiovascular risk factors.

Analysis of lipoprotein profiles of healthy cats by gel-permeation high-performance liquid chromatography

PubMed Central

MIZUTANI, Hisashi; SAKO, Toshinori; OKUDA, Hiroko; ARAI, Nobuaki; KURIYAMA, Koji; MORI, Akihiro; YOSHIMURA, Itaru; KOYAMA, Hidekazu

2016-01-01

Density gradient ultracentrifugation (DGUC) and gel electrophoresis are conventionally used to obtain lipoprotein profiles of animals. We recently applied high-performance liquid chromatography with a gel permeation column (GP-HPLC) and an on-line dual enzymatic system to dogs for lipoprotein profile analysis. We compared the GP-HPLC with DGUC as a method to obtain a feline lipoprotein profile. The lipoprotein profiles showed large and small peaks, which corresponded to high-density lipoprotein (HDL) and low-density lipoprotein (LDL), respectively, whereas very low-density lipoprotein (VLDL) and chylomicron (CM) were only marginally detected. This profile was very similar to that of dogs reported previously. Healthy cats also had a small amount of cholesterol-rich particles distinct from the normal LDL or HDL profile. There was no difference in lipoprotein profiles between the sexes, but males had a significantly larger LDL particle size (P=0.015). This study shows the feasibility of GP-HPLC for obtaining accurate lipoprotein profiles with small sample volumes and provides valuable reference data for healthy cats that should facilitate diagnoses. PMID:27170431

Influence of liver cancer on lipid and lipoprotein metabolism

PubMed Central

Jiang, Jingting; Nilsson-Ehle, Peter; Xu, Ning

2006-01-01

Liver plays a key role in the metabolism of plasma apolipoproteins, endogenous lipids and lipoproteins. Hepatocellular carcinoma (HCC) is one of the most common fatal malignant tumors in China and in other Southeast Asian countries. This has been attributed to the high incidence of hepatitis B infection. Hepatitis B proteins, such as the hepatitis B X protein (HBx) that is large hepatitis B surface protein could regulate transcription of many candidate genes for liver carcinogenesis. It has known that patients who suffered from acute hepatitis B could have lipid disorders such as decreased plasma level of high-density lipoproteins (HDL). Furthermore, aberrations of lipid metabolism are often seen in the chronic hepatitis B infection. Plasma lipid profiles could be changed under HCC. In majority of the reports in HCC, plasma levels of triglycerides (TG), cholesterol, free fatty acids (FFA), HDL, low-density lipoproteins (LDL), lipoprotein (a) (Lp(a)), apolipoprotein AI (apoAI) and apoB were slight to significantly decreased, however, in some cases plasma levels of TG and Lp(a) might be increased. It has been suggested that analysis of plasma levels of lipids, lipoproteins and apolipoproteins in the patients suffered from HCC reflects on the hepatic cellular impairment status. Studies revealed that alterations seen in the plasma levels of lipids, lipoproteins and apolipoproteins reflecting patients' pathologic conditions. Decreased serum levels of cholesterol and apoAI may indicate a poor prognosis. Human leukaemic cells and certain tumor tissues have a higher receptor-mediated uptake of HDL and LDL than the corresponding normal cells or tissues. LDL and HDL have therefore been proposed as a carrier for the water-insoluble anti-cancer agents. PMID:16515689

Apolipoprotein-containing lipoprotein subclasses and subclinical atherosclerosis in systemic lupus erythematosus.

PubMed

Kiani, Adnan N; Fang, Hong; Akhter, Ehtisham; Quiroga, Carmen; Simpson, Nancy; Alaupovic, Petar; Magder, Laurence S; Petri, Michelle

2015-03-01

Traditional classification of hyperlipidemia using high-density lipoprotein, low-density lipoprotein (LDL), and very low-density lipoprotein does not provide information on lipoprotein function. Apolipoproteins (Apos), which are protein components of plasma lipoproteins (including A, B, C, D, E) with their different composition, metabolic, and atherogenic properties, provide insight on lipoprotein functioning. In particular, the Apo B/A-I ratio is associated with atherogenic LDL and development of cardiovascular disease. We explored the baseline association between these nontraditional risk factors with subclinical measures of atherosclerosis (coronary artery calcification [CAC] and carotid intima-media thickness [IMT]) in systemic lupus erythematosus (SLE). A total of 58 SLE patients (97% women, 58% white, 40% African American, and 2% other, mean ± SD age 44 ± 11 years) had measurement of Apo and lipoproteins by immunoturbidimetric procedures, electroimmunoassays, and immunoprecipitation. CAC was measured by helical computed tomography and carotid IMT by carotid duplex. This study was based on the baseline assessment of subclinical atherosclerosis in the Lupus Atherosclerosis Prevention Study. The measurement of the lipoproteins was made on sera collected at the same time. There was no association between cardioprotective Apos (Apo A-I, LpA-I, LpA-I:A-II) and CAC (P < 0.15, P < 0.41, and P < 0.39, respectively) or carotid IMT (P < 0.97, P < 0.53, and P < 0.76, respectively). CAC and carotid IMT did not associate with atherogenic Apos either, including LpB:E+LpB:C:E, Apo B, LpB, LpB:C, Apo C-III, Apo C-III-HS, Apo C-III-HP, Apo C-III-R, LpA-II:B:C:D:E, and Apo B/Apo A-I. Measures of disease activity, including physician's global assessment and Systemic Lupus Erythematosus Disease Activity Index, were not associated with CAC or carotid IMT. Neither cardioprotective nor atherogenic lipoproteins were associated with measures of subclinical atherosclerosis in this

Advanced Plant Habitat Test Harvest

NASA Image and Video Library

2017-08-24

Arabidopsis thaliana plants are seen inside the growth chamber of the Advanced Plant Habitat (APH) Flight Unit No. 1 prior to harvest of half the plants. The harvest is part of an ongoing verification test of the APH unit, which is located inside the International Space Station Environmental Simulator in NASA Kennedy Space Center's Space Station Processing Facility. The APH undergoing testing at Kennedy is identical to one on the station and uses red, green and broad-spectrum white LED lights to grow plants in an environmentally controlled chamber. The seeds grown during the verification test will be grown on the station to help scientists understand how these plants adapt to spaceflight.

Advanced Plant Habitat Test Harvest

NASA Image and Video Library

2017-08-24

John "JC" Carver, a payload integration engineer with NASA Kennedy Space Center's Test and Operations Support Contract, uses a FluorPen to measure the chlorophyll fluorescence of Arabidopsis thaliana plants inside the growth chamber of the Advanced Plant Habitat (APH) Flight Unit No. 1. Half the plants were then harvested. The harvest is part of an ongoing verification test of the APH unit, which is located inside the International Space Station Environmental Simulator in Kennedy's Space Station Processing Facility. The APH undergoing testing at Kennedy is identical to one on the station and uses red, green and broad-spectrum white LED lights to grow plants in an environmentally controlled chamber. The seeds grown during the verification test will be grown on the station to help scientists understand how these plants adapt to spaceflight.

Glucosamine prevents in vitro collagen degradation in chondrocytes by inhibiting advanced lipoxidation reactions and protein oxidation

PubMed Central

Tiku, Moti L; Narla, Haritha; Jain, Mohit; Yalamanchili, Praveen

2007-01-01

Osteoarthritis (OA) affects a large segment of the aging population and is a major cause of pain and disability. At present, there is no specific treatment available to prevent or retard the cartilage destruction that occurs in OA. Recently, glucosamine sulfate has received attention as a putative agent that may retard cartilage degradation in OA. The precise mechanism of action of glucosamine is not known. We investigated the effect of glucosamine in an in vitro model of cartilage collagen degradation in which collagen degradation induced by activated chondrocytes is mediated by lipid peroxidation reaction. Lipid peroxidation in chondrocytes was measured by conjugated diene formation. Protein oxidation and aldehydic adduct formation were studied by immunoblot assays. Antioxidant effect of glucosamine was also tested on malondialdehyde (thiobarbituric acid-reactive substances [TBARS]) formation on purified lipoprotein oxidation for comparison. Glucosamine sulfate and glucosamine hydrochloride in millimolar (0.1 to 50) concentrations specifically and significantly inhibited collagen degradation induced by calcium ionophore-activated chondrocytes. Glucosamine hydrochloride did not inhibit lipid peroxidation reaction in either activated chondrocytes or in copper-induced oxidation of purified lipoproteins as measured by conjugated diene formation. Glucosamine hydrochloride, in a dose-dependent manner, inhibited malondialdehyde (TBARS) formation by oxidized lipoproteins. Moreover, we show that glucosamine hydrochloride prevents lipoprotein protein oxidation and inhibits malondialdehyde adduct formation in chondrocyte cell matrix, suggesting that it inhibits advanced lipoxidation reactions. Together, the data suggest that the mechanism of decreasing collagen degradation in this in vitro model system by glucosamine may be mediated by the inhibition of advanced lipoxidation reaction, preventing the oxidation and loss of collagen matrix from labeled chondrocyte matrix

Advanced nozzle and engine components test facility

NASA Technical Reports Server (NTRS)

Beltran, Luis R.; Delroso, Richard L.; Delrosario, Ruben

1992-01-01

A test facility for conducting scaled advanced nozzle and engine component research is described. The CE-22 test facility, located in the Engine Research Building of the NASA Lewis Research Center, contains many systems for the economical testing of advanced scale-model nozzles and engine components. The combustion air and altitude exhaust systems are described. Combustion air can be supplied to a model up to 40 psig for primary air flow, and 40, 125, and 450 psig for secondary air flow. Altitude exhaust can be simulated up to 48,000 ft, or the exhaust can be atmospheric. Descriptions of the multiaxis thrust stand, a color schlieren flow visualization system used for qualitative flow analysis, a labyrinth flow measurement system, a data acquisition system, and auxiliary systems are discussed. Model recommended design information and temperature and pressure instrumentation recommendations are included.

Influence of impaired lipoprotein biogenesis on surface and exoproteome of Streptococcus pneumoniae.

PubMed

Pribyl, Thomas; Moche, Martin; Dreisbach, Annette; Bijlsma, Jetta J E; Saleh, Malek; Abdullah, Mohammed R; Hecker, Michael; van Dijl, Jan Maarten; Becher, Dörte; Hammerschmidt, Sven

2014-02-07

Surface proteins are important for the fitness and virulence of the Gram-positive pathogen Streptococcus pneumoniae. They are crucial for interaction of the pathogen with its human host during infection. Therefore, the analysis of the pneumococcal surface proteome is an important task that requires powerful tools. In this study, two different methods, an optimized biotinylation approach and shaving with trypsin beads, were applied to study the pneumococcal surface proteome and to identify surface-exposed protein domains, respectively. The identification of nearly 95% of the predicted lipoproteins and 75% of the predicted sortase substrates reflects the high coverage of the two classical surface protein classes accomplished in this study. Furthermore, the biotinylation approach was applied to study the impact of an impaired lipoprotein maturation pathway on the cell envelope proteome and exoproteome. Loss of the lipoprotein diacylglyceryl transferase Lgt leads to striking changes in the lipoprotein distribution. Many lipoproteins disappear from the surface proteome and accumulate in the exoproteome. Further insights into lipoprotein processing in pneumococci are provided by immunoblot analyses of bacterial lysates and corresponding supernatant fractions. Taken together, the first comprehensive overview of the pneumococcal surface and exoproteome is presented, and a model for lipoprotein processing in S. pneumoniae is proposed.

Human native lipoprotein-induced de novo DNA methylation is associated with repression of inflammatory genes in THP-1 macrophages.

PubMed

Rangel-Salazar, Rubén; Wickström-Lindholm, Marie; Aguilar-Salinas, Carlos A; Alvarado-Caudillo, Yolanda; Døssing, Kristina B V; Esteller, Manel; Labourier, Emmanuel; Lund, Gertrud; Nielsen, Finn C; Rodríguez-Ríos, Dalia; Solís-Martínez, Martha O; Wrobel, Katarzyna; Wrobel, Kazimierz; Zaina, Silvio

2011-11-25

We previously showed that a VLDL- and LDL-rich mix of human native lipoproteins induces a set of repressive epigenetic marks, i.e. de novo DNA methylation, histone 4 hypoacetylation and histone 4 lysine 20 (H4K20) hypermethylation in THP-1 macrophages. Here, we: 1) ask what gene expression changes accompany these epigenetic responses; 2) test the involvement of candidate factors mediating the latter. We exploited genome expression arrays to identify target genes for lipoprotein-induced silencing, in addition to RNAi and expression studies to test the involvement of candidate mediating factors. The study was conducted in human THP-1 macrophages. Native lipoprotein-induced de novo DNA methylation was associated with a general repression of various critical genes for macrophage function, including pro-inflammatory genes. Lipoproteins showed differential effects on epigenetic marks, as de novo DNA methylation was induced by VLDL and to a lesser extent by LDL, but not by HDL, and VLDL induced H4K20 hypermethylation, while HDL caused H4 deacetylation. The analysis of candidate factors mediating VLDL-induced DNA hypermethylation revealed that this response was: 1) surprisingly, mediated exclusively by the canonical maintenance DNA methyltransferase DNMT1, and 2) independent of the Dicer/micro-RNA pathway. Our work provides novel insights into epigenetic gene regulation by native lipoproteins. Furthermore, we provide an example of DNMT1 acting as a de novo DNA methyltransferase independently of canonical de novo enzymes, and show proof of principle that de novo DNA methylation can occur independently of a functional Dicer/micro-RNA pathway in mammals.

Lipoprotein metabolism in Japanese centenarians: effects of apolipoprotein E polymorphism and nutritional status.

PubMed

Arai, Y; Hirose, N; Nakazawa, S; Yamamura, K; Shimizu, K; Takayama, M; Ebihara, Y; Osono, Y; Homma, S

2001-11-01

To assess the complex interaction of apolipoprotein (apo) E polymorphisms and environmental factors on lipoprotein profile in centenarians. Cross-sectional analysis. Tokyo metropolitan area. Seventy-five centenarians and 73 healthy older volunteers (mean age 63.1 +/- 10.0) living in the Tokyo metropolitan area. Plasma lipids and lipoproteins, cholesteryl ester transfer protein mass, apo E phenotype, body mass index, nutritional indices (serum albumin, prealbumin, transferrin), dietary intake, inflammation markers (C-reactive protein (CRP), interleukin-6 (IL-6)), activities of daily living, and cognitive function. In comparison with older people, the centenarians had low concentrations of total and low-density lipoprotein cholesterol (LDL-C) and a relative predominance of high-density lipoprotein 2 cholesterol. No environmental factor, except the number of apo E epsilon2 alleles, was a significant determinant of LDL-C and apo B, suggesting that the low apo B-containing lipoprotein in centenarians may be attributable to a genetic cause. Centenarians had elevated levels of lipoprotein (a) and decreased high-density lipoprotein cholesterol (HDL-C), which seem to be an unfavorable lipoprotein profile. Lower levels of HDL-C in the centenarians were associated with decreased serum albumin, elevated CRP and IL-6 levels, and cognitive impairment, suggesting that HDL-C could be a sensitive marker for frailty and comorbidity in the oldest old. Low levels of apo B-containing lipoproteins attributable to a genetic cause may be advantageous for longevity. Lipoprotein profiles in centenarians were consistently related to the subjects' nutritional status, inflammation markers, and apo E polymorphisms. The results provide evidence for the importance of maintaining nutritional status in the very old.

Effect of chromium chloride supplementation on glucose tolerance and serum lipids including high-density lipoprotein of adult men.

PubMed

Riales, R; Albrink, M J

1981-12-01

Chromium deficiency may cause insulin resistance, hyperinsulinemia, impaired glucose tolerance, and hyperlipidemia, recovered by chromium supplementation. The effect of chromium supplementation on serum lipids and glucose tolerance was tested in a double-blind 12-wk study of 23 healthy adult men aged 31 to 60 yr. Either 200 micrograms trivalent chromium in 5 ml water (Cr) or 5 ml plain water (W) was ingested daily 5 days each week. Half the subjects volunteered for glucose tolerance tests with insulin levels. At 12 wk high-density lipoprotein cholesterol increased in the Cr group from 35 to 39 mg/dl (p less than 0.05) but did not change in the water group (34 mg/dl). The largest increase in high-density lipoprotein cholesterol and decreases in insulin and glucose were found in those subjects having normal glucose levels together with elevated insulin levels at base-line. The data are thus consistent with the hypothesis that Cr supplementation raises high-density lipoprotein cholesterol and improves insulin sensitivity in those with evidence of insulin resistance but normal glucose tolerance.

Low density lipoprotein delays clearance of triglyceride-rich lipoprotein by human subcutaneous adipose tissue

PubMed Central

Bissonnette, Simon; Salem, Huda; Wassef, Hanny; Saint-Pierre, Nathalie; Tardif, Annie; Baass, Alexis; Dufour, Robert; Faraj, May

2013-01-01

Delayed clearance of triglyceride-rich lipoprotein (TRL) by white adipose tissue (WAT) promotes hypertriglyceridemia and elevated apoB-lipoproteins, which are primarily in the form of LDL. This study examines whether LDL promotes delayed clearance of TRL by WAT. Following the ingestion of a 13C-triolein-labeled high-fat meal, obese women with high plasma apoB (> median 0.93 g/l, N = 11, > 98% as IDL/LDL) had delayed clearance of postprandial 13C-triglyceride and 13C-NEFA over 6 h compared with controls. AUC6 h of plasma 13C-triglyceride and 13C-NEFA correlated with plasma apoB but not with LDL diameter or adipocyte area. There was no group difference in 13C-triolein oxidation rate, which suggests lower 13C-NEFA storage in peripheral tissue in women with high apoB. Ex vivo/in vitro plasma apoB correlated negatively with WAT 3H-lipid following a 4 h incubation of women's WAT with synthetic 3H-triolein-TRL. LDL-differentiated 3T3-L1 adipocytes had lower 3H-TRL hydrolysis and 3H-NEFA storage. Treatment of women's WAT with their own LDL decreased 3H-TRL hydrolysis and 3H-NEFA uptake. Finally, LDL, although not an LPL substrate, reduced LPL-mediated 3H-TRL hydrolysis as did VLDL and HDL. Exposure to LDL decreases TRL clearance by human WAT ex vivo. This may promote production of apoB-lipoproteins and hypertriglyceridemia through a positive-feedback mechanism in vivo. PMID:23417739

A clustering analysis of lipoprotein diameters in the metabolic syndrome

USDA-ARS?s Scientific Manuscript database

The presence of smaller low-density lipoproteins (LDL) has been associated with atherosclerosis risk, and the insulin resistance (IR) underlying the metabolic syndrome (MetS). In addition, some research has supported the association of very low-, low- and high-density lipoprotein (VLDL HDL) particle...

Impact of hormonal contraception and weight loss on high-density lipoprotein cholesterol efflux and lipoprotein particles in women with polycystic ovary syndrome.

PubMed

Dokras, Anuja; Playford, Martin; Kris-Etherton, Penny M; Kunselman, Allen R; Stetter, Christy M; Williams, Nancy I; Gnatuk, Carol L; Estes, Stephanie J; Sarwer, David B; Allison, Kelly C; Coutifaris, Christos; Mehta, Nehal; Legro, Richard S

2017-05-01

To study the effects of oral contraceptive pills (OCP), the first-line treatment for PCOS, on high-density lipoprotein cholesterol (HDL-C) function (reverse cholesterol efflux capacity) and lipoprotein particles measured using nuclear magnetic resonance spectroscopy in obese women. Secondary analysis of a randomized controlled trial (OWL-PCOS) of OCP or Lifestyle (intensive Lifestyle modification) or Combined (OCP + Lifestyle) treatment groups for 16 weeks. Eighty-seven overweight/obese women with PCOS at two academic centres. Change in HDL-C efflux capacity and lipoprotein particles. High-density lipoprotein cholesterol efflux capacity increased significantly at 16 weeks in the OCP group [0·11; 95% confidence interval (CI) 0·03, 0·18, P = 0·008] but not in the Lifestyle (P = 0·39) or Combined group (P = 0·18). After adjusting for HDL-C and TG levels, there was significant mean change in efflux in the Combined group (0·09; 95% CI 0·01, 0·15; P = 0·01). Change in HDL-C efflux correlated inversely with change in serum testosterone (r s = -0·21; P = 0·05). In contrast, OCP use induced an atherogenic low-density lipoprotein cholesterol (LDL-C) profile with increase in small (P = 0·006) and large LDL-particles (P = 0·002). Change in small LDL-particles correlated with change in serum testosterone (r s = -0·31, P = 0·009) and insulin sensitivity index (ISI; r s = -0·31, P = 0·02). Both Lifestyle and Combined groups did not show significant changes in the atherogenic LDL particles. Oral contraceptive pills use is associated with improved HDL-C function and a concomitant atherogenic LDL-C profile. Combination of a Lifestyle program with OCP use improved HDL-C function and mitigated adverse effects of OCP on lipoproteins. Our study provides evidence for use of OCP in overweight/obese women with PCOS when combined with Lifestyle changes. © 2017 John Wiley & Sons Ltd.

Biominetic High Density Lipoproteins for the Delivery of Therapeutic Oligonucleotides

NASA Astrophysics Data System (ADS)

Tripathy, Sushant

Advances in nanotechnology have brought about novel inorganic and hybrid nanoparticles with unique physico-chemical properties that make them suitable for a broad range of applications---from nano-circuitry to drug delivery. A significant part of those advancements have led to ground-breaking discoveries that have changed the approaches to formulation of therapeutics against diseases, such as cancer. Now-a-days the focus does not lie solely on finding a candidate small-molecule therapeutic with minimal adverse effects, but researchers are looking up to nanoparticles to improve biodistribution and biocompatibility profile of clinically proven therapeutics. The plethora of conjugation chemistries offered by currently extant inorganic nanoparticles have, in recent years, led to great leaps in the field of biomimicry---a modality that promises high biocompatibility. Further, in the pursuit of highly specific therapeutic molecules, researchers have turned to silencing oligonucleotides and some have already brought together the strengths of nanoparticles and silencing oligonucleotides in search of an efficacious therapy for cancer with minimal adverse effects. This dissertation work focuses on such a biomimetic platform---a gold nanoparticle based high density lipoprotein biomimetic (HDL NP), for the delivery of therapeutic oligonucleotides. The first chapter of this body of work introduces the molecular target of the silencing oligonucleotides---VEGFR2, and its role in the progression of solid tumor cancers. The background information also covers important aspects of natural high density lipoproteins (HDL), especially their innate capacity to bind and deliver exogenous and endogenous silencing oligonucleotides to tissues that express their high affinity receptor SRB1. We subsequently describe the synthesis of the biomimetic HDL NP and its oligonucleotide conjugates, and establish their biocompatibility. Further on, experimental data demonstrate the efficacy of silencing

Advanced In-Pile Instrumentation for Materials Testing Reactors

NASA Astrophysics Data System (ADS)

Rempe, J. L.; Knudson, D. L.; Daw, J. E.; Unruh, T. C.; Chase, B. M.; Davis, K. L.; Palmer, A. J.; Schley, R. S.

2014-08-01

The U.S. Department of Energy sponsors the Advanced Test Reactor (ATR) National Scientific User Facility (NSUF) program to promote U.S. research in nuclear science and technology. By attracting new research users - universities, laboratories, and industry - the ATR NSUF facilitates basic and applied nuclear research and development, advancing U.S. energy security needs. A key component of the ATR NSUF effort is to design, develop, and deploy new in-pile instrumentation techniques that are capable of providing real-time measurements of key parameters during irradiation. This paper describes the strategy developed by the Idaho National Laboratory (INL) for identifying instrumentation needed for ATR irradiation tests and the program initiated to obtain these sensors. New sensors developed from this effort are identified, and the progress of other development efforts is summarized. As reported in this paper, INL researchers are currently involved in several tasks to deploy real-time length and flux detection sensors, and efforts have been initiated to develop a crack growth test rig. Tasks evaluating `advanced' technologies, such as fiber-optics based length detection and ultrasonic thermometers, are also underway. In addition, specialized sensors for real-time detection of temperature and thermal conductivity are not only being provided to NSUF reactors, but are also being provided to several international test reactors.

Advanced Demonstration and Test Reactor Options Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petti, David Andrew; Hill, R.; Gehin, J.

Global efforts to address climate change will require large-scale decarbonization of energy production in the United States and elsewhere. Nuclear power already provides 20% of electricity production in the United States (U.S.) and is increasing in countries undergoing rapid growth around the world. Because reliable, grid-stabilizing, low emission electricity generation, energy security, and energy resource diversity will be increasingly valued, nuclear power’s share of electricity production has a potential to grow. In addition, there are non electricity applications (e.g., process heat, desalination, hydrogen production) that could be better served by advanced nuclear systems. Thus, the timely development, demonstration, and commercializationmore » of advanced nuclear reactors could diversify the nuclear technologies available and offer attractive technology options to expand the impact of nuclear energy for electricity generation and non-electricity missions. The purpose of this planning study is to provide transparent and defensible technology options for a test and/or demonstration reactor(s) to be built to support public policy, innovation and long term commercialization within the context of the Department of Energy’s (DOE’s) broader commitment to pursuing an “all of the above” clean energy strategy and associated time lines. This planning study includes identification of the key features and timing needed for advanced test or demonstration reactors to support research, development, and technology demonstration leading to the commercialization of power plants built upon these advanced reactor platforms. This planning study is consistent with the Congressional language contained within the fiscal year 2015 appropriation that directed the DOE to conduct a planning study to evaluate “advanced reactor technology options, capabilities, and requirements within the context of national needs and public policy to support innovation in nuclear energy�

Ginsenoside Rf, a component of ginseng, regulates lipoprotein metabolism through peroxisome proliferator-activated receptor {alpha}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Hyunghee; Gonzalez, Frank J.; Yoon, Michung

We investigated whether ginseng regulates lipoprotein metabolism by altering peroxisome proliferator-activated receptor {alpha} (PPAR{alpha})-mediated pathways, using a PPAR{alpha}-null mouse model. Administration of ginseng extract, ginsenosides, and ginsenoside Rf (Rf) to wild-type mice not only significantly increased basal levels of hepatic apolipoprotein (apo) A-I and C-III mRNA compared with wild-type controls, but also substantially reversed the reductions in mRNA levels of apo A-I and C-III expected following treatment with the potent PPAR{alpha} ligand Wy14,643. In contrast, no effect was detected in the PPAR{alpha}-null mice. Testing of eight main ginsenosides on PPAR{alpha} reporter gene expression indicated that Rf was responsible for themore » effects of ginseng on lipoprotein metabolism. Furthermore, the inhibition of PPAR{alpha}-dependent transactivation by Rf seems to occur at the level of DNA binding. These results demonstrate that ginseng component Rf regulates apo A-I and C-III mRNA and the actions of Rf on lipoprotein metabolism are mediated via interactions with PPAR{alpha}.« less

Correlation of structural stability with functional remodeling of high-density lipoproteins: the importance of being disordered.

PubMed

Guha, Madhumita; Gao, Xuan; Jayaraman, Shobini; Gursky, Olga

2008-11-04

High-density lipoproteins (HDLs) are protein-lipid assemblies that remove excess cell cholesterol and prevent atherosclerosis. HDLs are stabilized by kinetic barriers that decelerate protein dissociation and lipoprotein fusion. We propose that similar barriers modulate metabolic remodeling of plasma HDLs; hence, changes in particle composition that destabilize HDLs and accelerate their denaturation may accelerate their metabolic remodeling. To test this notion, we correlate existing reports on HDL-mediated cell cholesterol efflux and esterification, which are obligatory early steps in cholesterol removal, with our kinetic studies of HDL stability. The results support our hypothesis and show that factors accelerating cholesterol efflux and esterification in model discoidal lipoproteins (including reduced protein size, reduced fatty acyl chain length, and/or increased level of cis unsaturation) destabilize lipoproteins and accelerate their fusion and apolipoprotein dissociation. Oxidation studies of plasma spherical HDLs show a similar trend: mild oxidation by Cu(2+) or OCl(-) accelerates cell cholesterol efflux, protein dissociation, and HDL fusion, while extensive oxidation inhibits these reactions. Consequently, moderate destabilization may be beneficial for HDL functions by facilitating insertion of cholesterol and lipophilic enzymes, promoting dissociation of lipid-poor apolipoproteins, which are primary acceptors of cell cholesterol, and thereby accelerating HDL metabolism. Therefore, HDL stability must be delicately balanced to maintain the structural integrity of the lipoprotein assembly and ensure structural specificity necessary for interactions of HDL with its metabolic partners, while facilitating rapid HDL remodeling and turnover at key junctures of cholesterol transport. The inverse correlation between HDL stability and remodeling illustrates the functional importance of structural disorder in macromolecular assemblies stabilized by kinetic barriers.

Hydrolysis products generated by lipoprotein lipase and endothelial lipase differentially impact THP-1 macrophage cell signalling pathways.

PubMed

Essaji, Yasmin; Yang, Yanbo; Albert, Carolyn J; Ford, David A; Brown, Robert J

2013-08-01

Macrophages express lipoprotein lipase (LPL) and endothelial lipase (EL) within atherosclerotic plaques; however, little is known about how lipoprotein hydrolysis products generated by these lipases might affect macrophage cell signalling pathways. We hypothesized that hydrolysis products affect macrophage cell signalling pathways associated with atherosclerosis. To test our hypothesis, we incubated differentiated THP-1 macrophages with products from total lipoprotein hydrolysis by recombinant LPL or EL. Using antibody arrays, we found that the phosphorylation of six receptor tyrosine kinases and three signalling nodes--most associated with atherosclerotic processes--was increased by LPL derived hydrolysis products. EL derived hydrolysis products only increased the phosphorylation of tropomyosin-related kinase A, which is also implicated in playing a role in atherosclerosis. Using electrospray ionization-mass spectrometry, we identified the species of triacylglycerols and phosphatidylcholines that were hydrolyzed by LPL and EL, and we identified the fatty acids liberated by gas chromatography-mass spectrometry. To determine if the total liberated fatty acids influenced signalling pathways, we incubated differentiated THP-1 macrophages with a mixture of the fatty acids that matched the concentrations of liberated fatty acids from total lipoproteins by LPL, and we subjected cell lysates to antibody array analyses. The analyses showed that only the phosphorylation of Akt was significantly increased in response to fatty acid treatment. Overall, our study shows that macrophages display potentially pro-atherogenic signalling responses following acute treatments with LPL and EL lipoprotein hydrolysis products.

Activation of murine macrophages by lipoprotein and lipooligosaccharide of Treponema denticola.

PubMed

Rosen, G; Sela, M N; Naor, R; Halabi, A; Barak, V; Shapira, L

1999-03-01

We have recently demonstrated that the periodontopathogenic oral spirochete Treponema denticola possesses membrane-associated lipoproteins in addition to lipooligosaccharide (LOS). The aim of the present study was to test the potential of these oral spirochetal components to induce the production of inflammatory mediators by human macrophages, which in turn may stimulate tissue breakdown as observed in periodontal diseases. An enriched lipoprotein fraction (dLPP) from T. denticola ATCC 35404 obtained upon extraction of the treponemes with Triton X-114 was found to stimulate the production of nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), and interleukin-1 (IL-1) by mouse macrophages in a dose-dependent manner. Induction of NO by dLPP was at 25% of the levels obtained by Salmonella typhosa lipopolysaccharide (LPS) at similar concentrations, while IL-1 was produced at similar levels by both inducers. dLPP-mediated macrophage activation was unaffected by amounts of polymyxin B that neutralized the induction produced by S. typhosa LPS. dLPP also induced NO and TNF-alpha secretion from macrophages isolated from endotoxin-unresponsive C3H/HeJ mice to an extent similar to the stimulation produced in endotoxin-responsive mice. Purified T. denticola LOS also produced a concentration-dependent activation of NO and TNF-alpha in LPS-responsive and -nonresponsive mouse macrophages. However, macrophage activation by LOS was inhibited by polymyxin B. These results suggest that T. denticola lipoproteins and LOS may play a role in the inflammatory processes that characterize periodontal diseases.

A common factor suppresses thickening in young women with malar area port wine stains and delays low density lipoprotein elevation: is it estrogen?

PubMed

Klapman, M H; Sosa, V B; Yao, J F

2014-06-01

Port wine stains in the malar area of the face can develop thickening in early adult life. We began a study with a hypothesis that this thickening can be associated with elevation of low density lipoprotein. In a retrospective review, we divided 53 subjects with malar port wine stains into 4 groups, adults 25-39 years of age with thickening, that age group without thickening, adults 40+ years of age with thickening, and that age group without thickening. Low density lipoprotein levels in the subjects were compared to age and sex matched controls randomly selected from the general Dermatology clinic. The younger subjects with thickening demonstrated significantly higher low density lipoprotein levels than their controls (p .0082) and without thickening lower low density lipoprotein levels than their controls with great significance (p .00058). The subjects without thickening also consisted mainly of women. The low density lipoprotein levels in the older age groups, whether thickened or not, demonstrated no significant difference in low density lipoprotein levels between subjects and controls. This led to a new hypothesis that there is a factor in a subgroup of young adult women with malar port wine stains that suppresses thickening and delays the elevation of low density lipoprotein and that this factor might be estrogen. The implications of this hypothesis are that it could define a marker for a subset of the population that might be protected from the diseases associated with early elevation of low density lipoprotein and provide a source of cutaneous tissue for studying the basic science of this protection (although limited by cosmetic considerations). Future laboratory research to test the new hypothesis might include testing blood of women with malar port wine stains with or without thickening for estrogen and other sex hormones. It might also include skin biopsies to study receptors for estrogen, other sex hormones, and angiogenic factors in malar port wine

Elevated plasma low-density lipoprotein and high-density lipoprotein cholesterol levels in amenorrheic athletes: effects of endogenous hormone status and nutrient intake.

PubMed

Friday, K E; Drinkwater, B L; Bruemmer, B; Chesnut, C; Chait, A

1993-12-01

To determine the interactive effects of hormones, exercise, and diet on plasma lipids and lipoproteins, serum estrogen and progesterone levels, nutrient intake, and plasma lipid, lipoprotein, and apolipoprotein concentrations were measured in 24 hypoestrogenic amenorrheic and 44 eumenorrheic female athletes. When compared to eumenorrheic athletes, amenorrheic athletes had higher levels of plasma cholesterol (5.47 +/- 0.17 vs. 4.84 +/- 0.12 mmol/L, P = 0.003), triglyceride (0.75 +/- 0.06 vs. 0.61 +/- 0.03 mmol/L, P = 0.046), low-density lipoprotein (LDL; 3.16 +/- 0.15 vs. 2.81 +/- 0.09 mmol/L, P = 0.037), high-density lipoprotein (HDL; 1.95 +/- 0.07 vs. 1.73 +/- 0.05 mmol/L, P = 0.007), and HDL2 (0.84 +/- 0.06 vs. 0.68 +/- 0.04 mmol/L, P = 0.02) cholesterol. Plasma LDL/HDL cholesterol ratios, very low-density lipoprotein and HDL3 cholesterol, and apolipoprotein A-I and A-II levels were similar in the two groups. Amenorrheic athletes consumed less fat than eumenorrheic subjects (52 +/- 5 vs. 75 +/- 3 g/day, P = 0.02), but similar amounts of calories, cholesterol, protein, carbohydrate, and ethanol. HDL cholesterol levels in amenorrheic subjects correlated positively with the percent of dietary calories from fat (r = 0.42, n = 23, P = 0.045) but negatively with the percent from protein (r = -0.49, n = 23, P = 0.017). Thus, exercise-induced amenorrhea may adversely affect cardiovascular risk by increasing plasma LDL and total cholesterol. However, cardioprotective elevations in plasma HDL and HDL2 cholesterol may neutralize the risk of cardiovascular disease in amenorrheic athletes.

A high-density lipoprotein-mediated drug delivery system.

PubMed

Mo, Zhong-Cheng; Ren, Kun; Liu, Xing; Tang, Zhen-Li; Yi, Guang-Hui

2016-11-15

High-density lipoprotein (HDL) is a comparatively dense and small lipoprotein that can carry lipids as a multifunctional aggregate in plasma. Several studies have shown that increasing the levels or improving the functionality of HDL is a promising target for treating a wide variety of diseases. Among lipoproteins, HDL particles possess unique physicochemical properties, including naturally synthesized physiological components, amphipathic apolipoproteins, lipid-loading and hydrophobic agent-incorporating characteristics, specific protein-protein interactions, heterogeneity, nanoparticles, and smaller size. Recently, the feasibility and superiority of using HDL particles as drug delivery vehicles have been of great interest. In this review, we summarize the structure, constituents, biogenesis, remodeling, and reconstitution of HDL drug delivery systems, focusing on their delivery capability, characteristics, applications, manufacturing, and drug-loading and drug-targeting characteristics. Finally, the future prospects are presented regarding the clinical application and challenges of using HDL as a pharmacodelivery carrier. Copyright © 2016 Elsevier B.V. All rights reserved.

Autophagy-mediated longevity is modulated by lipoprotein biogenesis

PubMed Central

Seah, Nicole E.; de Magalhaes Filho, C. Daniel; Petrashen, Anna P.; Henderson, Hope R.; Laguer, Jade; Gonzalez, Julissa; Dillin, Andrew; Hansen, Malene; Lapierre, Louis R.

2016-01-01

ABSTRACT Autophagy-dependent longevity models in C. elegans display altered lipid storage profiles, but the contribution of lipid distribution to life-span extension is not fully understood. Here we report that lipoprotein production, autophagy and lysosomal lipolysis are linked to modulate life span in a conserved fashion. We find that overexpression of the yolk lipoprotein VIT/vitellogenin reduces the life span of long-lived animals by impairing the induction of autophagy-related and lysosomal genes necessary for longevity. Accordingly, reducing vitellogenesis increases life span via induction of autophagy and lysosomal lipolysis. Life-span extension due to reduced vitellogenesis or enhanced lysosomal lipolysis requires nuclear hormone receptors (NHRs) NHR-49 and NHR-80, highlighting novel roles for these NHRs in lysosomal lipid signaling. In dietary-restricted worms and mice, expression of VIT and hepatic APOB (apolipoprotein B), respectively, are significantly reduced, suggesting a conserved longevity mechanism. Altogether, our study demonstrates that lipoprotein biogenesis is an important mechanism that modulates aging by impairing autophagy and lysosomal lipolysis. PMID:26671266

Advanced Stirling Convertor Dynamic Test Approach and Results

NASA Technical Reports Server (NTRS)

Meer, David W.; Hill, Dennis; Ursic, Joseph

2009-01-01

The U.S. Department of Energy (DOE), Lockheed Martin (LM), and NASA Glenn Research Center (GRC) have been developing the Advanced Stirling Radioisotope Generator (ASRG) for use as a power system for space science missions. As part of the extended operation testing of this power system, the Advanced Stirling Converters (ASC) at NASA John H. Glenn Research Center undergo a vibration test sequence intended to simulate the vibration history of an ASC used in an ASRG for a space mission. This sequence includes testing at Workmanship and Flight Acceptance levels interspersed with periods of extended operation to simulate pre and post fueling. The final step in the test sequence utilizes additional testing at Flight Acceptance levels to simulate launch. To better replicate the acceleration profile seen by an ASC incorporated into an ASRG, the input spectra used in testing the convertors was modified based on dynamic testing of the ASRG Engineering Unit ( ASRG-EU) at Lockheed Martin. This paper presents the vibration test plan for current and future ASC units, including the modified input spectra, and the results of recent tests using these spectra. The test results include data from several accelerometers mounted on the convertors as well as the piston position and output power variables.

Advanced Stirling Convertor Durability Testing: Plans and Interim Results

NASA Technical Reports Server (NTRS)

Meer, David W.; Oriti, Salvatore M.

2012-01-01

The U.S. Department of Energy (DOE), Lockheed Martin Corporation (LM), and NASA Glenn Research Center (GRC) have been developing the Advanced Stirling Radioisotope Generator (ASRG) for use as a power system for space science missions. In support of this program, GRC has been involved in testing Stirling convertors, including the Advanced Stirling Convertor (ASC), for use in the ASRG. This testing includes electromagnetic interference/compatibility (EMI/EMC), structural dynamics, advanced materials, organics, and unattended extended operation. The purpose of the durability tests is to experimentally demonstrate the margins in the ASC design. Due to the high value of the hardware, previous ASC tests focused on establishing baseline performance of the convertors within the nominal operating conditions. The durability tests present the first planned extension of the operating conditions into regions beyond those intended to meet the product spec, where the possibility exists of lateral contact, overstroke, or over-temperature events. These tests are not intended to cause damage that would shorten the life of the convertors, so they can transition into extended operation at the conclusion of the tests. This paper describes the four tests included in the durability test sequence: 1) start/stop cycling, 2) exposure to constant acceleration in the lateral and axial directions, 3) random vibration at increased piston amplitude to induce contact events, and 4) overstroke testing to simulate potential failures during processing or during the mission life where contact events could occur. The paper also summarizes the analysis and simulation used to predict the results of each of these tests.

More Than Cholesterol Transporters: Lipoprotein Receptors in CNS Function and Neurodegeneration

PubMed Central

Lane-Donovan, Courtney E.; Philips, Gary T.; Herz, Joachim

2014-01-01

Members of the low-density lipoprotein (LDL) receptor gene family have a diverse set of biological functions that transcend lipid metabolism. Lipoprotein receptors have broad effects in both the developing and adult brain and participate in synapse development, cargo trafficking, and signal transduction. In addition, several family members play key roles in Alzheimer's disease pathogenesis and neurodegeneration. This review summarizes our current understanding of the role lipoprotein receptors play in CNS function and AD pathology, with a special emphasis on amyloid-independent roles in endocytosis and synaptic dysfunction. PMID:25144875

Future opportunities for advancing glucose test device electronics.

PubMed

Young, Brian R; Young, Teresa L; Joyce, Margaret K; Kennedy, Spencer I; Atashbar, Massood Z

2011-09-01

Advancements in the field of printed electronics can be applied to the field of diabetes testing. A brief history and some new developments in printed electronics components applicable to personal test devices, including circuitry, batteries, transmission devices, displays, and sensors, are presented. Low-cost, thin, and lightweight materials containing printed circuits with energy storage or harvest capability and reactive/display centers, made using new printing/imaging technologies, are ideal for incorporation into personal-use medical devices such as glucose test meters. Semicontinuous rotogravure printing, which utilizes flexible substrates and polymeric, metallic, and/or nano "ink" composite materials to effect rapidly produced, lower-cost printed electronics, is showing promise. Continuing research advancing substrate, "ink," and continuous processing development presents the opportunity for research collaboration with medical device designers. © 2011 Diabetes Technology Society.

Advanced regenerator testing in the Raytheon dual-use cryocoolerr

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schaefer, B. R.; Bellis, L.; Ellis, M. J.

2014-01-29

Significant progress has been made on the Raytheon low cost space cryocooler called the Dual-Use Cryocooler (DUC). Most notably, the DUC has been integrated and tested with an advanced regenerator. The advanced regenerator is a drop-in replacement for stainless steel screens and has shown significant thermodynamic performance improvements. This paper will compare the performance of two different regenerators and explain the benefits of the advanced regenerator.

Advanced Stirling Convertor Dynamic Test Approach and Results

NASA Technical Reports Server (NTRS)

Meer, David W.; Hill, Dennis; Ursic, Joseph J.

2010-01-01

The U.S. Department of Energy (DOE), Lockheed Martin Corporation (LM), and NASA Glenn Research Center (GRC) have been developing the Advanced Stirling Radioisotope Generator (ASRG) for use as a power system for space science missions. As part of the extended operation testing of this power system, the Advanced Stirling Convertors (ASC) at NASA GRC undergo a vibration test sequence intended to simulate the vibration history that an ASC would experience when used in an ASRG for a space mission. This sequence includes testing at workmanship and flight acceptance levels interspersed with periods of extended operation to simulate prefueling and post fueling. The final step in the test sequence utilizes additional testing at flight acceptance levels to simulate launch. To better replicate the acceleration profile seen by an ASC incorporated into an ASRG, the input spectra used in testing the convertors was modified based on dynamic testing of the ASRG Engineering Unit (ASRG EU) at LM. This paper outlines the overall test approach, summarizes the test results from the ASRG EU, describes the incorporation of those results into the test approach, and presents the results of applying the test approach to the ASC-1 #3 and #4 convertors. The test results include data from several accelerometers mounted on the convertors as well as the piston position and output power variables.

Detailed analysis of the plasma extracellular vesicle proteome after separation from lipoproteins.

PubMed

Karimi, Nasibeh; Cvjetkovic, Aleksander; Jang, Su Chul; Crescitelli, Rossella; Hosseinpour Feizi, Mohammad Ali; Nieuwland, Rienk; Lötvall, Jan; Lässer, Cecilia

2018-02-13

The isolation of extracellular vesicles (EVs) from blood is of great importance to understand the biological role of circulating EVs and to develop EVs as biomarkers of disease. Due to the concurrent presence of lipoprotein particles, however, blood is one of the most difficult body fluids to isolate EVs from. The aim of this study was to develop a robust method to isolate and characterise EVs from blood with minimal contamination by plasma proteins and lipoprotein particles. Plasma and serum were collected from healthy subjects, and EVs were isolated by size-exclusion chromatography (SEC), with most particles being present in fractions 8-12, while the bulk of the plasma proteins was present in fractions 11-28. Vesicle markers peaked in fractions 7-11; however, the same fractions also contained lipoprotein particles. The purity of EVs was improved by combining a density cushion with SEC to further separate lipoprotein particles from the vesicles, which reduced the contamination of lipoprotein particles by 100-fold. Using this novel isolation procedure, a total of 1187 proteins were identified in plasma EVs by mass spectrometry, of which several proteins are known as EV-associated proteins but have hitherto not been identified in the previous proteomic studies of plasma EVs. This study shows that SEC alone is unable to completely separate plasma EVs from lipoprotein particles. However, combining SEC with a density cushion significantly improved the separation of EVs from lipoproteins and allowed for a detailed analysis of the proteome of plasma EVs, thus making blood a viable source for EV biomarker discovery.

Differences in the Lipoprotein Distribution of Free and Liposome-Associated All-trans-Retinoic Acid in Human, Dog, and Rat Plasma Are Due to Variations in Lipoprotein Lipid and Protein Content

PubMed Central

Wasan, Kishor M.; Ramaswamy, Manisha; Ng, Samson P.; Wong, Wesley; Parrott, Steven C.; Ojwang, Joshua O.; Wallace, Thomas; Cossum, Paul A.

1998-01-01

The objective of the proposed study was to determine the distribution in plasma lipoprotein of free all-trans retinoic acid (ATRA) and liposomal ATRA (Atragen; composed of dimyristoyl phosphatidylcholine and soybean oil) following incubation in human, rat, and dog plasma. When ATRA and Atragen at concentrations of 1, 5, 10, and 25 μg/ml were incubated in human and rat plasma for 5, 60, and 180 min, the majority of the tretinoin was recovered in the lipoprotein-deficient plasma fraction. However, when ATRA and Atragen were incubated in dog plasma, the majority of the tretinoin (>40%) was recovered in the high-density lipoprotein (HDL) fraction. No differences in the plasma distribution between ATRA and Atragen were found. These data suggest that a significant percentage of tretinoin associates with plasma lipoproteins (primarily the HDL fraction) upon incubation in human, dog, and rat plasma. Differences between the lipoprotein lipid and protein profiles in human plasma and in dog and rat plasma influenced the plasma distribution of ATRA and Atragen. Differences in lipoprotein distribution between ATRA and Atragen were not observed, suggesting that the drug’s distribution in plasma is not influenced by its incorporation into these liposomes. PMID:9660998

Lipoprotein (a) Management: Lifestyle and Hormones.

PubMed

Garcia-Rios, Antonio; Leon-Acuna, Ana; Lopez-Miranda, Jose; Perez-Martinez, Pablo

2017-01-01

Cardiovascular disease (CVD) continues to be the first cause of mortality in developed countries. Moreover, far from diminishing, the cardiovascular risk factors leading towards the development of CVD are on the rise. Therefore, the preventive and therapeutic management which is currently in place is clearly not enough to stop this pandemic. In this context, a major resurgence in interest in lipoprotein (a) [Lp(a)] has occurred in light of its association with CVD. This series aims to review the basic and clinical aspects of Lp(a) biology. Specifically, the present review considers the current situation regarding the influence of lifestyle, hormones and other physiological or pathological conditions on Lp(a) plasma concentrations which might mitigate the harmful effects of this lipoprotein. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Advanced Materials Laboratory User Test Planning Guide

NASA Technical Reports Server (NTRS)

Orndoff, Evelyne

2012-01-01

Test process, milestones and inputs are unknowns to first-time users of the Advanced Materials Laboratory. The User Test Planning Guide aids in establishing expectations for both NASA and non-NASA facility customers. The potential audience for this guide includes both internal and commercial spaceflight hardware/software developers. It is intended to assist their test engineering personnel in test planning and execution. Material covered includes a roadmap of the test process, roles and responsibilities of facility and user, major milestones, facility capabilities, and inputs required by the facility. Samples of deliverables, test article interfaces, and inputs necessary to define test scope, cost, and schedule are included as an appendix to the guide.

Staphylococcus aureus utilizes host-derived lipoprotein particles as sources of exogenous fatty acids.

PubMed

Delekta, Phillip C; Shook, John C; Lydic, Todd A; Mulks, Martha H; Hammer, Neal D

2018-03-26

Methicillin-resistant Staphylococcus aureus (MRSA) is a threat to global health. Consequently, much effort has focused on the development of new antimicrobials that target novel aspects of S. aureus physiology. Fatty acids are required to maintain cell viability, and bacteria synthesize fatty acids using the type II fatty acid synthesis pathway (FASII). FASII is significantly different from human fatty acid synthesis, underscoring the therapeutic potential of inhibiting this pathway. However, many Gram-positive pathogens incorporate exogenous fatty acids, bypassing FASII inhibition and leaving the clinical potential of FASII inhibitors uncertain. Importantly, the source(s) of fatty acids available to pathogens within the host environment remains unclear. Fatty acids are transported throughout the body by lipoprotein particles in the form of triglycerides and esterified cholesterol. Thus, lipoproteins, such as low-density lipoprotein (LDL) represent a potentially rich source of exogenous fatty acids for S. aureus during infection. We sought to test the ability of LDLs to serve as a fatty acid source for S. aureus and show that cells cultured in the presence of human LDLs demonstrate increased tolerance to the FASII inhibitor, triclosan. Using mass spectrometry, we observed that host-derived fatty acids present in the LDLs are incorporated into the staphylococcal membrane and that tolerance to triclosan is facilitated by the fatty acid kinase A, FakA, and Geh, a triacylglycerol lipase. Finally, we demonstrate that human LDLs support the growth of S. aureus fatty acid auxotrophs. Together, these results suggest that human lipoprotein particles are a viable source of exogenous fatty acids for S. aureus during infection. IMPORTANCE Inhibition of bacterial fatty acid synthesis is a promising approach to combating infections caused by S. aureus and other human pathogens. However, S. aureus incorporates exogenous fatty acids into its phospholipid bilayer. Therefore, the

Hawaiian Electric Advanced Inverter Test Plan - Result Summary

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoke, Anderson; Nelson, Austin; Prabakar, Kumaraguru

This presentation is intended to share the results of lab testing of five PV inverters with the Hawaiian Electric Companies and other stakeholders and interested parties. The tests included baseline testing of advanced inverter grid support functions, as well as distribution circuit-level tests to examine the impact of the PV inverters on simulated distribution feeders using power hardware-in-the-loop (PHIL) techniques. hardware-in-the-loop (PHIL) techniques.

Lifecycle of a Lipoprotein from a Biophysical Perspective

NASA Astrophysics Data System (ADS)

Rutledge, John C.; Huser, Thomas; Voss, John; Chan, James; Parikh, Atul

The goal of our project was to understand how lipids and lipoproteins interact with cell membranes. This chapter will present the five major areas in which we have focused our attention on understanding how lipids and lipoproteins interact with cell membranes (Fig. 11.1): (1) triglycerides and vascular injury, (2) single lipoprotein analysis, (3) apolipoprotein E (apoE) conformation changes in the postprandial state, (4) triglyceride-rich lipoproteins (TGRLs) and endothelial cell inflammation, and (5) TGRL lipolysis products and monocyte activation. For over a hundred years, Western civilization has questioned how the food we eat translates into disease, and specifically atherosclerotic cardiovascular disease. Although most information indicates that this basic pathophysiological process is mediated through consumption of excess saturated fats, much remains unknown. After humans eat a meal, there is an elevation of triglycerides in the blood in the postprandial state. In normal individuals, triglycerides can rise after a meal by 50 to 100%. This has been documented many times in the past, including a paper by Hyson et al, (1998) [1]. In that study, normal healthy individuals were given a 40%-fat meal. Plasma triglycerides, which were modestly elevated initially, rose about 60% higher three to four hours after ingestion of the meal. Subsequently plasma triglycerides fell to baseline levels six hours after the meal. Even in these healthy individuals, a significant elevation of triglycerides was noted after ingestion of a moder ately high-fat meal.

[Lack of association between the S447X variant of the lipoprotein lipase gene and plasma lipids. A preliminary study].

PubMed

Zambrano Morales, Mariana; Fernández Salgado, Erika; Balzán Urdaneta, Ligia; Labastidas, Neila; Aranguren-Méndez, José; Connell, Lissette; Molero Paredes, Tania; Rojas, Alicia; Panunzio, Amelia

2014-06-01

The increase in lipid plasma values is an important cardiovascular risk factor. Lipoprotein lipase (LPL) plays an important role in the lipoprotein metabolism and metabolic and genetic factors may influence its levels and functions. The S447X variant of the lipoprotein lipase gene is associated with changes in plasma lipids in different populations. The objective of this research was to analyze the S447X variant of the LPL gene and its relation with plasma lipids of individuals in Zulia state, Venezuela. With this purpose, we studied 75 individuals (34 men and 41 women) between 20 and 60 years of age. Each subject had a medical history which included family history, anthropometric characteristics, nutritional status evaluation and biochemical tests. Genomic DNA was extracted for the molecular study and the polymerase chain reaction was used, followed by enzyme digestion, for restriction fragments length polymorphisms using the Hinf I enzyme. The individuals studied had normal levels of blood glucose, triglycerides, total cholesterol and low density lipoproteins (LDL-C) and slightly decreased levels of high density lipoproteins (HDL-C). The genotypic distribution of the LPL gene S447X variant in the studied population was 90.6% for the homozygous genotype SS447 and 9.4% for the heterozygote SX447. The genotype 447XX was not identified. The population was found in Hardy Weinberg genetic equilibrium. No association between the S447X polymorphism of lipoprotein lipase gene and plasma lipids was observed.

Rotor Performance at High Advance Ratio: Theory versus Test

NASA Technical Reports Server (NTRS)

Harris, Franklin D.

2008-01-01

Five analytical tools have been used to study rotor performance at high advance ratio. One is representative of autogyro rotor theory in 1934 and four are representative of helicopter rotor theory in 2008. The five theories are measured against three sets of well documented, full-scale, isolated rotor performance experiments. The major finding of this study is that the decades spent by many rotorcraft theoreticians to improve prediction of basic rotor aerodynamic performance has paid off. This payoff, illustrated by comparing the CAMRAD II comprehensive code and Wheatley & Bailey theory to H-34 test data, shows that rational rotor lift to drag ratios are now predictable. The 1934 theory predicted L/D ratios as high as 15. CAMRAD II predictions compared well with H-34 test data having L/D ratios more on the order of 7 to 9. However, the detailed examination of the selected codes compared to H-34 test data indicates that not one of the codes can predict to engineering accuracy above an advance ratio of 0.62 the control positions and shaft angle of attack required for a given lift. There is no full-scale rotor performance data available for advance ratios above 1.0 and extrapolation of currently available data to advance ratios on the order of 2.0 is unreasonable despite the needs of future rotorcraft. Therefore, it is recommended that an overly strong full-scale rotor blade set be obtained and tested in a suitable wind tunnel to at least an advance ratio of 2.5. A tail rotor from a Sikorsky CH-53 or other large single rotor helicopter should be adequate for this exploratory experiment.

Mutation of the Maturase Lipoprotein Attenuates the Virulence of Streptococcus equi to a Greater Extent than Does Loss of General Lipoprotein Lipidation▿

PubMed Central

Hamilton, Andrea; Robinson, Carl; Sutcliffe, Iain C.; Slater, Josh; Maskell, Duncan J.; Davis-Poynter, Nick; Smith, Ken; Waller, Andrew; Harrington, Dean J.

2006-01-01

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 (ΔprtM138-213, 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 (Δlgt190-685). Moreover, mucus production was significantly greater in both wild-type-infected and Δlgt190-685-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 Δlgt190-685 mutant did still exhibit signs of disease. In contrast, only the ΔprtM138-213 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 Δlgt190-685 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. PMID:17015455

Racial Differences in Mathematics Test Scores for Advanced Mathematics Students

ERIC Educational Resources Information Center

Minor, Elizabeth Covay

2016-01-01

Research on achievement gaps has found that achievement gaps are larger for students who take advanced mathematics courses compared to students who do not. Focusing on the advanced mathematics student achievement gap, this study found that African American advanced mathematics students have significantly lower test scores and are less likely to be…

PCOS is Associated with Atherogenic Changes in Lipoprotein Particle Number and Size Independent of Body Weight

PubMed Central

Sidhwani, Seema; Scoccia, Bert; Sunghay, Shwetha; Stephens-Archer, Chantale N.; Mazzone, Theodore; Sam, Susan

2011-01-01

Objective Adverse changes in lipoprotein particle number and size are common with insulin resistance and are associated with increased cardiovascular risk. Comprehensive information regarding lipoprotein particle number and size, and how these parameters relate to body weight, insulin resistance and hyperandrogenemia is lacking in PCOS. We tested the hypothesis that PCOS is associated with atherogenic changes in lipoprotein profile independent of body weight and examined the role of insulin resistance and androgens in these atherogenic changes. Design Case-control study performed at Clinical Research Center at an Academic Medical Center in United States. Patients and Measurements Fasting Blood was obtained from 25 PCOS and 25 control women of similar age and BMI. Lipoprotein particle number and size was determined by nuclear magnetic resonance and compared between the groups. Results The mean BMI for both groups was less than 30 kg/m2 (P=0.33). Women with PCOS had an increase in VLDL particle number (P=0.005), LDL particle number (P=0.02) and a decrease in HDL size (P=0.04). LDL size was borderline decreased (P=0.09). These differences persisted after adjustment for ethnicity, alcohol and tobacco intake and exercise. In stepwise regression models, bioavailable testosterone was the only predictor of LDL cholesterol, triglyceride, VLDL and LDL particle number. SHBG was the only predictor of LDL and HDL size. Conclusions Independent of body weight, PCOS was associated with changes in lipoprotein profile that increases risk for cardiovascular disease. These changes were present in a mostly non-obese group of women and were more closely related to androgens than fasting insulin. PMID:21521284

Use of lipoprotein particle measures for assessing coronary heart disease risk post-American Heart Association/American College of Cardiology guidelines: the Multi-Ethnic Study of Atherosclerosis.

PubMed

Steffen, Brian T; Guan, Weihua; Remaley, Alan T; Paramsothy, Pathmaja; Heckbert, Susan R; McClelland, Robyn L; Greenland, Philip; Michos, Erin D; Tsai, Michael Y

2015-02-01

The American College of Cardiology and American Heart Association have issued guidelines indicating that the contribution of apolipoprotein B-100 (ApoB) to cardiovascular risk assessment remains uncertain. The present analysis evaluates whether lipoprotein particle measures convey risk of coronary heart disease (CHD) in 4679 Multi-Ethnic Study of Atherosclerosis (MESA) participants. Cox regression analysis was performed to determine associations between lipids or lipoproteins and primary CHD events. After adjustment for nonlipid variables, lipoprotein particle levels in fourth quartiles were found to convey significantly greater risk of incident CHD when compared to first quartile levels (hazard ratio [HR]; 95% confidence interval [CI]): ApoB (HR, 1.84; 95% CI, 1.25-2.69), ApoB/ApoA-I (HR, 1.91; 95% CI, 1.32-2.76), total low-density lipoprotein-particles (LDL-P; HR, 1.77; 95% CI, 1.21-2.58), and the LDL-P/HDL-P (high-density lipoprotein-P) ratio (HR, 2.28; 95% CI, 1.54-3.37). Associations between lipoprotein particle measures and CHD were attenuated after adjustment for standard lipid panel variables. Using the American Heart Association/American College of Cardiology risk calculator as a baseline model for CHD risk assessment, significant net reclassification improvement scores were found for ApoB/ApoA-I (0.18; P=0.007) and LDL-P/high-density lipoprotein-P (0.15; P<0.001). C-statistics revealed no significant increase in CHD event discrimination for any lipoprotein measure. Lipoprotein particle measures ApoB/ApoA-I and LDL-P/high-density lipoprotein-P marginally improved net reclassification improvement scores, but null findings for corresponding c-statistic are not supportive of lipoprotein testing. The attenuated associations of lipoprotein particle measures with CHD after the adjustment for lipids indicate that their measurement does not detect risk that is unaccounted for by the standard lipid panel. However, the possibility that lipoprotein measures may

Non-high-density lipoprotein cholesterol vs low-density lipoprotein cholesterol as a risk factor for ischemic stroke: a result from the Kailuan study.

PubMed

Wu, Jianwei; Chen, Shengyun; Liu, Liping; Gao, Xiang; Zhou, Yong; Wang, Chunxue; Zhang, Qian; Wang, Anxin; Hussain, Mohammed; Sun, Baoying; Wu, Shouling; Zhao, Xingquan

2013-06-01

To compare the predictive value of serum low-density lipoprotein (LDL) cholesterol and non-high-density lipoprotein (non-HDL) cholesterol levels for ischemic stroke in the Chinese population. We performed a four-year cohort study of 95 778 men and women, aged 18-98 years, selected from the Kailuan study (2006-2007). Baseline LDL cholesterol levels were estimated using direct test method. Total cholesterol levels were estimated using endpoint test method. The predictive values of LDL cholesterol and non-HDL cholesterol for ischemic stroke were compared. During the follow-up period, there were 1153 incident cases of ischemic stroke. The hazard ratio (HR) for ischemic stroke in the top quintile of LDL cholesterol was the highest among five quintiles (HR: 1·25; 95% confidence interval (CI), 1·01-1·53). The HR in the top quintile of non-HDL cholesterol for ischemic stroke was also the highest among five quintiles (HR: 1·53; 95% CI, 1·24-1·88). Analysis of trends showed a significant positive relationship between ischemic stroke incidence and serum LDL cholesterol level, and non-HDL cholesterol level, respectively (both P < 0·05). The area under the curve of LDL cholesterol and non-HDL cholesterol for ischemic stroke was 0·51 and 0·56, respectively (P < 0·05 for the difference). Serum Non-HDL cholesterol level is a stronger predictor for the risk of ischemic stroke than serum LDL cholesterol level in the Chinese population.

SMART-DS: Synthetic Models for Advanced, Realistic Testing: Distribution

Science.gov Websites

statistical summary of the U.S. distribution systems World-class, high spatial/temporal resolution of solar Systems and Scenarios | Grid Modernization | NREL SMART-DS: Synthetic Models for Advanced , Realistic Testing: Distribution Systems and Scenarios SMART-DS: Synthetic Models for Advanced, Realistic

Activation of Murine Macrophages by Lipoprotein and Lipooligosaccharide of Treponema denticola

PubMed Central

Rosen, Graciela; Sela, Michael N.; Naor, Ronit; Halabi, Amal; Barak, Vivian; Shapira, Lior

1999-01-01

We have recently demonstrated that the periodontopathogenic oral spirochete Treponema denticola possesses membrane-associated lipoproteins in addition to lipooligosaccharide (LOS). The aim of the present study was to test the potential of these oral spirochetal components to induce the production of inflammatory mediators by human macrophages, which in turn may stimulate tissue breakdown as observed in periodontal diseases. An enriched lipoprotein fraction (dLPP) from T. denticola ATCC 35404 obtained upon extraction of the treponemes with Triton X-114 was found to stimulate the production of nitric oxide (NO), tumor necrosis factor alpha (TNF-α), and interleukin-1 (IL-1) by mouse macrophages in a dose-dependent manner. Induction of NO by dLPP was at 25% of the levels obtained by Salmonella typhosa lipopolysaccharide (LPS) at similar concentrations, while IL-1 was produced at similar levels by both inducers. dLPP-mediated macrophage activation was unaffected by amounts of polymyxin B that neutralized the induction produced by S. typhosa LPS. dLPP also induced NO and TNF-α secretion from macrophages isolated from endotoxin-unresponsive C3H/HeJ mice to an extent similar to the stimulation produced in endotoxin-responsive mice. Purified T. denticola LOS also produced a concentration-dependent activation of NO and TNF-α in LPS-responsive and -nonresponsive mouse macrophages. However, macrophage activation by LOS was inhibited by polymyxin B. These results suggest that T. denticola lipoproteins and LOS may play a role in the inflammatory processes that characterize periodontal diseases. PMID:10024558

Status of the irradiation test vehicle for testing fusion materials in the Advanced Test Reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsai, H.; Gomes, I.C.; Smith, D.L.

1998-09-01

The design of the irradiation test vehicle (ITV) for the Advanced Test Reactor (ATR) has been completed. The main application for the ITV is irradiation testing of candidate fusion structural materials, including vanadium-base alloys, silicon carbide composites, and low-activation steels. Construction of the vehicle is underway at the Lockheed Martin Idaho Technology Company (LMITCO). Dummy test trains are being built for system checkout and fine-tuning. Reactor insertion of the ITV with the dummy test trains is scheduled for fall 1998. Barring unexpected difficulties, the ITV will be available for experiments in early 1999.

Neuropathy Tests

MedlinePlus

... Mutation Mycophenolic Acid Mycoplasma Myoglobin Nicotine and Cotinine Non-High Density Lipoprotein Cholesterol Opioid Testing Osmolality Ova ... that make neuropathy worse Detect and evaluate complications Non-laboratory tests The diagnostic workup for neuropathy begins ...

Triglycerides Test

MedlinePlus

... Other names for a triglycerides test: TG, TRIG, lipid panel, fasting lipoprotein panel What is it used ... A triglycerides test is usually part of a lipid profile. Lipid is another word for fat. A ...

Synthetic high-density lipoprotein nanoconjugate targets neuroblastoma stem cells, blocking migration and self-renewal.

PubMed

Subramanian, Chitra; White, Peter T; Kuai, Rui; Kalidindi, Avinaash; Castle, Valerie P; Moon, James J; Timmermann, Barbara N; Schwendeman, Anna; Cohen, Mark S

2018-05-09

Pathways critical for neuroblastoma cancer stem cell function are targeted by 4,19,27-triacetyl withalongolide A (WGA-TA). Because neuroblastoma cells and their cancer stem cells highly overexpress the scavenger receptor class B type 1 receptor that binds to synthetic high-density lipoprotein, we hypothesized that a novel mimetic synthetic high-density lipoprotein nanoparticle would be an ideal carrier for the delivery of 4,19,27-triacetyl withalongolide to neuroblastoma and neuroblastoma cancer stem cells. Expression of scavenger receptor class B type 1 in validated human neuroblastoma cells was evaluated by quantitative polymerase chain reaction (qPCR) and Western blot. In vitro cellular uptake of synthetic high-density lipoprotein nanoparticles was observed with a fluorescence microscope. In vivo biodistribution of synthetic high-density lipoprotein nanoparticles was investigated with IVIS imaging. Self-renewal and migration/invasion were assessed by sphere formation and Boyden chamber assays, respectively. Viability was analyzed by CellTiter-Glo assay. Cancer stem cell markers were evaluated by flow cytometry. qPCR and Western blot analysis revealed a higher level of scavenger receptor class B type 1 expression and drug uptake in N-myc amplified neuroblastoma cells. In vitro uptake of synthetic high-density lipoprotein was almost completely blocked by excess synthetic high-density lipoprotein. The synthetic high-density lipoprotein nanoparticles mainly accumulated in the tumor and liver, but not in other organs. Synthetic HDL-4,19,27-triacetyl withalongolide showed a 1,000-fold higher potency than the carrier (synthetic high-density lipoprotein) alone (P < .01) to kill neuroblastoma cells. Additionally, a dose-dependent decrease in sphere formation, invasion, migration, and cancer stem cell markers was observed after treatment of neuroblastoma cells with synthetic high-density lipoprotein-4,19,27-triacetyl withalongolide A. Synthetic high-density lipoprotein is

Effects of Anabolic Steroids on Lipoprotein Profiles of Female Weight Lifters.

ERIC Educational Resources Information Center

Moffatt, Robert J.; And Others

1990-01-01

This study examined the effects of resistance exercise and anabolic steroids on lipoprotein profiles of female weightlifters. The study found that women who participate in resistance training have better lipoprotein profiles than their sedentary counterparts, but these changes do not offset the deleterious effects of steroid use. (SM)

Tests of Full-Scale Helicopter Rotors at High Advancing Tip Mach Numbers and Advance Ratios

NASA Technical Reports Server (NTRS)

Biggers, James C.; McCloud, John L., III; Stroub, Robert H.

2015-01-01

As a continuation of the studies of reference 1, three full-scale helicopter rotors have been tested in the Ames Research Center 40- by SO-foot wind tunnel. All three of them were two-bladed, teetering rotors. One of the rotors incorporated the NACA 0012 airfoil section over the entire length of the blade. This rotor was tested at advance ratios up to 1.05. Both of the other rotors were tapered in thickness and incorporated leading-edge camber over the outer 20 percent of the blade radius. The larger of these rotors was tested at advancing tip Mach numbers up to 1.02. Data were obtained for a wide range of lift and propulsive force, and are presented without discussion.

Utilization of individual lecithins in intestinal lipoprotein formation in the rat.

PubMed Central

Patton, G M; Clark, S B; Fasulo, J M; Robins, S J

1984-01-01

To determine the molecular species composition of lecithins of different nascent lipoproteins, high density lipoproteins (HDL), very low density lipoproteins (VLDL), and chylomicrons (CM) were isolated from the mesenteric lymph of rats. Lymph was collected at 0 degrees C with 5,5'-dithiobis-2-dinitrobenzoic acid added to inhibit lecithin-cholesterol acyl transferase. CM were separated by ultracentrifugation and HDL from VLDL by dextran SO4-MG+2 precipitation. Molecular species of lecithin were directly isolated by reverse phase high performance liquid chromatography. In fasted animals, the lecithin compositions of lymph HDL and VLDL were virtually the same and closely resembled the lecithin composition of intestinal mucosa. When bile lecithin was eliminated (by bile diversion), there was a marked change in lecithin composition of all lipoprotein and mucosal samples, which was most notable for a reduction in 16:0-species (which are predominant in bile) and a relative increase in the corresponding 18:0-species. Feeding unsaturated triglycerides (triolein, trilinolein, or a combination of triolein and trilinolein) also resulted in a change in HDL and VLDL lecithin composition. The effect was similar whether bile lecithin was present or eliminated and was notable for a reduction in 16:0-species, an increase in 18:0-species, and the emergence of large amounts of diunsaturated lecithins that corresponded to the fatty acid composition of the triglycerides fed (i.e., 18:1-18:1, 18:2-18:2, and 18:1-18:2 lecithins). When bile-diverted rats were infused via the duodenum with a mix of [14C]choline-labeled lecithins (isolated from the bile of other rats), the incorporation of infused lecithins into different lymph lipoproteins was distinctly different. Individual lecithins were incorporated to a variable extent into each lipoprotein. In fasted rats the specific activities of all major molecular species of lecithin were relatively greater in VLDL than HDL, indicating that HDL

High-density lipoprotein cholesterol subfractions and lecithin: cholesterol acyltransferase activity in collegiate soccer players.

PubMed

Imamura, H; Nagata, A; Oshikata, R; Yoshimura, Y; Miyamoto, N; Miyahara, K; Oda, K; Iide, K

2013-05-01

Many of the published data on the lipid profile of athletes is based on studies of endurance athletes. The data on soccer players are rare. The purpose of this study was to examine serum high-density lipoprotein cholesterol subfractions and lecithin:cholesterol acyltransferase activity in collegiate soccer players. 31 well-trained male collegiate soccer players were divided into 2 groups: 16 defenders and 15 offenders. They were compared with 16 sedentary controls. Dietary information was obtained with a food frequency questionnaire. The subjects were all non-smokers and were not taking any drug known to affect the lipid and lipoprotein metabolism. The offenders had significantly higher high-density lipoprotein cholesterol, high-density lipoprotein2 cholesterol, and apolipoprotein A-I than the defenders and controls, whereas the defenders had the significantly higher high-density lipoprotein2 cholesterol than the controls. Both groups of athletes had significantly higher lecithin:cholesterol acyltransferase activity than the controls. The results indicate that favorable lipid and lipoprotein profile could be obtained by vigorous soccer training. © Georg Thieme Verlag KG Stuttgart · New York.

Characterization of Two Metal Binding Lipoproteins as Vaccine Candidates for Enterococcal Infections

PubMed Central

Romero-Saavedra, Felipe; Laverde, Diana; Budin-Verneuil, Aurélie; Muller, Cécile; Bernay, Benoit; Benachour, Abdellah; Hartke, Axel; Huebner, Johannes

2015-01-01

Background Enterococcus faecium and faecalis are Gram-positive opportunistic pathogens that have become leading causes of nosocomial infections over the last decades. Especially multidrug resistant enterococci have become a challenging clinical problem worldwide. Therefore, new treatment options are needed and the identification of alternative targets for vaccine development has emerged as a feasible alternative to fight the infections caused by these pathogens. Results We extrapolate the transcriptomic data from a mice peritonitis infection model in E. faecalis to identify putative up-regulated surface proteins under infection conditions in E. faecium. After the bionformatic analyses two metal binding lipoproteins were identified to have a high homology (>72%) between the two species, the manganese ABC transporter substrate-binding lipoprotein (PsaAfm,) and the zinc ABC transporter substrate-binding lipoprotein (AdcAfm). These candidate lipoproteins were overexpressed in Escherichia coli and purified. The recombinant proteins were used to produce rabbit polyclonal antibodies that were able to induce specific opsonic antibodies that mediated killing of the homologous strain E. faecium E155 as well as clinical strains E. faecium E1162, Enterococcus faecalis 12030, type 2 and type 5. Mice were passively immunized with the antibodies raised against recombinant lipoproteins, showing significant reduction of colony counts in mice livers after the bacterial challenge and demonstrating the efficacy of these metal binding lipoproteins as promising vaccine candidates to treat infections caused by these enterococcal pathogens. Conclusion Overall, our results demonstrate that these two metal binding lipoproteins elicited specific, opsonic and protective antibodies, with an extensive cross-reactivity and serotype-independent coverage among these two important nocosomial pathogens. Pointing these two protein antigens as promising immunogens, that can be used as single

Advances in Testing Techniques for Digital Microfluidic Biochips

PubMed Central

Shukla, Vineeta; Hussin, Fawnizu Azmadi; Hamid, Nor Hisham; Zain Ali, Noohul Basheer

2017-01-01

With the advancement of digital microfluidics technology, applications such as on-chip DNA analysis, point of care diagnosis and automated drug discovery are common nowadays. The use of Digital Microfluidics Biochips (DMFBs) in disease assessment and recognition of target molecules had become popular during the past few years. The reliability of these DMFBs is crucial when they are used in various medical applications. Errors found in these biochips are mainly due to the defects developed during droplet manipulation, chip degradation and inaccuracies in the bio-assay experiments. The recently proposed Micro-electrode-dot Array (MEDA)-based DMFBs involve both fluidic and electronic domains in the micro-electrode cell. Thus, the testing techniques for these biochips should be revised in order to ensure proper functionality. This paper describes recent advances in the testing technologies for digital microfluidics biochips, which would serve as a useful platform for developing revised/new testing techniques for MEDA-based biochips. Therefore, the relevancy of these techniques with respect to testing of MEDA-based biochips is analyzed in order to exploit the full potential of these biochips. PMID:28749411

Advances in Testing Techniques for Digital Microfluidic Biochips.

PubMed

Shukla, Vineeta; Hussin, Fawnizu Azmadi; Hamid, Nor Hisham; Zain Ali, Noohul Basheer

2017-07-27

With the advancement of digital microfluidics technology, applications such as on-chip DNA analysis, point of care diagnosis and automated drug discovery are common nowadays. The use of Digital Microfluidics Biochips (DMFBs) in disease assessment and recognition of target molecules had become popular during the past few years. The reliability of these DMFBs is crucial when they are used in various medical applications. Errors found in these biochips are mainly due to the defects developed during droplet manipulation, chip degradation and inaccuracies in the bio-assay experiments. The recently proposed Micro-electrode-dot Array (MEDA)-based DMFBs involve both fluidic and electronic domains in the micro-electrode cell. Thus, the testing techniques for these biochips should be revised in order to ensure proper functionality. This paper describes recent advances in the testing technologies for digital microfluidics biochips, which would serve as a useful platform for developing revised/new testing techniques for MEDA-based biochips. Therefore, the relevancy of these techniques with respect to testing of MEDA-based biochips is analyzed in order to exploit the full potential of these biochips.

75 FR 75666 - Advanced Placement (AP) Test Fee Program

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-06

... DEPARTMENT OF EDUCATION [CFDA No. 84.330B] Advanced Placement (AP) Test Fee Program AGENCY: Office... AP Test Fee fiscal year (FY) 2011 competition. SUMMARY: On September 1, 2010, we published in the Federal Register (75 FR 53681) a notice inviting applications for the AP Test Fee FY 2011 competition...

X-Ray Calibration Facility/Advanced Video Guidance Sensor Test

NASA Technical Reports Server (NTRS)

Johnston, N. A. S.; Howard, R. T.; Watson, D. W.

2004-01-01

The advanced video guidance sensor was tested in the X-Ray Calibration facility at Marshall Space Flight Center to establish performance during vacuum. Two sensors were tested and a timeline for each are presented. The sensor and test facility are discussed briefly. A new test stand was also developed. A table establishing sensor bias and spot size growth for several ranges is detailed along with testing anomalies.

Low-Density Lipoproteins Oxidation and Endometriosis

PubMed Central

Polak, Grzegorz; Barczyński, Bartłomiej; Kwaśniewski, Wojciech; Bednarek, Wiesława; Wertel, Iwona; Derewianka-Polak, Magdalena; Kotarski, Jan

2013-01-01

The etiopathogenesis of endometriosis still remains unknown. Recent data provide new valuable information concerning the role of oxidative stress in the pathophysiology of the disease. It has been proved that levels of different lipid peroxidation end products are increased in both peritoneal fluid (PF) and serum of endometriotic patients. We assessed the concentration of oxidized low-density lipoproteins (oxLDL) in PF of 110 women with different stages of endometriosis and 119 women with serous (n = 78) or dermoid (n = 41) ovarian cysts, as the reference groups. PF oxLDL levels were evaluated by ELISA. We found that concentrations of oxLDL in PF of endometriotic women were significantly higher compared to women with serous but not dermoid ovarian cysts. Interestingly, by analyzing concentrations of oxLDL in women with different stages of the disease, it was noted that they are significantly higher only in the subgroup of patients with stage IV endometriosis as compared to women with ovarian serous cysts. In case of minimal, mild, and moderate disease, PF oxLDL levels were similar to those noted in reference groups. Our results indicate that disrupted oxidative status in the peritoneal cavity of women with endometriosis may play a role in the pathogenesis of advanced stages of the disease. PMID:23861560

Design and Status of RERTR Irradiation Tests in the Advanced Test Reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Daniel M. Wachs; Richard G. Ambrosek; Gray Chang

2006-10-01

Irradiation testing of U-Mo based fuels is the central component of the Reduced Enrichment for Research and Test Reactors (RERTR) program fuel qualification plan. Several RERTR tests have recently been completed or are planned for irradiation in the Advanced Test Reactor (ATR) located at the Idaho National Laboratory in Idaho Falls, ID. Four mini-plate experiments in various stages of completion are described in detail, including the irradiation test design, objectives, and irradiation conditions. Observations made during and after the in-reactor RERTR-7A experiment breach are summarized. The irradiation experiment design and planned irradiation conditions for full-size plate test are described. Progressmore » toward element testing will be reviewed.« less

Nuclear magnetic resonance lipoprotein abnormalities in newly-diagnosed type 2 diabetes and their association with preclinical carotid atherosclerosis.

PubMed

Amor, Antonio J; Catalan, Marta; Pérez, Antonio; Herreras, Zoe; Pinyol, Montserrat; Sala-Vila, Aleix; Cofán, Montserrat; Gilabert, Rosa; Ros, Emilio; Ortega, Emilio

2016-04-01

Atherogenic dyslipidemia is common in type 2 diabetes (T2DM) and predicts cardiovascular disease, but information on the association of its components with atherosclerosis is scarce. We aimed to assess differences in the lipoprotein profile in newly-diagnosed T2DM and matched control individuals and their associations with preclinical carotid atherosclerosis. In a case-control study, we evaluated lipoprotein profiles by nuclear magnetic resonance (NMR) spectroscopy and determined carotid intima-media thickness (IMT) and plaque presence (IMT ≥1.5 mm) by B-mode ultrasonography. We assessed 96 T2DM patients (median age 63 years, 44% women, 19% smokers, 54% hypertension, 38% dyslipidemia) and 90 non-diabetic controls matched for age, sex, and cardiovascular risk factors. In T2DM VLDL-particles (mainly large and enriched in cholesterol and triglycerides) were increased, and large HDL-particles (enriched in triglycerides and depleted in cholesterol) were reduced (p < 0.05; all comparisons). Regarding associations with preclinical atherosclerosis, VLDL triglyceride content (odds ratio [OR], 8.975; 95% confidence interval [CI], 2.330-34.576), total number of VLDL particles (OR, 2.713; CI, 1.601-4.598) and VLDL size (OR, 2.044; CI, 1.320-3.166), and the ratio cholesterol/triglycerides in HDL (OR, 0.638; CI, 0.477-0.852) were associated with plaque burden (≥3 plaques) independently of confounders, including conventional lipid levels. NMR-assessed advanced lipoprotein profile identifies lipid abnormalities associated with newly-diagnosed T2DM and preclinical atherosclerosis that are not captured by the traditional lipid profile. At this early stage of diabetes, NMR lipoproteins could be useful to identify candidates for a more comprehensive cardiovascular risk prevention strategy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Enhanced In-Pile Instrumentation at the Advanced Test Reactor

NASA Astrophysics Data System (ADS)

Rempe, Joy L.; Knudson, Darrell L.; Daw, Joshua E.; Unruh, Troy; Chase, Benjamin M.; Palmer, Joe; Condie, Keith G.; Davis, Kurt L.

2012-08-01

Many of the sensors deployed at materials and test reactors cannot withstand the high flux/high temperature test conditions often requested by users at U.S. test reactors, such as the Advanced Test Reactor (ATR) at the Idaho National Laboratory. To address this issue, an instrumentation development effort was initiated as part of the ATR National Scientific User Facility in 2007 to support the development and deployment of enhanced in-pile sensors. This paper provides an update on this effort. Specifically, this paper identifies the types of sensors currently available to support in-pile irradiations and those sensors currently available to ATR users. Accomplishments from new sensor technology deployment efforts are highlighted by describing new temperature and thermal conductivity sensors now available to ATR users. Efforts to deploy enhanced in-pile sensors for detecting elongation and real-time flux detectors are also reported, and recently-initiated research to evaluate the viability of advanced technologies to provide enhanced accuracy for measuring key parameters during irradiation testing are noted.

Lipoprotein(a): Biology and Clinical Importance

PubMed Central

McCormick, Sally P A

2004-01-01

Lipoprotein(a) [Lp(a)] is a unique lipoprotein that has emerged as an independent risk factor for developing vascular disease. Plasma Lp(a) levels above the common cut-off level of 300 mg/L place individuals at risk of developing heart disease particularly if combined with other lipid and thrombogenic risk factors. Studies in humans have shown Lp(a) levels to be hugely variable and under strict genetic control, largely by the apolipoprotein(a) [apo(a)] gene. In general, Lp(a) levels have proven difficult to manipulate, although some factors have been identified that can influence levels. Research has shown that Lp(a) has a high affinity for the arterial wall and displays many athero-thrombogenic properties. While a definite function for Lp(a) has not been identified, the last two decades of research have provided much information on the biology and clinical importance of Lp(a). PMID:18516206

Remnant cholesterol, low-density lipoprotein cholesterol, and blood pressure as mediators from obesity to ischemic heart disease.

PubMed

Varbo, Anette; Benn, Marianne; Smith, George Davey; Timpson, Nicholas J; Tybjaerg-Hansen, Anne; Nordestgaard, Børge G

2015-02-13

Obesity leads to increased ischemic heart disease (IHD) risk, but the risk is thought to be mediated through intermediate variables and may not be caused by increased weight per se. To test the hypothesis that the increased IHD risk because of obesity is mediated through lipoproteins, blood pressure, glucose, and C-reactive protein. Approximately 90 000 participants from Copenhagen were included in a Mendelian randomization design with mediation analyses. Associations were examined using conventional measurements of body mass index and intermediate variables and using genetic variants associated with these. During ≤22 years of follow-up 13 945 participants developed IHD. The increased IHD risk caused by obesity was partly mediated through elevated levels of nonfasting remnant cholesterol and low-density lipoprotein cholesterol, through elevated blood pressure, and possibly also through elevated nonfasting glucose levels; however, reduced high-density lipoprotein cholesterol and elevated C-reactive protein levels were not mediators in genetic analyses. The 3 intermediate variables that explained the highest excess risk of IHD from genetically determined obesity were low-density lipoprotein cholesterol with 8%, systolic blood pressure with 7%, and remnant cholesterol with 7% excess risk of IHD. Corresponding observational excess risks using conventional body mass index were 21%, 11%, and 20%, respectively. The increased IHD risk because of obesity was partly mediated through elevated levels of nonfasting remnant and low-density lipoprotein cholesterol and through elevated blood pressure. Our results suggest that there may be benefit to gain by reducing levels of these risk factors in obese individuals not able to achieve sustained weight loss. © 2014 American Heart Association, Inc.

Elevated Temperature Testing and Modeling of Advanced Toughened Ceramic Materials

NASA Technical Reports Server (NTRS)

Keith, Theo G.

2005-01-01

The purpose of this report is to provide a final report for the period of 12/1/03 through 11/30/04 for NASA Cooperative Agreement NCC3-776, entitled "Elevated Temperature Testing and Modeling of Advanced Toughened Ceramic Materials." During this final period, major efforts were focused on both the determination of mechanical properties of advanced ceramic materials and the development of mechanical test methodologies under several different programs of the NASA-Glenn. The important research activities made during this period are: 1. Mechanical properties evaluation of two gas-turbine grade silicon nitrides. 2) Mechanical testing for fuel-cell seal materials. 3) Mechanical properties evaluation of thermal barrier coatings and CFCCs and 4) Foreign object damage (FOD) testing.

Short-term cooling increases serum triglycerides and small high-density lipoprotein levels in humans.

PubMed

Hoeke, Geerte; Nahon, Kimberly J; Bakker, Leontine E H; Norkauer, Sabine S C; Dinnes, Donna L M; Kockx, Maaike; Lichtenstein, Laeticia; Drettwan, Diana; Reifel-Miller, Anne; Coskun, Tamer; Pagel, Philipp; Romijn, Fred P H T M; Cobbaert, Christa M; Jazet, Ingrid M; Martinez, Laurent O; Kritharides, Leonard; Berbée, Jimmy F P; Boon, Mariëtte R; Rensen, Patrick C N

Cold exposure and β3-adrenergic receptor agonism, which both activate brown adipose tissue, markedly influence lipoprotein metabolism by enhancing lipoprotein lipase-mediated catabolism of triglyceride-rich lipoproteins and increasing plasma high-density lipoprotein (HDL) levels and functionality in mice. However, the effect of short-term cooling on human lipid and lipoprotein metabolism remained largely elusive. The objective was to assess the effect of short-term cooling on the serum lipoprotein profile and HDL functionality in men. Body mass index-matched young, lean men were exposed to a personalized cooling protocol for 2 hours. Before and after cooling, serum samples were collected for analysis of lipids and lipoprotein composition by 1 H-nuclear magnetic resonance. Adenosine triphosphate-binding cassette A1 (ABCA1)-mediated cholesterol efflux capacity of HDL was measured using [ 3 H]cholesterol-loaded ABCA1-transfected Chinese hamster ovary cells. Short-term cooling increased serum levels of free fatty acids, triglycerides, and cholesterol. Cooling increased the concentration of large very low-density lipoprotein (VLDL) particles accompanied by increased mean size of VLDL particles. In addition, cooling enhanced the concentration of small LDL and small HDL particles as well as the cholesterol levels within these particles. The increase in small HDL was accompanied by increased ABCA1-dependent cholesterol efflux in vitro. Our data show that short-term cooling increases the concentration of large VLDL particles and increases the generation of small LDL and HDL particles. We interpret that cooling increases VLDL production and turnover, which results in formation of surface remnants that form small HDL particles that attract cellular cholesterol. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

High density lipoprotein cholesterol is associated with serum cortisol in older people.

PubMed

Varma, V K; Rushing, J T; Ettinger, W H

1995-12-01

To determine the associations between serum cortisol and HDL cholesterol, other lipoprotein lipids and cardiovascular risk factors, carotid atherosclerosis, and clinical heart disease in older people. A cross-sectional, observational, ancillary study of the Cardiovascular Health Study (CHS). A total of 245 community-dwelling people, 65 to 89 years old, were recruited consecutively for a 2-month period from the CHS cohort in Forsyth County, North Carolina. Cortisol was measured by radioimmunoassay in serum collected between 7:00 and 10:00 AM after an overnight fast. Cortisol levels were correlated with lipoprotein lipids, insulin, glucose, body mass index, waist-hip ratio, prevalent coronary heart disease, hypertension, diabetes, and carotid atherosclerosis by B-mode ultrasound. Serum cortisol was correlated negatively (r = -.24) with body mass index and waist-hip ratio (r = -.16) but was not related significantly to fasting insulin or glucose. Cortisol was not associated significantly with triglyceride and low density lipoprotein cholesterol but showed a positive correlation (r = .21) with high density lipoprotein cholesterol. The relationship between cortisol and high density lipoprotein cholesterol persisted after adjustment for gender, body mass index, waist-hip ratio, cigarette and alcohol use, triglyceride level, and diabetes. There was a trend toward a negative correlation between cortisol and measures of carotid atherosclerosis, but no significant relationship was indicated between cortisol and prevalent coronary heart disease, hypertension, or diabetes. Endogenous glucocorticoid levels correlated with HDL cholesterol levels and may play a role in the physiologic regulation of high density lipoprotein levels in older people.

General Aviation Flight Test of Advanced Operations Enabled by Synthetic Vision

NASA Technical Reports Server (NTRS)

Glaab, Louis J.; Hughhes, Monica F.; Parrish, Russell V.; Takallu, Mohammad A.

2014-01-01

A flight test was performed to compare the use of three advanced primary flight and navigation display concepts to a baseline, round-dial concept to assess the potential for advanced operations. The displays were evaluated during visual and instrument approach procedures including an advanced instrument approach resembling a visual airport traffic pattern. Nineteen pilots from three pilot groups, reflecting the diverse piloting skills of the General Aviation pilot population, served as evaluation subjects. The experiment had two thrusts: 1) an examination of the capabilities of low-time (i.e., <400 hours), non-instrument-rated pilots to perform nominal instrument approaches, and 2) an exploration of potential advanced Visual Meteorological Conditions (VMC)-like approaches in Instrument Meteorological Conditions (IMC). Within this context, advanced display concepts are considered to include integrated navigation and primary flight displays with either aircraft attitude flight directors or Highway In The Sky (HITS) guidance with and without a synthetic depiction of the external visuals (i.e., synthetic vision). Relative to the first thrust, the results indicate that using an advanced display concept, as tested herein, low-time, non-instrument-rated pilots can exhibit flight-technical performance, subjective workload and situation awareness ratings as good as or better than high-time Instrument Flight Rules (IFR)-rated pilots using Baseline Round Dials for a nominal IMC approach. For the second thrust, the results indicate advanced VMC-like approaches are feasible in IMC, for all pilot groups tested for only the Synthetic Vision System (SVS) advanced display concept.

[Residual risk: The roles of triglycerides and high density lipoproteins].

PubMed

Grammer, Tanja; Kleber, Marcus; Silbernagel, Günther; Scharnagl, Hubert; März, Winfried

2016-06-01

In clinical trials, the reduction of LDL-cholesterol (LDL-C) with statins reduces the incidence rate of cardiovascular events by approximately one third. This means, that a sizeable "residual risk" remains. Besides high lipoprotein (a), disorders in the metabolism of triglyceride-rich lipoproteins and high density liproteins have been implicated as effectors of the residual risk. Both lipoprotein parameters correlate inversely with each other. Therefore, the etiological contributions of triglycerides and / or of HDL for developing cardiovascular disease can hardly be estimated from either observational studies or from intervention studies. The largely disappointing results of intervention studies with inhibitors of the cholesteryl ester transfer protein and in particular the available set of genetically-epidemiological studies suggest that in the last decade, the importance of HDL cholesterol has been overvalued, while the importance of triglycerides has been underestimated. High triglycerides not always atherogenic, but only if they are associated with the accumulation relatively cholesterol-enriched, incompletely catabolized remnants of chylomicrons and very low density lipoproteins (familial type III hyperlipidemia, metabolic syndrome, diabetes mellitus). The normalization of the concentration of triglycerides and remnants by inhibiting the expression of apolipoprotein C3 is hence a new, promising therapeutic target. © Georg Thieme Verlag KG Stuttgart · New York.

Regulation of plasma cholesterol by hepatic low-density lipoprotein receptors.

PubMed

Kovanen, P T

1987-02-01

The endogenous lipoprotein system (very low-density lipoprotein [VLDL], intermediate-density lipoprotein [IDL], low-density lipoprotein [LDL] cascade) holds the key to understanding the mechanisms by which hormones, diet, and drugs interact to regulate the plasma cholesterol level. Crucial components of this system are hepatic LDL receptors that mediate the uptake and degradation of plasma LDL. With experimental animals, it has been possible to demonstrate that hepatic LDL receptors are sensitive to hormonal, dietary, and pharmacologic manipulation. The decrease in number of hepatic LDL receptors in hypothyroidism or after cholesterol feeding leads to elevation of plasma LDL cholesterol levels. Conversely, the increase in number of hepatic LDL receptors results in lowering of plasma LDL cholesterol levels. This can be observed in hyperthyroidism, during administration of pharmacologic doses of 17 alpha-ethinyl estradiol, or during treatment with cholesterol-lowering drugs such as the bile acid-binding resins and cholesterol-synthesis inhibitors. Since cholesterol excretion from the body occurs via the liver, the increased efficiency of disposal of plasma cholesterol by increasing hepatic LDL receptors will ultimately lead to depletion of excessive body cholesterol. Pharmacologic regulation of hepatic LDL receptors should be a valuable tool in the prevention and therapy of atherosclerosis.

Lipid and lipoprotein abnormalities in acute lymphoblastic leukemia survivors.

PubMed

Morel, Sophia; Leahy, Jade; Fournier, Maryse; Lamarche, Benoit; Garofalo, Carole; Grimard, Guy; Poulain, Floriane; Delvin, Edgard; Laverdière, Caroline; Krajinovic, Maja; Drouin, Simon; Sinnett, Daniel; Marcil, Valérie; Levy, Emile

2017-05-01

Survivors of acute lymphoblastic leukemia (ALL), the most common cancer in children, are at increased risk of developing late cardiometabolic conditions. However, the mechanisms are not fully understood. This study aimed to characterize the plasma lipid profile, Apo distribution, and lipoprotein composition of 80 childhood ALL survivors compared with 22 healthy controls. Our results show that, despite their young age, 50% of the ALL survivors displayed dyslipidemia, characterized by increased plasma triglyceride (TG) and LDL-cholesterol, as well as decreased HDL-cholesterol. ALL survivors exhibited lower plasma Apo A-I and higher Apo B-100 and C-II levels, along with elevated Apo C-II/C-III and B-100/A-I ratios. VLDL fractions of dyslipidemic ALL survivors contained more TG, free cholesterol, and phospholipid moieties, but less protein. Differences in Apo content were found between ALL survivors and controls for all lipoprotein fractions except HDL 3 HDL 2 , especially, showed reduced Apo A-I and raised Apo A-II, leading to a depressed Apo A-I/A-II ratio. Analysis of VLDL-Apo Cs disclosed a trend for higher Apo C-III 1 content in dyslipidemic ALL survivors. In conclusion, this thorough investigation demonstrates a high prevalence of dyslipidemia in ALL survivors, while highlighting significant abnormalities in their plasma lipid profile and lipoprotein composition. Special attention must, therefore, be paid to these subjects given the atherosclerotic potency of lipid and lipoprotein disorders. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Lipoprotein lipase-dependent binding and uptake of low density lipoproteins by THP-1 monocytes and macrophages: possible involvement of lipid rafts.

PubMed

Makoveichuk, Elena; Castel, Susanna; Vilaró, Senen; Olivecrona, Gunilla

2004-11-08

Lipoprotein lipase (LPL) is produced by cells in the artery wall and can mediate binding of lipoproteins to cell surface heparan sulfate proteoglycans (HSPG), resulting in endocytosis (the bridging function). Active, dimeric LPL may dissociate to inactive monomers, the main form found in plasma. We have studied binding/internalization of human low density lipoprotein (LDL), mediated by bovine LPL, using THP-1 monocytes and macrophages. Uptake of (125)I-LDL was similar in monocytes and macrophages and was not affected by the LDL-receptor family antagonist receptor-associated protein (RAP) or by the phagocytosis inhibitor cytochalasin D. In contrast, uptake depended on HSPG and on membrane cholesterol. Incubation in the presence of dexamethasone increased the endogenous production of LPL by the cells and also increased LPL-mediated binding of LDL to the cell surfaces. Monomeric LPL was bound to the cells mostly in a heparin-resistant fashion. We conclude that the uptake of LDL mediated by LPL dimers is receptor-independent and involves cholesterol-enriched membrane areas (lipid rafts). Dimeric and monomeric LPL differ in their ability to mediate binding/uptake of LDL, probably due to different mechanisms for binding/internalization.

78 FR 19691 - Applications for New Awards; Advanced Placement (AP) Test Fee Program

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-02

... DEPARTMENT OF EDUCATION Applications for New Awards; Advanced Placement (AP) Test Fee Program... Information Advanced Placement Test Fee Program. Notice inviting applications for new awards for fiscal year... Program: The AP Test Fee program awards grants to eligible State educational agencies (SEAs) to enable...

77 FR 8848 - Application for New Awards; Advanced Placement (AP) Test Fee Program

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-15

... DEPARTMENT OF EDUCATION Application for New Awards; Advanced Placement (AP) Test Fee Program... Information: Advanced Placement Test Fee Program. Notice inviting applications for new awards for fiscal year... Description Purpose of Program: The AP Test Fee program awards grants to eligible State educational agencies...

Interfering lipoproteins in magnetic field-assisted agglutination of superparamagnetic particles immunoassay.

PubMed

Cauet, Gilles; Daynès, Aurélien; Temurok, Nevzat

2016-04-01

The technology of magnetic field-assisted immuno-agglutination of superparamagnetic particles allows sensitive detection of biomarkers in whole blood. However, we observed non-specific agglutination (NSA), due to interfering plasma proteins, that negatively affects C-reactive protein immunoassay. The objective of the study was to identify the plasma proteins involved and to eliminate these interferences. Plasma was fractionated by size exclusion HPLC and each fraction was tested for non-specific agglutination. In addition, plasma proteins bound to magnetic particles were analyzed by SDS-gel electrophoresis and identified by mass spectrometry. We found that NSA was due to the binding of some lipoproteins to the particles. NSA was observed in the presence of purified LDL and VLDL but not HDL. NSA was mediated by the binding of ApoB100 to magnetic particles through its heparin binding sites. These interferences could be eliminated by addition of heparin or other polyanions like dextran sulfate to the assay buffer. NSA results from the binding of some plasma lipoproteins to magnetic particles. The use of a polyanion to eliminate these interferences allows the formulation of a stable reagent.

SVM prediction of ligand-binding sites in bacterial lipoproteins employing shape and physio-chemical descriptors.

PubMed

Kadam, Kiran; Prabhakar, Prashant; Jayaraman, V K

2012-11-01

Bacterial lipoproteins play critical roles in various physiological processes including the maintenance of pathogenicity and numbers of them are being considered as potential candidates for generating novel vaccines. In this work, we put forth an algorithm to identify and predict ligand-binding sites in bacterial lipoproteins. The method uses three types of pocket descriptors, namely fpocket descriptors, 3D Zernike descriptors and shell descriptors, and combines them with Support Vector Machine (SVM) method for the classification. The three types of descriptors represent shape-based properties of the pocket as well as its local physio-chemical features. All three types of descriptors, along with their hybrid combinations are evaluated with SVM and to improve classification performance, WEKA-InfoGain feature selection is applied. Results obtained in the study show that the classifier successfully differentiates between ligand-binding and non-binding pockets. For the combination of three types of descriptors, 10 fold cross-validation accuracy of 86.83% is obtained for training while the selected model achieved test Matthews Correlation Coefficient (MCC) of 0.534. Individually or in combination with new and existing methods, our model can be a very useful tool for the prediction of potential ligand-binding sites in bacterial lipoproteins.

Next Generation Advanced Video Guidance Sensor Development and Test

NASA Technical Reports Server (NTRS)

Howard, Richard T.; Bryan, Thomas C.; Lee, Jimmy; Robertson, Bryan

2009-01-01

The Advanced Video Guidance Sensor (AVGS) was the primary docking sensor for the Orbital Express mission. The sensor performed extremely well during the mission, and the technology has been proven on orbit in other flights too. Parts obsolescence issues prevented the construction of more AVGS units, so the next generation of sensor was designed with current parts and updated to support future programs. The Next Generation Advanced Video Guidance Sensor (NGAVGS) has been tested as a breadboard, two different brassboard units, and a prototype. The testing revealed further improvements that could be made and demonstrated capability beyond that ever demonstrated by the sensor on orbit. This paper presents some of the sensor history, parts obsolescence issues, radiation concerns, and software improvements to the NGAVGS. In addition, some of the testing and test results are presented. The NGAVGS has shown that it will meet the general requirements for any space proximity operations or docking need.

Assembly of high-density lipoprotein.

PubMed

Yokoyama, Shinji

2006-01-01

Mammalian somatic cells do not catabolize cholesterol and need to export it for its homeostasis at the levels of cells and whole bodies. This reaction may reduce intracellularly accumulated cholesterol in excess and would contribute to prevention or regression of the initial stage of atherosclerosis. High-density lipoprotein (HDL) is thought to play a main role in this reaction, and 2 independent mechanisms are proposed for this reaction. First, cholesterol is exchanged in a nonspecific physicochemical manner between cell surface and extracellular lipoproteins, and cholesterol esterification on HDL provides a driving force for net removal of cell cholesterol. Second, apolipoproteins directly interact with cells and generate HDL by removing cellular phospholipid and cholesterol. This reaction is a major source of plasma HDL and is mediated by a membrane protein, ABCA1. Lipid-free or lipid-poor helical apolipoproteins primarily recruit cellular phospholipid to assemble HDL particles, and cholesterol enrichment in these particles is regulated independently. ABCA1 is a rate-limiting factor of the HDL assembly and is regulated by transcriptional factors and posttranscriptional factors. Posttranscriptional regulation of ABCA1 includes modulation of its calpain-mediated degradation.

Iodination of Escherichia coli with chloramine T: selective labeling of the outer membrane lipoprotein.

PubMed Central

Munford, R S; Gotschlich, E C

1977-01-01

Iodination of Escherichia coli cells with chloramine T preferentially labels the free and murein-bound forms of the outer membrane lipoprotein. Iodination for 15 s at 15 degrees C labels the two forms of the lipoprotein almost exclusively, whereas iodination for 60 s at 25 degrees C also labels the other major outer membrane proteins. Chloramine T iodination is a rapid, simple technique for labeling the outer membrane lipoprotein. PMID:400793

Lipoprotein marker for hypertriglyceridemia

DOEpatents

Cubicciotti, Roger S.; Karu, Alexander E.; Krauss, Ronald M.

1986-01-01

Methods and compositions are provided for the detection of a particular low density lipoprotein which has been found to be a marker for patients suffering from type IV hypertriglyceridemia. A monoclonal antibody capable of specifically binding to a characteristic epitopic site on this LDL subspecies can be utilized in a wide variety of immunoassays. Hybridoma cell line SPL.IVA5A1 was deposited at the American Type Culture Collection on Mar. 29, 1984, and granted accession no. HB 8535.

LDL Particle Testing

MedlinePlus

... Mutation Mycophenolic Acid Mycoplasma Myoglobin Nicotine and Cotinine Non-High Density Lipoprotein Cholesterol Opioid Testing Osmolality Ova ... the group concluded that both tests were nearly equivalent in their ability to assess CVD risk and ...

Recent advances in testing of microsphere drug delivery systems.

PubMed

Andhariya, Janki V; Burgess, Diane J

2016-01-01

This review discusses advances in the field of microsphere testing. In vitro release-testing methods such as sample and separate, dialysis membrane sacs and USP apparatus IV have been used for microspheres. Based on comparisons of these methods, USP apparatus IV is currently the method of choice. Accelerated in vitro release tests have been developed to shorten the testing time for quality control purposes. In vitro-in vivo correlations using real-time and accelerated release data have been developed, to minimize the need to conduct in vivo performance evaluation. Storage stability studies have been conducted to investigate the influence of various environmental factors on microsphere quality throughout the product shelf life. New tests such as the floating test and the in vitro wash-off test have been developed along with advancement in characterization techniques for other physico-chemical parameters such as particle size, drug content, and thermal properties. Although significant developments have been made in microsphere release testing, there is still a lack of guidance in this area. Microsphere storage stability studies should be extended to include microspheres containing large molecules. An agreement needs to be reached on the use of particle sizing techniques to avoid inconsistent data. An approach needs to be developed to determine total moisture content of microspheres.

Research priorities and history of advanced composite compression testing

NASA Technical Reports Server (NTRS)

Baumann, K. J.

1981-01-01

Priorities for standard compression testing research in advanced laminated fibrous composite materials are presented along with a state of the art survey (completed in 1979) including history and commentary on industrial test methods. Historically apparent research priorities and consequent (lack of) progress are supporting evidence for newly derived priorities.

The relationship among brain natriuretic peptide (BNP), cholesterol and lipoprotein.

PubMed

Takeuchi, Hidekazu; Sata, Masataka

2012-01-01

To study the relationship among brain natriuretic peptide (BNP), cholesterol and lipoprotein. A retrospective, cross-sectional study. Tokushima University Hospital area. A retrospective study of 46 patients (nine inpatients and 37 outpatients) with angina pectoris or arrhythmias who were seen at Tokushima University Hospital Cardiovascular Division and had measurements of their BNP, fatty acid and lipid profile. The average age of patients was 57±17 years, and 39% were male subjects. BNP, dihomo-γ-linolenic acid, arachidonic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), apolipoproteinA1, apolipoprotein A2 (ApoA2), apolipoprotein B (ApoB), apolipoprotein C2, apolipoprotein C3, apolipoprotein E, total cholesterol (TC), triglyceride, high density lipoprotein cholesterol and low density lipoprotein cholesterol. The baseline characteristics of the patients were shown in table 1 and the data of lipoprotein were shown in table 2. Table 3 shows the relationship among BNP, cholesterol and lipoprotein. The authors found significant negative correlation between serum levels of BNP and ApoA2 (figure 1; r=-0.458, p=0.001), serum levels of BNP and ApoB (figure 2; r=-0.328, p=0.026) and serum levels of BNP and TC (figure 3; r=-0.383, p=0.010). There is a possibility that dietary EPA and DHA may modulate cardiac mitochondrial and autonomic nervous system dysfunction via fatty-acids-PPARs-PTEN-PI3K/Akt-SREBPs system and affect serum BNP levels indirectly. BNP had significant negative correlation with ApoA2, ApoB and TC. The findings suggest that increasing serum levels of ApoA2, ApoB and TC may have an effect on improving heart function. But the mechanism is presently unclear.

The relationship among brain natriuretic peptide (BNP), cholesterol and lipoprotein

PubMed Central

Takeuchi, Hidekazu; Sata, Masataka

2012-01-01

Objective To study the relationship among brain natriuretic peptide (BNP), cholesterol and lipoprotein. Design A retrospective, cross-sectional study. Setting Tokushima University Hospital area. Patients A retrospective study of 46 patients (nine inpatients and 37 outpatients) with angina pectoris or arrhythmias who were seen at Tokushima University Hospital Cardiovascular Division and had measurements of their BNP, fatty acid and lipid profile. The average age of patients was 57±17 years, and 39% were male subjects. Main outcome measures BNP, dihomo-γ-linolenic acid, arachidonic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), apolipoproteinA1, apolipoprotein A2 (ApoA2), apolipoprotein B (ApoB), apolipoprotein C2, apolipoprotein C3, apolipoprotein E, total cholesterol (TC), triglyceride, high density lipoprotein cholesterol and low density lipoprotein cholesterol. Results The baseline characteristics of the patients were shown in table 1 and the data of lipoprotein were shown in table 2. Table 3 shows the relationship among BNP, cholesterol and lipoprotein. The authors found significant negative correlation between serum levels of BNP and ApoA2 (figure 1; r=−0.458, p=0.001), serum levels of BNP and ApoB (figure 2; r=−0.328, p=0.026) and serum levels of BNP and TC (figure 3; r=-0.383, p=0.010). There is a possibility that dietary EPA and DHA may modulate cardiac mitochondrial and autonomic nervous system dysfunction via fatty-acids-PPARs-PTEN-PI3K/Akt-SREBPs system and affect serum BNP levels indirectly. Conclusion BNP had significant negative correlation with ApoA2, ApoB and TC. The findings suggest that increasing serum levels of ApoA2, ApoB and TC may have an effect on improving heart function. But the mechanism is presently unclear. PMID:27326018

Effects of an evidence-based computerized virtual clinician on low-density lipoprotein and non-high-density lipoprotein cholesterol in adults without cardiovascular disease: The Interactive Cholesterol Advisory Tool.

PubMed

Block, Robert C; Abdolahi, Amir; Niemiec, Christopher P; Rigby, C Scott; Williams, Geoffrey C

2016-12-01

There is a lack of research on the use of electronic tools that guide patients toward reducing their cardiovascular disease risk. We conducted a 9-month clinical trial in which participants who were at low (n = 100) and moderate (n = 23) cardiovascular disease risk-based on the National Cholesterol Education Program III's 10-year risk estimator-were randomized to usual care or to usual care plus use of an Interactive Cholesterol Advisory Tool during the first 8 weeks of the study. In the moderate-risk category, an interaction between treatment condition and Framingham risk estimate on low-density lipoprotein and non-high-density lipoprotein cholesterol was observed, such that participants in the virtual clinician treatment condition had a larger reduction in low-density lipoprotein and non-high-density lipoprotein cholesterol as their Framingham risk estimate increased. Perceptions of the Interactive Cholesterol Advisory Tool were positive. Evidence-based information about cardiovascular disease risk and its management was accessible to participants without major technical challenges. © The Author(s) 2015.

[Postprandial lipemia as an atherosclerotic risk factor and fat tolerance test].

PubMed

Ishikawa, T

1999-12-01

Most of our lives are spent in the postprandial state, during which vessel walls are exposed to triglyceride rich lipoproteins-namely, chylomicron and chylomicron remnants. Recent studies showed that coronary artery disease patients even with normal fasting lipid levels had higher concentrations of postprandial lipoproteins than patients without coronary artery disease. Postprandial lipoprotein responses are influenced by various factors such as the postabsorptive concentrations of plasma triglycerides, lipoprotein lipase activity, polymorphisms of apolipoprotein B and apolipoprotein E, dietary fatty acid contents. Oral fat tolerance test is performed to see the postprandial lipoprotein responses. Triglycerides, apolipoprotein B, retinyl-palmitate and remnant like particles in plasma and subfractionated triglyceride rich lipoproteins are measured.

Advanced Crew Escape Suits (ACES): Particle Impact Test

NASA Technical Reports Server (NTRS)

Rosales, Keisa R.; Stoltzfus, Joel M.

2009-01-01

NASA Johnson Space Center (JSC) requested NASA JSC White Sands Test Facility to assist in determining the effects of impaired anodization on aluminum parts in advanced crew escape suits (ACES). Initial investigation indicated poor anodization could lead to an increased risk of particle impact ignition, and a lack of data was prevalent for particle impact of bare (unanodized) aluminum; therefore, particle impact tests were performed. A total of 179 subsonic and 60 supersonic tests were performed with no ignition of the aluminum targets. Based on the resulting test data, WSTF found no increased particle impact hazard was present in the ACES equipment.

Advanced recovery systems wind tunnel test report

NASA Technical Reports Server (NTRS)

Geiger, R. H.; Wailes, W. K.

1990-01-01

Pioneer Aerospace Corporation (PAC) conducted parafoil wind tunnel testing in the NASA-Ames 80 by 120 test sections of the National Full-Scale Aerodynamic Complex, Moffett Field, CA. The investigation was conducted to determine the aerodynamic characteristics of two scale ram air wings in support of air drop testing and full scale development of Advanced Recovery Systems for the Next Generation Space Transportation System. Two models were tested during this investigation. Both the primary test article, a 1/9 geometric scale model with wing area of 1200 square feet and secondary test article, a 1/36 geometric scale model with wing area of 300 square feet, had an aspect ratio of 3. The test results show that both models were statically stable about a model reference point at angles of attack from 2 to 10 degrees. The maximum lift-drag ratio varied between 2.9 and 2.4 for increasing wing loading.

Enraf Series 854 advanced technology gauge (ATG) acceptance test procedure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huber, J.H.

1996-09-11

This Acceptance Test Procedure was written to test the Enraf Series 854 Advanced Technology Gauge (ATG) prior to installation in the Tank Farms. The procedure sets various parameters and verifies that the gauge is functional.

Thermal transitions in the low-density lipoprotein and lipids of the egg yolk of hens.

PubMed

Smith, M B; Back, J F

1975-05-22

1. Differential sanning calorimetry and light-scattering have been used to investigate temperature-dependent transitions in low-density lipoprotein and in lipids from hens' egg yolk. Yolks of different fatty acid composition were obtained by varying the dietary lipid and by adding methyl sterculate to the hen's diet. 2. Lipoprotein solutions in 50 percent glycerol/water gave characteristic melting curves between -25 degrees C and 50 degrees C, and on cooling showed increases in light-scattering between 10 degrees C and -20 degrees C. The temperatures at which major changes occurred depended on the proportions of saturated and unsaturated fatty acids. 3. The thermal transitions in the intact lipoprotein in glycerol solution were reversible, but with marked hysteresis. Lipid extracted from the lipoprotein did not show temperature hystersis but the transition heats and melting curves similar to those of the intact lipoprotein. The results support the hypothesis of a "lipid-core" structure for low-density lipoproteins. 4. Scanning calorimetry of egg-yolk lecithins indicated a strong dependence of transition temperature on water content in the rane 3 percent-20 percent water. A rise in the mid-temperature of the liquid-crystalline to gel transition as the water content is lowered on freezing may be the primary event in the irreversible gelation of egg yolk and aggregation of lipoprotein.

The plasma parameter log (TG/HDL-C) as an atherogenic index: correlation with lipoprotein particle size and esterification rate in apoB-lipoprotein-depleted plasma (FER(HDL)).

PubMed

Dobiásová, M; Frohlich, J

2001-10-01

To evaluate if logarithm of the ratio of plasma concentration of triglycerides to HDL-cholesterol (Log[TG/HDL-C]) correlates with cholesterol esterification rates in apoB-lipoprotein-depleted plasma (FER(HDL)) and lipoprotein particle size. We analyzed previous data dealing with the parameters related to the FER(HDL) (an indirect measure of lipoprotein particle size). In a total of 1433 subjects from 35 cohorts with various risk of atherosclerosis (cord plasma, children, healthy men and women, pre- and postmenopausal women, patients with hypertension, type 2 diabetes, dyslipidemia and patients with positive or negative angiography findings) were studied. The analysis revealed a strong positive correlation (r = 0.803) between FER(HDL) and Log(TG/HDL-C). This parameter, which we propose to call "atherogenic index of plasma" (AIP) directly related to the risk of atherosclerosis in the above cohorts. We also confirmed in a cohort of 35 normal subjects a significant inverse correlation of LDL size with FER(HDL) (r = -0.818) and AIP (r = -0.776). Values of AIP correspond closely to those of FER(HDL) and to lipoprotein particle size and thus could be used as a marker of plasma atherogenicity.

Apolipoprotein(a) isoform size, lipoprotein(a) concentration, and coronary artery disease: a mendelian randomisation analysis.

PubMed

Saleheen, Danish; Haycock, Philip C; Zhao, Wei; Rasheed, Asif; Taleb, Adam; Imran, Atif; Abbas, Shahid; Majeed, Faisal; Akhtar, Saba; Qamar, Nadeem; Zaman, Khan Shah; Yaqoob, Zia; Saghir, Tahir; Rizvi, Syed Nadeem Hasan; Memon, Anis; Mallick, Nadeem Hayyat; Ishaq, Mohammad; Rasheed, Syed Zahed; Memon, Fazal-Ur-Rehman; Mahmood, Khalid; Ahmed, Naveeduddin; Frossard, Philippe; Tsimikas, Sotirios; Witztum, Joseph L; Marcovina, Santica; Sandhu, Manjinder; Rader, Daniel J; Danesh, John

2017-07-01

The lipoprotein(a) pathway is a causal factor in coronary heart disease. We used a genetic approach to distinguish the relevance of two distinct components of this pathway, apolipoprotein(a) isoform size and circulating lipoprotein(a) concentration, to coronary heart disease. In this mendelian randomisation study, we measured lipoprotein(a) concentration and determined apolipoprotein(a) isoform size with a genetic method (kringle IV type 2 [KIV2] repeats in the LPA gene) and a serum-based electrophoretic assay in patients and controls (frequency matched for age and sex) from the Pakistan Risk of Myocardial Infarction Study (PROMIS). We calculated odds ratios (ORs) for myocardial infarction per 1-SD difference in either LPA KIV2 repeats or lipoprotein(a) concentration. In a genome-wide analysis of up to 17 503 participants in PROMIS, we identified genetic variants associated with either apolipoprotein(a) isoform size or lipoprotein(a) concentration. Using a mendelian randomisation study design and genetic data on 60 801 patients with coronary heart disease and 123 504 controls from the CARDIoGRAMplusC4D consortium, we calculated ORs for myocardial infarction with variants that produced similar differences in either apolipoprotein(a) isoform size in serum or lipoprotein(a) concentration. Finally, we compared phenotypic versus genotypic ORs to estimate whether apolipoprotein(a) isoform size, lipoprotein(a) concentration, or both were causally associated with coronary heart disease. The PROMIS cohort included 9015 patients with acute myocardial infarction and 8629 matched controls. In participants for whom KIV2 repeat and lipoprotein(a) data were available, the OR for myocardial infarction was 0·93 (95% CI 0·90-0·97; p<0·0001) per 1-SD increment in LPA KIV2 repeats after adjustment for lipoprotein(a) concentration and conventional lipid concentrations. The OR for myocardial infarction was 1·10 (1·05-1·14; p<0·0001) per 1-SD increment in lipoprotein

Low-density lipoprotein reconstituted by pyropheophorbide cholesteryl oleate as target-specific photosensitizer.

PubMed

Zheng, Gang; Li, Hui; Zhang, Min; Lund-Katz, Sissel; Chance, Britton; Glickson, Jerry D

2002-01-01

To target tumors overexpressing low-density lipoprotein receptors (LDLr), a pyropheophorbide cholesterol oleate conjugate was synthesized and successfully reconstituted into the low-density lipoprotein (LDL) lipid core. Laser scanning confocal microscopy studies demonstrated that this photosensitizer-reconstituted LDL can be internalized via LDLr by human hepatoblastoma G(2) (HepG(2)) tumor cells.

Fitness, Heart Disease, and High-Density Lipoproteins: A Look at the Relationships.

ERIC Educational Resources Information Center

McCunney, Robert J.

1987-01-01

The role of fitness in preventing coronary heart disease is explored. Research on high-density lipoprotein, which has been found to be one of the most critical determinants of risk, is reviewed. The relationship between fitness, high-density lipoprotein, and coronary heart disease is assessed, and clinical implications are spelled out. (MT)

Structural Dynamics Testing of Advanced Stirling Convertor Components

NASA Technical Reports Server (NTRS)

Oriti, Salvatore M.; Williams, Zachary Douglas

2013-01-01

NASA Glenn Research Center has been supporting the development of Stirling energy conversion for use in space. Lockheed Martin has been contracted by the Department of Energy to design and fabricate flight-unit Advanced Stirling Radioisotope Generators, which utilize Sunpower, Inc., free-piston Advanced Stirling Convertors. The engineering unit generator has demonstrated conversion efficiency in excess of 20 percent, offering a significant improvement over existing radioisotope-fueled power systems. NASA Glenn has been supporting the development of this generator by developing the convertors through a technology development contract with Sunpower, and conducting research and experiments in a multitude of areas, such as high-temperature material properties, organics testing, and convertor-level extended operation. Since the generator must undergo launch, several launch simulation tests have also been performed at the convertor level. The standard test sequence for launch vibration exposure has consisted of workmanship and flight acceptance levels. Together, these exposures simulate what a flight convertor will experience. Recently, two supplementary tests were added to the launch vibration simulation activity. First was a vibration durability test of the convertor, intended to quantify the effect of vibration levels up to qualification level in both the lateral and axial directions. Second was qualification-level vibration of several heater heads with small oxide inclusions in the material. The goal of this test was to ascertain the effect of the inclusions on launch survivability to determine if the heater heads were suitable for flight.

Determining the risk of cardiovascular disease using ion mobility of lipoproteins

DOEpatents

Benner, W. Henry; Krauss, Ronald M.; Blanche, Patricia J.

2010-05-11

A medical diagnostic method and instrumentation system for analyzing noncovalently bonded agglomerated biological particles is described. The method and system comprises: a method of preparation for the biological particles; an electrospray generator; an alpha particle radiation source; a differential mobility analyzer; a particle counter; and data acquisition and analysis means. The medical device is useful for the assessment of human diseases, such as cardiac disease risk and hyperlipidemia, by rapid quantitative analysis of lipoprotein fraction densities. Initially, purification procedures are described to reduce an initial blood sample to an analytical input to the instrument. The measured sizes from the analytical sample are correlated with densities, resulting in a spectrum of lipoprotein densities. The lipoprotein density distribution can then be used to characterize cardiac and other lipid-related health risks.

Advance Noise Control Fan II: Test Rig Fan Risk Management Study

NASA Technical Reports Server (NTRS)

Lucero, John

2013-01-01

Since 1995 the Advanced Noise Control Fan (ANCF) has significantly contributed to the advancement of the understanding of the physics of fan tonal noise generation. The 9'x15' WT has successfully tested multiple high speed fan designs over the last several decades. This advanced several tone noise reduction concepts to higher TRL and the validation of fan tone noise prediction codes.

Relationship between Icodextrin use and decreased level of small low-density lipoprotein cholesterol fractioned by high-performance gel permeation chromatography

PubMed Central

2013-01-01

Background Because of the absorption of glucose in peritoneal dialysis (PD) solution, PD patients show an atherogenic lipid profile, which is predictive of poor survival in PD patients. Lipoprotein subclasses consist of a continuous spectrum of particles of different sizes and densities (fraction). In this study, we investigated the lipoprotein fractions in PD patients with controlled serum low-density lipoprotein (LDL) cholesterol level, and evaluated the effects of icodextrin on lipid metabolism. Methods Forty-nine PD patients were enrolled in this cross-sectional study in Japan. The proportions of cholesterol levels to total cholesterol level (cholesterol proportion) in 20 lipoprotein fractions were measured using an improved method of high-performance gel permeation chromatography (HPGPC). Results Twenty-six patients used icodextrin. Although no significant differences in cholesterol levels in LDL and high-density lipoprotein (HDL) were observed between the patients using icodextrin (icodextrin group) and control groups, HPGPC showed that the icodextrin group had significantly lower cholesterol proportions in the small LDL (t-test, p=0.053) and very small LDL (p=0.019), and significantly higher cholesterol proportions in the very large HDL and large HDL than the control group (p=0.037; p=0.066, respectively). Multivariate analysis adjusted for patient characteristics and statin use showed that icodextrin use was negatively associated with the cholesterol proportions in the small LDL (p=0.037) and very small LDL (p=0.026), and positively with those in the very large HDL (p=0.040), large HDL (p=0.047), and medium HDL (p=0.009). Conclusions HPGPC showed the relationship between icodextrin use and the cholesterol proportions in lipoprotein fractions in PD patients. These results suggest that icodextrin may improve atherogenic lipid profiles in a manner different from statin. PMID:24161017

Advanced Capabilities for Wind Tunnel Testing in the 21st Century

NASA Technical Reports Server (NTRS)

Kegelman, Jerome T.; Danehy, Paul M.; Schwartz, Richard J.

2010-01-01

Wind tunnel testing methods and test technologies for the 21st century using advanced capabilities are presented. These capabilities are necessary to capture more accurate and high quality test results by eliminating the uncertainties in testing and to facilitate verification of computational tools for design. This paper discusses near term developments underway in ground testing capabilities, which will enhance the quality of information of both the test article and airstream flow details. Also discussed is a selection of new capability investments that have been made to accommodate such developments. Examples include advanced experimental methods for measuring the test gas itself; using efficient experiment methodologies, including quality assurance strategies within the test; and increasing test result information density by using extensive optical visualization together with computed flow field results. These points could be made for both major investments in existing tunnel capabilities or for entirely new capabilities.

Advances in the management of dyslipidemia.

PubMed

Kampangkaew, June; Pickett, Stephen; Nambi, Vijay

2017-07-01

Cardiovascular disease is the leading cause of morbidity and mortality in the United States and therapies aimed at lipid modification are important for the reduction of cardiovascular risk. There have been many exciting advances in lipid management over the recent years. This review discusses these recent advances as well as the direction of future studies. Several recent clinical trials support low-density lipoprotein cholesterol (LDL-c) reduction beyond maximal statin therapy for improved cardiovascular outcomes. Ezetimibe reduced LDL-c beyond maximal statin therapy and was associated with improved cardiovascular outcomes for high-risk populations. Further LDL-c reduction may also be achieved with proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibition and a recent trial, Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER), was the first to show reduction in cardiovascular events for evolocumab. Additional outcome studies of monoclonal antibody and RNA-targeted PCSK9 inhibitors are underway. Quantitative high-density lipoprotein cholesterol (HDL-c) improvements have failed to have clinical impact to date; most recently, cholesteryl ester transfer protein inhibitors and apolipoprotein infusions have demonstrated disappointing results. There are still ongoing trials in both of these areas, but some newer therapies are focusing on HDL functionality and not just the absolute HDL-c levels. There are several ongoing studies in triglyceride reduction including fatty acid therapy, inhibition of apolipoprotein C-3 or ANGTPL3 and peroxisome proliferator-activated receptor-α agonists. Lipid management continues to evolve and these advances have the potential to change clinical practice in the coming years.

In vitro production of beta-very low density lipoproteins and small, dense low density lipoproteins in mildly hypertriglyceridemic plasma: role of activities of lecithin:cholester acyltransferase, cholesterylester transfer proteins and lipoprotein lipase.

PubMed

Chung, B H; Segrest, J P; Franklin, F

1998-12-01

As a model for the formation of beta-very low density lipoproteins (VLDL) and small, dense LDL by the intraplasma metabolic activities in vivo, lipoproteins in fresh plasma were interacted in vitro with endogenous lecithin:cholesterol acyltransferase (LCAT) and cholesterylester transfer proteins (CETP) and subsequently with purified lipoprotein lipase (LpL). The LCAT and CETP reactions in a mildly hypertriglyceridemic (HTG) plasma at 37 degrees C for 18 h resulted in (1) esterification of about 45% plasma unesterified cholesterol (UC), (2) a marked increase in cholesterylester (CE) (+129%) and a decrease in triglyceride (TG) (-45%) in VLDL, and (3) a marked increase of TG (+ 341%) with a small net decrease of CE (-3.6%) in LDL, causing a significant alteration in the TG/CE of VLDL (from 8.0 to 1.9) and of LDL (from 0.20 to 0.93). The LDL in LCAT and CETP-reacted plasma is larger and more buoyant than that in control plasma. In vitro lipolysis of control and LCAT and CETP-reacted plasma by LpL, which hydrolyzed >90% of VLDL-TG and about 50-60% of LDL-TG, converted most of VLDL in control plasma (>85%) but less than half (40%) of VLDL in LCAT and CETP-reacted plasma into the IDL-LDL density fraction and transformed the large, buoyant LDL in the LCAT and CETP-reacted plasma into particles smaller and denser than those in the control plasma. The remnants that accumulated in the VLDL density region of the postlipolysis LCAT and CETP-reacted plasma contained apo B-100 and E but little or no detectable apo Cs and consisted of particles having pre-beta and beta-electrophoretic mobilities. The inhibition of LCAT during incubation of plasma, which lessened the extent of alteration in VLDL and LDL core lipids, increased the extent of lipolytic removal of VLDL from the VLDL density region but lowered the extent of alteration in the size and density of LDL. The LCAT, CETP and/or LpL-mediated alterations in the density of LDL in normolipidemic fasting plasma were less pronounced

Acute effects of ingestion of black and green tea on lipoprotein oxidation.

PubMed

Hodgson, J M; Puddey, I B; Croft, K D; Burke, V; Mori, T A; Caccetta, R A; Beilin, L J

2000-05-01

Tea has been associated with a reduced risk of cardiovascular disease. One proposed mechanism of this risk reduction involves inhibition of lipoprotein oxidation in vivo by antioxidant polyphenolic compounds derived from tea. However, controlled interventions uniformly failed to show that ingestion of tea can inhibit LDL oxidation ex vivo. The absence of effects in previous studies may be due to the isolation of LDL particles from polyphenolic compounds that are present in the aqueous phase of serum. The objective of this study was to examine the acute effects of ingestion of black and green tea on ex vivo Cu(2+)-induced lipoprotein oxidation without prior isolation of lipoproteins from serum. The acute effects of 4 hot drinks-green tea and black tea (each at a dose equivalent to 4 standard cups), water matched to the teas for caffeine content, and water-were assessed in 20 healthy men by using a Latin-square design. The lag time to lipoprotein diene formation, slope of the propagation phase of the oxidation curve, and area under the oxidation curve were calculated. Urinary concentrations of 4-O-methylgallic acid were used as a marker of uptake and metabolism of polyphenolic compounds from tea. Significant increases in urinary 4-O-methylgallic acid for black and green tea (P < 0. 0001) were observed. Caffeine did not significantly influence lipoprotein oxidation. Compared with the water control, there was a greater lag time for black tea (5.4 +/- 2.9 min; P = 0.05) that was of borderline significance and a similar trend for green tea (4.4 +/- 2.8 min; P = 0.17). Slope and area under the oxidation curve were not altered. Black tea has a mild acute effect on ex vivo lipoprotein oxidation in human serum. 2000;71:-7.

Mice with chimeric livers are an improved model for human lipoprotein metabolism.

PubMed

Ellis, Ewa C S; Naugler, Willscott Edward; Nauglers, Scott; Parini, Paolo; Mörk, Lisa-Mari; Jorns, Carl; Zemack, Helen; Sandblom, Anita Lövgren; Björkhem, Ingemar; Ericzon, Bo-Göran; Wilson, Elizabeth M; Strom, Stephen C; Grompe, Markus

2013-01-01

Rodents are poor model for human hyperlipidemias because total cholesterol and low density lipoprotein levels are very low on a normal diet. Lipoprotein metabolism is primarily regulated by hepatocytes and we therefore assessed whether chimeric mice extensively repopulated with human cells can model human lipid and bile acid metabolism. FRG [ F ah(-/-) R ag2(-/-)Il2r g (-/-)]) mice were repopulated with primary human hepatocytes. Serum lipoprotein lipid composition and distribution (VLDL, LDL, and HDL) was analyzed by size exclusion chromatography. Bile was analyzed by LC-MS or by GC-MS. RNA expression levels were measured by quantitative RT-PCR. Chimeric mice displayed increased LDL and VLDL fractions and a lower HDL fraction compared to wild type, thus significantly shifting the ratio of LDL/HDL towards a human profile. Bile acid analysis revealed a human-like pattern with high amounts of cholic acid and deoxycholic acid (DCA). Control mice had only taurine-conjugated bile acids as expcted, but highly repopulated mice had glycine-conjugated cholic acid as found in human bile. RNA levels of human genes involved in bile acid synthesis including CYP7A1, and CYP27A1 were significantly upregulated as compared to human control liver. However, administration of recombinant hFGF19 restored human CYP7A1 levels to normal. Humanized-liver mice showed a typical human lipoprotein profile with LDL as the predominant lipoprotein fraction even on a normal diet. The bile acid profile confirmed presence of an intact enterohepatic circulation. Although bile acid synthesis was deregulated in this model, this could be fully normalized by FGF19 administration. Taken together these data indicate that chimeric FRG-mice are a useful new model for human lipoprotein and bile-acid metabolism.

Acoustic flight testing of advanced design propellers on a JetStar aircraft

NASA Technical Reports Server (NTRS)

Lasagna, P.; Mackall, K.

1981-01-01

Advanced turboprop-powered aircraft have the potential to reduce fuel consumption by 15 to 30 percent as compared with an equivalent technology turbofan-powered aircraft. An important obstacle to the use of advanced design propellers is the cabin noise generated at Mach numbers up to .8 and at altitudes up to 35,000 feet. As part of the NASA Aircraft Energy Efficiency Program, the near-field acoustic characteristics on a series of advanced design propellers are investigated. Currently, Dryden Flight Research Center is flight testing a series of propellers on a JetStar airplane. The propellers used in the flight test were previously tested in wind tunnels at the Lewis Research Center. Data are presented showing the narrow band spectra, acoustic wave form, and acoustic contours on the fuselage surface. Additional flights with the SR-3 propeller and other advanced propellers are planned in the future.

Comparison of guinea-pig serum lipoproteins after iodination by two different methods.

PubMed Central

Weech, P K; McTaggart, F; Mills, G L

1978-01-01

1. Guinea-pig low-density lipoproteins were isolated by ultracentrifugation and iodinated either by the IC1 method or by the chloramine-T procedure. 2. The efficiency of labelling by both methods was essentially the same. 3. When the two products were compared by ultracentrifugation, gel chromatography and immunodiffusion analysis, no significant difference in their properties was detected. 4. When they were compared by gradient-gel electrophoresis, aggregates were found in the product of the IC1 method, but not in the lipoprotein iodinated by the chloramine-T process. 5. Both products were metabolized by the guinea pig with essentially the same fractional catabolic rate. 6. The fractional catabolic rate of lipoprotein iodinated by the chloramine-T method was not significantly different from that of lipoprotein biologically labelled in the protein moiety with [75Se]selenomethionine. 7. It is concluded that the products of both methods of iodination are almost equally acceptable, provided that the optimum conditions for the chloramine-T reaction are carefully established. Images Fig. 4. Fig. 5. PMID:206260

Glucose, lipid, and lipoprotein levels in sheep naturally infected with Fasciola hepatica.

PubMed

Kozat, Süleyman; Denizhan, Vural

2010-06-01

This study was designed to investigate serum glucose, lipid, and lipoprotein in sheep naturally infected with Fasciola hepatica. Ten healthy sheep and 15 infected with F. hepatica were used in study. Serum concentrations of total protein (TP), albumin, glucose, cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoproteins (VLDL), and serum activities of AST, ALT, GGT, and LDH were measured using a Roche-Cobas Integra 800 auto-analyzer. At day 0 (prior to treatment) and on the 28th day (after treatment) the serum concentrations of TP, albumin, glucose, cholesterol, triglyceride, HDL, LDL, and VLDL values in sheep with F. hepatica were significantly lower than those of the control group, while serum activities of AST, ALT, GGT, and LDH of lambs with F. hepatica were significantly higher than those of the control group. At day 56 (after treatment), none of the variables was significantly different between control sheep and those that received treatment for fascioliasis (P > 0.05). Nutritional management may be used to reduce the impact of fascioliasis.

The Design and Testing of the LSSIF Advanced Thermal Control System

NASA Technical Reports Server (NTRS)

Henson, Robert A.; Keller, John R.

1995-01-01

The Life Support Systems Integration Facility (LSSIF) provides a platform to design and evaluate advanced manned space systems at NASA Johnson Space Center (JSC). The LSSIF Early Human Testing Initiative requires the integration of such subsystems to enable human occupancy of the 6 meter chamber for a 90 day closed volume test. The Advanced Thermal Control System (TCS) is an important component of the integrated system by supplying coolant to the subsystems within the chamber, such as the Air Revitalization System. The TCS incorporates an advanced high efficiency, heat pump to reject waste heat from the chamber to an external sink or 'lift' temperature that emulates a Lunar environment. The heat pump is the High Lift Heat Pump, developed by Foster-Miller, Inc., and is the main test article of the TCS. The heat pump prototype utilizes a non-CFC refrigerant in a design where the thermal requirements exceed existing terrestrial technology. These operating requirements provide a unique opportunity to design and test an advanced integrated thermal system and the associated controls. The design, control, and systems integration of the heat pump and the TCS also have terrestrial technology application. This paper addresses the design of the TCS and the heat pump, along with the control scheme to fully test the heat pump. Design approaches utilized in the LSSIF TCS are promoted for implementation in terrestrial thermal systems. The results of the preliminary thermal and fluid analyses used to develop the control of the thermal systems will also be discussed. The paper includes objectives for the 90 day human test and the test setup. Finally, conclusions will be drawn and recommendations for Earth design application are submitted.

Information on the Advanced Plant Experiment (APEX) Test Facility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Curtis Lee

The purpose of this report provides information related to the design of the Oregon State University Advanced Plant Experiment (APEX) test facility. Information provided in this report have been pulled from the following information sources: Reference 1: R. Nourgaliev and et.al, "Summary Report on NGSAC (Next-Generation Safety Analysis Code) Development and Testing," Idaho National Laboratory, 2011. Note that this is report has not been released as an external report. Reference 2: O. Stevens, Characterization of the Advanced Plant Experiment (APEX) Passive Residual Heat Removal System Heat Exchanger, Master Thesis, June 1996. Reference 3: J. Reyes, Jr., Q. Wu, and J.more » King, Jr., Scaling Assessment for the Design of the OSU APEX-1000 Test Facility, OSU-APEX-03001 (Rev. 0), May 2003. Reference 4: J. Reyes et al, Final Report of the NRC AP600 Research Conducted at Oregon State University, NUREG/CR-6641, July 1999. Reference 5: K. Welter et al, APEX-1000 Confirmatory Testing to Support AP1000 Design Certification (non-proprietary), NUREG-1826, August 2005.« less

Genetic risk scores associated with baseline lipoprotein subfraction concentrations do not associate with their responses to fenofibrate

USDA-ARS?s Scientific Manuscript database

Lipoprotein subclass concentrations are modifiable markers of cardiovascular disease risk. Fenofibrate is known to show beneficial effects on lipoprotein subclasses, but little is known about the role of genetics in mediating the responses of lipoprotein subclasses to fenofibrate. A recent genomewid...

Genome-wide association study indicates variants associated with insulin signaling and inflammation mediate lipoprotein responses to fenofibrate

USDA-ARS?s Scientific Manuscript database

A shift towards overall larger very low-density lipoprotein (VLDL), and smaller low-density lipoprotein and high-density lipoprotein (HDL) diameters occurs in insulin resistance (IR), which reflects shifts in the distribution of the subfraction concentrations. Fenofibrate, indicated for hypertriglyc...

Hydrolysis of diacylglycerols by lipoprotein lipase.

PubMed

Morley, N H; Kuksis, A; Buchnea, D; Myher, J J

1975-05-10

Enantiomeric diacylglycerols were emulsified, mole for mole, with lyso(1-acyl) lecithin and were hydrolyzed with lipoprotein lipase in NH4Cl-beef serum albumin buffer at pH 8.6 after a brief incubation with delipidated rat serum. The enzyme was prepared from lyophilized and dialyzed bovine skim milk in a 4 percent solution. The course of hydrolysis for each set of enantiomers was determined by gas-liquid chromatography of the masses of the diacylglycerols remaining or monoacylglycerols released in the medium between 0 and 15 min. The majority of sets of sn-1,2- and 2,3-diacylglycerols, including an isotope-labeled true enantiomeric set which was assessed by mass spectrometry, demonstrated preference by the enzyme for lipolysis at position 1 but with less specificity than previously was shown in sn-triacylglycerol hydrolysis. The results preclude the possibility that the predominance of sn-2,3-diacylglycerol intermediates during triacylglycerol hydrolysis is due solely to a preferential breakdown of the 1,2-isomers and reinforce the conclusion that lipoprotein lipase is specific for position 1.

Mechanistic studies of high-density lipoproteins.

PubMed

Kashyap, M L

1998-12-17

There is increasing evidence that high-density lipoprotein (HDL) and its subfractions are protective against atherosclerotic cardiovascular disease. Physical exercise, weight reduction, smoking cessation, diabetes mellitus control, and specific drugs, including niacin, fibrates, and estrogens, are effective methods to increase HDL levels. Niacin is the oldest and most powerful clinical agent for raising HDL levels. Niaspan, an extended-release niacin formulation, is as potent as immediate-release niacin in increasing levels of HDL cholesterol; subfractions HDL2 and HDL3; apolipoprotein A-I, the major protein of HDL, and its cardioprotective subfraction lipoprotein A-I. Recent research from our laboratory suggests a novel mechanism by which niacin inhibits hepatic removal of HDL-apoprotein A-I without interfering with the removal of cholesterol carried by HDL, thus augmenting reverse cholesterol transport. Other mechanistic studies indicate that fibrates and estrogens stimulate the synthesis and production of HDL-apoprotein A-I. Because niacin decreases HDL-apoprotein A-I removal, and fibrates and estrogens increase HDL-apoprotein A-I production, combinations of niacin with these agents may raise HDL levels more than fibrates or estrogens alone.

[Lipoproteins as a specific circulatory transport system].

PubMed

Titov, V N

1998-01-01

In accordance with the systemic approach, each circulatory transport system is highly specific and transports an elementary substance from cell to cell in the hydrated medium. In the author's opinion, the lipoprotein system has also a functional specificity and carries the elementary substance fatty acid in the blood stream. A great variety of fatty acids, the individuality of their physicochemical properties, great stereochemic differences of saturated and polyenic fatty acids make their transport virtually impossible. The steric individuality of fatty acids can be reduced if the acids are covalently bonded by a matrix as complex lipids. For formation of complex lipids, nature prefers esterification of fatty acids with alcohols which have a varying hydrophoby, such as glycerol, sphingosine, cholesterol, cetyl alcohol. The steric differences of saturated and polyenic fatty acids form a basis for their being structurized in different lipids. Triacyl glycerides are a transport form of saturated, monounsaturated fatty acids and their transforms and give rise to a crystalline phase. Phospholipids and cholesterol esters are a transport form of mainly polyunsaturated fatty acids in the polar phase in the former case and in the crystalline phase in the latter one. The individual apolipoproteins structure complex lipids into individual lipoprotein particles and transport them in the hydrated medium of blood flow. Saturated fatty acids chiefly transport lipoprotein particles formed by apoB-48- and apoB-100-isoproteins. Polyenic acids transport mainly high-density apoA-1-lipoprotein particles, which makes up a main physiological function of the latter. Cholesterol is nothing more than a matrix; it reesterifies polyenic fatty acids from the polar transport form of phospholipids into the unpolar transport form of cholesterol esters. Cholesterol esterification of polyenic fatty acids may structure complex lipid in the unpolar phase and transport it to the cells via apoB-100

Analysis of interior noise ground and flight test data for advanced turboprop aircraft applications

NASA Technical Reports Server (NTRS)

Simpson, M. A.; Tran, B. N.

1991-01-01

Interior noise ground tests conducted on a DC-9 aircraft test section are described. The objectives were to study ground test and analysis techniques for evaluating the effectiveness of interior noise control treatments for advanced turboprop aircraft, and to study the sensitivity of the ground test results to changes in various test conditions. Noise and vibration measurements were conducted under simulated advanced turboprop excitation, for two interior noise control treatment configurations. These ground measurement results were compared with results of earlier UHB (Ultra High Bypass) Demonstrator flight tests with comparable interior treatment configurations. The Demonstrator is an MD-80 test aircraft with the left JT8D engine replaced with a prototype UHB advanced turboprop engine.

Analysis of interior noise ground and flight test data for advanced turboprop aircraft applications

NASA Astrophysics Data System (ADS)

Simpson, M. A.; Tran, B. N.

1991-08-01

Interior noise ground tests conducted on a DC-9 aircraft test section are described. The objectives were to study ground test and analysis techniques for evaluating the effectiveness of interior noise control treatments for advanced turboprop aircraft, and to study the sensitivity of the ground test results to changes in various test conditions. Noise and vibration measurements were conducted under simulated advanced turboprop excitation, for two interior noise control treatment configurations. These ground measurement results were compared with results of earlier UHB (Ultra High Bypass) Demonstrator flight tests with comparable interior treatment configurations. The Demonstrator is an MD-80 test aircraft with the left JT8D engine replaced with a prototype UHB advanced turboprop engine.

Effects of dietary coconut oil, butter and safflower oil on plasma lipids, lipoproteins and lathosterol levels.

PubMed

Cox, C; Sutherland, W; Mann, J; de Jong, S; Chisholm, A; Skeaff, M

1998-09-01

The aim of this present study was to determine plasma levels of lathosterol, lipids, lipoproteins and apolipoproteins during diets rich in butter, coconut fat and safflower oil. The study consisted of sequential six week periods of diets rich in butter, coconut fat then safflower oil and measurements were made at baseline and at week 4 in each diet period. Forty-one healthy Pacific island polynesians living in New Zealand participated in the trial. Subjects were supplied with some foods rich in the test fats and were given detailed dietary advice which was reinforced regularly. Plasma lathosterol concentration (P < 0.001), the ratio plasma lathosterol/cholesterol (P=0.04), low density lipoprotein (LDL) cholesterol (P<0.001) and apoB (P<0.001) levels were significantly different among the diets and were significantly lower during coconut and safflower oil diets compared with butter diets. Plasma total cholesterol, HDL cholesterol and apoA-levels were also significantly (P< or =0.001) different among the diets and were not significantly different between buffer and coconut diets. These data suggest that cholesterol synthesis is lower during diets rich in coconut fat and safflower oil compared with diets rich in butter and might be associated with lower production rates of apoB-containing lipoproteins.

Modified Lipoprotein-Derived Lipid Particles Accumulate in Human Stenotic Aortic Valves

PubMed Central

Lehti, Satu; Käkelä, Reijo; Hörkkö, Sohvi; Kummu, Outi; Helske-Suihko, Satu; Kupari, Markku; Werkkala, Kalervo; Kovanen, Petri T.; Öörni, Katariina

2013-01-01

In aortic stenosis plasma lipoprotein-derived lipids accumulate in aortic valves. Here, we first compared the lipid compositions of stenotic aortic valves and atherosclerotic plaque cores. Both pathological tissues were found to be enriched in cholesteryl linoleate, a marker of extracellularly accumulated lipoproteins. In addition, a large proportion of the phospholipids were found to contain arachidonic acid, the common precursor of a number of proinflammatory lipid mediators. Next, we isolated and characterized extracellular lipid particles from human stenotic and non-stenotic control valves, and compared them to plasma lipoproteins from the same subjects. The extracellular valvular lipid particles were isolated from 15 stenotic and 14 non-stenotic aortic valves. Significantly more apoB-100-containing lipid particles were found in the stenotic than in the non-stenotic valves. The majority of the lipid particles isolated from the non-stenotic valves had sizes (23±6.2 nm in diameter) similar to those of plasma low density lipoprotein (LDL) (22±1.5 nm), while the lipid particles from stenotic valves were not of uniform size, their sizes ranging from 18 to more than 500 nm. The lipid particles showed signs of oxidative modifications, and when compared to isolated plasma LDL particles, the lipid particles isolated from the stenotic valves had a higher sphingomyelin/phosphatidylcholine –ratio, and also higher contents of lysophosphatidylcholine and unesterified cholesterol. The findings of the present study reveal, for the first time, that in stenotic human aortic valves, infiltrated plasma lipoproteins have undergone oxidative and lipolytic modifications, and become fused and aggregated. The generated large lipid particles may contribute to the pathogenesis of human aortic stenosis. PMID:23762432

Maturation of high-density lipoproteins

PubMed Central

Shih, Amy Y.; Sligar, Stephen G.; Schulten, Klaus

2009-01-01

Human high-density lipoproteins (HDLs) are involved in the transport of cholesterol. The mechanism by which HDL assembles and functions is not well understood owing to a lack of structural information on circulating spherical HDL. Here, we report a series of molecular dynamics simulations that describe the maturation of discoidal HDL into spherical HDL upon incorporation of cholesterol ester as well as the resulting atomic level structure of a mature circulating spherical HDL particle. Sixty cholesterol ester molecules were added in a stepwise fashion to a discoidal HDL particle containing two apolipoproteins wrapped around a 160 dipalmitoylphosphatidylcholine lipid bilayer. The resulting matured particle, captured in a coarse-grained description, was then described in a consistent all-atom representation and analysed in chemical detail. The simulations show that maturation results from the formation of a highly dynamic hydrophobic core comprised of cholesterol ester surrounded by phospholipid and protein; the two apolipoprotein strands remain in a belt-like conformation as seen in the discoidal HDL particle, but with flexible N- and C-terminal helices and a central region stabilized by salt bridges. In the otherwise flexible lipoproteins, a less mobile central region provides an ideal location to bind lecithin cholesterol acyltransferase, the key enzyme that converts cholesterol to cholesterol ester during HDL maturation. PMID:19570799

Lipid transfer proteins in the assembly of apoB-containing lipoproteins.

PubMed

Sirwi, Alaa; Hussain, M Mahmood

2018-04-12

A better understanding of intracellular lipoprotein assembly may help identify proteins with important roles in lipid disorders. ApoB-containing lipoproteins are macromolecular lipid and protein micelles that act as specialized transport vehicles for hydrophobic lipids. They are assembled predominantly in enterocytes and hepatocytes to transport dietary and endogenous fat, respectively, to different tissues. Assembly occurs in the endoplasmic reticulum and is dependent on lipid re-synthesis in the endoplasmic reticulum and on a chaperone, namely microsomal triglyceride transfer protein. Precursors for lipid synthesis are obtained from extracellular sources and from cytoplasmic lipid droplets. Microsomal triglyceride transfer protein is the major and essential lipid transfer protein that transfers phospholipids and triacylglycerols to nascent apoB for the assembly of lipoproteins. Assembly is aided by cell death-inducing DFF45-like effector B and by phospholipid transfer protein, which may facilitate additional deposition of triacylglycerols and phospholipids, respectively, to apoB. Here, we summarize the current understanding of the different steps in the assembly of apoB-containing lipoproteins and discuss the role of lipid transfer proteins in these steps to help identify new clinical targets for lipid-associated disorders, such as heart disease. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Pyrene-Labeled Amphiphiles: Dynamic And Structural Probes Of Membranes And Lipoproteins

NASA Astrophysics Data System (ADS)

Pownall, Henry J.; Homan, Reynold; Massey, John B.

1987-01-01

Lipids and proteins are important functional and structural components of living organisms. Although proteins are frequently found as soluble components of plasma or the cell cytoplasm, many lipids are much less soluble and separate into complex assemblies that usually contain proteins. Cell membranes and plasma lipoproteins' are two important macro-molecular assemblies that contain both lipids and proteins. Cell membranes are composed of a variety of lipids and proteins that form an insoluble bilayer array that has relatively little curvature over distances of several nm. Plasma lipoproteins are different in that they are much smaller, water-soluble, and have highly curved surfaces. A model of a high density lipoprotein (HDL) is shown in Figure 1. This model (d - 10 nm) contains a surface of polar lipids and proteins that surrounds a small core of insoluble lipids, mostly triglycerides and cholesteryl esters. The low density (LDL) (d - 25 nm) and very low density (VLDL) (d 90 nm) lipoproteins have similar architectures, except the former has a cholesteryl ester core and the latter a core that is almost exclusively triglyceride (Figure 1). The surface proteins of HDL are amphiphilic and water soluble; the single protein of LDL is insoluble, whereas VLDL contains both soluble and insoluble proteins. The primary structures of all of these proteins are known.

[Physical activity, dietary habits and plasma lipoproteins in young men and women].

PubMed

Malara, Marzena; Lutosławska, Grazyna

2010-01-01

There are studies suggesting that in young women strenuous physical activity and inadequate daily energy intake cause unfavorable changes in lipoprotein profile. However until know data concerning this issue are contradictory, possibly due to small number of participants. This study aimed at evaluation of lipoprotein profile in young men and women with different weekly physical activity together with their dietary habits. A total of 202 subjects volunteered to participate of the study--54 female and 56 male students of physical education and 46 female and 49 male students representing other specialization. Daily energy and macronutrient intakes were assessed using FOOD 2 computer program. Plasma TG, TC and HDL-C were assayed colorimetically using Randox commercial kits (Great Britain). It has been demonstrated that high physical activity adversely affects lipoprotein profile in young women characterized by higher TC and LDL-C in comparison with women with low physical activity and with men with high physical activity. The effect of high physical activity on plasma lipoproteins is equivocal. Active men are characterized by higher HDL, but also by higher frequency of unfavorable plasma TC and similar frequency of unfavorable plasma LDL-C C as compared with their less active counterparts. The mean daily energy intake in highly active men and women covered 82% and 72.2% recommended intake, respectively. It seems feasible that in both sexes high physical activity and inadequate energy intake brings about unfavorable changes in plasma lipoproteins.

Excessive centrifugal fields damage high density lipoprotein[S

PubMed Central

Munroe, William H.; Phillips, Martin L.; Schumaker, Verne N.

2015-01-01

HDL is typically isolated ultracentrifugally at 40,000 rpm or greater, however, such high centrifugal forces are responsible for altering the recovered HDL particle. We demonstrate that this damage to HDL begins at approximately 30,000 rpm and the magnitude of loss increases in a rotor speed-dependent manner. The HDL is affected by elevated ultracentrifugal fields resulting in a lower particle density due to the shedding of associated proteins. To circumvent the alteration of the recovered HDL, we utilize a KBr-containing density gradient and a lowered rotor speed of 15,000 rpm to separate the lipoproteins using a single 96 h centrifugation step. This recovers the HDL at two density ranges; the bulk of the material has a density of about 1.115 g/ml, while lessor amounts of material are recovered at >1.2 g/ml. Thus, demonstrating the isolation of intact HDL is possible utilizing lower centrifuge rotor speeds. PMID:25910941

Test Protocols for Advanced Inverter Interoperability Functions - Appendices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, Jay Dean; Gonzalez, Sigifredo; Ralph, Mark E.

2013-11-01

Distributed energy resources (DER) such as photovoltaic (PV) systems, when deployed in a large scale, are capable of influencing significantly the operation of power systems. Looking to the future, stakeholders are working on standards to make it possible to manage the potentially complex interactions between DER and the power system. In 2009, the Electric Power Research Institute (EPRI), Sandia National Laboratories (SNL) with the U.S. Department of Energy (DOE), and the Solar Electric Power Association (SEPA) initiated a large industry collaborative to identify and standardize definitions for a set of DER grid support functions. While the initial effort concentrated onmore » grid-tied PV inverters and energy storage systems, the concepts have applicability to all DER. A partial product of this on-going effort is a reference definitions document (IEC TR 61850-90-7, Object models for power converters in distributed energy resources (DER) systems) that has become a basis for expansion of related International Electrotechnical Commission (IEC) standards, and is supported by US National Institute of Standards and Technology (NIST) Smart Grid Interoperability Panel (SGIP). Some industry-led organizations advancing communications protocols have also embraced this work. As standards continue to evolve, it is necessary to develop test protocols to independently verify that the inverters are properly executing the advanced functions. Interoperability is assured by establishing common definitions for the functions and a method to test compliance with operational requirements. This document describes test protocols developed by SNL to evaluate the electrical performance and operational capabilities of PV inverters and energy storage, as described in IEC TR 61850-90-7. While many of these functions are not now required by existing grid codes or may not be widely available commercially, the industry is rapidly moving in that direction. Interoperability issues are already

Helicobacter pylori infection is an independent risk factor of early and advanced colorectal neoplasm.

PubMed

Kim, Tae Jun; Kim, Eun Ran; Chang, Dong Kyung; Kim, Young-Ho; Baek, Sun-Young; Kim, Kyunga; Hong, Sung Noh

2017-06-01

The role of Helicobacter pylori (H. pylori) in the development of colorectal neoplasm remains controversial. We examined the association between H. pylori infection and colorectal neoplasm in a large sample of healthy participants who underwent screening colonoscopy. A cross-sectional study of 8916 men, who participated in a regular health-screening examination that included an H. pylori-specific immunoglobulin G antibody test and colonoscopy, was conducted to evaluate the association between H. pylori and colorectal neoplasm. Multivariable analyses adjusted for age, body mass index, smoking status, alcohol intake, regular exercise, regular aspirin use, and family history of colorectal cancer showed that the odds ratio (OR) (95% confidence interval [CI]) for any adenoma and advanced neoplasm was 1.32 (1.07-1.61) and 1.90 (1.05-3.56) in participants with H. pylori infection and without H. pylori infection, respectively. The association persisted after further adjustment for inflammatory markers or metabolic variables including fasting blood glucose, triglycerides, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol. Regarding the location, a positive association was confined to cases with proximal adenomas and was observed similarly in all the evaluated subgroups. In a large-scale study, carefully controlled for confounding factors, involving asymptomatic participants without a history of colonoscopy, H. pylori infection was significantly associated with the risk of any colorectal adenoma and advanced colorectal neoplasm. Prospective studies are necessary to determine whether H. pylori eradication can reduce this risk. © 2017 John Wiley & Sons Ltd.

Comparison of human plasma low- and high-density lipoproteins as substrates for lecithin: cholesterol acyltransferase.

PubMed

Barter, P J; Hopkins, G J; Gorjatschko, L

1984-01-17

A recent observation that lecithin: cholesterol acyltransferase (EC 2.3.1.43) interacts with both low-density lipoproteins (LDL) and high-density lipoproteins (HDL) in human plasma is in apparent conflict with an earlier finding that the purified enzyme, while highly reactive with isolated HDL, was only minimally reactive with LDL. There is evidence, however, that lecithin: cholesterol acyltransferase may exist physiologically as a component of a complex with other proteins and that studies with the isolated enzyme may therefore provide misleading results. Consequently, interactions of the enzyme with isolated human lipoproteins have been re-examined in incubations containing lecithin: cholesterol acyltransferase as a component of human lipoprotein-free plasma in which a physiologically active complex of the enzyme with other proteins may have been preserved. In this system there was a ready esterification of the free cholesterol associated with both LDL and HDL-subfraction 3 (HDL3) in reactions that obeyed typical enzyme-saturation kinetics. For a given preparation of lipoprotein-free plasma the Vmax values with LDL and with HDL3 were virtually identical. The apparent Km for free cholesterol associated with HDL3 was 5.6 X 10(-5) M, while for that associated with LDL it was 4.1 X 10(-4) M. This implied that, in terms of free cholesterol concentration, the affinity of HDL3 for lecithin: cholesterol acyltransferase was about 7-times greater than that of LDL. When expressed in terms of lipoprotein particle concentration, however, it was apparent that the affinity of LDL for the enzyme was considerably greater than that of HDL3. When the lipoprotein fractions were equated in terms of lipoprotein surface area, the apparent affinities of the two fractions for the enzyme were found to be comparable.

Genetic evidence for a role of adiponutrin in the metabolism of apolipoprotein B-containing lipoproteins

PubMed Central

Kollerits, Barbara; Coassin, Stefan; Beckmann, Noam D.; Teumer, Alexander; Kiechl, Stefan; Döring, Angela; Kavousi, Maryam; Hunt, Steven C.; Lamina, Claudia; Paulweber, Bernhard; Kutalik, Zoltán; Nauck, Matthias; van Duijn, Cornelia M.; Heid, Iris M.; Willeit, Johann; Brandstätter, Anita; Adams, Ted D.; Mooser, Vincent; Aulchenko, Yurii S.; Völzke, Henry; Kronenberg, Florian

2009-01-01

Adiponutrin (PNPLA3) is a predominantly liver-expressed transmembrane protein with phospholipase activity that is regulated by fasting and feeding. Recent genome-wide association studies identified PNPLA3 to be associated with hepatic fat content and liver function, thus pointing to a possible involvement in the hepatic lipoprotein metabolism. The aim of this study was to examine the association between two common variants in the adiponutrin gene and parameters of lipoprotein metabolism in 23 274 participants from eight independent West-Eurasian study populations including six population-based studies [Bruneck (n = 800), KORA S3/F3 (n = 1644), KORA S4/F4 (n = 1814), CoLaus (n = 5435), SHIP (n = 4012), Rotterdam (n = 5967)], the SAPHIR Study as a healthy working population (n = 1738) and the Utah Obesity Case-Control Study including a group of 1037 severely obese individuals (average BMI 46 kg/m2) and 827 controls from the same geographical region of Utah. We observed a strong additive association of a common non-synonymous variant within adiponutrin (rs738409) with age-, gender-, and alanine-aminotransferase-adjusted lipoprotein concentrations: each copy of the minor allele decreased levels of total cholesterol on average by 2.43 mg/dl (P = 8.87 × 10−7), non-HDL cholesterol levels by 2.35 mg/dl (P = 2.27 × 10−6) and LDL cholesterol levels by 1.48 mg/dl (P = 7.99 × 10−4). These associations remained significant after correction for multiple testing. We did not observe clear evidence for associations with HDL cholesterol or triglyceride concentrations. In conclusion, our study suggests that adiponutrin is involved in the metabolism of apoB-containing lipoproteins. PMID:19729411

Interaction between the APOC3 gene promoter polymorphisms, saturated fat intake and plasma lipoproteins.

PubMed

Brown, Sherine; Ordovás, José M; Campos, Hannia

2003-10-01

To test the hypothesis that APOC3 gene polymorphisms modulate the effect of saturated fat (SAT) intake on plasma lipoproteins and LDL size. We studied 336 randomly selected residents from Costa Rica. APOC3 polymorphisms were genotyped in the promoter region (T-455C, T-625del) and the C3238G 3' untranslated region (UTR). Dietary intake was assessed by a validated food-frequency questionnaire (FFQ) and median saturated fat intake (11%) was used to define low and high exposure to saturated fat. Allele frequencies were 0.49, 0.51 and 0.19 for the APOC3-455C, -625de1, and APOC3 3238G alleles, respectively. Significant gene-diet interactions were found for total (P<0.0004) and LDL cholesterol (P<0.01). In homozygotes for the APOC3-455T-625T alleles, saturated fat intake was associated with a 13% increase in total cholesterol (P<0.001) and a 20% increase in LDL cholesterol (P<0.001). In contrast, no association between plasma lipoproteins and saturated fat intake was found among carriers of the APOC3-455C-625del allele. The APOC3 3238G UTR allele did not modify the observed association. Compared to a diet high in saturated fat, a habitually low saturated fat diet is associated with a beneficial lipoprotein profile only among homozygotes of the APOC3 promoter 455T-625T polymorphism.

Expression of lipoprotein receptor and apolipoprotein E genes by perinatal rat lipid-laden pulmonary fibroblasts.

PubMed

McGowan, S E; Doro, M M; Jackson, S

Lipid-laden interstitial fibroblasts (LIFs) are abundant during alveolar septal formation in rats and accumulate droplets of neutral lipids. The mechanisms controlling lipid acquisition by LIFs are incompletely understood and accumulation varies during postnatal development, because lipid droplets are usually a transient phenotype. We hypothesized that plasma lipoproteins may be an important source of lipids and that the cells may alter their acquisition of lipoproteins by changing the expression of lipoprotein receptors and apolipoprotein E. We quantified the accumulation low-density lipoproteins (LDLs) and very-low-density lipoproteins (VLDLs) by LIFs and the expression of LDL and VLDL receptors mRNA and protein at various perinatal ages and found no significant age-related differences. Apolipoprotein E mRNA was maximal at postnatal day 15, whereas immunoreactive apolipoprotein E protein was maximal at gestational day 21, suggesting complex regulation. Our findings indicate that the age-related difference in the lipid droplet contents of LIFs is not primarily related to differences in LDL or VLDL receptor expression. They suggest that changes in the quantities of plasma lipoproteins, which are presented to LIFs in the lung at various perinatal ages, are more likely to be responsible for age-related alterations in lipid droplet size and abundance.

A1C Test

MedlinePlus

... Mutation Mycophenolic Acid Mycoplasma Myoglobin Nicotine and Cotinine Non-High Density Lipoprotein Cholesterol Opioid Testing Osmolality Ova ... as older RBCs die and younger RBCs (with non-glycated hemoglobin) take their place. This test may ...

Negatively Cooperative Binding of High Density Lipoprotein to the HDL Receptor SR-BI†

PubMed Central

Nieland, Thomas J.F.; Xu, Shangzhe; Penman, Marsha; Krieger, Monty

2011-01-01

Scavenger receptor class B, type I (SR-BI) is a high-density lipoprotein (HDL) receptor, which also binds low density lipoprotein (LDL), and mediates the cellular selective uptake of cholesteryl esters from lipoproteins. SR-BI also is a co-receptor for hepatitis C virus and a signaling receptor that regulates cell metabolism. Many investigators have reported that lipoproteins bind to SR-BI via a single class of independent (not interacting), high affinity binding sites (one site model). We have re-investigated the ligand concentration dependence of 125I-HDL binding to SR-BI and SR-BI-mediated specific uptake of [3H]CE from [3H]CE-HDL using an expanded range of ligand concentrations (<1 µg protein/ml, lower than previously reported). Scatchard and non-linear least squares model fitting analyses of the binding and uptake data were both inconsistent with a single class of independent binding sites binding univalent lipoprotein ligands. The data are best fit by models in which SR-BI has either two independent classes of binding sites, or one class of sites exhibiting negative cooperativity due to either classic allostery or ensemble effects (‘ lattice model’). Similar results were observed for LDL. Application of the ‘infinite dilution’ dissociation rate method established that the binding of 125I-HDL to SR-BI at 4 °C exhibits negative cooperativity. The unexpected complexity of the interactions of lipoproteins with SR-BI should be taken into account when interpreting the results of experiments that explore the mechanism(s) by which SR-BI mediates ligand binding, lipid transport and cell signaling. PMID:21254782

Body mass index and glycemic control influence lipoproteins in children with type 1 diabetes.

PubMed

Vaid, Shalini; Hanks, Lynae; Griffin, Russell; Ashraf, Ambika P

2016-01-01

Patients with type 1 diabetes mellitus (T1DM) have an extremely high risk of cardiovascular disease (CVD) morbidity and mortality. It is well known that dyslipidemia is a subclinical manifestation of atherosclerosis. To analyze presence and predicting factors of lipoprotein abnormalities prevalent in children with T1DM and whether race-specific differences exist between non-Hispanic white (NHW) and non-Hispanic black (NHB) in the lipoprotein characteristics. A retrospective electronic chart review including 600 (123 NHB and 477 NHW) T1DM patients aged 7.85 ± 3.75 years who underwent lipoprotein analysis. Relative to NHW counterparts, NHB T1DM subjects had a higher HbA1c, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), apoB 100, lipoprotein (a), and high-density lipoprotein cholesterol (HDL-c), HDL-2, and HDL-3. Body mass index (BMI) was positively associated with TC, LDL-c, apoB 100, and non-HDL-c and inversely associated with HDL, HDL-2, and HDL-3. HbA1c was positively associated with TC, LDL-c, apoB 100, non-HDL-c, and HDL-3. Multilinear regression analysis demonstrated that HbA1c was positively associated with apoB 100 in both NHB and NHW, and BMI was a positive determinant of apoB 100 in NHW only. Poor glycemic control and high BMI may contribute to abnormal lipoprotein profiles. Glycemic control (in NHB and NHW) and weight management (in NHW) may have significant implications in T1DM. ApoB 100 concentrations in subjects with T1DM were determined by modifiable risk factors, BMI, HbA1C, and blood pressure, indicating the importance of adequate weight, glycemic, and blood pressure control for better diabetes care and likely lower CVD risk. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Cardiomyocyte Regulation of Systemic Lipid Metabolism by the Apolipoprotein B-Containing Lipoproteins in Drosophila

PubMed Central

Ishikawa, Zachary

2017-01-01

The heart has emerged as an important organ in the regulation of systemic lipid homeostasis; however, the underlying mechanism remains poorly understood. Here, we show that Drosophila cardiomyocytes regulate systemic lipid metabolism by producing apolipoprotein B-containing lipoproteins (apoB-lipoproteins), essential lipid carriers that are so far known to be generated only in the fat body. In a Drosophila genetic screen, we discovered that when haplo-insufficient, microsomal triglyceride transfer protein (mtp), required for the biosynthesis of apoB-lipoproteins, suppressed the development of diet-induced obesity. Tissue-specific inhibition of Mtp revealed that whereas knockdown of mtp only in the fat body decreases systemic triglyceride (TG) content on normal food diet (NFD) as expected, knockdown of mtp only in the cardiomyocytes also equally decreases systemic TG content on NFD, suggesting that the cardiomyocyte- and fat body-derived apoB-lipoproteins serve similarly important roles in regulating whole-body lipid metabolism. Unexpectedly, on high fat diet (HFD), knockdown of mtp in the cardiomyocytes, but not in fat body, protects against the gain in systemic TG levels. We further showed that inhibition of the Drosophila apoB homologue, apolipophorin or apoLpp, another gene essential for apoB-lipoprotein biosynthesis, affects systemic TG levels similarly to that of Mtp inhibition in the cardiomyocytes on NFD or HFD. Finally, we determined that HFD differentially alters Mtp and apoLpp expression in the cardiomyocytes versus the fat body, culminating in higher Mtp and apoLpp levels in the cardiomyocytes than in fat body and possibly underlying the predominant role of cardiomyocyte-derived apoB-lipoproteins in lipid metabolic regulation. Our findings reveal a novel and significant function of heart-mediated apoB-lipoproteins in controlling lipid homeostasis. PMID:28095410

Triglyceride-rich lipoproteins as a causal factor for cardiovascular disease

PubMed Central

Toth, Peter P

2016-01-01

Approximately 25% of US adults are estimated to have hypertriglyceridemia (triglyceride [TG] level ≥150 mg/dL [≥1.7 mmol/L]). Elevated TG levels are associated with increased cardiovascular disease (CVD) risk, and severe hypertriglyceridemia (TG levels ≥500 mg/dL [≥5.6 mmol/L]) is a well-established risk factor for acute pancreatitis. Plasma TG levels correspond to the sum of the TG content in TG-rich lipoproteins (TRLs; ie, very low-density lipoproteins plus chylomicrons) and their remnants. There remains some uncertainty regarding the direct causal role of TRLs in the progression of atherosclerosis and CVD, with cardiovascular outcome studies of TG-lowering agents, to date, having produced inconsistent results. Although low-density lipoprotein cholesterol (LDL-C) remains the primary treatment target to reduce CVD risk, a number of large-scale epidemiological studies have shown that elevated TG levels are independently associated with increased incidence of cardiovascular events, even in patients treated effectively with statins. Genetic studies have further clarified the causal association between TRLs and CVD. Variants in several key genes involved in TRL metabolism are strongly associated with CVD risk, with the strength of a variant’s effect on TG levels correlating with the magnitude of the variant’s effect on CVD. TRLs are thought to contribute to the progression of atherosclerosis and CVD via a number of direct and indirect mechanisms. They directly contribute to intimal cholesterol deposition and are also involved in the activation and enhancement of several proinflammatory, proapoptotic, and procoagulant pathways. Evidence suggests that non-high-density lipoprotein cholesterol, the sum of the total cholesterol carried by atherogenic lipoproteins (including LDL, TRL, and TRL remnants), provides a better indication of CVD risk than LDL-C, particularly in patients with hypertriglyceridemia. This article aims to provide an overview of the

Small, qualitative changes in fatty acid intake decrease plasma low-density lipoprotein-cholesterol levels in mildly hypercholesterolemic outpatients on their usual high-fat diets.

PubMed

Lecerf, Jean-Michel; Luc, Gérald; Marécaux, Nadine; Bal, Sylvie; Bonte, Jean-Paul; Lacroix, Brigitte; Cayzeele, Amélie

2009-01-01

The diet is the first step in managing hypercholesterolemia. The objective of the present study is to assess whether moderate changes in dietary fatty acids improve plasma lipid parameters in mildly hypercholesterolemic outpatients. Using a randomized double-blind study, 121 outpatients within two groups received an isocaloric amount of unsaturated margarine or butter. Clinical and anthropometric measurements and a 3-day food record were made. Chi-square and Fisher's tests were used to compare qualitative variables and the general linear procedure was used to compare the groups. Additional analyses were performed after adjustment. There was a significant difference (P <0.03) in low-density lipoprotein-cholesterol levels between the groups. Total cholesterol, low-density lipoprotein-cholesterol, non-high-density lipoprotein-cholesterol and apolipoprotein B values decreased in the unsaturated group in comparison with the saturated group. Low-density lipoprotein-cholesterol changes were correlated with the variation in polyunsaturated fatty acid intake and with plasma phospholipid linoleic acid levels. A small change in saturated by polyunsaturated fatty acid intake may improve plasma lipid parameters in mildly hypercholesterolemic subjects.

Interior noise control ground test studies for advanced turboprop aircraft applications

NASA Technical Reports Server (NTRS)

Simpson, Myles A.; Cannon, Mark R.; Burge, Paul L.; Boyd, Robert P.

1989-01-01

The measurement and analysis procedures are documented, and the results of interior noise control ground tests conducted on a DC-9 aircraft test section are summarized. The objectives of these tests were to study the fuselage response characteristics of treated and untreated aircraft with aft-mount advanced turboprop engines and to analyze the effectiveness of selected noise control treatments in reducing passenger cabin noise on these aircraft. The results of fuselage structural mode surveys, cabin cavity surveys and sound intensity surveys are presented. The performance of various structural and cabin sidewall treatments is assessed, based on measurements of the resulting interior noise levels under simulated advanced turboprop excitation.

Advanced Stirling Convertor Testing at NASA Glenn Research Center

NASA Technical Reports Server (NTRS)

Wilson, Scott D.; Poriti, Sal

2010-01-01

The NASA Glenn Research Center (GRC) has been testing high-efficiency free-piston Stirling convertors for potential use in radioisotope power systems (RPSs) since 1999. The current effort is in support of the Advanced Stirling Radioisotope Generator (ASRG), which is being developed by the U.S. Department of Energy (DOE), Lockheed Martin Space Systems Company (LMSSC), Sunpower, Inc., and the NASA GRC. This generator would use two high-efficiency Advanced Stirling Convertors (ASCs) to convert thermal energy from a radioisotope heat source into electricity. As reliability is paramount to a RPS capable of providing spacecraft power for potential multi-year missions, GRC provides direct technology support to the ASRG flight project in the areas of reliability, convertor and generator testing, high-temperature materials, structures, modeling and analysis, organics, structural dynamics, electromagnetic interference (EMI), and permanent magnets to reduce risk and enhance reliability of the convertor as this technology transitions toward flight status. Convertor and generator testing is carried out in short- and long-duration tests designed to characterize convertor performance when subjected to environments intended to simulate launch and space conditions. Long duration testing is intended to baseline performance and observe any performance degradation over the life of the test. Testing involves developing support hardware that enables 24/7 unattended operation and data collection. GRC currently has 14 Stirling convertors under unattended extended operation testing, including two operating in the ASRG Engineering Unit (ASRG-EU). Test data and high-temperature support hardware are discussed for ongoing and future ASC tests with emphasis on the ASC-E and ASC-E2.

Diet and the role of lipoproteins, lipases, and thyroid hormones in coronary lesion growth

NASA Technical Reports Server (NTRS)

Barth, Jacques D.; Jansen, Hans; Reiber, Johan H. C.; Birkenhager, Jan C.; Kromhout, Daan

1987-01-01

The relationships between the coronary lesion growth and the blood contents of lipoprotein fractions, thyroic hormones, and the lipoprotein lipase activity were investigated in male patients with severe coronary atherosclerosis, who participated in a lipid-lowering dietary intervention program. A quantitative computer-assisted image-processing technique was used to assess the severity of coronary obstructions at the beginning of the program and at its termination two years later. Based on absolute coronary scores, patients were divided into a no-lesion growth group (14 patients) and a progression group (21 paients). At the end of the trial, the very-low-density lipoprotein cholesterol and triglycerides were found to be significantly higher, while the high-density lipoprotein cholesterol and hepatic lipase (HL) were lower in the progression group. Multivariate regression analysis showed HL to be the most important determinant of changes in coronary atherosclerotic lesions.

Advancing Test Capabilities at NASA Wind Tunnels

NASA Technical Reports Server (NTRS)

Bell, James

2015-01-01

NASA maintains twelve major wind tunnels at three field centers capable of providing flows at 0.1 M 10 and unit Reynolds numbers up to 45106m. The maintenance and enhancement of these facilities is handled through a unified management structure under NASAs Aeronautics and Evaluation and Test Capability (AETC) project. The AETC facilities are; the 11x11 transonic and 9x7 supersonic wind tunnels at NASA Ames; the 10x10 and 8x6 supersonic wind tunnels, 9x15 low speed tunnel, Icing Research Tunnel, and Propulsion Simulator Laboratory, all at NASA Glenn; and the National Transonic Facility, Transonic Dynamics Tunnel, LAL aerothermodynamics laboratory, 8 High Temperature Tunnel, and 14x22 low speed tunnel, all at NASA Langley. This presentation describes the primary AETC facilities and their current capabilities, as well as improvements which are planned over the next five years. These improvements fall into three categories. The first are operations and maintenance improvements designed to increase the efficiency and reliability of the wind tunnels. These include new (possibly composite) fan blades at several facilities, new temperature control systems, and new and much more capable facility data systems. The second category of improvements are facility capability advancements. These include significant improvements to optical access in wind tunnel test sections at Ames, improvements to test section acoustics at Glenn and Langley, the development of a Supercooled Large Droplet capability for icing research, and the development of an icing capability for large engine testing. The final category of improvements consists of test technology enhancements which provide value across multiple facilities. These include projects to increase balance accuracy, provide NIST-traceable calibration characterization for wind tunnels, and to advance optical instruments for Computational Fluid Dynamics (CFD) validation. Taken as a whole, these individual projects provide significant

Wave Energy Prize - 1/50th Testing - Advanced Ocean Energy @ VT

DOE Data Explorer

Wesley Scharmen

2016-01-29

This submission of data includes all the 1/50th scale testing data completed on the Wave Energy Prize for the for the Advanced Ocean Energy @VT team, and includes: 1/50th test data (raw & processed) 1/50th test data video and pictures 1/50th Test plans and testing documents SSTF_Submission (summarized results)

Postprandial triglyceride-rich lipoproteins regulate perilipin-2 and perilipin-3 lipid-droplet-associated proteins in macrophages.

PubMed

Varela, Lourdes M; López, Sergio; Ortega-Gómez, Almudena; Bermúdez, Beatriz; Buers, Insa; Robenek, Horst; Muriana, Francisco J G; Abia, Rocío

2015-04-01

Lipid accumulation in macrophages contributes to atherosclerosis. Within macrophages, lipids are stored in lipid droplets (LDs); perilipin-2 and perilipin-3 are the main LD-associated proteins. Postprandial triglyceride (TG)-rich lipoproteins induce LD accumulation in macrophages. The role of postprandial lipoproteins in perilipin-2 and perilipin-3 regulation was studied. TG-rich lipoproteins (TRLs) induced the levels of intracellular TGs, LDs and perilipin-2 protein expression in THP-1 macrophages and in Apoe(-/-) mice bone-marrow-derived macrophages with low and high basal levels of TGs. Perilipin-3 was only synthesized in mice macrophages with low basal levels of TGs. The regulation was dependent on the fatty acid composition of the lipoproteins; monounsaturated and polyunsaturated fatty acids (PUFAs) more strongly attenuated these effects compared with saturated fatty acids. In THP-1 macrophages, immunofluorescence microscopy and freeze-fracture immunogold labeling indicated that the lipoproteins translocated perilipin-3 from the cytoplasm to the LD surface; only the lipoproteins that were rich in PUFAs suppressed this effect. Chemical inhibition showed that lipoproteins induced perilipin-2 protein expression through the peroxisome proliferator-activated nuclear receptor (PPAR) PPARα and PPARγ pathways. Overall, our data indicate that postprandial TRLs may be involved in atherosclerotic plaque formation through the regulation of perilipin-2 and perilipin-3 proteins in macrophages. Because the fatty acid composition of the lipoproteins is dependent on the type of fat consumed, the ingestion of olive oil, which is rich in monounsaturated fatty acids, and fish oil, which is rich in omega-3 fatty acids, can be considered a good nutritional strategy to reduce the risk of atherosclerosis by LD-associated proteins decrease. Copyright © 2015 Elsevier Inc. All rights reserved.

The influence of a high level of corn oil on rat serum lipoproteins.

PubMed

Narayan, K A; McMullen, J J; Butler, D P; Wakefield, T; Calhoun, W K

1976-01-01

Although the stated requirement for linoleic acid in humans is less than 2% of the dietary calories, recently there has been considerable emphasis on the necessity to substitute dietary polyunsaturates for saturates in order to reduce serum cholesterol levels. In this study we have sought to determine the nutritional consequences of feeding a very high level of linoleate to rats. Three groups of thirty adult animals each were fed a semipurified diet consisting by weight of casein 17%; mineral mixture 5.5%; vitamin mixture in glucose 2.2%; cellulose fiber 3.0%; and corn oil 0% (group A), 10% (group B) or 40% (group C), which was provided at the expense of glucose. At the end of four weeks on the diets, blood was obtained in the fasting state from 16 rats in each group. The serum was ultracentrifugally fractionated into six classes of lipoproteins and analyzed for lipid composition and protein content. Disc gel electrophoresis using lipid and protein stains established that the various lipoprotein subclasses were reasonably free of adjacent density fractions. Although the total serum cholesterol levels were practically the same in the three groups, the cholesterol moiety of the major low density lipoproteins, LDL2 (d 1.019-1.050), but not of very low density lipoproteins, VLDL (d 1.006) or low density lipoproteins, LDL1 (d 1.006-1.019), was substantially and very significantly increased in rats fed the high level of corn oil as compared to the other groups. The concentration of the very low density lipoproteins was significantly lower in group C than in the groups A and B. The LDL2 concentration but not that of LDL1 was significantly greater in group C as compared to group A. The cholesterol/total lipid ratio was significantly greater in both LDL2 and LDL1 but not in VLDL of group C as compared with group A. The serum high density lipoproteins were relatively less influenced by the ingestion of an excessive level of corn oil at this time period. The serum lipoprotein

Plasma lipoprotein and apolipoprotein distribution as a function of density in the rainbow trout (Salmo gairdneri).

PubMed Central

Babin, P J

1987-01-01

I have previously described [Babin (1987) J. Biol. Chem. 262, 4290-4296] the apolipoprotein composition of the major classes of trout plasma lipoproteins. The present work describes the use of an isopycnic density gradient centrifugation procedure and sequential flotation ultracentrifugation to show: (1) the presence of intermediate density lipoproteins (IDL) in the plasma, between 1.015 and 1.040 g/ml; (2) the existence of a single type of Mr 240,000 apoB-like in the low density lipoproteins (LDL, 1.040 less than p less than 1.085 g/ml); (3) the presence of apoA-I-like (Mr 25,000) in the densest LDL; (4) the adequacy of 1.085 g/ml as a cutoff between the LDL and high density lipoproteins (HDL); (5) the accumulation of Mr 55,000 and 76,000 apolipoproteins and apoA-like apolipoproteins in the 1.21 g/ml infranatant. The fractionation of trout lipoprotein spectrum thus furnishes the distribution of the different lipoprotein classes and leads to the description of the constituent apolipoproteins, which account for about 36% of circulating plasma proteins in this species. Images Fig. 2. Fig. 3. PMID:3689318

Port-of-entry advanced sorting system (PASS) operational test

DOT National Transportation Integrated Search

1998-12-01

In 1992 the Oregon Department of Transportation undertook an operational test of the Port-of-Entry Advanced Sorting System (PASS), which uses a two-way communication automatic vehicle identification system, integrated with weigh-in-motion, automatic ...

Pharmacologic management of isolated low high-density lipoprotein syndrome.

PubMed

Bermúdez, Valmore; Cano, Raquel; Cano, Clímaco; Bermúdez, Fernando; Arraiz, Nailet; Acosta, Luis; Finol, Freddy; Pabón, María Rebeca; Amell, Anilsa; Reyna, Nadia; Hidalgo, Joaquin; Kendall, Paúl; Manuel, Velasco; Hernández, Rafael

2008-01-01

High-density lipoprotein (HDL) cholesterol is a heterogeneous group of lipoproteins exhibiting a variety of properties like prostacyclin production stimulation, decrease in platelet aggregation, endothelial cell apoptosis inhibition, and low-density lipoprotein oxidation blockade. Epidemiologic studies have shown an inverse relation between HDL cholesterol levels and cardiovascular risk. Low HDL cholesterol is associated with increased risk for myocardial infarction, stroke, sudden death, peripheral artery disease, and postangioplasty restenosis. In contrast, high HDL levels are associated with longevity and protection against atherosclerotic disease development. Given the evolving epidemic of obesity, diabetes mellitus, and metabolic syndrome, the prevalence of low HDL will continue to rise. In the United States, low HDL is present in 35% of men, 15% of women, and approximately 63% of patients with coronary artery disease. Data extracted from the Framingham study highlight that 1-mg increase in HDL levels decreases by 2% to 3% the risk of cardiovascular disease. There is no doubt regarding clinical importance about isolated low HDL, but relatively few clinicians consider a direct therapeutic intervention of this dyslipidemia. In this sense, lifestyle measures should be the first-line strategy to manage low HDL levels. On the other hand, pharmacologic options include niacin, fibrates, and statins. Fibrates appear to reduce risk preferentially in patients with low HDL with metabolic syndrome, whereas statins reduce risk across all levels of HDL. Torcetrapib, a cholesteryl esters transfer protein inhibitor, represented a hope to raise this lipoprotein; however, all clinical trials on this drug had ceased after ILLUMINATE, RADIANCE and ERASE trials had recorded an increase in mortality, rates of myocardial infarction, angina, and heart failure. In the near future, drugs as beta-glucans, Apo-A1 mimetic peptides, and ACAT inhibitors, are the new promises to treat this

Telemetry Tests Of The Advanced Receiver II

NASA Technical Reports Server (NTRS)

Hinedi, Sami M.; Bevan, Roland P.; Marina, Miguel

1993-01-01

Report describes telemetry tests of Advanced Receiver II (ARX-II): digital radio receiving subsystem operating on intermediate-frequency output of another receiving subsystem called "multimission receiver" (MMR), detecting carrier, subcarrier, and data-symbol signals transmitted by spacecraft, and extracts Doppler information from signals. Analysis of data shows performance of MMR/ARX-II system comparable and sometimes superior to performances of Blk-III/BPA and Blk-III/SDA/SSA systems.

Distinct Lipoprotein Curves in Normal Weight, Overweight, and Obese Children and Adolescents.

PubMed

Interator, Hagar; Lebenthal, Yael; Hoshen, Moshe; Safra, Inbar; Balicer, Ran; Leshno, Moshe; Shamir, Raanan

2017-12-01

Pediatric lipoprotein curves are based on population-based samples. As obesity, may alter lipoprotein levels, cutoffs not adjusted for body mass index (BMI) are potentially inappropriate. We aimed to develop distinct serum lipid curves based on sex- and BMI-percentiles for children and adolescents. Cross-sectional analysis included all healthy children and adolescents (age range 2-17 years) with available serum lipid concentrations (n = 152,820 of approximately 1.2 million children and adolescents per study year). These children and adolescents were categorized according to sex- and age-stratified BMI-percentiles: 100,375 normal weight (5th-85th percentile), 26,028 overweight (85th-95th percentile) and 26,417 obese (≥95th percentile) individuals. Excluded were individuals with hyperlipidemia, gastrointestinal disease, thyroid disease and lipid-lowering medications. Lambda-Mu-Sigma, smoothed percentile lipid curves were computed. Obese children had a lipid profile pattern throughout childhood and adolescence similar to that of normal weight subjects but with a significant upward shift in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides (TGs) and a downward shift in high-density lipoprotein-cholesterol (HDL-C). Obese boys had 13 mg/dL higher TC levels (P < 0.001), 11 mg/dL higher LDL-C levels, 15 mg/dL higher non-HDL-C levels, and 5 mg/dL lower HDL-C levels (P < 0.001). Obese girls had 6 mg/dL higher TC levels, 7 mg/dL higher LDL-C levels, 11 mg/dl higher non-HDL-C levels, and 6 mg/dL lower HDL-C levels (P < 0.001). Across a large, nationally representative cohort of children and adolescents, lipoprotein levels were found to vary in relation to weight status. On the basis of these findings, it is suggested that when evaluating the lipid profile in the pediatric population, in addition to sex-based curves, clinical decision making may require

Overview of an Advanced Hypersonic Structural Concept Test Program

NASA Technical Reports Server (NTRS)

Stephens, Craig A.; Hudson, Larry D.; Piazza, Anthony

2007-01-01

This viewgraph presentation provides an overview of hypersonics M&S advanced structural concepts development and experimental methods. The discussion on concepts development includes the background, task objectives, test plan, and current status of the C/SiC Ruddervator Subcomponent Test Article (RSTA). The discussion of experimental methods examines instrumentation needs, sensors of interest, and examples of ongoing efforts in the development of extreme environment sensors.

Lipoprotein composition and oxidative modification during therapy with gemfibrozil and lovastatin in patients with combined hyperlipidaemia

PubMed Central

Vázquez, M; Zambón, D; Hernández, Y; Adzet, T; Merlos, M; Ros, E; Laguna, J C

1998-01-01

Aims To evaluate the resistance to oxidation of human lipoproteins after hypolipidaemic therapy. Methods VLDL and LDL samples were obtained from patients with Familial Combined Hyperlipidaemia included in a randomized, double-blind, cross-over study, with 8 weeks of active treatment (gemfibrozil, 600 mg twice daily, or lovastatin, 40 mg daily) and a 4-week wash-out period. Oxidation related analytes after Cu-induced oxidation of VLDL and LDL have been investigated. Further, in order to relate possible changes in oxidative behaviour to lipoprotein composition, the proportion of the lipid species transported by lipoproteins (triglycerides, phospholipids, and cholesteryl esters), the molar composition of fatty acids for each lipoprotein lipid, and the content of antioxidant vitamins in plasma (vitamin C) and lipoproteins (vitamin E) have been studied. Results Both drugs reduced the plasma concentration of apo-B lipoproteins (−23% gemfibrozil, −26% lovastatin), but whereas lovastatin affected mainly LDL-cholesterol (−30%), gemfibrozil reduced triglycerides (−49%) and VLDL-cholesterol (−48%). Lovastatin treatment had no effect on the lipid and protein composition, the fatty acid profile, or the vitamin E content of either VLDL or LDL; likewise, lipoprotein oxidation markers (Cu-induced conjugated dienes, thiobarbituric acid reactive substances formation, and lysine residues) were similar before and after lovastatin treatment. Gemfibrozil therapy also had no effect on lipoprotein oxidation; nevertheless, it consistently: a) decreased the proportion of LDL-triglycerides (−32%), and b) increased the proportion (molar%) of 18:3 n-6 in VLDL triglycerides (+140%), phospholipids (+363%) and cholesteryl esters (+53%). Conclusions Based on these results, lovastatin and gemfibrozil do not adversely affect lipoprotein oxidation in patients with mixed dyslipidaemia. In the case of gemfibrozil, this occurs in spite of an increased proportion of some polyunsaturated fatty

Relationship of pericardial fat with lipoprotein distribution: The Multi-Ethnic study of atherosclerosis.

PubMed

Ong, Kwok-Leung; Ding, Jingzhong; McClelland, Robyn L; Cheung, Bernard M Y; Criqui, Michael H; Barter, Philip J; Rye, Kerry-Anne; Allison, Matthew A

2015-08-01

Pericardial fat and lipoprotein abnormalities contribute to increased risk of cardiovascular disease (CVD). We investigated the relationship between pericardial fat volume and lipoprotein distribution, and whether the association of pericardial fat volume with subclinical atherosclerosis and incident CVD events differs according to lipoprotein distribution. We analyzed data from 5407 participants from the Multi-Ethnic Study of Atherosclerosis who had measurements of pericardial fat volume, lipoprotein distribution, carotid intima-media thickness (IMT), and coronary artery calcium (CAC). All participants were free of clinically apparent CVD at baseline. Incident CVD was defined as any adjudicated CVD event. After adjusting for demographic factors, traditional risk factors, and biomarkers of inflammation and hemostasis, a larger pericardial fat volume was associated with higher large VLDL particle (VLDL-P) concentration and small HDL particle (HDL-P) concentration, and smaller HDL-P size (regression coefficients = 0.585 nmol/L, 0.366 μmol/L, and -0.025 nm per SD increase in pericardial fat volume respectively, all P < 0.05). The association of pericardial fat volume with large VLDL-P concentration and HDL-P size, but not small HDL-P concentration, remained significant after further adjusting for each other as well as LDL cholesterol, HDL cholesterol, and triglycerides. The relationship of pericardial fat volume with incident CVD events, carotid IMT, and prevalence and severity of CAC did not differ by quartiles of large VLDL-P concentration, small HDL-P concentration, or HDL-P size (P for interaction>0.05). Pericardial fat is associated with atherogenic lipoprotein abnormalities. However, its relationship with subclinical atherosclerosis and incident CVD events does not differ according to lipoprotein distribution. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Low-density lipoprotein electronegativity is a novel cardiometabolic risk factor.

PubMed

Hsu, Jing-Fang; Chou, Tzu-Chieh; Lu, Jonathan; Chen, Shu-Hua; Chen, Fang-Yu; Chen, Ching-Chu; Chen, Jeffrey L; Elayda, MacArthur; Ballantyne, Christie M; Shayani, Steven; Chen, Chu-Huang

2014-01-01

Low-density lipoprotein (LDL) plays a central role in cardiovascular disease (CVD) development. In LDL chromatographically resolved according to charge, the most electronegative subfraction-L5-is the only subfraction that induces atherogenic responses in cultured vascular cells. Furthermore, increasing evidence has shown that plasma L5 levels are elevated in individuals with high cardiovascular risk. We hypothesized that LDL electronegativity is a novel index for predicting CVD. In 30 asymptomatic individuals with metabolic syndrome (MetS) and 27 healthy control subjects, we examined correlations between plasma L5 levels and the number of MetS criteria fulfilled, CVD risk factors, and CVD risk according to the Framingham risk score. L5 levels were significantly higher in MetS subjects than in control subjects (21.9±18.7 mg/dL vs. 11.2±10.7 mg/dL, P:0.01). The Jonckheere trend test revealed that the percent L5 of total LDL (L5%) and L5 concentration increased with the number of MetS criteria (P<0.001). L5% correlated with classic CVD risk factors, including waist circumference, body mass index, waist-to-height ratio, smoking status, blood pressure, and levels of fasting plasma glucose, triglyceride, and high-density lipoprotein. Stepwise regression analysis revealed that fasting plasma glucose level and body mass index contributed to 28% of L5% variance. The L5 concentration was associated with CVD risk and contributed to 11% of 30-year general CVD risk variance when controlling the variance of waist circumference. Our findings show that LDL electronegativity was associated with multiple CVD risk factors and CVD risk, suggesting that the LDL electronegativity index may have the potential to be a novel index for predicting CVD. Large-scale clinical trials are warranted to test the reliability of this hypothesis and the clinical importance of the LDL electronegativity index.

Olive oil supplemented with Coenzyme Q(10): effect on plasma and lipoprotein oxidative status.

PubMed

Brugè, Francesca; Bacchetti, Tiziana; Principi, Federica; Scarpa, Emanuele-Salvatore; Littarru, Gian Paolo; Tiano, Luca

2012-01-01

Olive oil consumption is associated with protective cardiovascular properties, including some beneficial modifications in lipoprotein profile and composition. Coenzyme Q(10) (CoQ(10)) exerts a protective effect on plasma lipoproteins. Aim of the study was to investigate whether extra virgin (EV) olive oil enriched with CoQ(10) affects CoQ(10) levels and oxidative status in plasma and in isolated lipoproteins. Twelve subjects were administered 20 mL olive oil per day for 2 weeks, followed by 2 weeks of olive oil enriched with 20 mg and 2 more weeks with 40 mg of CoQ(10). Plasma and isolated lipoproteins were collected in each phase of the study and subsequently analyzed to assess lipid profile, CoQ10 levels, ORAC assay, resistance of lipoproteins to peroxidation and paroxonase 1 activity. Plasma CoQ(10) levels significantly increased with the 20 mg (+73%) and 40 mg dose (+170%), while the percentage of oxidized CoQ(10) decreased. A significant inverse correlation was found in plasma between percentage of oxidized CoQ(10) and total antioxidant capacity. A lower susceptibility of LDL to peroxidation was also found. Finally, a positive correlation was observed between concentration of CoQ(10) in HDL and paraoxonase-1 activity. EV olive oil enriched with both doses of CoQ(10) significantly affects its bioavailability and plasma redox status. These changes are associated with a decreased susceptibility of plasma lipoproteins to peroxidation associated with a chain-breaking antioxidant activity of the formulation. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

Lipoproteins, cholesterol homeostasis and cardiac health.

PubMed

Daniels, Tyler F; Killinger, Karen M; Michal, Jennifer J; Wright, Raymond W; Jiang, Zhihua

2009-06-29

Cholesterol is an essential substance involved in many functions, such as maintaining cell membranes, manufacturing vitamin D on surface of the skin, producing hormones, and possibly helping cell connections in the brain. When cholesterol levels rise in the blood, they can, however, have dangerous consequences. In particular, cholesterol has generated considerable notoriety for its causative role in atherosclerosis, the leading cause of death in developed countries around the world. Homeostasis of cholesterol is centered on the metabolism of lipoproteins, which mediate transport of the lipid to and from tissues. As a synopsis of the major events and proteins that manage lipoprotein homeostasis, this review contributes to the substantial attention that has recently been directed to this area. Despite intense scrutiny, the majority of phenotypic variation in total cholesterol and related traits eludes explanation by current genetic knowledge. This is somewhat disappointing considering heritability estimates have established these traits as highly genetic. Thus, the continued search for candidate genes, mutations, and mechanisms is vital to our understanding of heart disease at the molecular level. Furthermore, as marker development continues to predict risk of vascular illness, this knowledge has the potential to revolutionize treatment of this leading human disease.

Novel lipoprotein density profiling in healthy dogs of various breeds, healthy miniature schnauzers, and miniature schnauzers with hyperlipidemia

PubMed Central

2013-01-01

Background Despite the importance of abnormalities in lipoprotein metabolism in clinical canine medicine, the fact that most previously used methods for lipoprotein profiling are rather laborious and time-consuming has been a major obstacle to the wide clinical application and use of lipoprotein profiling in this species. The aim of the present study was to assess the feasibility of a continuous lipoprotein density profile (CLPDP) generated within a bismuth sodium ethylenediaminetetraacetic acid (NaBiEDTA) density gradient to characterize and compare the lipoprotein profiles of healthy dogs of various breeds, healthy Miniature Schnauzers, and Miniature Schnauzers with primary hypertriacylglycerolemia. A total of 35 healthy dogs of various breeds with serum triacylglycerol (TAG) and cholesterol concentrations within their respective reference intervals were selected for use as a reference population. Thirty-one Miniature Schnauzers with serum TAG and cholesterol concentrations within their respective reference intervals and 31 Miniature Schnauzers with hypertriacylglyceridemia were also included in the study. Results The results suggest that CLPDP using NaBiEDTA provides unique diagnostic information in addition to measurements of serum TAG and cholesterol concentrations and that it is a useful screening method for dogs with suspected lipoprotein metabolism disorders. Using the detailed and continuous density distribution information provided by the CLPDP, important differences in lipoprotein profiles can be detected even among dogs that have serum TAG and cholesterol concentrations within the reference interval. Miniature Schnauzers with serum TAG and cholesterol concentrations within the reference interval had significantly different lipoprotein profiles than dogs of various other breeds. In addition, it was further established that specific lipoprotein fractions are associated with hypertriacylglyceridemia in Miniature Schnauzers. Conclusions The results of the

Fetal macrosomia related to maternal poorly controlled type 1 diabetes strongly impairs serum lipoprotein concentrations and composition

PubMed Central

Merzouk, H; Bouchenak, M; Loukidi, B; Madani, S; Prost, J; Belleville, J

2000-01-01

Aims—To determine the effects of fetal macrosomia related to maternal type 1 diabetes on the lipid transport system. Methods—Serum lipoprotein concentrations and composition and lecithin:cholesterol acyltransferase (LCAT) activity were investigated in macrosomic newborns (mean birth weight, 4650 g; SEM, 90) and their mothers with poorly controlled type 1 diabetes, in appropriate for gestational age newborns (mean birth weight, 3616 g; SEM, 68) and their mothers with well controlled type 1 diabetes, and macrosomic (mean birth weight, 4555 g; SEM, 86) or appropriate for gestational age (mean birth weight, 3290 g; SEM, 45) newborns and their healthy mothers. Results—In mothers with well controlled type 1 diabetes, serum lipids, apolipoproteins, and lipoproteins were comparable with those of healthy mothers. Similarly, in their infants, these parameters did not differ from those of appropriate for gestational age newborns. Serum triglyceride, very low density lipoprotein (VLDL), apolipoprotein B100 (apo B100), and high density lipoprotein (HDL) triglyceride concentrations were higher, whereas serum apo A-I and HDL3 concentrations were lower in mothers with diabetes and poor glycaemic control than in healthy mothers. Their macrosomic newborns had higher concentrations in all serum lipids and lipoproteins, with high apo A-I and apo B100 values compared with appropriate for gestational age newborns. In macrosomic infants of healthy mothers, there were no significant differences in lipoprotein profiles compared with those of appropriate for gestational age infants. LCAT activity was similar in both groups of mothers and newborns. Conclusion—Poorly controlled maternal type 1 diabetes and fetal macrosomia were associated with lipoprotein abnormalities. Macrosomic lipoprotein profiles related to poor metabolic control of type 1 diabetes appear to have implications for later metabolic diseases. Key Words: apolipoproteins • lipids • lipoproteins • lecithin

Space station experiment definition: Advanced power system test bed

NASA Technical Reports Server (NTRS)

Pollard, H. E.; Neff, R. E.

1986-01-01

A conceptual design for an advanced photovoltaic power system test bed was provided and the requirements for advanced photovoltaic power system experiments better defined. Results of this study will be used in the design efforts conducted in phase B and phase C/D of the space station program so that the test bed capabilities will be responsive to user needs. Critical PV and energy storage technologies were identified and inputs were received from the idustry (government and commercial, U.S. and international) which identified experimental requirements. These inputs were used to develop a number of different conceptual designs. Pros and cons of each were discussed and a strawman candidate identified. A preliminary evolutionary plan, which included necessary precursor activities, was established and cost estimates presented which would allow for a successful implementation to the space station in the 1994 time frame.

Effect of dietary fat source on lipoprotein composition and plasma lipid concentrations in pigs.

PubMed

Faidley, T D; Luhman, C M; Galloway, S T; Foley, M K; Beitz, D C

1990-10-01

Most studies of the effects of dietary fat sources on plasma lipid components have used diets with extreme fat compositions; the current study was designed to more nearly mimic human dietary fat intake. Young growing pigs were fed diets containing either 20 or 40% of energy as soy oil, beef tallow or a 50/50 blend of soy oil and tallow. Different dietary fats did not affect concentrations of cholesterol, triacylglycerol or protein in plasma or major lipoprotein fractions. The concentration of phospholipid was less in plasma and in very low density lipoproteins with soy oil feeding than with tallow feeding. The weight percentage of cholesteryl ester in the low density lipoprotein fraction tended to be greater with 40% than with 20% tallow and tended to be less with 40% than with 20% soy oil. Phospholipid as a weight percentage of low density lipoprotein was least in pigs fed soy oil. Tallow feeding increased the percentage of myristic, palmitic, palmitoleic and oleic acids in plasma, relative to both other groups. Soy oil feeding increased the percentage of linoleic and linolenic acids. These moderate diets were not hypercholesterolemic, but they did alter plasma fatty acid composition and phospholipid concentrations in plasma and very low density lipoprotein.

Low-fat dietary pattern and lipoprotein risk factors: the Women's Health Initiative Dietary Modification Trial1234

PubMed Central

Curb, J David; Eaton, Charles B; Kooperberg, Charles; Ockene, Judith; Kostis, John B; Pettinger, Mary; Rajkovic, Aleksandar; Robinson, Jennifer G; Rossouw, Jacques; Sarto, Gloria; Shikany, James M; Van Horn, Linda

2010-01-01

Background: The Women's Health Initiative Dietary Modification Trial tested the effects on chronic disease of a dietary pattern lower in fat and higher in vegetables, fruit, and grains. Objective: The objective was to evaluate the effects of dietary carbohydrate changes on lipids and lipoprotein composition. Design: Postmenopausal women were randomly assigned to an intervention or a comparison group for a mean of 8.1 y. Lipoprotein analyses and subclasses were based on subsamples of 2730 and 209 participants, respectively. Results: At year 6, the total reported fat intake was 7.8% lower and carbohydrate intake was 7.6% higher in the intervention group than in the comparison group. Triglyceride change between groups differed by 2.3, 3.8, and −0.8 mg/dL at 1, 3, and 6 y, respectively, and HDL-cholesterol change differed by −1.6, −0.7, and −1.0 mg/dL at 1, 3, and 6 y, respectively. Changes did not differ by age, ethnicity, or obesity. In diabetic intervention women who were white, the triglyceride difference between the intervention and comparison groups was 33.8 mg/dL, whereas in black women with diabetes (n = 50 in the intervention group; n = 83 in the comparison group), the triglyceride difference was 6.4 mg/dL (P for 3-factor interaction = 0.049). No significant changes were observed in apolipoprotein or lipoprotein particles. Reductions in LDL cholesterol varied by quartile of reported lowering of saturated or trans fat. Conclusions: The replacement of 7–8% of fat intake with complex carbohydrates over 6 y was not associated with clinically adverse effects on triglycerides, HDL cholesterol, or lipoprotein subclasses. Diabetic white women with higher triglyceride concentrations may have greater increases in triglycerides. PMID:20164311

The Associations of Indices of Obesity with Lipoprotein Subfractions in Japanese American, African American and Korean Men

PubMed Central

Hirooka, Nobutaka; Shin, Chol; Masaki, Kamal H.; Edmundowicz, Daniel; Choo, Jina; Barinas-Mitchell, Emma J.M.; Willcox, Bradley J.; Sutton-Tyrrell, Kim; El-Saed, Aiman; Miljkovic-Gacic, Iva; Ohkubo, Takayoshi; Miura, Katsuyuki; Ueshima, Hirotsugu; Kuller, Lewis H.; Sekikawa, Akira

2013-01-01

Background Both indices of obesity and lipoprotein subfractions contribute to coronary heart disease risk. However, associations between indices of obesity and lipoprotein subfractions remain undetermined across different ethnic groups. This study aims to examine the associations of indices of obesity in Japanese Americans (JA), African Americans (AA) and Koreans with lipoprotein subfractions. Methods A population-based sample of 230 JA, 91 AA, and 291 Korean men aged 40–49 was examined for indices of obesity, i.e., visceral and subcutaneous adipose tissue (VAT and SAT, respectively), waist circumference (WC), and body-mass index (BMI), and for lipoprotein subfractions by nuclear-magnetic-resonance spectroscopy. Multiple regression analyses were performed in each of the three ethnic groups to examine the associations of each index of obesity with lipoprotein. Results VAT had significant positive associations with total and small low-density lipoprotein (LDL) and a significant negative association with large high-density lipoprotein (HDL) in all three ethnicities (p < 0.01). SAT, WC, and BMI had significant positive associations with total and small LDL in only JA and Koreans, while these indices had significant inverse associations with large HDL in all ethnic groups (p < 0.01). Compared to SAT, VAT had larger R2 values in the associations with total and small LDL and large HDL in all three ethnic groups. Conclusions VAT is significantly associated with total and small LDL and large HDL in all three ethnic groups. The associations of SAT, WC, and BMI with lipoprotein subfractions are weaker compared to VAT in all three ethnic groups. PMID:25068101

Association between ABCG1 polymorphism rs1893590 and high-density lipoprotein (HDL) in an asymptomatic Brazilian population.

PubMed

Zago, V H S; Scherrer, D Z; Parra, E S; Panzoldo, N B; Alexandre, F; Nakandakare, E R; Quintão, E C R; de Faria, E C

2015-03-01

ATP binding cassette transporter G1 (ABCG1) promotes lipidation of nascent high-density lipoprotein (HDL) particles, acting as an intracellular transporter. SNP rs1893590 (c.-204A > C) of ABCG1 gene has been previously studied and reported as functional over plasma HDL-C and lipoprotein lipase activity. This study aimed to investigate the relationships of SNP rs1893590 with plasma lipids and lipoproteins in a large Brazilian population. Were selected 654 asymptomatic and normolipidemic volunteers from both genders. Clinical and anthropometrical data were taken and blood samples were drawn after 12 h fasting. Plasma lipids and lipoproteins, as well as HDL particle size and volume were determined. Genomic DNA was isolated for SNP rs1893590 detection by TaqMan(®) OpenArray(®) Real-Time PCR Plataform (Applied Biosystems). Mann-Whitney U, Chi square and two-way ANOVA were the used statistical tests. No significant differences were found in the comparison analyses between the allele groups for all studied parameters. Conversely, significant interactions were observed between SNP and age over plasma HDL-C, were volunteers under 60 years with AA genotype had increased HDL-C (p = 0.048). Similar results were observed in the group with body mass index (BMI) < 25 kg/m(2), where volunteers with AA genotype had higher HDL-C levels (p = 0.0034), plus an increased HDL particle size (p = 0.01). These findings indicate that SNP rs1893590 of ABCG1 has a significant impact over HDL-C under asymptomatic clinical conditions in an age and BMI dependent way.

Advances in Educational and Psychological Testing: Theory and Applications. Evaluation in Education and Human Services Series.

ERIC Educational Resources Information Center

Hambleton, Ronald K., Ed.; Zaal, Jac N., Ed.

The 14 chapters of this book focus on the technical advances, advances in applied settings, and emerging topics in the testing field. Part 1 discusses methodological advances, Part 2 considers developments in applied settings, and Part 3 reviews emerging topics in the field of testing. Part 1 papers include: (1) "Advances in…

Serum high density lipoprotein cholesterol, alcohol, and coronary mortality in male smokers.

PubMed Central

Paunio, M.; Virtamo, J.; Gref, C. G.; Heinonen, O. P.

1996-01-01

OBJECTIVE--To determine whether the increase in mortality from coronary heart disease with high concentration (> 1.75 mmol/l) of high density lipoprotein cholesterol could be due to alcohol intake. DESIGN--Cohort study. SETTING--Placebo group of the alpha tocopherol, beta carotene cancer prevention (ATBC) study of south western population in Finland. PARTICIPANTS--7052 male smokers aged 50-69 years enrolled to the ATBC study in the 1980s. MAIN OUTCOME MEASURES--The relative and absolute rates adjusted for risk factors for clinically or pathologically verified deaths from coronary heart disease for different concentrations of high density lipoprotein cholesterol with and without stratification for alcohol intake. Similar rates were also calculated for different alcohol consumption groups. RESULTS--During the average follow up period of 6.7 years 258 men died from verified coronary heart disease. Coronary death rate steadily decreased with increasing concentration of high density lipoprotein cholesterol until a high concentration. An increase in the rate was observed above 1.75 mmol/l. This increase occurred among those who reported alcohol intake. Mortality was associated with alcohol intake in a J shaped dose response, and those who reported consuming more than five drinks a day (heavy drinkers) had the highest death rate. Mortality was higher in heavy drinkers than in non-drinkers or light or moderate drinkers in all high density lipoprotein categories from 0.91 mmol/l upward. CONCLUSIONS--Mortality from coronary heart disease increases at concentrations of high density lipoprotein cholesterol over 1.75 mmol/l. The mortality was highest among heavy drinkers, but an increase was found among light drinkers also. PMID:8634563

Effect of losartan and spironolactone on triglyceride-rich lipoproteins in diabetic nephropathy

PubMed Central

Srivastava, Anand; Adams-Huet, Beverley; Vega, Gloria L; Toto, Robert D

2016-01-01

Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) can improve dyslipidemia in patients with diabetes and albuminuria. Whether combined ACEi+ARB or ACEi+mineralocorticoid receptor blockade improves dyslipidemia is not known. We hypothesized long-term administration of either losartan 100 mg or spironolactone 25 mg once daily added onto lisinopril 80 mg once daily would improve dyslipidemia in diabetic nephropathy (DN). We measured lipid levels, very-low-density (V), intermediate-density (I), low-density (LDL), high-density (HDL) lipoprotein, LDL particle size with their respective cholesterol (C) and apolipoprotein B levels (ApoB), and urine albumin/creatinine ratio (UACR) at 12-week interval during a 48-week randomized, double-blind placebo-controlled trial in 81 patients with DN. Plasma lipids and lipoprotein C were analyzed enzymatically and Apo B was determined chemically. Data were analyzed by mixed model repeated measures. ΔUACR differed among treatment arms (placebo −24.6%, los −38.2%, spiro −51.6%, p=0.02). No correlation existed between ΔUACR and ΔTG or any of the lipid or lipoprotein measurements. Compared with placebo losartan, but not spironolactone, decreased TG (−20.9% vs +34.3%, p<0.01), V+I C(−18.8% vs +21.3%, p<0.01), and V+I-ApoB (−13.2% vs +21%, p<0.01). There were no significant changes in body weight, HbA1c or other lipoprotein variables. We conclude losartan improves dyslipidemia in patients with DN. We speculate the mechanism improved clearance of VLDL and remnant lipoproteins. Trial registration number NCT00381134; Results. PMID:27388615

Potential use of cholesterol lipoprotein profile to confirm obesity status in dogs.

PubMed

Mori, Nobuko; Lee, Peter; Kondo, Kazuo; Kido, Toshimi; Saito, Terumasa; Arai, Toshiro

2011-04-01

A common sign of obesity, in dogs, is hyperlipidemia, which is characterized by hypercholesterolemia and/or hypertriglycemia. Hyperlipidemia can be caused by a quantitative increase in circulating lipoproteins (LP) or by a higher lipid concentration in the various LP classes. In this study, we sought to determine whether aberrations occur with cholesterol lipoprotein profile, especially with sub HDL-cholesterol fraction % in obese dogs. Using clinically healthy and disease free (no overt signs) body condition score classified obese dogs, of all ages, we attempted to determine the influence of age, gender and obesity status on cholesterol lipoprotein profiling. Overall, no aberration in pattern was observed in obese dogs <8 years of age. However, in older obese animals (≥8 years of age), the general aberration pattern to cholesterol lipoprotein observed was that a significant decrease in HDL2 and 3 fraction % occurs with a concomitant increase in either HDL1-Cho or VLDL and LDL -Cho fraction % depending on gender. Linear regression analysis indicated that obesity status appears to significantly affect total cholesterol, HDL2 and 3-Cho, VLDL and LDL-Cho levels (P=0.02, 0.046, and 0.045, respectively), whereas it is borderline with HDL1-Cho (P=0.062). On the other hand, age significantly influenced TG, Total cholesterol, and HDL1-Cho levels (P=0.009, 0.006, and 0.002, respectively), while gender influenced VLDL and LDL-Cho (P=0.024) level. Therefore, aberrations in cholesterol lipoprotein profile pattern might be of potential use to assess and diagnose obesity status, in conjunction with BCS, especially of older overweight animals which might be considered borderline obese. © Springer Science+Business Media B.V. 2011

Serum prolactin, leptin, lipids and lipoproteins levels during antipsychotics treatment in Parkinson's disease and related psychosis.

PubMed

Rustembegovic, Avdo; Sofic, Emin; Wichart, Ildiko

2006-01-01

Weight gain is a common adverse effect associated with the use of most typical and atypical antipsychotic. Aim of this study was to investigate serum prolactin, leptin, cholesterol, triglyceride, lipoproteins, such high density lipoprotein (HDL), and low density lipoprotein (LDL) levels in patients with Parkinson's disease (PD)-related psychosis during long-term medication with atypical antipsychotic. The study population comprised 40 patients, who were divided into 4 groups: olanzapine (n=10), risperidone (n=10), seroquel (n=10) monotherapy, a group of 10 patients receiving only antiparkinson drugs and a control group of 8 healthy persons. The patients were evaluated at baseline and at the sixth and twelfth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), and fasting serum prolactin, leptin, lipids and lipoproteins levels. Treatment of patients with olanzapine caused marked increase of serum LDL, cholesterol, triglyceride, and leptin levels (p<0,02). No changes in HDL concentrations. There was positive relationship between serum leptin, lipid levels and BMI. However, treatment of patients with seroquel did not cause changes in serum prolactin, leptin, lipids, and lipoproteins levels. Our results suggest that treatment of patients with PD-related psychosis with seroquel appears to have minimal influence on serum leptin, prolactin, lipids, lipoproteins and BMI compared with olanzapine and risperidone.

Standardizing biomarker testing for Canadian patients with advanced lung cancer

PubMed Central

Melosky, B.; Blais, N.; Cheema, P.; Couture, C.; Juergens, R.; Kamel-Reid, S.; Tsao, M.-S.; Wheatley-Price, P.; Xu, Z.; Ionescu, D.N.

2018-01-01

Background The development and approval of both targeted and immune therapies for patients with advanced non-small cell lung cancer (nsclc) has significantly improved patient survival rates and quality of life. Biomarker testing for patients newly diagnosed with nsclc, as well as for patients progressing after treatment with epidermal growth factor receptor (EGFR) inhibitors, is the standard of care in Canada and many parts of the world. Methods A group of thoracic oncology experts in the field of thoracic oncology met to describe the standard for biomarker testing for lung cancer in the Canadian context, focusing on evidence-based recommendations for standard-of-care testing for EGFR, anaplastic lymphoma kinase (ALK), ROS1, BRAF V600 and programmed death-ligand (PD-L1) at the time of diagnosis of advanced disease and EGFR T790M upon progression. As well, additional exploratory molecules and targets are likely to impact future patient care, including MET exon 14 skipping mutations and whole gene amplification, RET translocations, HER2 (ERBB2) mutations, NTRK, RAS (KRAS and NRAS), as well as TP53. Results The standard of care must include the incorporation of testing for novel biomarkers as they become available, as it will be difficult for national guidelines to keep pace with technological advances in this area. Conclusions Canadian patients with nsclc should be treated equally; the minimum standard of care is defined in this paper. PMID:29507487

The renaissance of lipoprotein(a): Brave new world for preventive cardiology?

PubMed

Ellis, Katrina L; Boffa, Michael B; Sahebkar, Amirhossein; Koschinsky, Marlys L; Watts, Gerald F

2017-10-01

Lipoprotein(a) [Lp(a)] is a highly heritable cardiovascular risk factor. Although discovered more than 50 years ago, Lp(a) has recently re-emerged as a major focus in the fields of lipidology and preventive cardiology owing to findings from genetic studies and the possibility of lowering elevated plasma concentrations with new antisense therapy. Data from genetic, epidemiological and clinical studies have provided compelling evidence establishing Lp(a) as a causal risk factor for atherosclerotic cardiovascular disease. Nevertheless, major gaps in knowledge remain and the identification of the mechanistic processes governing both Lp(a) pathobiology and metabolism are an ongoing challenge. Furthermore, the complex structure of Lp(a) presents a major obstacle to the accurate quantification of plasma concentrations, and a universally accepted and standardized approach for measuring Lp(a) is required. Significant progress has been made in the development of novel therapeutics for selectively lowering Lp(a). However, before these therapies can be widely implemented further investigations are required to assess their efficacy, safety, and cost-efficiency in the prevention of cardiovascular events. We review recent advances in molecular and biochemical aspects, epidemiology, and pathobiology of Lp(a), and provide a contemporary update on the significance of Lp(a) in clinical medicine. "Progress lies not in enhancing what is, but in advancing toward what will be." (Khalil Gibran). Copyright © 2017 Elsevier Ltd. All rights reserved.

Validation test of advanced technology for IPV nickel-hydrogen flight cells: Update

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Hall, Stephen W.

1992-01-01

Individual pressure vessel (IPV) nickel-hydrogen technology was advanced at NASA Lewis and under Lewis contracts with the intention of improving cycle life and performance. One advancement was to use 26 percent potassium hydroxide (KOH) electrolyte to improve cycle life. Another advancement was to modify the state-of-the-art cell design to eliminate identified failure modes. The modified design is referred to as the advanced design. A breakthrough in the low-earth-orbit (LEO) cycle life of IPV nickel-hydrogen cells has been previously reported. The cycle life of boiler plate cells containing 26 percent KOH electrolyte was about 40,000 LEO cycles compared to 3,500 cycles for cells containing 31 percent KOH. The boiler plate test results are in the process of being validated using flight hardware and real time LEO testing at the Naval Weapons Support Center (NWSC), Crane, Indiana under a NASA Lewis Contract. An advanced 125 Ah IPV nickel-hydrogen cell was designed. The primary function of the advanced cell is to store and deliver energy for long-term, LEO spacecraft missions. The new features of this design are: (1) use of 26 percent rather than 31 percent KOH electrolyte; (2) use of a patented catalyzed wall wick; (3) use of serrated-edge separators to facilitate gaseous oxygen and hydrogen flow within the cell, while still maintaining physical contact with the wall wick for electrolyte management; and (4) use of a floating rather than a fixed stack (state-of-the-art) to accommodate nickel electrode expansion due to charge/discharge cycling. The significant improvements resulting from these innovations are: extended cycle life; enhanced thermal, electrolyte, and oxygen management; and accommodation of nickel electrode expansion. The advanced cell design is in the process of being validated using real time LEO cycle life testing of NWSC, Crane, Indiana. An update of validation test results confirming this technology is presented.

The Effects of Extended Release Niacin on Lipoprotein Sub-Particle Concentrations in HIV-Infected Patients

PubMed Central

Lin, Chunrong; Grandinetti, Andrew; Shikuma, Cecilia; Souza, Scott; Parikh, Nisha; Nakamoto, Beau; Kallianpur, Kalpana J

2013-01-01

With the advent of highly active antiretroviral therapy (HAART), Cardiovascular Disease (CVD) has emerged as the leading cause of death in Human Immunodeficiency Virus (HIV) infected patients. An atherogenic lipoprotein phenotype has been described in HIV- infected patients with a predominance of small, low density lipoprotein (SLDL) particles with accompanying elevated triglycerides and reduced high density lipoprotein cholesterol. This randomized controlled pilot study was conducted to evaluate the efficacy of Extended Release Niacin (ERN) in improving the lipid profile in HIV patients. A total of 17 HIV positive subjects on HAART therapy with High Density Lipoprotein Cholesterol (HDL) levels below 40mg/dl and Low Density Lipoprotein Cholesterol (LDL) below 130mg/dl were enrolled. Nine were randomized to be treated with ERN titrated from a starting level of 500mg/night and titrated to a level of 1500mg/night. Eight patients were assigned to the control arm. No placebo was used. Lipoprotein profiles of the subjects were analyzed at baseline and at the end of 12 weeks using Nuclear Magnetic Resonance (NMR) spectroscopy. At the end of 12 weeks, NMR spectroscopic analysis revealed a significant increase in overall LDL size (1.2% in ERN treated subjects vs 2.0% decrease in control patients, P=.04) and a decrease in small LDL particle concentration (17.0% in ERN treated subjects vs 21.4% increase in control patients, P=.03) in subjects receiving ERN as compared to those in the control group. Only 1 subject receiving ERN developed serious flushing which was attributed to an accidental overdose of the drug. This pilot study demonstrates that ERN therapy in HIV-infected patients with low HDL is safe and effective in improving the lipoprotein profile in these patients. PMID:23795312

The effects of exercise on the lipoprotein subclass profile: a meta-analysis of 10 interventions

PubMed Central

Sarzynski, Mark A.; Burton, Jeffrey; Rankinen, Tuomo; Blair, Steven N.; Church, Timothy S.; Després, Jean-Pierre; Hagberg, James M.; Landers-Ramos, Rian; Leon, Arthur S.; Mikus, Catherine R.; Rao, D.C.; Seip, Richard L.; Skinner, James S.; Slentz, Cris A.; Thompson, Paul D.; Wilund, Kenneth R.; Kraus, William E.; Bouchard, Claude

2015-01-01

Objective The goal was to examine lipoprotein subclass responses to regular exercise as measured in 10 exercise interventions derived from six cohorts. Methods Nuclear magnetic resonance spectroscopy was used to quantify average particle size, total and subclass concentrations of very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein particles (VLDL-P, LDL-P, and HDL-P, respectively) before and after an exercise intervention in 1,555 adults from six studies, encompassing 10 distinct exercise programs: APOE (N=106), DREW (N=385), GERS (N=79), HERITAGE (N=715), STRRIDE I (N=168) and II (N=102). Random-effects meta-analyses were performed to evaluate the overall estimate of mean change across the unadjusted and adjusted mean change values from each exercise group. Results Meta-analysis of unadjusted data showed that regular exercise induced significant decreases in the concentration of large VLDL-P, small LDL-P, and medium HDL-P and mean VLDL-P size, with significant increases in the concentration of large LDL-P and large HDL-P and mean LDL-P size. These changes remained significant in meta-analysis with adjustment for age, sex, race, baseline body mass index, and baseline trait value. Conclusions Despite differences in exercise programs and study populations, regular exercise produced putatively beneficial changes in the lipoprotein subclass profile across 10 exercise interventions. Further research is needed to examine how exercise-induced changes in lipoprotein subclasses may be associated with (concomitant changes in) cardiovascular disease risk. PMID:26520888

Low-density lipoprotein cholesterol versus particle number in middle school children.

PubMed

Mietus-Snyder, Michele; Drews, Kimberly L; Otvos, James D; Willi, Steven M; Foster, Gary D; Jago, Russell; Buse, John B

2013-08-01

To characterize lipids and lipoproteins in a diverse school-based cohort and identify features associated with discordance between low-density lipoprotein cholesterol (LDL-C) and LDL particle (LDL-P). Sixth-grade children enrolled in the HEALTHY trial (n = 2384; mean age 11.3 ± 0.6 years; 54.2% female) were evaluated for standard lipids, lipoprotein particles measured by nuclear magnetic resonance, and homeostatic model of insulin resistance. Characteristics of subgroups with values of LDL-C and LDL-P discordant by >20 percentile units, an amount reasoned to be clinically significant, were compared. Four-hundred twenty-eight (18%) of children were in the LDL-P < LDL-C subgroup and 375 (16%) in the LDL-P > LDL-C subgroup. Those with LDL-P > LDL-C had significantly greater body mass index, waist circumference, homeostatic model of insulin resistance, triglycerides, systolic and diastolic blood pressure, and reflected a greater Hispanic ethnic composition but fewer of black race than both the concordant (LDL-P ≅ LDL-C) and opposite discordant (LDL-P < LDL-C) subgroups. There is as much lipoprotein cholesterol compositional heterogeneity in sixth graders as has been described in adults and a discordant atherogenic phenotype of LDL-P > LDL-C, common in obesity, is often missed when only LDL-C is considered. Conversely, many children with moderate-risk cholesterol measures (75th to 99th percentile) have a lower LDL-P burden. Copyright © 2013 Mosby, Inc. All rights reserved.

Sphingosine 1-phosphate, present in serum-derived lipoproteins, activates matriptase.

PubMed

Benaud, Christelle; Oberst, Michael; Hobson, John P; Spiegel, Sarah; Dickson, Robert B; Lin, Chen-Yong

2002-03-22

We describe here a novel biological function of sphingosine 1-phosphate (S1P): the activation of a serine protease, matriptase. Matriptase is a type II integral membrane serine protease, expressed on the surface of a variety of epithelial cells; it may play an important role in tissue remodeling. We have previously reported that the activation of matriptase is regulated by serum. We have now identified the bioactive component from serum. First, the activity was observed to co-purify with lipoproteins by conventional liquid chromatography and immunoaffinity chromatography. The ability of lipoproteins to induce the activation of matriptase was further confirmed with commercial preparations of low density lipoprotein (LDL) and very low density lipoprotein (VLDL). Next, we observed that the bioactive component of LDL is associated with the phospholipid components of LDL. Fractionation of lipid components of LDL by thin layer chromatography (TLC) revealed that the bioactive component of LDL comigrates with S1P. Nanomolar concentrations of commercially obtained S1P were then observed to induce the rapid activation of matriptase on the surfaces of nontransformed human mammary epithelial cells. Other structurally related sphingolipids, including dihydro-S1P, ceramide 1-phosphates, and sphingosine phosphocholine as well as lysophosphatidic acid, can also induce the activation of matriptase, but at significantly higher concentrations than S1P. Furthermore, S1P-dependent matriptase activation is dependent on Ca(2+) but not via G(i) protein-coupled receptors. Our results demonstrate that bioactive phospholipids can function as nonprotein activators of a cell surface protease, suggesting a possible mechanistic link between S1P and normal and possibly pathologic tissue remodeling.

Effects of obeticholic acid on lipoprotein metabolism in healthy volunteers.

PubMed

Pencek, R; Marmon, T; Roth, J D; Liberman, A; Hooshmand-Rad, R; Young, M A

2016-09-01

The bile acid analogue obeticholic acid (OCA) is a selective farnesoid X receptor (FXR) agonist in development for treatment of several chronic liver diseases. FXR activation regulates lipoprotein homeostasis. The effects of OCA on cholesterol and lipoprotein metabolism in healthy individuals were assessed. Two phase I studies were conducted to evaluate the effects of repeated oral doses of 5, 10 or 25 mg OCA on lipid variables after 14 or 20 days of consecutive administration in 68 healthy adults. Changes in HDL and LDL cholesterol levels were examined, in addition to nuclear magnetic resonance analysis of particle sizes and sub-fraction concentrations. OCA elicited changes in circulating cholesterol and particle size of LDL and HDL. OCA decreased HDL cholesterol and increased LDL cholesterol, independently of dose. HDL particle concentrations declined as a result of a reduction in medium and small HDL. Total LDL particle concentrations increased because of an increase in large LDL particles. Changes in lipoprotein metabolism attributable to OCA in healthy individuals were found to be consistent with previously reported changes in patients receiving OCA with non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. © 2016 John Wiley & Sons Ltd.

Central nervous system regulation of intestinal lipid and lipoprotein metabolism.

PubMed

Farr, Sarah; Taher, Jennifer; Adeli, Khosrow

2016-02-01

In response to nutrient availability, the small intestine and brain closely communicate to modulate energy homeostasis and metabolism. The gut-brain axis involves complex nutrient sensing mechanisms and an integration of neuronal and hormonal signaling. This review summarizes recent evidence implicating the gut-brain axis in regulating lipoprotein metabolism, with potential implications for the dyslipidemia of insulin resistant states. The intestine and brain possess distinct mechanisms for sensing lipid availability, which triggers subsequent regulation of feeding, glucose homeostasis, and adipose tissue metabolism. More recently, central receptors, neuropeptides, and gut hormones that communicate with the brain have been shown to modulate hepatic and intestinal lipoprotein metabolism via parasympathetic and sympathetic signaling. Gut-derived glucagon-like peptides appear to be particularly important in modulating the intestinal secretion of chylomicron particles via a novel brain-gut axis. Dysregulation of these pathways may contribute to postprandial diabetic dyslipidemia. Emerging evidence implicates the central and enteric nervous systems in controlling many aspects of lipid and lipoprotein metabolism. Bidirectional communication between the gut and brain involving neuronal pathways and gut peptides is critical for regulating feeding and metabolism, and forms a neuroendocrine circuit to modulate dietary fat absorption and intestinal production of atherogenic chylomicron particles.

Variations in Paper Electrophoretic Serum Lipoprotein Patterns in Healthy Subjects

PubMed Central

Buckley, G. C.; Little, J. A.; Csima, A.

1970-01-01

The normal variations in the paper electrophoretic lipoprotein patterns in 240 healthy Canadian males and females, aged 10 to 59 years, have been described and compared with serum cholesterol and triglyceride levels. The incidence of abnormal chylomicra, beta and pre-beta lipoproteins was similar in both sexes and increased with age in both sexes. Chylomicron bands and/or pre-beta trails from the origin occurred in 4% of subjects, pre-beta bands in 27% and “abnormally” dense beta bands in 28%. Five per cent of subjects were considered to have definite hyperlipoproteinemia, another 19% had slight and 21% had questionable hyperlipoproteinemia. Fifty-five per cent were normal. PMID:5538493

Hybrid and plug-in hybrid electric vehicle performance testing by the US Department of Energy Advanced Vehicle Testing Activity

NASA Astrophysics Data System (ADS)

Karner, Donald; Francfort, James

The Advanced Vehicle Testing Activity (AVTA), part of the U.S. Department of Energy's FreedomCAR and Vehicle Technologies Program, has conducted testing of advanced technology vehicles since August 1995 in support of the AVTA goal to provide benchmark data for technology modeling, and vehicle development programs. The AVTA has tested full size electric vehicles, urban electric vehicles, neighborhood electric vehicles, and hydrogen internal combustion engine powered vehicles. Currently, the AVTA is conducting baseline performance, battery benchmark and fleet tests of hybrid electric vehicles (HEV) and plug-in hybrid electric vehicles (PHEV). Testing has included all HEVs produced by major automotive manufacturers and spans over 2.5 million test miles. Testing is currently incorporating PHEVs from four different vehicle converters. The results of all testing are posted on the AVTA web page maintained by the Idaho National Laboratory.

Phospholipid transfer protein plays a major role in the initiation of apolipoprotein B-containing lipoprotein assembly in mouse primary hepatocytes.

PubMed

Manchekar, Medha; Liu, Yanwen; Sun, Zhihuan; Richardson, Paul E; Dashti, Nassrin

2015-03-27

In this study, we tested the hypothesis that phospholipid transfer protein (PLTP) is a plausible mediator of phospholipid (PL) transfer to the N-terminal 1000 residues of apoB (apoB:1000) leading to the initiation of apoB-containing lipoprotein assembly. To this end, primary hepatocytes from wild type (WT) and PLTP knock-out (KO) mice were transduced with adenovirus-apoB:1000 with or without co-transduction with adenovirus-PLTP, and the assembly and secretion of apoB:1000-containing lipoproteins were assessed. PLTP deficiency resulted in a 65 and 72% reduction in the protein and lipid content, respectively, of secreted apoB:1000-containing lipoproteins. Particles secreted by WT hepatocytes contained 69% PL, 9% diacylglycerol (DAG), and 23% triacylglycerol (TAG) with a stoichiometry of 46 PL, 6 DAG, and 15 TAG molecules per apoB:1000. PLTP absence drastically altered the lipid composition of apoB:1000 lipoproteins; these particles contained 46% PL, 13% DAG, and 41% TAG with a stoichiometry of 27 PL, 10 DAG, and 23 TAG molecules per apoB:1000. Reintroduction of Pltp gene into PLTP-KO hepatocytes stimulated the lipidation and secretion of apoB:1000-containing lipoproteins by ∼3-fold; the lipid composition and stoichiometry of these particles were identical to those secreted by WT hepatocytes. In contrast to the WT, apoB:1000 in PLTP-KO hepatocytes was susceptible to intracellular degradation predominantly in the post-endoplasmic reticulum, presecretory compartment. Reintroduction of Pltp gene into PLTP-KO hepatocytes restored the stability of apoB:1000. These results provide compelling evidence that in hepatocytes initial recruitment of PL by apoB:1000 leading to the formation of the PL-rich apoB-containing initiation complex is mediated to a large extent by PLTP. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Phospholipid Transfer Protein Plays a Major Role in the Initiation of Apolipoprotein B-containing Lipoprotein Assembly in Mouse Primary Hepatocytes*

PubMed Central

Manchekar, Medha; Liu, Yanwen; Sun, Zhihuan; Richardson, Paul E.; Dashti, Nassrin

2015-01-01

In this study, we tested the hypothesis that phospholipid transfer protein (PLTP) is a plausible mediator of phospholipid (PL) transfer to the N-terminal 1000 residues of apoB (apoB:1000) leading to the initiation of apoB-containing lipoprotein assembly. To this end, primary hepatocytes from wild type (WT) and PLTP knock-out (KO) mice were transduced with adenovirus-apoB:1000 with or without co-transduction with adenovirus-PLTP, and the assembly and secretion of apoB:1000-containing lipoproteins were assessed. PLTP deficiency resulted in a 65 and 72% reduction in the protein and lipid content, respectively, of secreted apoB:1000-containing lipoproteins. Particles secreted by WT hepatocytes contained 69% PL, 9% diacylglycerol (DAG), and 23% triacylglycerol (TAG) with a stoichiometry of 46 PL, 6 DAG, and 15 TAG molecules per apoB:1000. PLTP absence drastically altered the lipid composition of apoB:1000 lipoproteins; these particles contained 46% PL, 13% DAG, and 41% TAG with a stoichiometry of 27 PL, 10 DAG, and 23 TAG molecules per apoB:1000. Reintroduction of Pltp gene into PLTP-KO hepatocytes stimulated the lipidation and secretion of apoB:1000-containing lipoproteins by ∼3-fold; the lipid composition and stoichiometry of these particles were identical to those secreted by WT hepatocytes. In contrast to the WT, apoB:1000 in PLTP-KO hepatocytes was susceptible to intracellular degradation predominantly in the post-endoplasmic reticulum, presecretory compartment. Reintroduction of Pltp gene into PLTP-KO hepatocytes restored the stability of apoB:1000. These results provide compelling evidence that in hepatocytes initial recruitment of PL by apoB:1000 leading to the formation of the PL-rich apoB-containing initiation complex is mediated to a large extent by PLTP. PMID:25638820

Liver heparan sulfate proteoglycans mediate clearance of triglyceride-rich lipoproteins independently of LDL receptor family members

PubMed Central

MacArthur, Jennifer M.; Bishop, Joseph R.; Stanford, Kristin I.; Wang, Lianchun; Bensadoun, André; Witztum, Joseph L.; Esko, Jeffrey D.

2007-01-01

We examined the role of hepatic heparan sulfate in triglyceride-rich lipoprotein metabolism by inactivating the biosynthetic gene GlcNAc N-deacetylase/N-sulfotransferase 1 (Ndst1) in hepatocytes using the Cre-loxP system, which resulted in an approximately 50% reduction in sulfation of liver heparan sulfate. Mice were viable and healthy, but they accumulated triglyceride-rich lipoprotein particles containing apoB-100, apoB-48, apoE, and apoCI-IV. Compounding the mutation with LDL receptor deficiency caused enhanced accumulation of both cholesterol- and triglyceride-rich particles compared with mice lacking only LDL receptors, suggesting that heparan sulfate participates in the clearance of cholesterol-rich lipoproteins as well. Mutant mice synthesized VLDL normally but showed reduced plasma clearance of human VLDL and a corresponding reduction in hepatic VLDL uptake. Retinyl ester excursion studies revealed that clearance of intestinally derived lipoproteins also depended on hepatocyte heparan sulfate. These findings show that under normal physiological conditions, hepatic heparan sulfate proteoglycans play a crucial role in the clearance of both intestinally derived and hepatic lipoprotein particles. PMID:17200715

Metabolic alterations, HFE gene mutations and atherogenic lipoprotein modifications in patients with primary iron overload.

PubMed

Meroño, Tomás; Brites, Fernando; Dauteuille, Carolane; Lhomme, Marie; Menafra, Martín; Arteaga, Alejandra; Castro, Marcelo; Saez, María Soledad; Ballerga, Esteban González; Sorroche, Patricia; Rey, Jorge; Lesnik, Philippe; Sordá, Juan Andrés; Chapman, M John; Kontush, Anatol; Daruich, Jorge

2015-05-01

Iron overload (IO) has been associated with glucose metabolism alterations and increased risk of cardiovascular disease (CVD). Primary IO is associated with mutations in the HFE gene. To which extent HFE gene mutations and metabolic alterations contribute to the presence of atherogenic lipoprotein modifications in primary IO remains undetermined. The present study aimed to assess small, dense low-density lipoprotein (LDL) levels, chemical composition of LDL and high-density lipoprotein (HDL) particles, and HDL functionality in IO patients. Eighteen male patients with primary IO and 16 sex- and age-matched controls were recruited. HFE mutations (C282Y, H63D and S65C), measures of insulin sensitivity and secretion (calculated from the oral glucose tolerance test), chemical composition and distribution profile of LDL and HDL subfractions (isolated by gradient density ultracentrifugation) and HDL functionality (as cholesterol efflux and antioxidative activity) were studied. IO patients compared with controls exhibited insulin resistance (HOMA-IR (homoeostasis model assessment-estimated insulin resistance): +93%, P< 0.001). Metabolic profiles differed across HFE genotypes. C282Y homozygotes (n=7) presented a reduced β-cell function and insulin secretion compared with non-C282Y patients (n=11) (-58% and -73%, respectively, P< 0.05). In addition, C282Y homozygotes featured a predominance of large, buoyant LDL particles (C282Y: 43±5; non-C282Y: 25±8; controls: 32±7%; P< 0.001), whereas non-C282Y patients presented higher amounts of small, dense LDL (C282Y: 23±5; non-C282Y: 39±10; controls: 26±4%; P< 0.01). HDL particles were altered in C282Y homozygotes. However, HDL functionality was conserved. In conclusion, metabolic alterations and HFE gene mutations are involved in the presence of atherogenic lipoprotein modifications in primary IO. To what extent such alterations could account for an increase in CVD risk remains to be determined.

Advanced Technologies and Methodology for Automated Ultrasonic Testing Systems Quantification

DOT National Transportation Integrated Search

2011-04-29

For automated ultrasonic testing (AUT) detection and sizing accuracy, this program developed a methodology for quantification of AUT systems, advancing and quantifying AUT systems imagecapture capabilities, quantifying the performance of multiple AUT...

Metabolism of triglyceride-rich lipoproteins and transfer of lipids to high-density lipoproteins (HDL) in vegan and omnivore subjects.

PubMed

Vinagre, J C; Vinagre, C G; Pozzi, F S; Slywitch, E; Maranhão, R C

2013-01-01

Vegan diet excludes all foodstuffs of animal origin and leads to cholesterol lowering and possibly reduction of cardiovascular disease risk. The aim was to investigate whether vegan diet improves the metabolic pathway of triglyceride-rich lipoproteins, consisting in lipoprotein lipolysis and removal from circulation of the resulting remnants and to verify whether the diet alters HDL metabolism by changing lipid transfers to this lipoprotein. 21 vegan and 29 omnivores eutrophic and normolipidemic subjects were intravenously injected triglyceride-rich emulsions labeled with (14)C-cholesterol oleate and (3)H-triolein: fractional clearance rates (FCR, in min(-1)) were calculated from samples collected during 60 min for radioactive counting. Lipid transfer to HDL was assayed by incubating plasma samples with a donor nanoemulsion labeled with radioactive lipids; % lipids transferred to HDL were quantified in supernatant after chemical precipitation of non-HDL fractions and nanoemulsion. Serum LDL cholesterol was lower in vegans than in omnivores (2.1 ± 0.8, 2.7 ± 0.7 mmol/L, respectively, p < 0,05), but HDL cholesterol and triglycerides were equal. Cholesteryl ester FCR was greater in vegans than in omnivores (0.016 ± 0.012, 0.003 ± 0.003, p < 0.01), whereas triglyceride FCR was equal (0.024 ± 0.014, 0.030 ± 0.016, N.S.). Cholesteryl ester transfer to HDL was lower in vegans than in omnivores (2.7 ± 0.6, 3.5 ± 1.5%, p < 0,05). Free-cholesterol, triglyceride and phospholipid transfer were equal, as well as HDL size. Remnant removal from circulation, estimated by cholesteryl oleate FCR was faster in vegans, but the lipolysis process, estimated by triglyceride FCR was equal. Increased removal of atherogenic remnants and diminution of cholesteryl ester transfer may favor atherosclerosis prevention by vegan diet. Copyright © 2011 Elsevier B.V. All rights reserved.

Effect of pistachio consumption on plasma lipoprotein subclasses in pre-diabetic subjects.

PubMed

Hernández-Alonso, P; Salas-Salvadó, J; Baldrich-Mora, M; Mallol, R; Correig, X; Bulló, M

2015-04-01

Nuts have been demonstrated to improve several cardiovascular risk factors and the lipid profile in diabetic and pre-diabetic subjects. However, analysis of conventional serum lipid profiles does not completely explain the atherogenic risk associated with pre-diabetes. We therefore investigated whether chronic consumption of pistachio modifies the lipoprotein subclasses to a healthier profile in pre-diabetic subjects. Randomized cross-over clinical trial in 54 subjects with pre-diabetes. Subjects consumed a pistachio-supplemented diet (PD, 50% carbohydrates, 33% fat, including 57 g/d of pistachios daily) and a control diet (CD, 55% carbohydrates, 30% fat) for 4 months each, separated by a 2-week wash-out. Diets were isocaloric and matched for protein, fiber and saturated fatty acids. Nuclear magnetic resonance (NMR) was performed to determine changes in plasma lipoprotein subclasses. Small low-density lipoprotein particles (sLDL-P) significantly decreased after pistachio consumption compared to the nut-free diet (P = 0.023). The non-high-density lipoprotein particles (non-HDL-P i.e. VLDL-P plus LDL-P) significantly decreased under the PD compared to CD (P = 0.041). The percentage of sHDL-P increased by 2.23% after the PD compared with a reduction of 0.08% after the CD (P = 0.014). Consequently, the overall size of HDL-P significantly decreased in the PD (P = 0.007). Chronic pistachio consumption could modify the lipoprotein particle size and subclass concentrations independently of changes in total plasma lipid profile, which may help to explain the decreased risk of cardiovascular disease and mortality associated with those individuals who frequently consumed nuts. This study is registered at www.clinicaltrials.gov as NCT01441921. Copyright © 2015 Elsevier B.V. All rights reserved.

Advanced Grid Support Functionality Testing for Florida Power and Light

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nelson, Austin; Martin, Gregory; Hurtt, James

This report describes the results of laboratory testing of advanced photovoltaic (PV) inverter testing undertaken by the National Renewable Energy Laboratory (NREL) on behalf of the Florida Power and Light Company (FPL). FPL recently commissioned a 1.1 MW-AC PV installation on a solar carport at the Daytona International Speedway in Daytona Beach, Florida. In addition to providing a source of clean energy production, the site serves as a live test bed with 36 different PV inverters from eight different manufacturers. Each inverter type has varied support for advanced grid support functions (GSFs) that are becoming increasingly commonplace, and are beingmore » required through revised interconnection standards such as UL1741, IEEE1547, and California (CA) Rule 21. FPL is interested in evaluating the trade-offs between different GSFs, their compliance to emerging standards, and their effects on efficiency and reliability. NREL has provided a controlled laboratory environment to undertake such a study. This work covered nine different classes of tests to compare inverter capabilities and performance for four different inverters that were selected by FPL. The test inverters were all three-phase models rated between 24-36 kW, and containing multiple PV input power point trackers. Advanced grid support functions were tested for functional behavior, and included fixed power factor operation, voltage-ride through, frequency ride-through, volt-var control, and frequency-Watt control. Response to abnormal grid conditions with GSFs enabled was studied through anti-islanding, fault, and load rejection overvoltage tests. Finally, efficiency was evaluated across a range of operating conditions that included power factor, output power, and input voltage variations. Test procedures were derived from requirements of a draft revision of UL741, CA Rule 21, and/or previous studies at NREL. This reports summarizes the results of each test case, providing a comparative performance

Advancement of proprotor technology. Task 2: Wind-tunnel test results

NASA Technical Reports Server (NTRS)

1971-01-01

An advanced-design 25-foot-diameter flightworthy proprotor was tested in the NASA-Ames Large-Scale Wind Tunnel. These tests, have verified and confirmed the theory and design solutions developed as part of the Army Composite Aircraft Program. This report presents the test results and compares them with theoretical predictions. During performance tests, the results met or exceeded predictions. Hover thrust 15 percent greater than the predicted maximum was measured. In airplane mode, propulsive efficiencies (some of which exceeded 90 percent) agreed with theory.

Relationship between lipoprotein (a) and micro/macro complications in type 2 diabetes mellitus: a forgotten target.

PubMed

Toro, Rocio; Segura, Eduardo; Nuñez-Cortes, Jesús Millan; Pedro-Botet, Juan Carlos; Quezada-Feijoo, Maribel; Mangas, Alipio

2015-03-01

Increased lipoprotein (a) serum concentrations seems to be a cardiovascular risk factor; this has not been confirmed in extracoronary atherosclerosis complications. We therefore wished to gain a deeper insight into relationship between the plasma concentrations of lipoprotein (a) and the micro- and macro-vascular complications of type 2 diabetes mellitus and to identify possible differences in this association. This is a descriptive observational cross-sectional study. Two-hundred and seventeen elderly patients with type 2 diabetes mellitus were included from the internal medicine outclinic. Anthropometric data, analytical data (insulin reserve, basal and postprandial peptide C, glycosylated hemoglobin, renal parameters, lipid profile and clinical data as hypertension, obesity, micro- and macrovascular complications were collected. Patients were grouped according to the type 2 diabetes mellitus time of evolution. The mean plasma concentration of lipoprotein (a) was 22.2 ± 17.3 mg/dL (22.1 ± 15.9 mg/dL for males, and 22.1 ± 18.4 mg/dL for females). Patients with hypertension, coronary heart disease, cerebrovascular accident, microalbuminuria and proteinuria presented a statistically significant increased level of lipoprotein (a). Similarly, the patients with hyperlipoprotein (a) (≥ 30 mg/dL) presented significantly increased levels of urea and total cholesterol. In the multivariate regression model, the level of lipoprotein (a) is positively correlated with coronary heart disease and diabetic nephropathy (P < 0.01 and P < 0.005, respectively). The elevation of plasma levels of lipoprotein (a) are associated with the development of coronary heart disease and diabe tic nephropathy. Therefore, we consider that the determination of lipoprotein (a) may be a prognostic marker of vascular complications in patients with type 2 diabetes mellitus.

77 FR 24480 - Application for New Awards; Advanced Placement (AP) Test Fee Program-Reopening the AP Test Fee...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-24

... DEPARTMENT OF EDUCATION Application for New Awards; Advanced Placement (AP) Test Fee Program--Reopening the AP Test Fee Fiscal Year 2012 Competition AGENCY: Office of Elementary and Secondary Education (OESE), Department of Education. ACTION: Notice reopening the AP Test Fee fiscal year 2012 competition...

Plasma chamber testing of advanced photovoltaic solar array coupons

NASA Technical Reports Server (NTRS)

Hillard, G. Barry

1994-01-01

The solar array module plasma interactions experiment is a space shuttle experiment designed to investigate and quantify the high voltage plasma interactions. One of the objectives of the experiment is to test the performance of the Advanced Photovoltaic Solar Array (APSA). The material properties of array blanket are also studied as electric insulators for APSA arrays in high voltage conditions. Three twelve cell prototype coupons of silicon cells were constructed and tested in a space simulation chamber.

THhe MLA Foreign Language Proficiency Tests for Teachers and Advanced Students.

ERIC Educational Resources Information Center

del Olmo, Guillermo

1967-01-01

The development, design, and purposes of these advanced proficiency tests are discussed, along with brief descriptions of their seven component parts--listening comprehension, speaking, reading, writing, applied linguistics, civilization and culture, and professional preparation. Some of the research inspired by the tests is identified. (AF)

Lipoprotein Subfractions in Metabolic Syndrome and Obesity: Clinical Significance and Therapeutic Approaches

PubMed Central

Nikolic, Dragana; Katsiki, Niki; Montalto, Giuseppe; Isenovic, Esma R.; Mikhailidis, Dimitri P.; Rizzo, Manfredi

2013-01-01

Small, dense low density lipoprotein (sdLDL) represents an emerging cardiovascular risk factor, since these particles can be associated with cardiovascular disease (CVD) independently of established risk factors, including plasma lipids. Obese subjects frequently have atherogenic dyslipidaemia, including elevated sdLDL levels, in addition to elevated triglycerides (TG), very low density lipoprotein (VLDL) and apolipoprotein-B, as well as decreased high density lipoprotein cholesterol (HDL-C) levels. Obesity-related co-morbidities, such as metabolic syndrome (MetS) are also characterized by dyslipidaemia. Therefore, agents that favourably modulate LDL subclasses may be of clinical value in these subjects. Statins are the lipid-lowering drug of choice. Also, anti-obesity and lipid lowering drugs other than statins could be useful in these patients. However, the effects of anti-obesity drugs on CVD risk factors remain unclear. We review the clinical significance of sdLDL in being overweight and obesity, as well as the efficacy of anti-obesity drugs on LDL subfractions in these individuals; a short comment on HDL subclasses is also included. Our literature search was based on PubMed and Scopus listings. Further research is required to fully explore both the significance of sdLDL and the efficacy of anti-obesity drugs on LDL subfractions in being overweight, obesity and MetS. Improving the lipoprotein profile in these patients may represent an efficient approach for reducing cardiovascular risk. PMID:23507795

ApoE and the role of very low density lipoproteins in adipose tissue inflammation

USDA-ARS?s Scientific Manuscript database

Our goal was too identify the role of triglyceride-rich lipoproteins and apoE, a major apolipoprotein in triglyceride-rich lipoproteins, in adipose tissue inflammation with high-fat diet induced obesity. Male apoE-/- and C57BL/6J wild-type mice fed high fat diets for 12 weeks were assessed for metab...

Low-density-lipoprotein (LDL)-bound flavonoids increase the resistance of LDL to oxidation and glycation under pathophysiological concentrations of glucose in vitro.

PubMed

Wu, Chi-Hao; Lin, Jer-An; Hsieh, Wen-Ching; Yen, Gow-Chin

2009-06-10

The higher susceptibility of low-density lipoprotein (LDL) to oxidation and glycation in diabetes has been shown to be related to poor glycemic control. The aim of this study was to determine whether LDL-bound flavonoids attenuate high-glucose (HG)-mediated LDL oxidation and glycation. For this purpose, human plasma was preincubated with individual flavonoids for 3 h, followed by sequential ultracentrifugation and extensive dialysis to remove unbound flavonoid samples. Enriched LDL was subsequently isolated and challenged for its resistance to oxidation and glycation. Results showed that glucose (5-30 mM) dose-dependently accelerates copper (Cu(2+))-mediated LDL oxidative modification. The enrichment of flavonoids such as luteolin, naringenin, and kaempferol significantly increased the resistance of LDL to oxidation and prevented endogenous alpha-tocopherol consumption caused by HG/Cu(2+) (p < 0.05). The long-term glycation of LDL, which was measured by advanced glycation endproducts (AGEs)-related fluorescence and boronate affinity chromatography, was found to be inhibited by LDL-bound flavonoids in the following order: rutin > luteolin > quercetin > kaempferol > naringenin > catechin approximately EC > naringin. Moreover, a solid-phase extraction system with HPLC-diode array detection provided evidence that flavonoids were bound to LDL particles to a certain extent concurrently facilitating the lipoprotein antioxidant and antiglycation activities. In conclusion, this study supports the hypothesis that HG promoted oxidative and glycative modifications of LDL. This is the first study to show that the introduction of flavonoids into LDL particles protects the lipoprotein against glycotoxin-mediated adverse effects.

A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation

NASA Astrophysics Data System (ADS)

Duivenvoorden, Raphaël; Tang, Jun; Cormode, David P.; Mieszawska, Aneta J.; Izquierdo-Garcia, David; Ozcan, Canturk; Otten, Maarten J.; Zaidi, Neeha; Lobatto, Mark E.; van Rijs, Sarian M.; Priem, Bram; Kuan, Emma L.; Martel, Catherine; Hewing, Bernd; Sager, Hendrik; Nahrendorf, Matthias; Randolph, Gwendalyn J.; Stroes, Erik S. G.; Fuster, Valentin; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J. M.

2014-01-01

Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show that this effect is mediated through the inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show that they accumulate in atherosclerotic lesions in which they directly affect plaque macrophages. Finally, we demonstrate that a 3-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a 1-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation.

Correlates of serum lipids and lipoproteins in Congolese patients with arterial hypertension.

PubMed

Lepira, F B; M'Buyamba-Kabangu, J R; Kayembe, K P; Nseka, M N

2005-01-01

The purpose of this study was to assess the prevalence of dyslipidaemia and the correlates of serum lipids and lipoproteins among Congolese subjects with and without arterial hypertension. One hundred hypertensive patients attending the outpatient clinics at the University of Kinshasa Hospital, and 100 age- and sex-matched controls recruited among hospital personnel or blood donors entered the case-control study. Their blood pressure (BP), heart rate (HR), body mass index (BMI), waist-to-hip ratio (WHR), serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), plasma fibrinogen (only in patients) and fasting glucose, serum uric acid, creatinine and creatinine clearance (CrCl) were compared using the Student's t-test or Chi-square test as appropriate. Associations between continuous variables were assessed with Pearson correlation coefficients, and correlates of lipids and lipoproteins were determined using multiple linear-regression analysis. Compared to healthy controls, hypertensive patients had greater BMI (p or= 6.20 mmol/l. In hypertensive patients, TC (r = 0.24; p < 0.01) and LDL-C (r = 0.20; p < 0.05) were positively correlated to plasma fibrinogen. A positive correlation was also observed between TC and

Vascular access in lipoprotein apheresis: a retrospective analysis from the UK's largest lipoprotein apheresis centre.

PubMed

Doherty, Daniel J; Pottle, Alison; Malietzis, George; Hakim, Nadey; Barbir, Mahmoud; Crane, Jeremy S

2018-01-01

Lipoprotein apheresis (LA) has proven to be an effective, safe and life-saving therapy. Vascular access is needed to facilitate this treatment but has recognised complications. Despite consistency in treatment indication and duration there are no guidelines in place. The aim of this study is to characterise vascular access practice at the UK's largest LA centre and forward suggestions for future approaches. A retrospective analysis of vascular access strategies was undertaken in all patients who received LA treatment in the low-density lipoprotein (LDL) Apheresis Unit at Harefield Hospital (Middlesex, UK) from November 2000 to March 2016. Fifty-three former and current patients underwent 4260 LA treatments. Peripheral vein cannulation represented 79% of initial vascular access strategies with arteriovenous (AV) fistula use accounting for 15%. Last used method of vascular access was peripheral vein cannulation in 57% versus AV fistula in 32%. Total AV fistula failure rate was 37%. Peripheral vein cannulation remains the most common method to facilitate LA. Practice trends indicate a move towards AV fistula creation; the favoured approach receiving support from the expert body in this area. AV fistula failure rate is high and of great concern, therefore we suggest the implementation of upper limb ultrasound vascular mapping in all patients who meet treatment eligibility criteria. We encourage close ties between apheresis units and specialist surgical centres to facilitate patient counselling and monitoring. Further prospective data regarding fistula failure is needed in this expanding treatment field.

The association of very-low-density lipoprotein with ankle-brachial index in peritoneal dialysis patients with controlled serum low-density lipoprotein cholesterol level

PubMed Central

2013-01-01

Background Peripheral artery disease (PAD) represents atherosclerotic disease and is a risk factor for death in peritoneal dialysis (PD) patients, who tend to show an atherogenic lipid profile. In this study, we investigated the relationship between lipid profile and ankle-brachial index (ABI) as an index of atherosclerosis in PD patients with controlled serum low-density lipoprotein (LDL) cholesterol level. Methods Thirty-five PD patients, whose serum LDL cholesterol level was controlled at less than 120mg/dl, were enrolled in this cross-sectional study in Japan. The proportions of cholesterol level to total cholesterol level (cholesterol proportion) in 20 lipoprotein fractions and the mean size of lipoprotein particles were measured using an improved method, namely, high-performance gel permeation chromatography. Multivariate linear regression analysis was adjusted for diabetes mellitus and cardiovascular and/or cerebrovascular diseases. Results The mean (standard deviation) age was 61.6 (10.5) years; PD vintage, 38.5 (28.1) months; ABI, 1.07 (0.22). A low ABI (0.9 or lower) was observed in 7 patients (low-ABI group). The low-ABI group showed significantly higher cholesterol proportions in the chylomicron fraction and large very-low-density lipoproteins (VLDLs) (Fractions 3–5) than the high-ABI group (ABI>0.9). Adjusted multivariate linear regression analysis showed that ABI was negatively associated with serum VLDL cholesterol level (parameter estimate=-0.00566, p=0.0074); the cholesterol proportions in large VLDLs (Fraction 4, parameter estimate=-3.82, p=0.038; Fraction 5, parameter estimate=-3.62, p=0.0039) and medium VLDL (Fraction 6, parameter estimate=-3.25, p=0.014); and the size of VLDL particles (parameter estimate=-0.0352, p=0.032). Conclusions This study showed that the characteristics of VLDL particles were associated with ABI among PD patients. Lowering serum VLDL level may be an effective therapy against atherosclerosis in PD patients after the

Advanced radial inflow turbine rotor program: Design and dynamic testing

NASA Technical Reports Server (NTRS)

Rodgers, C.

1976-01-01

The advancement of small, cooled, radial inflow turbine technology in the area of operation at higher turbine inlet temperature is discussed. The first step was accomplished by designing, fabricating, and subjecting to limited mechanical testing an advanced gas generator rotating assembly comprising a radial inflow turbine and two-stage centrifugal compressor. The radial inflow turbine and second-stage compressor were designed as an integrally machined monorotor with turbine cooling taking place basically by conduction to the compressor. Design turbine inlet rotor gas temperature, rotational speed, and overall gas generator compressor pressure ratio were 1422 K (2560 R), 71,222 rpm, and 10/1 respectively. Mechanical testing on a fabricated rotating assembly and bearing system covered 1,000 cold start/stop cycles and three spins to 120 percent design speed (85,466 rpm).

Interfacial Tension and Surface Pressure of High Density Lipoprotein, Low Density Lipoprotein, and Related Lipid Droplets

PubMed Central

Ollila, O. H. Samuli; Lamberg, Antti; Lehtivaara, Maria; Koivuniemi, Artturi; Vattulainen, Ilpo

2012-01-01

Lipid droplets play a central role in energy storage and metabolism on a cellular scale. Their core is comprised of hydrophobic lipids covered by a surface region consisting of amphiphilic lipids and proteins. For example, high and low density lipoproteins (HDL and LDL, respectively) are essentially lipid droplets surrounded by specific proteins, their main function being to transport cholesterol. Interfacial tension and surface pressure of these particles are of great interest because they are related to the shape and the stability of the droplets and to protein adsorption at the interface. Here we use coarse-grained molecular-dynamics simulations to consider a number of related issues by calculating the interfacial tension in protein-free lipid droplets, and in HDL and LDL particles mimicking physiological conditions. First, our results suggest that the curvature dependence of interfacial tension becomes significant for particles with a radius of ∼5 nm, when the area per molecule in the surface region is <1.4 nm2. Further, interfacial tensions in the used HDL and LDL models are essentially unaffected by single apo-proteins at the surface. Finally, interfacial tensions of lipoproteins are higher than in thermodynamically stable droplets, suggesting that HDL and LDL are kinetically trapped into a metastable state. PMID:22995496

MicroRNAs and lipoproteins: a connection beyond atherosclerosis?

PubMed Central

Norata, Giuseppe Danilo; Sala, Federica; Catapano, Alberico Luigi; Fernández-Hernando, Carlos

2014-01-01

MicroRNAs (miRNAs) are involved in the pathogenesis of a number of cardiovascular diseases. In this review article, we have summarized the role of miRNAs in regulating lipid metabolism and how their therapeutical inhibition may lead to new approaches to treat cardiometabolic diseases, including atherosclerosis and metabolic syndrome. Specific miRNAs, such as miR-33a and -33b, represent one of the most interesting and attractive targets for metabolic-related disorders and anti-miR33 approaches are under intensive investigation. In addition to miR-33, other miRNAs, including miR-122, are also emerging as key players in lipid metabolism. More recently miRNAs were shown to exert their activities in a paracrine manner and also systemically. The latter is possible due to lipid-carriers, including lipoproteins, that transport and protect miRNAs from degradation. The emerging strong connection between miRNAs, lipoproteins and lipid metabolism indicates the existence of a reciprocal modulation that might go beyond atherosclerosis. PMID:23260873

Very low density lipoprotein receptor in Alzheimer disease.

PubMed

Helbecque, N; Amouyel, P

2000-08-15

The apolipoprotein (APO) E4 isoform is associated with an accelerated rate of Alzheimer disease (AD) expression in sporadic as well as late-onset familial forms of the disease but the precise mechanism is unknown. In an attempt to approach the possible mechanisms involved, APOE receptors have been studied. They all belong to the low density lipoprotein (LDL) receptor family and share the same structural motifs. Some of them are preferentially expressed in the brain such as the LDL receptor related protein, the apolipoprotein E receptor 2, and the very low density lipoprotein (VLDL) receptor. These receptors have been suspected to be involved in Alzheimer disease at various levels. Among them, the VLDL receptor was extensively explored. Although genetic studies conducted on a polymorphism in the promoter of the VLDL receptor in Japanese and Caucasian populations gave divergent results, this does not exclude a possible involvement of the VLDL receptor in AD. Copyright 2000 Wiley-Liss, Inc.

Cholesterol concentrations in lipoprotein fractions separated by anion-exchange-high-performance liquid chromatography in healthy dogs and dogs with hypercholesterolemia.

PubMed

Oda, Hitomi; Mori, Akihiro; Hirowatari, Yuji; Takoura, Toshie; Manita, Daisuke; Takahashi, Tomoya; Shono, Saori; Onozawa, Eri; Mizutani, Hisashi; Miki, Yohei; Itabashi, Yukiko; Sako, Toshinori

2017-10-01

Anion-exchange (AEX)-high-performance liquid chromatography (HPLC) for measurement of cholesterol can be used to separate serum lipoproteins (high-density lipoprotein (HDL); low-density lipoprotein (LDL); intermediate-density lipoprotein (IDL); very-low-density lipoprotein (VLDL)) in humans. However, AEX-HPLC has not been applied in veterinary practice. We had three objectives: (i) the validation of AEX-HPLC methods including the correlation of serum cholesterol concentration in lipoprotein fraction measured by AEX-HPLC and gel permeation-HPLC (GP-HPLC) in healthy dogs and those with hypercholesterolemia was investigated; (ii) the reference intervals of lipoprotein fractions measured by AEX-HPLC from healthy dogs (n=40) was established; (iii) lipoprotein fractions from the serum of healthy dogs (n=12) and dogs with hypercholesterolemia (n=23) were compared. Analytic reproducibility and precision of AEX-HPLC were acceptable. Positive correlation between serum concentrations of total cholesterol (Total-Chol), HDL cholesterol (HDL-Chol), LDL cholesterol (LDL-Chol)+IDL cholesterol (IDL-Chol), and VLDL cholesterol (VLDL-Chol) was noted for AEX-HPLC and GP-HPLC in healthy dogs and dogs with hypercholesterolemia. Reference intervals measured by AEX-HPLC for serum concentrations of Total-Chol, HDL-Chol, and LDL-Chol were determined to be 2.97-9.32, 2.79-6.57, 0.16-3.28mmol/L (2.5-97.5% interval), respectively. Furthermore, there was significant difference in lipoprotein profiles between healthy and dogs with hypercholesterolemia. These results suggest that AEX-HPLC can be used to evaluate lipoprotein profiles in dogs and could be a new useful indicator of hyperlipidemia in dogs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Central nervous system regulation of hepatic lipid and lipoprotein metabolism.

PubMed

Taher, Jennifer; Farr, Sarah; Adeli, Khosrow

2017-02-01

Hepatic lipid and lipoprotein metabolism is an important determinant of fasting dyslipidemia and the development of fatty liver disease. Although endocrine factors like insulin have known effects on hepatic lipid homeostasis, emerging evidence also supports a regulatory role for the central nervous system (CNS) and neuronal networks. This review summarizes evidence implicating a bidirectional liver-brain axis in maintaining metabolic lipid homeostasis, and discusses clinical implications in insulin-resistant states. The liver utilizes sympathetic and parasympathetic afferent and efferent fibers to communicate with key regulatory centers in the brain including the hypothalamus. Hypothalamic anorexigenic and orexigenic peptides signal to the liver via neuronal networks to modulate lipid content and VLDL production. In addition, peripheral hormones such as insulin, leptin, and glucagon-like-peptide-1 exert control over hepatic lipid by acting directly within the CNS or via peripheral nerves. Central regulation of lipid metabolism in other organs including white and brown adipose tissue may also contribute to hepatic lipid content indirectly via free fatty acid release and changes in lipoprotein clearance. The CNS communicates with the liver in a bidirectional manner to regulate hepatic lipid metabolism and lipoprotein production. Impairments in these pathways may contribute to dyslipidemia and hepatic steatosis in insulin-resistant states.

21-Methylpyrenyl-cholesterol stably and specifically associates with lipoprotein peripheral hemi-membrane: A new labelling tool

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gaibelet, Gérald; CEA, SB2SM and UMR8221 CNRS, IBiTec-Saclay, Gif-sur-Yvette; Tercé, François

Highlights: •21-Methylpyrenyl-cholesterol specifically and stably associates to lipoproteins. •It is not esterified by LCAT, and thus reliably labels their peripheral hemi-membrane. •HDL vs. LDL are well distinguishable by various fluorescent labelling characteristics. •LDL peripheral hemi-membrane harbors cholesterol-rich ordered lipid (micro)domains. •Cultured cells can be stained by such labelled lipoproteins-mediated delivery. -- Abstract: Lipoproteins are important biological components. However, they have few convenient fluorescent labelling probes currently reported, and their physiological reliability can be questioned. We compared the association of two fluorescent cholesterol derivatives, 22-nitrobenzoxadiazole-cholesterol (NBD-Chol) and 21-methylpyrenyl-cholesterol (Pyr-met-Chol), to serum lipoproteins and to purified HDL and LDL. Both lipoproteins couldmore » be stably labelled by Pyr-met-Chol, but virtually not by NBD-Chol. At variance with NBD-Chol, LCAT did not esterify Pyr-met-Chol. The labelling characteristics of lipoproteins by Pyr-met-Chol were well distinguishable between HDL and LDL, regarding dializability, associated probe amount and labelling kinetics. We took benefit of the pyrene labelling to approach the structural organization of LDL peripheral hemi-membrane, since Pyr-met-Chol-labelled LDL, but not HDL, presented a fluorescence emission of pyrene excimers, indicating that the probe was present in an ordered lipid micro-environment. Since the peripheral membrane of LDL contains more sphingomyelin (SM) than HDL, this excimer formation was consistent with the existence of cholesterol- and SM-enriched lipid microdomains in LDL, as already suggested in model membranes of similar composition and reminiscent to the well-described “lipid rafts” in bilayer membranes. Finally, we showed that Pyr-met-Chol could stain cultured PC-3 cells via lipoprotein-mediated delivery, with a staining pattern well different to that observed with

Advanced Marketing Core Curriculum. Test Items and Assessment Techniques.

ERIC Educational Resources Information Center

Smith, Clifton L.; And Others

This document contains duties and tasks, multiple-choice test items, and other assessment techniques for Missouri's advanced marketing core curriculum. The core curriculum begins with a list of 13 suggested textbook resources. Next, nine duties with their associated tasks are given. Under each task appears one or more citations to appropriate…

Validation test of 125 Ah advanced design IPV nickel-hydrogen flight cells

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Hall, Stephen W.

1993-01-01

An update of validation test results confirming the advanced design nickel-hydrogen cell is presented. An advanced 125 Ah individual pressure vessel (IPV) nickel-hydrogen cell was designed. The primary function of the advanced cell is to store and deliver energy for long-term, Low-Earth-Orbit (LEO) spacecraft missions. The new features of this design, which are not incorporated in state-of-the-art design cells, are: (1) use of 26 percent rather than 31 percent potassium hydroxide (KOH) electrolyte; (2) use of a patented catalyzed wall wick; (3) use of serrated-edge separators to facilitate gaseous oxygen and hydrogen flow within the cell, while still maintaining physical contact with the wall wick for electrolyte management; and (4) use of a floating rather than a fixed stack (state-of-the-art) to accommodate nickel electrode expansion due to charge/discharge cycling. The significant improvements resulting from these innovations are extended cycle life; enhanced thermal, electrolyte, and oxygen management; and accommodation of nickel electrode expansion. Six 125 Ah flight cells based on this design were fabricated by Eagle-Picher. Three of the cells contain all of the advanced features (test cells) and three are the same as the test cells except they do not have catalyst on the wall wick (control cells). All six cells are in the process of being evaluated in a LEO cycle life test at the Naval Weapons Support Center, Crane, IN, under a NASA Lewis Research Center contract. The catalyzed wall wick cells have been cycled for over 19000 cycles with no cell failures in the continuing test. Two of the noncatalyzed wall wick cells failed (cycles 9588 and 13,900).

75 FR 15443 - Advancing the Development of Diagnostic Tests and Biomarkers for Tuberculosis; Public Workshop...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-29

...] Advancing the Development of Diagnostic Tests and Biomarkers for Tuberculosis; Public Workshop; Request for... workshop entitled ``Advancing the Development of Diagnostic Tests and Biomarkers for Tuberculosis (TB... Tuberculosis in the United States, Committee on the Elimination of Tuberculosis in the United States, Division...

Serum lipoprotein (a) concentration in patients with nephrotic syndrome and its clinical implication.

PubMed

Yang, X; Wang, H; Zhu, Z; Deng, A

1998-01-01

Serum lipoprotein(a) [Lp(a)] concentration was determined in 42 patients with primary nephrotic syndrome (NS) and the relationships between Lp (a) and plasma lipids, apolipoproteins, serum creatinine (Scr), albumin, urinary proteins (Upro) were also analyzed. The results showed that: (1) serum Lp(a) concentrations in the patients with NS were higher than those in healthy controls; (2) the levels of serum Lp(a) were correlated positively with total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), apolipoprotein B (Apo-B), Upros (Upro). It is concluded that the NS patients had the potential risk of suffering from coronary artery disease, glomerular sclerosis and thrombosis. The remission of NS may partially decrease the serum Lp(a) levels. Further studies are needed to explore the prevention and treatment of dislipedemia in patients with NS.

Advanced Gun System (AGS) Dynamic Characterization: Modal Test and Analysis, High-Frequency Analysis.

DTIC Science & Technology

1999-12-01

frequency data (to 10 kHz) in the AGS test. 3.2 High-Frequency Damping Determination by Wavelet Transform. The continuous wavelet transform (CWT...ARMY RESEARCH LABORATORY MmOSm Hi Advanced Gun System ( AGS ) Dynamic Characterization: Modal Test and Analysis, High-Frequency Analysis by Morris...this report when it is no longer needed. Do not return it to the originator. ERRATA SHEET re: ARL-TR-2138 "Advanced Gun System ( AGS ) Dynamic

Effects of soy bean on serum paraoxonase 1 activity and lipoproteins in hyperlipidemic postmenopausal women.

PubMed

Shidfar, Farzad; Ehramphosh, Elham; Heydari, Iraj; Haghighi, Ladan; Hosseini, Sharieh; Shidfar, Shahrzad

2009-05-01

Because of an unfavorable serum lipoprotein profile, postmenopausal women are at risk of cardiovascular disease. Soy protein may help protect against these risk factors, although its effect on paraoxonase 1 (PON1) is not clear. The aim of the present study was to determine the effects of soy protein on serum concentration of lipoproteins and PON1 activity in hypercholesterolemic postmenopausal women. In a double-blind randomized clinical trial with a parallel design, 52 hypercholesterolemic postmenopausal women were randomly assigned to 50 g/day soy protein containing 164 mg isoflavones or placebo, for 10 weeks. Serum lipoproteins and PON1 activity were measured at baseline and at the 10th week. There was significant increase in PON1 activity (P=0.029) and a significant decrease in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), LDL-C/high-density lipoprotein cholesterol (HDL-C), triacylglycerol/HDL-C and TC/HDL-C in the soy group compared with the placebo group (P=0.001, P=0.008, P=0.012, P=0.04 and P=0.029, respectively) at the end of the study. Similarly, PON1 activity was significantly increased (P=0.015) and LDL-C, TC, LDL-C/HDL-C, triacylglycerol/HDL-C and TC/HDL-C were significantly decreased (P=0.001, P=0.002, P=0.001, P=0.016 and P=0.001) at the end of the study compared with the beginning value in soy group. Soy protein reduces the cardiovascular disease risk in postmenopausal women because of both modest reductions in serum lipoproteins and an increase in PON1 activity.

Testing and Implementation of Advanced Reynolds Stress Models

NASA Technical Reports Server (NTRS)

Speziale, Charles G.

1997-01-01

A research program was proposed for the testing and implementation of advanced turbulence models for non-equilibrium turbulent flows of aerodynamic importance that are of interest to NASA. Turbulence models that are being developed in connection with the Office of Naval Research ARI in Non-equilibrium are provided for implementation and testing in aerodynamic flows at NASA Langley Research Center. Close interactions were established with researchers at Nasa Langley RC and refinements to the models were made based on the results of these tests. The models that have been considered include two-equation models with an anisotropic eddy viscosity as well as full second-order closures. Three types of non-equilibrium corrections to the models have been considered in connection with the ARI on Nonequilibrium Turbulence: conducted for ONR.

Relation of Cholesterol and Lipoprotein Parameters with Carotid Artery Plaque Characteristics: the Atherosclerosis Risk in Communities (ARIC) Carotid MRI Study

PubMed Central

Virani, Salim S.; Catellier, Diane J.; Pompeii, Lisa A.; Nambi, Vijay; Hoogeveen, Ron C.; Wasserman, Bruce A.; Coresh, Josef; Mosley, Thomas H.; Otvos, James D.; Sharrett, A. Richey; Boerwinkle, Eric; Ballantyne, Christie M.

2011-01-01

Objective There is a paucity of data regarding relations of apolipoproteins (apolipoprotein B [ApoB] and apolipoprotein A-1 [Apo A-1]), lipoprotein particle measures (low-density lipoprotein particle concentration [LDLp] and high-density lipoprotein particle concentration [HDLp]), and lipoprotein cholesterol measures (low-density lipoprotein cholesterol [LDL-C], non–high-density lipoprotein cholesterol [non– HDL-C], and high-density lipoprotein cholesterol [HDL-C]) with atherosclerotic plaque burden, plaque eccentricity, and lipid-rich core presence as a marker of high-risk plaques. Methods Carotid artery magnetic resonance imaging was performed in 1,670 Atherosclerosis Risk in Communities study participants. Vessel wall and lipid cores were measured; normalized wall index (NWI), standard deviation (SD) of wall thickness (measure of plaque eccentricity) were calculated; and lipid cores were detected in vessels with ≥1.5 mm thickness. Fasting concentrations of cholesterol, ApoB and Apo A-1, and LDLp and HDLp were measured. Results Measures of plaque burden (carotid wall volume, wall thickness, and NWI) were positively associated with atherogenic cholesterol and lipoproteins (p<0.05 for total cholesterol, LDL-C, non–HDL-C, ApoB, and LDLp), but not with HDL-C, Apo A-1, or HDLp. SD of wall thickness was associated with total cholesterol (p 0.01) and non-HDL-C (p 0.02). Although measures of atherogenic or anti-atherogenic cholesterol or lipoprotein were not individually associated with detection of a lipid-rich core, their ratios (total cholesterol/HDL-C, non–HDL-C/ HDL-C, and LDLp/HDLp) were associated with lipid-rich core presence (p≤0.05). Conclusion Extent of carotid atherosclerosis is associated with atherogenic cholesterol and lipoproteins. Atherogenic/anti-atherogenic cholesterol or particle ratios were associated with presence of a detectable lipid-rich core. PMID:21868017

Relation of cholesterol and lipoprotein parameters with carotid artery plaque characteristics: the Atherosclerosis Risk in Communities (ARIC) carotid MRI study.

PubMed

Virani, Salim S; Catellier, Diane J; Pompeii, Lisa A; Nambi, Vijay; Hoogeveen, Ron C; Wasserman, Bruce A; Coresh, Josef; Mosley, Thomas H; Otvos, James D; Sharrett, A Richey; Boerwinkle, Eric; Ballantyne, Christie M

2011-12-01

There is a paucity of data regarding relations of apolipoproteins (apolipoprotein B [ApoB] and apolipoprotein A-1 [Apo A-1]), lipoprotein particle measures (low-density lipoprotein particle concentration [LDLp] and high-density lipoprotein particle concentration [HDLp]), and lipoprotein cholesterol measures (low-density lipoprotein cholesterol [LDL-C], non-high-density lipoprotein cholesterol [non-HDL-C], and high-density lipoprotein cholesterol [HDL-C]) with atherosclerotic plaque burden, plaque eccentricity, and lipid-rich core presence as a marker of high-risk plaques. Carotid artery magnetic resonance imaging was performed in 1670 Atherosclerosis Risk in Communities study participants. Vessel wall and lipid cores were measured; normalized wall index (NWI), standard deviation (SD) of wall thickness (measure of plaque eccentricity) were calculated; and lipid cores were detected in vessels with ≥ 1.5mm thickness. Fasting concentrations of cholesterol, ApoB and Apo A-1, and LDLp and HDLp were measured. Measures of plaque burden (carotid wall volume, wall thickness, and NWI) were positively associated with atherogenic cholesterol and lipoproteins (p < 0.05 for total cholesterol, LDL-C, non-HDL-C, ApoB, and LDLp), but not with HDL-C, Apo A-1, or HDLp. SD of wall thickness was associated with total cholesterol (p 0.01) and non-HDL-C (p 0.02). Although measures of atherogenic or anti-atherogenic cholesterol or lipoprotein were not individually associated with detection of a lipid-rich core, their ratios (total cholesterol/HDL-C, non-HDL-C/HDL-C, and LDLp/HDLp) were associated with lipid-rich core presence (p ≤ 0.05). Extent of carotid atherosclerosis is associated with atherogenic cholesterol and lipoproteins. Atherogenic/anti-atherogenic cholesterol or particle ratios were associated with presence of a detectable lipid-rich core. Published by Elsevier Ireland Ltd.

A randomized trial and novel SPR technique identifies altered lipoprotein-LDL receptor binding as a mechanism underlying elevated LDL-cholesterol in APOE4s

PubMed Central

Calabuig-Navarro, M. V.; Jackson, K. G.; Kemp, C. F.; Leake, D. S.; Walden, C. M.; Lovegrove, J. A.; Minihane, A. M.

2017-01-01

At a population level APOE4 carriers (~25% Caucasians) are at higher risk of cardiovascular diseases. The penetrance of genotype is however variable and influenced by dietary fat composition, with the APOE4 allele associated with greater LDL-cholesterol elevation in response to saturated fatty acids (SFA). The etiology of this greater responsiveness is unknown. Here a novel surface plasmon resonance technique (SPR) is developed and used, along with hepatocyte (with the liver being the main organ modulating lipoprotein metabolism and plasma lipid levels) uptake studies to establish the impact of dietary fatty acid composition on, lipoprotein-LDL receptor (LDLR) binding, and hepatocyte uptake, according to APOE genotype status. In men prospectively recruited according to APOE genotype (APOE3/3 common genotype, or APOE3/E4), triglyceride-rich lipoproteins (TRLs) were isolated at fasting and 4–6 h following test meals rich in SFA, unsaturated fat and SFA with fish oil. In APOE4s a greater LDLR binding affinity of postprandial TRL after SFA, and lower LDL binding and hepatocyte internalization, provide mechanisms for the greater LDL-cholesterol raising effect. The SPR technique developed may be used for the future study of the impact of genotype, and physiological and behavioral variables on lipoprotein metabolism. Trial registration number NCT01522482. PMID:28276521

Mapping Antigenic Sites of an Immunodominant Surface Lipoprotein of Mycoplasma agalactiae, AvgC, with the Use of Synthetic Peptides

PubMed Central

Santona, Antonella; Carta, Franco; Fraghí, Peppinetta; Turrini, Franco

2002-01-01

As a first step toward the design of an epitope vaccine to prevent contagious agalactia, the strongly immunogenic 55-kDa protein of Mycoplasma agalactiae was studied and found to correspond to the AvgC protein encoded by the avgC gene. The avg genes of M. agalactiae, which encode four variable surface lipoproteins, display a significant homology to the vsp (variable membrane surface lipoproteins) genes of the bovine pathogen Mycoplasma bovis at their promoter region as well as their N-terminus-encoding regions. Some members of the Vsp family are known to be involved in cytoadhesion to host cells. In order to localize immunogenic peptides in the AvgC antigen, the protein sequence was submitted to epitope prediction analysis, and five sets of overlapping peptides, corresponding to five selected regions, were synthesized by Spot synthesis. Reactive peptides were selected by immunobinding assay with sera from infected sheep. The three most immunogenic epitopes were shown to be surface exposed by immunoprecipitation assays, and one of these was specifically recognized by all tested sera. Our study indicates that selected epitopes of the AvgC lipoprotein may be used to develop a peptide-based vaccine which is effective against M. agalactiae infection. PMID:11748179

Advanced Stirling Convertor Testing at NASA Glenn Research Center

NASA Technical Reports Server (NTRS)

Oriti, Salvatore M.; Blaze, Gina M.

2007-01-01

The U.S. Department of Energy (DOE), Lockheed Martin Space Systems (LMSS), Sunpower Inc., and NASA Glenn Research Center (GRC) have been developing an Advanced Stirling Radioisotope Generator (ASRG) for use as a power system on space science and exploration missions. This generator will make use of the free-piston Stirling convertors to achieve higher conversion efficiency than currently available alternatives. The ASRG will utilize two Advanced Stirling Convertors (ASC) to convert thermal energy from a radioisotope heat source to electricity. NASA GRC has initiated several experiments to demonstrate the functionality of the ASC, including: in-air extended operation, thermal vacuum extended operation, and ASRG simulation for mobile applications. The in-air and thermal vacuum test articles are intended to provide convertor performance data over an extended operating time. These test articles mimic some features of the ASRG without the requirement of low system mass. Operation in thermal vacuum adds the element of simulating deep space. This test article is being used to gather convertor performance and thermal data in a relevant environment. The ASRG simulator was designed to incorporate a minimum amount of support equipment, allowing integration onto devices powered directly by the convertors, such as a rover. This paper discusses the design, fabrication, and implementation of these experiments.

Lipoproteins of slow-growing Mycobacteria carry three fatty acids and are N-acylated by Apolipoprotein N-Acyltransferase BCG_2070c

PubMed Central

2013-01-01

Background Lipoproteins are virulence factors of Mycobacterium tuberculosis. Bacterial lipoproteins are modified by the consecutive action of preprolipoprotein diacylglyceryl transferase (Lgt), prolipoprotein signal peptidase (LspA) and apolipoprotein N- acyltransferase (Lnt) leading to the formation of mature triacylated lipoproteins. Lnt homologues are found in Gram-negative and high GC-rich Gram-positive, but not in low GC-rich Gram-positive bacteria, although N-acylation is observed. In fast-growing Mycobacterium smegmatis, the molecular structure of the lipid modification of lipoproteins was resolved recently as a diacylglyceryl residue carrying ester-bound palmitic acid and ester-bound tuberculostearic acid and an additional amide-bound palmitic acid. Results We exploit the vaccine strain Mycobacterium bovis BCG as model organism to investigate lipoprotein modifications in slow-growing mycobacteria. Using Escherichia coli Lnt as a query in BLASTp search, we identified BCG_2070c and BCG_2279c as putative lnt genes in M. bovis BCG. Lipoproteins LprF, LpqH, LpqL and LppX were expressed in M. bovis BCG and BCG_2070c lnt knock-out mutant and lipid modifications were analyzed at molecular level by matrix-assisted laser desorption ionization time-of-flight/time-of-flight analysis. Lipoprotein N-acylation was observed in wildtype but not in BCG_2070c mutants. Lipoprotein N- acylation with palmitoyl and tuberculostearyl residues was observed. Conclusions Lipoproteins are triacylated in slow-growing mycobacteria. BCG_2070c encodes a functional Lnt in M. bovis BCG. We identified mycobacteria-specific tuberculostearic acid as further substrate for N-acylation in slow-growing mycobacteria. PMID:24093492

Lipoproteins of slow-growing Mycobacteria carry three fatty acids and are N-acylated by apolipoprotein N-acyltransferase BCG_2070c.

PubMed

Brülle, Juliane K; Tschumi, Andreas; Sander, Peter

2013-10-05

Lipoproteins are virulence factors of Mycobacterium tuberculosis. Bacterial lipoproteins are modified by the consecutive action of preprolipoprotein diacylglyceryl transferase (Lgt), prolipoprotein signal peptidase (LspA) and apolipoprotein N- acyltransferase (Lnt) leading to the formation of mature triacylated lipoproteins. Lnt homologues are found in Gram-negative and high GC-rich Gram-positive, but not in low GC-rich Gram-positive bacteria, although N-acylation is observed. In fast-growing Mycobacterium smegmatis, the molecular structure of the lipid modification of lipoproteins was resolved recently as a diacylglyceryl residue carrying ester-bound palmitic acid and ester-bound tuberculostearic acid and an additional amide-bound palmitic acid. We exploit the vaccine strain Mycobacterium bovis BCG as model organism to investigate lipoprotein modifications in slow-growing mycobacteria. Using Escherichia coli Lnt as a query in BLASTp search, we identified BCG_2070c and BCG_2279c as putative lnt genes in M. bovis BCG. Lipoproteins LprF, LpqH, LpqL and LppX were expressed in M. bovis BCG and BCG_2070c lnt knock-out mutant and lipid modifications were analyzed at molecular level by matrix-assisted laser desorption ionization time-of-flight/time-of-flight analysis. Lipoprotein N-acylation was observed in wildtype but not in BCG_2070c mutants. Lipoprotein N- acylation with palmitoyl and tuberculostearyl residues was observed. Lipoproteins are triacylated in slow-growing mycobacteria. BCG_2070c encodes a functional Lnt in M. bovis BCG. We identified mycobacteria-specific tuberculostearic acid as further substrate for N-acylation in slow-growing mycobacteria.

Isolation, molecular properties, and kinetic characterization of lipoprotein lipase from rat heart

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, J.; Scanu, A.M.

1977-06-25

Lipoprotein lipase was isolated to electrophoretic and chromatographic purity from rat heart acetone/ether powder by a combination of n-butyl alcohol precipitation and heparin/sepharose affinity column chromatography. By sedimentation equilibrium ultracentrifugation in 6 M guanidine hydrochloride, and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the enzyme was found to have a minimum molecular weight of about 34,000. It had a relative abundance of glutamic acid and contains 3.3 percent carbohydrate by weight. The composition was as follows, in moles per 34,000 g: mannose (neutral sugars), 5.1; sialic acid, 0.8; and glucosamine, 2.3. When tested against a triolein emulsion, the enzyme was activemore » only in the presence of apolipoprotein glutamic acid (apo C-II); it was inactivated by 1 M NaCl and by apolipoproteins serine and alanine isolated from human serum very low density lipoprotein. In order to define the kinetics of hydrolysis of triglyceride by lipoprotein lipase, we carried out studies on monomolecular films of glyceryl tri(1-/sup 14/C)octanoate. In the presence of excess apo C-II, the hydrolysis followed first order time course and yielded a second order rate constant of 1.85 x 10/sup 5/ M/sup -1/ S/sup -1/. The apparent first order rate constants, k/sub exp/, were proportional to enzyme concentrations over at least a 5-fold range. When enzyme concentrations of 0.22, 0.35, and 0.66 ..mu..g/ml were used, the rate of hydrolysis increased as a function of apo C-II concentration and reached a maximum at a concentration of apo C-II corresponding to a molar ratio of enzyme to apo C-II of about 1 : 1, respectively, which suggests the formation of a stoichiometric complex. The availability of a pure enzyme and the knowledge of its kinetics should stimulate further studies on the molecular basis of enzyme action.« less

Abnormalities of High Density Lipoproteins in Abetalipoproteinemia*

PubMed Central

Jones, John W.; Ways, Peter

1967-01-01

Detailed studies of the high density lipoproteins from three patients with abetalipoproteinemia have revealed the following principal abnormalities: 1) High density lipoprotein 3 (HDL3) is reduced in both absolute and relative concentration, although HDL2 is present in normal amounts. 2) The phospholipid distribution of both HDL fractions is abnormal, with low concentrations of lecithin and an increased percentage (though normal absolute quantity) of sphingomyelin. 3) In both HDL fractions, lecithin contains less linoleate and more oleate than normal. The cholesteryl esters are also low in linoleic acid, and the sphingomyelin is high in nervonic acid. Dietary intake influences the linoleic acid concentration within 2 weeks, and perhaps sooner, but the elevated sphingomyelin nervonic acid is little affected by up to 6 months of corn oil supplementation. Qualitatively similar changes in fatty acid composition, but not phospholipid distribution, are also found in other malabsorption states. The available evidence suggests that the abnormally low levels of HDL3 and the deranged phospholipid distribution are more specific for abetalipoproteinemia than the fatty acid abnormalities. However, the absence of these abnormalities in obligate heterozygous subjects makes their relationship to the primary defect of abetalipoproteinemia difficult to assess. Images PMID:6027078

Impact of avocado-enriched diets on plasma lipoproteins: A meta-analysis.

PubMed

Peou, Sokunthea; Milliard-Hasting, Brittany; Shah, Sachin A

2016-01-01

Optimizing plasma lipoproteins is the primary goal of pharmacotherapy and diet interventions in people at risk for cardiovascular diseases. Avocados offer a rich source of monounsaturated fat and may pose beneficial effects on the lipid profile. We aimed to perform a meta-analysis of randomized clinical trials assessing the impact of avocados on TC, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and/or triglycerides (TG). We searched PUBMED, Cumulative Index to Nursing and Allied Health Literature, Index to Nursing and Allied Health Literature, and the Cochrane Database of Systemic Reviews from their inception to February 2015. The weighted mean difference from baseline was calculated for all endpoints. Subgroup analyses were performed to assess heterogeneity, and funnel plots inspected to assess publication bias. Ten unique studies (n = 229) were included. Avocado consumption significantly reduced TC, LDL-C, and TG by -18.80 mg/dL (95% confidence interval [CI], -24.56 to -13.05; I(2), 46.9%), -16.50 mg/dL (95% CI, -22.91 to -10.10; I(2), 72.5%), -27.20 mg/dL (95% CI, -44.41 to -9.99; I(2), 91.1%) respectively. High-density lipoprotein cholesterol decreased nonsignificantly by -0.18 mg/dL (95% CI, -3.23 to 2.88; I(2), 84.8%). Avocado-substituted diets significantly decrease TC, LDL-C, and TG levels. Substituting dietary fats with avocados versus adding to the free diet should be the primary recommendation strategy. Larger trials looking at the impact of avocados on major adverse cardiovascular events are warranted. Copyright © 2016 National Lipid Association. All rights reserved.

Test Standard Developed for Determining the Slow Crack Growth of Advanced Ceramics at Ambient Temperature

NASA Technical Reports Server (NTRS)

Choi, Sung R.; Salem, Jonathan A.

1998-01-01

The service life of structural ceramic components is often limited by the process of slow crack growth. Therefore, it is important to develop an appropriate testing methodology for accurately determining the slow crack growth design parameters necessary for component life prediction. In addition, an appropriate test methodology can be used to determine the influences of component processing variables and composition on the slow crack growth and strength behavior of newly developed materials, thus allowing the component process to be tailored and optimized to specific needs. At the NASA Lewis Research Center, work to develop a standard test method to determine the slow crack growth parameters of advanced ceramics was initiated by the authors in early 1994 in the C 28 (Advanced Ceramics) committee of the American Society for Testing and Materials (ASTM). After about 2 years of required balloting, the draft written by the authors was approved and established as a new ASTM test standard: ASTM C 1368-97, Standard Test Method for Determination of Slow Crack Growth Parameters of Advanced Ceramics by Constant Stress-Rate Flexural Testing at Ambient Temperature. Briefly, the test method uses constant stress-rate testing to determine strengths as a function of stress rate at ambient temperature. Strengths are measured in a routine manner at four or more stress rates by applying constant displacement or loading rates. The slow crack growth parameters required for design are then estimated from a relationship between strength and stress rate. This new standard will be published in the Annual Book of ASTM Standards, Vol. 15.01, in 1998. Currently, a companion draft ASTM standard for determination of the slow crack growth parameters of advanced ceramics at elevated temperatures is being prepared by the authors and will be presented to the committee by the middle of 1998. Consequently, Lewis will maintain an active leadership role in advanced ceramics standardization within ASTM

Low-Density Lipoprotein Electronegativity Is a Novel Cardiometabolic Risk Factor

PubMed Central

Lu, Jonathan; Chen, Shu-Hua; Chen, Fang-Yu; Chen, Ching-Chu; Chen, Jeffrey L.; Elayda, MacArthur; Ballantyne, Christie M.; Shayani, Steven; Chen, Chu-Huang

2014-01-01

Background Low-density lipoprotein (LDL) plays a central role in cardiovascular disease (CVD) development. In LDL chromatographically resolved according to charge, the most electronegative subfraction–L5–is the only subfraction that induces atherogenic responses in cultured vascular cells. Furthermore, increasing evidence has shown that plasma L5 levels are elevated in individuals with high cardiovascular risk. We hypothesized that LDL electronegativity is a novel index for predicting CVD. Methods In 30 asymptomatic individuals with metabolic syndrome (MetS) and 27 healthy control subjects, we examined correlations between plasma L5 levels and the number of MetS criteria fulfilled, CVD risk factors, and CVD risk according to the Framingham risk score. Results L5 levels were significantly higher in MetS subjects than in control subjects (21.9±18.7 mg/dL vs. 11.2±10.7 mg/dL, P:0.01). The Jonckheere trend test revealed that the percent L5 of total LDL (L5%) and L5 concentration increased with the number of MetS criteria (P<0.001). L5% correlated with classic CVD risk factors, including waist circumference, body mass index, waist-to-height ratio, smoking status, blood pressure, and levels of fasting plasma glucose, triglyceride, and high-density lipoprotein. Stepwise regression analysis revealed that fasting plasma glucose level and body mass index contributed to 28% of L5% variance. The L5 concentration was associated with CVD risk and contributed to 11% of 30-year general CVD risk variance when controlling the variance of waist circumference. Conclusion Our findings show that LDL electronegativity was associated with multiple CVD risk factors and CVD risk, suggesting that the LDL electronegativity index may have the potential to be a novel index for predicting CVD. Large-scale clinical trials are warranted to test the reliability of this hypothesis and the clinical importance of the LDL electronegativity index. PMID:25203525

Particle numbers of lipoprotein subclasses and arterial stiffness among middle-aged men from the ERA JUMP study.

PubMed

Vishnu, A; Choo, J; Masaki, K H; Mackey, R H; Barinas-Mitchell, E; Shin, C; Willcox, B J; El-Saed, A; Seto, T B; Fujiyoshi, A; Miura, K; Lee, S; Sutton-Tyrrell, K; Kuller, L H; Ueshima, H; Sekikawa, A

2014-02-01

We examined the association between serum lipoprotein subclasses and the three measures of arterial stiffness, that is, (i) carotid-femoral pulse wave velocity (cfPWV), which is a gold standard measure of central arterial stiffness, (ii) brachial-ankle PWV (baPWV), which is emerging as a combined measure of central and peripheral arterial stiffness and (iii) femoral-ankle PWV (faPWV), which is a measure of peripheral arterial stiffness. Among a population-based sample of 701 apparently healthy Caucasian, Japanese American and Korean men aged 40-49 years, concentrations of lipoprotein particles were assessed by nuclear magnetic resonance (NMR) spectroscopy, and the PWV was assessed with an automated waveform analyzer (VP2000, Omron, Japan). Multiple linear regressions were performed to analyse the association between each NMR lipoprotein subclasses and PWV measures, after adjusting for cardiovascular risk factors and other confounders. A cutoff of P<0.01 was used for determining significance. All PWV measures had significant correlations with total and small low-density lipoprotein particle number (LDL-P) (all P<0.0001) but not LDL cholesterol (LDL-C) (all P>0.1), independent of race and age. In multivariate regression analysis, no NMR lipoprotein subclass was significantly associated with cfPWV (all P>0.01). However, most NMR lipoprotein subclasses had significant associations with both baPWV and faPWV (P<0.01). In this study of healthy middle-aged men, as compared with cfPWV, both baPWV and faPWV had stronger associations with particle numbers of lipoprotein subclasses. Our results may suggest that both baPWV and faPWV are related to arterial stiffness and atherosclerosis, whereas cfPWV may represent arterial stiffness alone.

Advanced Video Guidance Sensor (AVGS) Development Testing

NASA Technical Reports Server (NTRS)

Howard, Richard T.; Johnston, Albert S.; Bryan, Thomas C.; Book, Michael L.

2004-01-01

NASA's Marshall Space Flight Center was the driving force behind the development of the Advanced Video Guidance Sensor, an active sensor system that provides near-range sensor data as part of an automatic rendezvous and docking system. The sensor determines the relative positions and attitudes between the active sensor and the passive target at ranges up to 300 meters. The AVGS uses laser diodes to illuminate retro-reflectors in the target, a solid-state camera to detect the return from the target, and image capture electronics and a digital signal processor to convert the video information into the relative positions and attitudes. The AVGS will fly as part of the Demonstration of Autonomous Rendezvous Technologies (DART) in October, 2004. This development effort has required a great deal of testing of various sorts at every phase of development. Some of the test efforts included optical characterization of performance with the intended target, thermal vacuum testing, performance tests in long range vacuum facilities, EMI/EMC tests, and performance testing in dynamic situations. The sensor has been shown to track a target at ranges of up to 300 meters, both in vacuum and ambient conditions, to survive and operate during the thermal vacuum cycling specific to the DART mission, to handle EM1 well, and to perform well in dynamic situations.

Characterization of blood lipoproteins and validation of cholesterol and triacylglycerol assays for free-ranging polar bears (Ursus maritimus).

PubMed

Whiteman, John P; Frank, Nicholas; Greller, Katie A; Harlow, Henry J; Ben-David, Merav

2013-05-01

Blood triacylglycerol (TG) and lipoproteins are important variables for evaluating nutritional status of wildlife, but measurements are often expensive and difficult. Performance of a small, portable blood analyzer intended for human medical diagnostics was evaluated in measuring these variables in plasma and serum from free-ranging polar bears (Ursus maritimus), which are experiencing nutritional stress related to sea ice loss. The analyzer accurately tracked changes in concentration of total cholesterol (Ctotal), cholesterol associated with high-density lipoprotein (CHDL), and TG during a validation protocol of diluting samples and spiking them with exogenous cholesterol and glycerol. Values of Ctotal and TG agreed well with values obtained by other methods (ultracentrifugation followed by colorimetric assays); agreement was variable for values of cholesterol associated with specific lipoproteins. Similar to a study of captive polar bears, ultracentrifugation methods revealed greater TG in very low-density lipoproteins than in low-density lipoprotein, which is unusual and merits additional study.

Emerging strategies of targeting lipoprotein lipase for metabolic and cardiovascular diseases

PubMed Central

Geldenhuys, Werner J.; Lin, Li; Darvesh, Altaf S.; Sadana, Prabodh

2017-01-01

Although statins and other pharmacological approaches have improved the management of lipid abnormalities, there exists a need for newer treatment modalities especially for the management of hypertriglyceridemia. Lipoprotein lipase (LPL), by promoting hydrolytic cleavage of the triglyceride core of lipoproteins, is a crucial node in the management of plasma lipid levels. Although LPL expression and activity modulation is observed as a pleiotropic action of some the commonly used lipid lowering drugs, the deliberate development of drugs targeting LPL has not occurred yet. In this review, we present the biology of LPL, highlight the LPL modulation property of currently used drugs and review the novel emerging approaches to target LPL. PMID:27771332

Measurement of low-density lipoprotein cholesterol in assessment and management of cardiovascular disease risk.

PubMed

Jialal, I; Remaley, A T

2014-07-01

The deposition of cholesterol in the arterial wall by the infiltration of low-density lipoproteins (LDLs) is a key step in the development of atherosclerosis. In this Commentary, we discuss recent recommendations for clinical laboratory measurement of low-density lipoprotein cholesterol (LDL-C) and its utility both for assessing cardiovascular disease risk and as a tool in the management of patients receiving lipid-lowering therapy.

Serum lipoprotein (a) concentrations among Arab children: a hospital-based study in Kuwait.

PubMed

Alsaeid, M; Alsaeid, K; Fatania, H R; Sharma, P N; Abd-Elsalam, R

1998-09-01

Elevated lipoprotein (a) [Lp(a)] is an independent risk factor for premature atherosclerosis and coronary heart disease, both of which are prevalent among Kuwaitis. Our objective was to measure serum lipids, including Lp(a), in Arab children and compare them with values reported for other ethnic groups. To that end, serum concentrations of Lp(a), total cholesterol [T-CHOL], high density lipoprotein [HDL], low density lipoprotein [LDL], and triglyceride [TG] were assessed in 103 Arab children. The mean and median Lp(a) were 140.4 mg/l and 95 mg/l, respectively. The Lp(a) frequency distribution was skewed to the right with the highest frequencies appearing at low levels. Serum Lp(a) correlated positively with T-CHOL and LDL but did not correlate with age, HDL and TG. Only nine children (8.7%) had serum Lp(a) levels associated with increased cardiovascular risk, namely > or = 300 mg/l.

Lipid and Lipoprotein Biomarkers and the Risk of Ischemic Stroke in Postmenopausal Women

PubMed Central

Berger, Jeffrey S.; McGinn, Aileen P.; Howard, Barbara V.; Kuller, Lewis; Manson, JoAnn E.; Otvos, Jim; Curb, J. David; Eaton, Charles B; Kaplan, Robert C.; Lynch, John K.; Rosenbaum, Daniel M.; Wassertheil-Smoller, Sylvia

2012-01-01

Background Few studies simultaneously investigated lipids and lipoprotein biomarkers as predictors of ischemic stroke. The value of these biomarkers as independent predictors of ischemic stroke remains controversial. Methods We conducted a prospective nested case-control study among postmenopausal women from the Women’s Health Initiative Observational Study to assess the relationship between fasting lipids (total cholesterol, LDL-C, HDL-C, and triglycerides), lipoproteins (LDL, HDL and VLDL particle number and size, IDL particle number, and lipoprotein [a]) and risk of ischemic stroke. Among women free of stroke at baseline, 774 ischemic stroke patients were matched according to age and race to controls using a 1:1 ratio. Results In bivariate analysis, baseline triglycerides (P<0.001), IDL particles (P<0.01), LDL particles (P<0.01), VLDL triglyceride (P<0.001), VLDL particles (P<0.01), VLDL size (P<0.001), LDL size (P=0.03), and total/HDL cholesterol ratio (P<0.01) were significantly higher among women with incident ischemic stroke, while levels of HDL-C (P<0.01) and HDL size (P<0.01) were lower. No significant baseline difference for total cholesterol (P=0.15), LDL-C (P=0.47), and lipoprotein (a) (P=0.11) was observed. In multivariable analysis, triglycerides, (OR for the highest vs lowest quartile, 1.56; 95% CI, 1.13-2.17, P for trend =0.02), VLDL size (OR 1.59, 95% CI, 1.10-2.28, P for trend =0.03) and IDL particle number (OR 1.46, 95% CI, 1.04-2.04, P for trend =0.02) were significantly associated with ischemic stroke. Conclusion Among a panel of lipid and lipoprotein biomarkers, baseline triglycerides, VLDL size and IDL particle number were significantly associated with incident ischemic stroke in postmenopausal women. PMID:22308251

Aerobic Exercise and Lipids and Lipoproteins in Women: A Meta-Analysis of Randomized Controlled Trials

PubMed Central

Kelley, George A.; Kelley, Kristi S.; Tran, Zung VU

2007-01-01

Background Cardiovascular disease (CVD) in women is the leading cause of mortality in the United States, and less than optimal lipid and lipoprotein levels are major risk factors for CVD. The purpose of this study was to use the meta-analytic approach to examine the effects of aerobic exercise on lipids and lipoproteins in women. Methods Studies were retrieved via computerized literature searches, review of reference lists, hand searching selected journals, and expert review of our reference list. The inclusion of studies was limited to randomized controlled trials published in the English language literature between January 1955 and January 2003 in which aerobic exercise was used as the primary intervention in adult women aged ≥18 years. One or more of the following lipids and lipoproteins were assessed: total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). Results Using a random effects model, statistically significant improvements were observed for all lipids and lipoproteins (TC, X̄ ± SEM, −4.3 ± 1.3 mg/dl, 95% CI −6.9 to −1.7 mg/dl; HDL-C, X̄± SEM, 1.8 ± 0.9 mg/dl, 95% CI 0.1 to 3.5 mg/dl; LDL-C, X̄ ± SEM, −4.4 ± 1.1 mg/dl, 95% CI −6.5 to −2.2 mg/dl; TG, X̄ ± SEM, −4.2 ± 2.1 mg/dl, 95% CI −8.4 to −0.1 mg/dl). Reductions of approximately 2%, 3%, and 5%, respectively, were observed for TC, LDL-C, and TG, whereas an increase of 3% was observed for HDL-C. Conclusions Aerobic exercise is efficacious for increasing HDL-C and decreasing TC, LDL-C, and TG in women. PMID:15650348

Role of heparanase on hepatic uptake of intestinal derived lipoprotein and fatty streak formation in mice.

PubMed

Planer, David; Metzger, Shulamit; Zcharia, Eyal; Wexler, Isaiah D; Vlodavsky, Israel; Chajek-Shaul, Tova

2011-04-04

Heparanase modulates the level of heparan sulfate proteoglycans (HSPGs) which have an important role in multiple cellular processes. Recent studies indicate that HSPGs have an important function in hepatic lipoprotein handling and processes involving removal of lipoprotein particles. To determine the effects of decreased HSPGs chain length on lipoprotein metabolism and atherosclerosis, transgenic mice over-expressing the human heparanase gene were studied. Hepatic lipid uptake in hpa-Tg mice were evaluated by giving transgenic mice oral fat loads and labeled retinol. Sections of aorta from mice over-expressing heparanase (hpa-Tg) and controls (C57/BL6) fed an atherogenic diet were examined for evidence of atherosclerosis. Heparanase over-expression results in reduced hepatic clearance of postprandial lipoproteins and higher levels of fasting and postprandial serum triglycerides. Heparanase over-expression also induces formation of fatty streaks in the aorta. The mean lesion cross-sectional area in heparanase over-expressing mice was almost 6 times higher when compared to control mice (23,984 µm(2)±5,922 vs. 4,189 µm(2)±1,130, p<0.001). Over-expression of heparanase demonstrates the importance of HSPGs for the uptake of intestinal derived lipoproteins and its role in the formation of fatty streaks.

Role of Heparanase on Hepatic Uptake of Intestinal Derived Lipoprotein and Fatty Streak Formation in Mice

PubMed Central

Planer, David; Metzger, Shulamit; Zcharia, Eyal; Wexler, Isaiah D.; Vlodavsky, Israel; Chajek-Shaul, Tova

2011-01-01

Background Heparanase modulates the level of heparan sulfate proteoglycans (HSPGs) which have an important role in multiple cellular processes. Recent studies indicate that HSPGs have an important function in hepatic lipoprotein handling and processes involving removal of lipoprotein particles. Principal Findings To determine the effects of decreased HSPGs chain length on lipoprotein metabolism and atherosclerosis, transgenic mice over-expressing the human heparanase gene were studied. Hepatic lipid uptake in hpa-Tg mice were evaluated by giving transgenic mice oral fat loads and labeled retinol. Sections of aorta from mice over-expressing heparanase (hpa-Tg) and controls (C57/BL6) fed an atherogenic diet were examined for evidence of atherosclerosis. Heparanase over-expression results in reduced hepatic clearance of postprandial lipoproteins and higher levels of fasting and postprandial serum triglycerides. Heparanase over-expression also induces formation of fatty streaks in the aorta. The mean lesion cross-sectional area in heparanase over-expressing mice was almost 6 times higher when compared to control mice (23,984 µm2±5,922 vs. 4,189 µm2±1,130, p<0.001). Conclusions Over-expression of heparanase demonstrates the importance of HSPGs for the uptake of intestinal derived lipoproteins and its role in the formation of fatty streaks. PMID:21483695

Effects of dietary medium-chain triglycerides on plasma lipids and lipoprotein distribution and food aversion in cats.

PubMed

Trevizan, Luciano; de Mello Kessler, Alexandre; Bigley, Karen E; Anderson, Wendy H; Waldron, Mark K; Bauer, John E

2010-04-01

To determine possible diet aversion and lipid and lipoprotein alterations in cats fed diets containing medium-chain triglycerides (MCTs). 19 clinically normal adult female cats. Cats were assigned to 2 groups (low MCT diet [n = 10] and high MCT diet [9]) and fed the diets for 9 weeks according to metabolic body weight (100 kcal of metabolizable energy [ME] x kg(-0.67)/d). Daily consumption records and weekly body weight and body condition score (BCS) were used to adjust amounts fed and calculate daily ME factors for each cat to maintain ideal BCS. Blood samples were obtained after withholding food on days 0, 14, 28, and 56 for measurement of plasma triglyceride and total cholesterol concentrations and lipoprotein-cholesterol distributions. Repeated-measures ANOVA and Tukey multiple comparison tests were performed. No diet differences were found for food consumption, body weight, BCS, and ME factors. A significant increase in plasma triglyceride concentration was detected for the high MCT diet; however, values were within the reference ranges. No diet effects were observed for total cholesterol concentrations or lipoprotein-cholesterol distributions, although increases over time were observed. Inclusion of MCT in diets of cats did not result in feed refusal and had minimal effects on lipid metabolism. Such diets may be useful for both clinically normal cats and cats with metabolic disorders. The MCT oils are an example of a bioactive dietary lipid that may benefit feline metabolism and can serve as a useful functional food ingredient for cats.

Advanced Ground Systems Maintenance Cryogenics Test Lab Control System Upgrade Project

NASA Technical Reports Server (NTRS)

Harp, Janice Leshay

2014-01-01

This project will outfit the Simulated Propellant Loading System (SPLS) at KSC's Cryogenics Test Laboratory with a new programmable logic control system. The control system upgrade enables the Advanced Ground Systems Maintenace Element Integration Team and other users of the SPLS to conduct testing in a controls environment similar to that used at the launch pad.

Association of height and pubertal timing with lipoprotein subclass profile: exploring the role of genetic and environmental effects.

PubMed

Jelenkovic, Aline; Bogl, Leonie H; Rose, Richard J; Kangas, Antti J; Soininen, Pasi; Ala-Korpela, Mika; Kaprio, Jaakko; Silventoinen, Karri

2013-01-01

Little is known about the relationship between growth and lipoprotein profile. We aimed to analyze common genetic and environmental factors in the association of height from late childhood to adulthood and pubertal timing with serum lipid and lipoprotein subclass profile. A longitudinal cohort of Finnish twin pairs (FinnTwin12) was analyzed using self-reported height at 11-12, 14, 17 years and measured stature at adult age (21-24 years). Data were available for 719 individual twins including 298 complete pairs. Serum lipids and lipoprotein subclasses were measured by proton nuclear magnetic resonance spectroscopy. Multivariate variance component models for twin data were fitted. Cholesky decomposition was used to partition the phenotypic covariation among traits into additive genetic and unique environmental correlations. In men, the strongest associations for both adult height and puberty were observed with total cholesterol, low-density lipoprotein cholesterol, intermediate-density lipoprotein cholesterol, and low-density lipoprotein particle subclasses (max. r = -0.19). In women, the magnitude of the correlations was weaker (max. r = -0.13). Few associations were detected between height during adolescence and adult lipid profile. Early onset of puberty was related to an adverse lipid profile, but delayed pubertal development in girls was associated with an unfavorable profile, as well. All associations were mediated mainly by additive genetic factors, but unique environmental effects cannot be disregarded. Early puberty and shorter adult height relate to higher concentrations of atherogenic lipids and lipoprotein particles in early adulthood. Common genetic effects behind these phenotypes substantially contribute to the observed associations. Copyright © 2013 Wiley Periodicals, Inc.

Simvastatin but not bezafibrate decreases plasma lipoprotein-associated phospholipase A₂ mass in type 2 diabetes mellitus: relevance of high sensitive C-reactive protein, lipoprotein profile and low-density lipoprotein (LDL) electronegativity.

PubMed

Constantinides, Alexander; de Vries, Rindert; van Leeuwen, Jeroen J J; Gautier, Thomas; van Pelt, L Joost; Tselepis, Alexandros D; Lagrost, Laurent; Dullaart, Robin P F

2012-10-01

Plasma lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) levels predict incident cardiovascular disease, impacting Lp-PLA(2) as an emerging therapeutic target. We determined Lp-PLA(2) responses to statin and fibrate administration in type 2 diabetes mellitus, and assessed relationships of changes in Lp-PLA(2) with subclinical inflammation and lipoprotein characteristics. A placebo-controlled cross-over study (three 8-week treatment periods with simvastatin (40 mg daily), bezafibrate (400mg daily) and their combination) was carried out in 14 male type 2 diabetic patients. Plasma Lp-PLA(2) mass was measured by turbidimetric immunoassay. Plasma Lp-PLA(2) decreased (-21 ± 4%) in response to simvastatin (p<0.05 from baseline and placebo), but was unaffected by bezafibrate (1 ± 5%). The drop in Lp-PLA(2) during combined treatment (-17 ± 3%, p<0.05) was similar compared to that during simvastatin alone. The Lp-PLA(2) changes during the 3 active lipid lowering treatment periods were related positively to baseline levels of high sensitive C-reactive protein, non-HDL cholesterol, triglycerides, the total cholesterol/HDL cholesterol ratio and less LDL electronegativity (p<0.02 to p<0.01), and inversely to baseline Lp-PLA(2) (p<0.01). LpPLA(2) responses correlated inversely with changes in non-HDL cholesterol, triglycerides and the total cholesterol/HDL cholesterol ratio during treatment (p<0.05 to p<0.02). In type 2 diabetes mellitus, plasma Lp-PLA(2) is likely to be lowered by statin treatment only. Enhanced subclinical inflammation and more severe dyslipidemia may predict diminished LpPLA(2) responses during lipid lowering treatment, which in turn appear to be quantitatively dissociated from decreases in apolipoprotein B lipoproteins. Conventional lipid lowering treatment may be insufficient for optimal LpPLA(2) lowering in diabetes mellitus. Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Streptococcal Serum Opacity Factor Increases Hepatocyte Uptake of Human Plasma High Density Lipoprotein-Cholesterol1

PubMed Central

Gillard, Baiba K.; Rosales, Corina; Pillai, Biju K.; Lin, Hu Yu; Courtney, Harry S.; Pownall, Henry J.

2010-01-01

Serum opacity factor (SOF), a virulence determinant of Streptococcus pyogenes, converts plasma high density lipoproteins (HDL) to three distinct species: lipid-free apolipoprotein (apo) A-I, neo HDL, a small discoidal HDL-like particle, and a large cholesteryl ester-rich microemulsion (CERM), that contains the cholesterol esters (CE) of up to ~400,000 HDL particles and apo E as its major protein. Similar SOF reaction products are obtained with HDL, total plasma lipoproteins and whole plasma. We hypothesized that hepatic uptake of CERM-CE via multiple apo E dependent receptors would be faster than that of HDL-CE. We tested our hypothesis using human hepatoma cells and lipoprotein receptor-specific Chinese hamster ovary (CHO) cells. [3H]CE uptake by HepG2 and Huh7 cells from HDL after SOF treatment, which transfers >90% of HDL-CE to CERM, was respectively 2.4 and 4.5 times faster than from control HDL. CERM-[3H]CE uptake was inhibited by LDL and HDL, suggestive of uptake by both the LDL receptor (LDL-R) and scavenger receptor class B type I (SR-BI). Studies in CHO cells specifically expressing LDL-R and SR-BI confirmed CERM-[3H]CE uptake by both receptors. RAP and heparin inhibit CERM-[3H]CE but not HDL-[3H]CE uptake thereby implicating LRP-1 and cell surface proteoglycans in this process. These data demonstrate that SOF treatment of HDL increases CE uptake via multiple hepatic apo E receptors. In so doing, SOF might increase hepatic disposal of plasma cholesterol in a way that is therapeutically useful. PMID:20879789

Roles of the low density lipoprotein receptor and related receptors in inhibition of lipoprotein(a) internalization by proprotein convertase subtilisin/kexin type 9.

PubMed

Romagnuolo, Rocco; Scipione, Corey A; Marcovina, Santica M; Gemin, Matthew; Seidah, Nabil G; Boffa, Michael B; Koschinsky, Marlys L

2017-01-01

Elevated plasma concentrations of lipoprotein(a) (Lp(a)) are a causal risk factor for cardiovascular disease. The mechanisms underlying Lp(a) clearance from plasma remain unclear, which is an obvious barrier to the development of therapies to specifically lower levels of this lipoprotein. Recently, it has been documented that monoclonal antibody inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) can lower plasma Lp(a) levels by 30%. Since PCSK9 acts primarily through the low density lipoprotein receptor (LDLR), this result is in conflict with the prevailing view that the LDLR does not participate in Lp(a) clearance. To support our recent findings in HepG2 cells that the LDLR can act as a bona fide receptor for Lp(a) whose effects are sensitive to PCSK9, we undertook a series of Lp(a) internalization experiments using different hepatic cells, with different variants of PCSK9, and with different members of the LDLR family. We found that PCSK9 decreased Lp(a) and/or apo(a) internalization by Huh7 human hepatoma cells and by primary mouse and human hepatocytes. Overexpression of human LDLR appeared to enhance apo(a)/Lp(a) internalization in both types of primary cells. Importantly, internalization of Lp(a) by LDLR-deficient mouse hepatocytes was not affected by PCSK9, but the effect of PCSK9 was restored upon overexpression of human LDLR. In HepG2 cells, Lp(a) internalization was decreased by gain-of-function mutants of PCSK9 more than by wild-type PCSK9, and a loss-of function variant had a reduced ability to influence Lp(a) internalization. Apo(a) internalization by HepG2 cells was not affected by apo(a) isoform size. Finally, we showed that very low density lipoprotein receptor (VLDLR), LDR-related protein (LRP)-8, and LRP-1 do not play a role in Lp(a) internalization or the effect of PCSK9 on Lp(a) internalization. Our findings are consistent with the idea that PCSK9 inhibits Lp(a) clearance through the LDLR, but do not exclude other effects of

Roles of the low density lipoprotein receptor and related receptors in inhibition of lipoprotein(a) internalization by proprotein convertase subtilisin/kexin type 9

PubMed Central

Marcovina, Santica M.; Gemin, Matthew; Seidah, Nabil G.; Boffa, Michael B.

2017-01-01

Elevated plasma concentrations of lipoprotein(a) (Lp(a)) are a causal risk factor for cardiovascular disease. The mechanisms underlying Lp(a) clearance from plasma remain unclear, which is an obvious barrier to the development of therapies to specifically lower levels of this lipoprotein. Recently, it has been documented that monoclonal antibody inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) can lower plasma Lp(a) levels by 30%. Since PCSK9 acts primarily through the low density lipoprotein receptor (LDLR), this result is in conflict with the prevailing view that the LDLR does not participate in Lp(a) clearance. To support our recent findings in HepG2 cells that the LDLR can act as a bona fide receptor for Lp(a) whose effects are sensitive to PCSK9, we undertook a series of Lp(a) internalization experiments using different hepatic cells, with different variants of PCSK9, and with different members of the LDLR family. We found that PCSK9 decreased Lp(a) and/or apo(a) internalization by Huh7 human hepatoma cells and by primary mouse and human hepatocytes. Overexpression of human LDLR appeared to enhance apo(a)/Lp(a) internalization in both types of primary cells. Importantly, internalization of Lp(a) by LDLR-deficient mouse hepatocytes was not affected by PCSK9, but the effect of PCSK9 was restored upon overexpression of human LDLR. In HepG2 cells, Lp(a) internalization was decreased by gain-of-function mutants of PCSK9 more than by wild-type PCSK9, and a loss-of function variant had a reduced ability to influence Lp(a) internalization. Apo(a) internalization by HepG2 cells was not affected by apo(a) isoform size. Finally, we showed that very low density lipoprotein receptor (VLDLR), LDR-related protein (LRP)-8, and LRP-1 do not play a role in Lp(a) internalization or the effect of PCSK9 on Lp(a) internalization. Our findings are consistent with the idea that PCSK9 inhibits Lp(a) clearance through the LDLR, but do not exclude other effects of

Metabolic profiles and lipoprotein lipid concentrations in non-obese and obese patients with polycystic ovarian disease.

PubMed

Mahabeer, S; Naidoo, C; Norman, R J; Jialal, I; Reddi, K; Joubert, S M

1990-10-01

Clinical parameters, androgen status and lipoprotein lipid profiles were assessed in 10 non-obese and 10 obese patients with polycystic ovarian disease (PCOD) and reference subjects matched for age, height and weight. Both obese and non-obese women with PCOD had significantly higher androgen levels when compared to the reference groups. When comparison of lipoprotein lipid profiles were made between groups, non-obese women with PCOD had significantly higher total cholesterol, triglycerides and LDL-cholesterol levels than non-obese reference subjects. Obese PCOD women manifested significantly higher total cholesterol, LDL-cholesterol, cholesterol/HDL, and LDL/HDL values than did obese reference subjects. Correlations between serum androgens and lipoprotein lipid concentrations in PCOD and normal women were unhelpful. Both non-obese and obese patients with PCOD had significantly higher systolic and diastolic blood pressures (BPs) than the reference groups. Thus, both non-obese and obese women with PCOD manifest hyperandrogenaemia which may result in a male pattern of lipoprotein lipid concentrations.

Correlation of Serum Lipoprotein Ratios with Insulin Resistance in Infertile Women with Polycystic Ovarian Syndrome: A Case Control Study.

PubMed

Ghaffarzad, Aisa; Amani, Reza; Mehrzad Sadaghiani, Mahzad; Darabi, Masoud; Cheraghian, Bahman

2016-01-01

Dyslipidemia and insulin resistance (IR), occurring in most infertile women with polycystic ovarian syndrome (PCOS), increase the risk of cardiovascular disease (CVD) and type 2 diabetes. This study aimed to assess the relationships between lipoprotein ratios and IR in PCOS women. Thirty six infertile women with PCOS selected based on Androgen Excess Society (AES) criteria and 29 healthy women matched for age were recruited to this case-control study. After physical measurements, fasting serum glucose (Glu), insulin and lipid profile levels [triglycerides (TGs), total cholesterol (TC), low-density lipoproteincholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C)] were measured, while lipoprotein ratios (TC/HDL-C, LDL-C/HDL-C, TG/HDL-C) were calculated. IR was also calculated using homeostasis model assessment (HOMA)-IR. The optimal cutoffs of lipoprotein ratios in relation to HOMA-IR were calculated based on the Receiver Operating Characteristics (ROC) curve analysis using the area under curve (AUC). Waist circumference (WC), insulin levels, HOMA-IR, TG levels, and all lipoprotein ratios were significantly higher, while HDL-C was lower in PCOS group as compared to healthy controls. All lipoprotein ratios, TG levels, and WC are significantly correlated with insulin levels and HOMA-IR. Among lipoprotein ratios, the highest AUC of the ROC belonged to TG/HDL-C ratio with sensitivity of 63.6% and specificity of 84.4% (TG/HDL-C>3.19) as a marker of IR in infertile PCOS women. Lipoprotein ratios, particularly TG/HDL-C, are directly correlated with insulin levels and can be used as a marker of IR (HOMA-IR) in infertile PCOS patients.

Dietary Resistant Starch Supplementation Increases High-Density Lipoprotein Particle Number in Pigs Fed a Western Diet.

PubMed

Rideout, Todd C; Harding, Scott V; Raslawsky, Amy; Rempel, Curtis B

2017-05-04

Resistant starch (RS) has been well characterized for its glycemic control properties; however, there is little consensus regarding the influence of RS on blood lipid concentrations and lipoprotein distribution and size. Therefore, this study aimed to characterize the effect of daily RS supplementation in a controlled capsule delivery on biomarkers of cardiovascular (blood lipids, lipoproteins) and diabetes (glucose, insulin) risk in a pig model. Twelve 8-week-old male Yorkshire pigs were placed on a synthetic Western diet and randomly divided into two groups (n = 6/group) for 30 days: (1) a placebo group supplemented with capsules containing unmodified pre-gelatinized potato starch (0 g/RS/day); and (2) an RS group supplemented with capsules containing resistant potato starch (10 g/RS/day). Serum lipids including total-cholesterol (C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides did not differ (p > 0.05) between the RS and placebo groups. Although the total numbers of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) particles were similar (p > 0.05) between the two groups, total high-density lipoprotein (HDL) particles were higher (+28%, p < 0.05) in the RS group compared with placebo, resulting from an increase (p < 0.05) in the small HDL subclass particles (+32%). Compared with the placebo group, RS supplementation lowered (p < 0.05) fasting serum glucose (-20%) and improved (p < 0.05) insulin resistance as estimated by Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) without a change in insulin. Additionally, total serum glucagon-like-peptide 1 (GLP-1) was higher (+141%, p < 0.05) following RS supplementation compared with placebo. This data suggests that in addition to the more well-characterized effect of RS intake in lowering blood glucose and improving insulin sensitivity, the consumption of RS may be beneficial in lipid management strategies by enhancing total

Threshold level or not for low-density lipoprotein cholesterol.

PubMed

Barter, P J; Sacks, F M

2001-05-01

As drugs, such as the statins, and other therapies demonstrate the ability to significantly lower levels of low-density lipoprotein cholesterol (LDL-C), one issue is whether there is a lower threshold below which no further decline in coronary heart disease occurs. Those who evaluate the data from multiple trials and conclude that no significant decrease in coronary event rates occurs at or below 125 mg/dL suggest using this level as a guideline for clinical application of cholesterol-lowering therapy. On the other hand, analysis of the results of the same population and primary prevention studies concludes that no such threshold exists. The issues affected by the decision of whether to use a threshold include costs to the healthcare system for additional physician time, tests, and medication; unknown clinical events and safety related to very low LDL-C; and resource prioritization to an unestablished therapeutic approach.

Lipoprotein Particle Concentrations May Explain the Absence of Coronary Protection in the Women's Health Initiative Hormone Trials

PubMed Central

Hsia, Judith; Otvos, James D.; Rossouw, Jacques E.; Wu, LieLing; Wassertheil-Smoller, Sylvia; Hendrix, Susan L.; Robinson, Jennifer G.; Lund, Bernedine; Kuller, Lewis H.

2009-01-01

Objective The Women's Health Initiative randomized hormone trials unexpectedly demonstrated an increase in early coronary events. In an effort to explain this finding, we examined lipoprotein particle concentrations and their interactions with hormone therapy in a case–control substudy. Methods and Results We randomized 16 608 postmenopausal women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or to placebo, and 10 739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo, and measured lipoprotein subclasses by nuclear magnetic resonance spectroscopy at baseline and year 1 in 354 women with early coronary events and matched controls. Postmenopausal hormone therapy raised high-density lipoprotein cholesterol and particle concentration and reduced low-density lipoprotein cholesterol (LDL-C; all P<0.001 versus placebo). In contrast, neither unopposed estrogen nor estrogen with progestin lowered low-density lipoprotein particle concentration (LDL-P). Conclusions Postmenopausal hormone therapy–induced reductions in LDL-C were not paralleled by favorable effects on LDL-P. This finding may account for the absence of coronary protection conferred by estrogen in the randomized hormone trials. PMID:18599797

Lipoprotein lipase: genetics, lipid uptake, and regulation.

PubMed

Merkel, Martin; Eckel, Robert H; Goldberg, Ira J

2002-12-01

Lipoprotein lipase (LPL) regulates the plasma levels of triglyceride and HDL. Three aspects are reviewed. 1) Clinical implications of human LPL gene variations: common mutations and their effects on plasma lipids and coronary heart disease are discussed. 2) LPL actions in the nervous system, liver, and heart: the discussion focuses on LPL and tissue lipid uptake. 3) LPL gene regulation: the LPL promoter and its regulatory elements are described.

Advanced orbiting systems test-bedding and protocol verification

NASA Technical Reports Server (NTRS)

Noles, James; De Gree, Melvin

1989-01-01

The Consultative Committee for Space Data Systems (CCSDS) has begun the development of a set of protocol recommendations for Advanced Orbiting Systems (SOS). The AOS validation program and formal definition of AOS protocols are reviewed, and the configuration control of the AOS formal specifications is summarized. Independent implementations of the AOS protocols by NASA and ESA are discussed, and cross-support/interoperability tests which will allow the space agencies of various countries to share AOS communication facilities are addressed.

Effect of the Probiotic Saccharomyces boulardii on Cholesterol and Lipoprotein Particles in Hypercholesterolemic Adults: A Single-Arm, Open-Label Pilot Study.

PubMed

Ryan, Jennifer Joan; Hanes, Douglas Allen; Schafer, Morgan Beth; Mikolai, Jeremy; Zwickey, Heather

2015-05-01

Elevated blood cholesterol levels are a major risk factor for coronary artery disease, the leading cause of death worldwide. Probiotics have been investigated as potential cholesterol-lowering therapies, but no previous studies have assessed the effect of the probiotic yeast Saccharomyces boulardii on cholesterol levels in human volunteers. The objective of this study was to examine the effect of S. boulardii on serum cholesterol and lipoprotein particles in hypercholesterolemic adults. This study was a single-arm, open-label pilot study. Twelve hypercholesterolemic participants were recruited into the study; one dropped out. Participants took 5.6×10(10) colony forming unit (CFU) encapsulated S. boulardii (Saccharomyces cerevisiae var. boulardii CNCM I-1079) twice daily for an 8-week period. Fasting concentrations of cholesterol (total cholesterol, low-density lipoprotein-cholesterol [LDL-C], high-density lipoprotein-cholesterol [HDL-C], and triglycerides), lipoprotein particles (very-low-density lipoprotein-particle [VLDL-P], remnant lipoprotein particle [RLP-P], total LDL-P, LDL III-P, LDL IV-P, total HDL-P, and HDL 2b-P), and additional cardiovascular biomarkers (apo B-100, lipoprotein [a], high-sensitivity C-reactive protein, homocysteine, fibrinogen, and insulin) were measured at baseline, after 4 weeks, and after 8 weeks. Remnant lipoprotein particles decreased by 15.5% (p=0.03) over the 8-week period. The remaining outcome measures were not significantly altered. In this pilot study, 8 weeks of daily supplementation with S. boulardii lowered remnant lipoprotein, a predictive biomarker and potential therapeutic target in the treatment and prevention of coronary artery disease.

Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

PubMed Central

Chapman, M. John; Ginsberg, Henry N.; Amarenco, Pierre; Andreotti, Felicita; Borén, Jan; Catapano, Alberico L.; Descamps, Olivier S.; Fisher, Edward; Kovanen, Petri T.; Kuivenhoven, Jan Albert; Lesnik, Philippe; Masana, Luis; Nordestgaard, Børge G.; Ray, Kausik K.; Reiner, Zeljko; Taskinen, Marja-Riitta; Tokgözoglu, Lale; Tybjærg-Hansen, Anne; Watts, Gerald F.

2011-01-01

Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (≥1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (<1.0 mmol/L or 40 mg/dL) may provide further benefit. The first step should be lifestyle interventions together with consideration of compliance with pharmacotherapy and secondary causes of dyslipidaemia. If inadequately corrected, adding niacin or a fibrate, or intensifying LDL-C lowering therapy may be considered. Treatment decisions regarding statin combination therapy should take into account relevant safety concerns, i.e. the risk of elevation of blood glucose, uric acid or liver enzymes with niacin, and myopathy, increased serum creatinine and cholelithiasis with fibrates. These recommendations will facilitate reduction in the substantial cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal. PMID:21531743

Consumption of high-dose vitamin C (1250 mg per day) enhances functional and structural properties of serum lipoprotein to improve anti-oxidant, anti-atherosclerotic, and anti-aging effects via regulation of anti-inflammatory microRNA.

PubMed

Kim, Seong-Min; Lim, So-Mang; Yoo, Jeong-Ah; Woo, Moon-Jea; Cho, Kyung-Hyun

2015-11-01

Background Although the health effects of vitamin C are well known, its physiological effect on serum lipoproteins and microRNA still remain to be investigated, especially daily consumption of a high dosage. Objectives To investigate the physiological effect of vitamin C on serum lipoprotein metabolism in terms of its anti-oxidant and anti-glycation activities, and gene expression via microRNA regulation. Methods We analyzed blood parameters and lipoprotein parameters in young subjects (n = 46, 22 ± 2 years old) including smokers who consumed a high dose of vitamin C (1250 mg) daily for 8 weeks. Results Antioxidant activity of serum was enhanced with the elevation of Vit C content in plasma during 8 weeks consumption. In the LDL fraction, the apo-B48 band disappeared at 8 weeks post-consumption in all subjects. In the HDL fraction, apoA-I expression was enhanced by 20% at 8 weeks, especially in male smokers. In the lipoprotein fraction, all subjects showed significantly reduced contents of advanced glycated end products and reactive oxygen species (ROS). Triglyceride (TG) contents in each LDL and HDL fraction were significantly reduced in all groups following the Vit C consumption, suggesting that the lipoprotein was changed to be more anti-inflammatory and atherogenic properties. Phagocytosis of LDL, which was purified from each individual, into macrophages was significantly reduced at 8-weeks post-consumption of vitamin C. Anti-inflammatory and anti-senescence effects of HDL from all subjects were enhanced after the 8-weeks consumption. The expression level of microRNA 155 in HDL3 was reduced by 49% and 75% in non-smokers and smokers, respectively. Conclusion The daily consumption of a high dose of vitamin C for 8 weeks resulted in enhanced anti-senescence and anti-atherosclerotic effects via an improvement of lipoprotein parameters and microRNA expression through anti-oxidation and anti-glycation, especially in smokers.

High triglycerides and low high-density lipoprotein cholesterol lipid profile in rheumatoid arthritis: A potential link among inflammation, oxidative status, and dysfunctional high-density lipoprotein.

PubMed

Rodríguez-Carrio, Javier; Alperi-López, Mercedes; López, Patricia; López-Mejías, Raquel; Alonso-Castro, Sara; Abal, Francisco; Ballina-García, Francisco J; González-Gay, Miguel Á; Suárez, Ana

The interactions between inflammation and lipid profile in rheumatoid arthritis (RA) are poorly understood. The lipid profile study in RA has been biased toward lipoprotein levels, whereas those of triglycerides (TGs) and lipoprotein functionality have been underestimated. Since recent findings suggest a role for TG and TG-rich lipoproteins (TRL) on inflammation, we aimed to evaluate a combined lipid profile characterized by high TG and low high-density lipoprotein cholesterol levels (TG high HDL low ) in RA. Lipid profiles were analyzed in 113 RA patients, 113 healthy controls, and 27 dyslipemic subjects. Levels of inflammatory mediators, paraoxonase-1 (PON1) activity, and total antioxidant capacity were quantified in serum. PON1-rs662 status was evaluated by real-time polymerase chain reaction. The TG high HDL low profile was detected in 29/113 RA patients. Although no differences in prevalence compared with healthy controls or dyslipemic subjects were observed, this profile was associated with increased tumor necrosis factor α (P = .004), monocyte chemotactic protein (P = .004), interferon-gamma-inducible protein-10 (P = .018), and leptin (P < .001) serum levels in RA, where decreased PON1 activity and total antioxidant capacity were found. TG high HDL low prevalence was lower among anti-TNFα-treated patients (P = .004). When RA patients were stratified by PON1-rs662 status, these associations remained in the low-activity genotype (QQ). Finally, a poor clinical response on TNFα blockade was related to an increasing prevalence of the TG high HDL low profile over treatment (P = .021) and higher TRL levels at baseline (P = .042). The TG high HDL low profile is associated with systemic inflammation, decreased PON1 activity, and poor clinical outcome on TNFα blockade in RA, suggesting a role of TRL and HDL dysfunction as the missing link between inflammation and lipid profile. Copyright © 2017 National Lipid Association. Published by Elsevier Inc

Test Protocols for Advanced Inverter Interoperability Functions – Main Document

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, Jay Dean; Gonzalez, Sigifredo; Ralph, Mark E.

2013-11-01

Distributed energy resources (DER) such as photovoltaic (PV) systems, when deployed in a large scale, are capable of influencing significantly the operation of power systems. Looking to the future, stakeholders are working on standards to make it possible to manage the potentially complex interactions between DER and the power system. In 2009, the Electric Power Research Institute (EPRI), Sandia National Laboratories (SNL) with the U.S. Department of Energy (DOE), and the Solar Electric Power Association (SEPA) initiated a large industry collaborative to identify and standardize definitions for a set of DER grid support functions. While the initial effort concentrated onmore » grid-tied PV inverters and energy storage systems, the concepts have applicability to all DER. A partial product of this on-going effort is a reference definitions document (IEC TR 61850-90-7, Object models for power converters in distributed energy resources (DER) systems) that has become a basis for expansion of related International Electrotechnical Commission (IEC) standards, and is supported by US National Institute of Standards and Technology (NIST) Smart Grid Interoperability Panel (SGIP). Some industry-led organizations advancing communications protocols have also embraced this work. As standards continue to evolve, it is necessary to develop test protocols to independently verify that the inverters are properly executing the advanced functions. Interoperability is assured by establishing common definitions for the functions and a method to test compliance with operational requirements. This document describes test protocols developed by SNL to evaluate the electrical performance and operational capabilities of PV inverters and energy storage, as described in IEC TR 61850-90-7. While many of these functions are not currently required by existing grid codes or may not be widely available commercially, the industry is rapidly moving in that direction. Interoperability issues are

Novel role of ADAMTS-5 protein in proteoglycan turnover and lipoprotein retention in atherosclerosis.

PubMed

Didangelos, Athanasios; Mayr, Ursula; Monaco, Claudia; Mayr, Manuel

2012-06-01

Atherosclerosis is initiated by the retention of lipoproteins on proteoglycans in the arterial intima. However, the mechanisms leading to proteoglycan accumulation and lipoprotein retention are poorly understood. In this study, we set out to investigate the role of ADAMTS-5 (a disintegrin and metalloprotease with thrombospondin motifs-5) in the vasculature. ADAMTS-5 was markedly reduced in atherosclerotic aortas of apolipoprotein E-null (apoE(-/-)) mice. The reduction of ADAMTS-5 was accompanied by accumulation of biglycan and versican, the major lipoprotein-binding proteoglycans, in atherosclerosis. ADAMTS-5 activity induced the release of ADAMTS-specific versican (DPEAAE(441)) and aggrecan ((374)ALGS) fragments as well as biglycan and link protein from the aortic wall. Fibroblast growth factor 2 (FGF-2) inhibited ADAMTS-5 expression in isolated aortic smooth muscle cells and blocked the spontaneous release of ADAMTS-generated versican and aggrecan fragments from aortic explants. In aortas of ADAMTS-5-deficient mice, DPEAAE(441) versican neoepitopes were not detectable. Instead, biglycan levels were increased, highlighting the role of ADAMTS-5 in the catabolism of vascular proteoglycans. Importantly, ADAMTS-5 proteolytic activity reduced the LDL binding ability of biglycan and released LDL from human aortic lesions. This study provides the first evidence implicating ADAMTS-5 in the regulation of proteoglycan turnover and lipoprotein retention in atherosclerosis.

Subfractions of high-density lipoprotein (HDL) and dysfunctional HDL in chronic kidney disease patients.

PubMed

Rysz-Górzyńska, Magdalena; Banach, Maciej

2016-08-01

A number of studies have shown that chronic kidney disease (CKD) is associated with increased risk for cardiovascular disease (CVD). Chronic kidney disease is characterized by significant disturbances in lipoprotein metabolism, including differences in quantitative and qualitative content of high-density lipoprotein (HDL) particles. Recent studies have revealed that serum HDL cholesterol levels do not predict CVD in CKD patients; thus CKD-induced modifications in high-density lipoprotein (HDL) may be responsible for the increase in CV risk in CKD patients. Various methods are available to separate several subclasses of HDL and confirm their atheroprotective properties. However, under pathological conditions associated with inflammation and oxidation, HDL can progressively lose normal biological activities and be converted into dysfunctional HDL. In this review, we highlight the current state of knowledge on subfractions of HDL and HDL dysfunction in CKD.

Sedimentation, viscosity and partial specific volumes of membrane proteins and lipoproteins

PubMed Central

Brown, A. D.; Netschey, A.

1967-01-01

1. Lipoproteins or defatted proteins from the membrane of Halobacterium halobium were dissolved in 0·02m-phosphate buffer, pH7·4, with or without urea (8m). Physicochemical measurements were made on these solutions with and without addition of sodium chloride. 2. In the presence of 8m-urea the lipoproteins could be resolved into two sedimenting groups. The faster group had an average apparent molecular weight of 390 000; sedimentation coefficients of the slower group could not be determined. 3. Proteins that had been defatted by extraction with a chloroform–methanol mixture could also be resolved into two groups distinguished by their sedimentation velocities. Sedimentation coefficients of both groups were readily determined. The average apparent molecular weight of the faster group of defatted proteins in 8m-urea was 340 000 and that of the slower group was 97 000. It is concluded that attachment of lipid does not affect the state of aggregation of the proteins in 8m-urea. 4. Intrinsic viscosities of lipoproteins and defatted proteins were higher than is customary for globular proteins and suggest expanded highly-solvated molecules, consistent with the `denaturing' action on the proteins of solutions of low ionic strength. ImagesFig. 1. PMID:6033765

ADVANCED HEAT TRANSFER TEST FACILITY, TRA666A. ELEVATIONS. ROOF FRAMING PLAN. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

ADVANCED HEAT TRANSFER TEST FACILITY, TRA-666A. ELEVATIONS. ROOF FRAMING PLAN. CONCRETE BLOCK SIDING. SLOPED ROOF. ROLL-UP DOOR. AIR INTAKE ENCLOSURE ON NORTH SIDE. F.C. TORKELSON 842-MTR-666-A5, 8/1966. INL INDEX NO. 531-0666-00-851-152258, REV. 2. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

Hyphenating size‐exclusion chromatography with electrospray mass spectrometry; using on‐line liquid‐liquid extraction to study the lipid composition of lipoprotein particles

PubMed Central

Osei, Michael; Griffin, Julian L.

2015-01-01

Rationale Lipoproteins belong to the most commonly measured clinical biochemical parameters. Lipidomics is an orthogonal approach and aims to profile the individual lipid molecules that jointly form the lipoprotein particles. However, in the first step of the extraction of lipid molecules from serum, an organic solvent is used leading to dissociation of the lipoproteins. Thus far it has been impossible to combine lipidomics and lipoprotein analysis in one analytical system. Methods Human plasma was diluted in phosphate‐buffered saline (PBS) and injected onto a Superose 6 PC 3.2 column with PBS as a mobile phase to separate lipoproteins. The eluent was led to a Syrris FLLEX module, which also received CHCl3/MeOH (3:1). The two phases were mixed and subsequently separated using a Teflon membrane in an especially designed pressurized flow chamber. The organic phase was led to a standard electrospray source of an Orbitrap mass spectrometer. Results Size‐exclusion chromatography (SEC) has been commonly applied to separate lipoproteins and is considered a practical alternative to ultracentrifugation. Through the on‐line liquid‐liquid extraction method it becomes possible to obtained detailed mass spectra of lipids across different lipoprotein fractions. The extracted ion chromatograms of specific lipid signals showed their distribution against the size of lipoprotein particles. Conclusions The application of on‐line liquid‐liquid extraction allows for the continuous electrospray‐based mass spectral analysis of SEC eluent, providing the detailed lipid composition of lipoprotein particles separated by size. This approach provides new possibilities for the study of the biochemistry of lipoproteins. © 2015 The Authors. Rapid Communications in Mass Spectrometry Published by John Wiley & Sons Ltd. PMID:26443395

Standardization Efforts for Mechanical Testing and Design of Advanced Ceramic Materials and Components

NASA Technical Reports Server (NTRS)

Salem, Jonathan A.; Jenkins, Michael G.

2003-01-01

Advanced aerospace systems occasionally require the use of very brittle materials such as sapphire and ultra-high temperature ceramics. Although great progress has been made in the development of methods and standards for machining, testing and design of component from these materials, additional development and dissemination of standard practices is needed. ASTM Committee C28 on Advanced Ceramics and ISO TC 206 have taken a lead role in the standardization of testing for ceramics, and recent efforts and needs in standards development by Committee C28 on Advanced Ceramics will be summarized. In some cases, the engineers, etc. involved are unaware of the latest developments, and traditional approaches applicable to other material systems are applied. Two examples of flight hardware failures that might have been prevented via education and standardization will be presented.

Advanced Guidance and Control Methods for Reusable Launch Vehicles: Test Results

NASA Technical Reports Server (NTRS)

Hanson, John M.; Jones, Robert E.; Krupp, Don R.; Fogle, Frank R. (Technical Monitor)

2002-01-01

There are a number of approaches to advanced guidance and control (AG&C) that have the potential for achieving the goals of significantly increasing reusable launch vehicle (RLV) safety/reliability and reducing the cost. In this paper, we examine some of these methods and compare the results. We briefly introduce the various methods under test, list the test cases used to demonstrate that the desired results are achieved, show an automated test scoring method that greatly reduces the evaluation effort required, and display results of the tests. Results are shown for the algorithms that have entered testing so far.

High-density lipoprotein-like particle formation of Synuclein variants.

PubMed

Eichmann, Cédric; Kumari, Pratibha; Riek, Roland

2017-01-01

α-Synuclein (α-Syn) is an intrinsically disordered protein in solution whose fibrillar aggregates are the hallmark of Parkinson's disease (PD). Although the specific function of α-Syn is still unclear, its high structural plasticity is key for the interactions of α-Syn with biological membranes. Recently, it has been observed that α-Syn is able to form high-density lipoprotein-like (HDL-like) particles that are reminiscent of self-assembling phospholipid bilayer nanodiscs. Here, we extended our preparation method for the production of α-Syn lipoprotein particles to the β- and γ-Syn variants, and the PD-related familial α-Syn mutants. We show that all human Syns can form stable and homogeneous populations of HDL-like particles with distinct morphologies. Our results characterize the impact of the individual Syns on the formation capacity of these particles and indicate that Syn HDL-like particles are neither causing toxicity nor a toxicity-related loss of α-Syn in PD. © 2016 Federation of European Biochemical Societies.

Multidimensional profiling of plasma lipoproteins by size exclusion chromatography followed by reverse-phase protein arrays

PubMed Central

Dernick, Gregor; Obermüller, Stefan; Mangold, Cyrill; Magg, Christine; Matile, Hugues; Gutmann, Oliver; von der Mark, Elisabeth; Handschin, Corinne; Maugeais, Cyrille; Niesor, Eric J.

2011-01-01

The composition of lipoproteins and the association of proteins with various particles are of much interest in the context of cardiovascular disease. Here, we describe a technique for the multidimensional analysis of lipoproteins and their associated apolipoproteins. Plasma is separated by size exclusion chromatography (SEC), and fractions are analyzed by reverse-phase arrays. SEC fractions are spotted on nitrocellulose slides and incubated with different antibodies against individual apolipoproteins or antibodies against various apolipoproteins. In this way, tens of analytes can be measured simultaneously in 100 μl of plasma from a single SEC separation. This methodology is particularly suited to simultaneous analysis of multiple proteins that may change their distribution to lipoproteins or alter their conformation, depending on factors that influence circulating lipoprotein size or composition. We observed changes in the distribution of exchangeable apolipoproteins following addition of recombinant apolipoproteins or interaction with exogenous compounds. While the cholesteryl ester transfer protein (CETP)-dependent formation of pre-β-HDL was inhibited by the CETP inhibitors torcetrapib and anacetrapib, it was not reduced by the CETP modulator dalcetrapib. This finding was elucidated using this technique. PMID:21971713

Core lipid, surface lipid and apolipoprotein composition analysis of lipoprotein particles as a function of particle size in one workflow integrating asymmetric flow field-flow fractionation and liquid chromatography-tandem mass spectrometry

PubMed Central

Jones, Jeffery I.; Gardner, Michael S.; Schieltz, David M.; Parks, Bryan A.; Toth, Christopher A.; Rees, Jon C.; Andrews, Michael L.; Carter, Kayla; Lehtikoski, Antony K.; McWilliams, Lisa G.; Williamson, Yulanda M.; Bierbaum, Kevin P.; Pirkle, James L.; Barr, John R.

2018-01-01

Lipoproteins are complex molecular assemblies that are key participants in the intricate cascade of extracellular lipid metabolism with important consequences in the formation of atherosclerotic lesions and the development of cardiovascular disease. Multiplexed mass spectrometry (MS) techniques have substantially improved the ability to characterize the composition of lipoproteins. However, these advanced MS techniques are limited by traditional pre-analytical fractionation techniques that compromise the structural integrity of lipoprotein particles during separation from serum or plasma. In this work, we applied a highly effective and gentle hydrodynamic size based fractionation technique, asymmetric flow field-flow fractionation (AF4), and integrated it into a comprehensive tandem mass spectrometry based workflow that was used for the measurement of apolipoproteins (apos A-I, A-II, A-IV, B, C-I, C-II, C-III and E), free cholesterol (FC), cholesterol esters (CE), triglycerides (TG), and phospholipids (PL) (phosphatidylcholine (PC), sphingomyelin (SM), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and lysophosphatidylcholine (LPC)). Hydrodynamic size in each of 40 size fractions separated by AF4 was measured by dynamic light scattering. Measuring all major lipids and apolipoproteins in each size fraction and in the whole serum, using total of 0.1 ml, allowed the volumetric calculation of lipoprotein particle numbers and expression of composition in molar analyte per particle number ratios. Measurements in 110 serum samples showed substantive differences between size fractions of HDL and LDL. Lipoprotein composition within size fractions was expressed in molar ratios of analytes (A-I/A-II, C-II/C-I, C-II/C-III. E/C-III, FC/PL, SM/PL, PE/PL, and PI/PL), showing differences in sample categories with combinations of normal and high levels of Total-C and/or Total-TG. The agreement with previous studies indirectly validates the AF4-LC-MS/MS approach and

Port-of-entry Advanced Sorting System (PASS) operational test : final report

DOT National Transportation Integrated Search

1998-12-01

In 1992 the Oregon Department of Transportation undertook an operational test of the Port-of-Entry Advanced Sorting System (PASS), which uses a two-way communication automatic vehicle identification system, integrated with weigh-in-motion, automatic ...

Moderate alcohol consumption and changes in postprandial lipoproteins of premenopausal and postmenopausal women: a diet-controlled, randomized intervention study.

PubMed

van der Gaag, M S; Sierksma, A; Schaafsma, G; van Tol, A; Geelhoed-Mieras, T; Bakker, M; Hendriks, H F

2000-01-01

Moderate alcohol consumption is associated with a reduced risk of coronary heart disease. Earlier studies in men have shown that moderate alcohol consumption affects lipoprotein metabolism and hemostasis. In this diet-controlled, randomized, crossover trial, we investigated the effect on lipoprotein metabolism of moderate consumption of red wine or red grape juice with evening dinner for 3 weeks in premenopausal women using oral contraceptives and in postmenopausal women. After 3 weeks, blood samples were collected 1 hour before dinner up to 19 hours after starting dinner at 2-hour or 4-hour intervals. Plasma triglyceride concentrations and very low density lipoprotein (VLDL) triglyceride levels peaked 3 hours after dinner with wine in both premenopausal and postmenopausal women. After wine consumption, the overall high-density lipoprotein (HDL) cholesterol level was increased in postmenopausal women (mean increase 0.17 mmol/L, or 12%, p = 0.03), and the plasma low-density lipoprotein (LDL) cholesterol level was reduced in premenopausal women (mean reduction 0.35 mmol/L, or 12%, p = 0.01) as compared with grape juice consumption. The findings suggest that postprandial lipoprotein metabolism after moderate alcohol consumption differs between oral contraceptive-using premenopausal women and postmenopausal women. The response of postmenopausal women to alcohol resembled the response found in earlier studies in men.

Functional Roles of the Interaction of APP and Lipoprotein Receptors

PubMed Central

Pohlkamp, Theresa; Wasser, Catherine R.; Herz, Joachim

2017-01-01

The biological fates of the key initiator of Alzheimer’s disease (AD), the amyloid precursor protein (APP), and a family of lipoprotein receptors, the low-density lipoprotein (LDL) receptor-related proteins (LRPs) and their molecular roles in the neurodegenerative disease process are inseparably interwoven. Not only does APP bind tightly to the extracellular domains (ECDs) of several members of the LRP group, their intracellular portions are also connected through scaffolds like the one established by FE65 proteins and through interactions with adaptor proteins such as X11/Mint and Dab1. Moreover, the ECDs of APP and LRPs share common ligands, most notably Reelin, a regulator of neuronal migration during embryonic development and modulator of synaptic transmission in the adult brain, and Agrin, another signaling protein which is essential for the formation and maintenance of the neuromuscular junction (NMJ) and which likely also has critical, though at this time less well defined, roles for the regulation of central synapses. Furthermore, the major independent risk factors for AD, Apolipoprotein (Apo) E and ApoJ/Clusterin, are lipoprotein ligands for LRPs. Receptors and ligands mutually influence their intracellular trafficking and thereby the functions and abilities of neurons and the blood-brain-barrier to turn over and remove the pathological product of APP, the amyloid-β peptide. This article will review and summarize the molecular mechanisms that are shared by APP and LRPs and discuss their relative contributions to AD. PMID:28298885

Effects of daily ingestion of chilli on serum lipoprotein oxidation in adult men and women.

PubMed

Ahuja, Kiran D K; Ball, Madeleine J

2006-08-01

Laboratory studies have shown that the resistance of isolated LDL-cholesterol or linoleic acid to oxidation is increased in incubations with chilli extracts or capsaicin--the active ingredient of chilli. It is unknown if these in vitro antioxidative effects also occur in the serum of individuals eating chilli regularly. The present study investigated the effects of regular consumption of chilli on in vitro serum lipoprotein oxidation and total antioxidant status (TAS) in healthy adult men and women. In a randomised cross-over study, twenty-seven participants (thirteen men and fourteen women) ate 'freshly chopped chilli' blend (30 g/d; 55% cayenne chilli) and no chilli (bland) diets, for 4 weeks each. Use of other spices, such as cinnamon, ginger, garlic and mustard, was restricted to minimum amounts. At the end of each dietary period serum samples were analysed for lipids, lipoproteins, TAS and Cu-induced lipoprotein oxidation. Lag time (before initiation of oxidation) and rate of oxidation (slope of propagation phase) were calculated. There was no difference in the serum lipid, lipoproteins and TAS at the end of the two dietary periods. In the whole group, the rate of oxidation was significantly lower (mean difference -0.23 absorbance x10(-3)/min; P=0.04) after the chilli diet, compared with the bland diet. In women, lag time was higher (mean difference 9.61 min; P<0.001) after the chilli diet, compared with the bland diet. In conclusion, regular consumption of chilli for 4 weeks increases the resistance of serum lipoproteins to oxidation.

Methionine deficiency in rats fed soy protein induces hypercholesterolemia and potentiates lipoprotein susceptibility to peroxidation.

PubMed

Moundras, C; Rémésy, C; Levrat, M A; Demigné, C

1995-09-01

A number of studies have provided evidence that plant proteins, especially soy protein, have a cholesterol-lowering effect as compared with casein. However, dietary supply of sulfur amino acids may be deficient when soy protein is present in the diet at a suboptimal level, which could affect lipid metabolism. Accordingly, in rats fed 13% protein diets, soy protein feeding resulted in a cholesterol-increasing effect (+18%), which could be counteracted by methionine supplementation (0.4%). In contrast, soy protein was effective in decreasing plasma triglyceride, as compared with levels in rats fed casein; this triglyceride-lowering effect was entirely abolished by methionine supplementation. The hypercholesterolemic effect of soy protein was characterized by a higher cholesterol content in low-density lipoprotein (LDL) and high-density lipoprotein 1 (HDL1) fractions, together with a marked induction of hepatic hydroxymethyl glutaryl coenzyme A (HMG CoA) reductase activity and to a lesser extent cholesterol 7 alpha-hydroxylase. There was practically no induction of these enzymes, as compared with levels in rats fed casein diets, when the soy protein diet was supplemented with methionine. Very-low-density lipoprotein (VLDL) plus LDL susceptibility to peroxidation was higher in rats fed soy protein than in casein-fed rats, which could reflect in part the lack of sulfur amino acid availability, since methionine supplementation led to a partial recovery of lipoprotein resistance to peroxidation. These findings suggest that amino acid imbalance could be atherogenic by increasing circulating cholesterol and leading to a higher lipoprotein susceptibility to peroxidation.

Fragrance patch tests prepared in advance may give false-negative reactions.

PubMed

Mowitz, Martin; Svedman, Cecilia; Zimerson, Erik; Bruze, Magnus

2014-11-01

Several of the ingredients in fragrance mix I (FM I) have been shown to evaporate from petrolatum preparations applied in test chambers to an extent that can be suspected to affect the patch test result. To compare the reactivity towards FM I and fragrance mix II (FM II) when they are applied in test chambers in advance and immediately prior to the patch test occasion. Seven hundred and ninety-five consecutive patients were simultaneously patch tested with duplicate samples of FM I and FM II. One sample was applied in the test chamber 6 days in advance (6D sample), and the other sample was applied immediately before the patients were patch tested (fresh sample). Twenty-two (2.8%) patients reacted exclusively to the fresh sample of FM I, 6 (0.7%) reacted exclusively to the 6D sample, and 22 (2.8%) reacted to both samples. The corresponding numbers for FM II were 9 (1.1%) for the fresh sample, 6 (0.7%) for the 6D sample and 12 (1.5%) for both samples. There was a statistically significant difference between the numbers of patients reacting to the fresh and 6D samples of FM I. No corresponding difference was observed for FM II. This can probably be explained by differences in volatilities between the ingredients of FM I and FM II. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The age dependency of gene expression for plasma lipids, lipoproteins, and apolipoproteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Snieder, H.; Doornen, L.J.P. van; Boomsma, D.I.

The aim of this study was to investigate and disentangle the genetic and nongenetic causes of stability and change in lipids and (apo)lipoproteins that occur during the lifespan. Total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and lipoprotein(a) (Lp[a]) were measured in a group of 160 middle-aged parents and their twin offspring (first project) and in a group of 203 middle-aged twin pairs (second project). Combining the data of both projects enabled the estimation of the extent to which measured lipid parameters are influenced by different genes in adolescence and adulthood. To thatmore » end, an extended quantitative genetic model was specified, which allowed the estimation of heritabilities for each sex and generation separately. Heritabilities were similar for both sexes and both generations. Larger variances in the parental generation could be ascribed to proportional increases in both unique environmental and additive genetic variance from childhood to adulthood, which led to similar heritability estimates in adolescent and middle-aged twins. Although the magnitudes of heritabilities were similar across generations, results showed that, for total cholesterol, triglycerides, HDL, and LDL, partly different genes are expressed in adolescence compared to adulthood. For triglycerides, only 46% of the genetic variance was common to both age groups; for total cholesterol this was 80%. Intermediate values were found for HDL (66%) and LDL (76%). For ApoA1, ApoB, and Lp(a), the same genes seem to act in both generations. 56 refs., 2 figs., 5 tabs.« less

Accuracy of the Enhanced Liver Fibrosis Test vs FibroTest, Elastography, and Indirect Markers in Detection of Advanced Fibrosis in Patients With Alcoholic Liver Disease.

PubMed

Thiele, Maja; Madsen, Bjørn Stæhr; Hansen, Janne Fuglsang; Detlefsen, Sönke; Antonsen, Steen; Krag, Aleksander

2018-04-01

Alcohol is the leading cause of cirrhosis and liver-related mortality, but we lack serum markers to detect compensated disease. We compared the accuracy of the Enhanced Liver Fibrosis test (ELF), the FibroTest, liver stiffness measurements (made by transient elastography and 2-dimensional shear-wave elastography), and 6 indirect marker tests in detection of advanced liver fibrosis (Kleiner stage ≥F3). We performed a prospective study of 10 liver fibrosis markers (patented and not), all performed on the same day. Patients were recruited from primary centers (municipal alcohol rehabilitation, n = 128; 6% with advanced fibrosis) and secondary health care centers (hospital outpatient clinics, n = 161; 36% with advanced fibrosis) in the Region of Southern Denmark from 2013 through 2016. Biopsy-verified fibrosis stage was used as the reference standard. The primary aim was to validate ELF in detection of advanced fibrosis in patients with alcoholic liver disease recruited from primary and secondary health care centers, using the literature-based cutoff value of 10.5. Secondary aims were to assess the diagnostic accuracy of ELF for significant fibrosis and cirrhosis and to determine whether combinations of fibrosis markers increase diagnostic yield. The ELF identified patients with advanced liver fibrosis with an area under the receiver operating characteristic curve (AUROC) of 0.92 (95% confidence interval 0.89-0.96); findings did not differ significantly between patients from primary vs secondary care (P = .917). ELF more accurately identified patients with advanced liver fibrosis than indirect marker tests, but ELF and FibroTest had comparable diagnostic accuracies (AUROC of FibroTest, 0.90) (P = .209 for comparison with ELF). Results from the ELF and FibroTest did not differ significantly from those of liver stiffness measurement in intention-to-diagnose analyses (AUROC for transient elastography, 0.90), but did differ in the per-protocol analysis (AUROC for

Non-high-density lipoprotein cholesterol: an important predictor of stroke and diabetes-related mortality in Japanese elderly diabetic patients.

PubMed

Araki, Atsushi; Iimuro, Satoshi; Sakurai, Takashi; Umegaki, Hiroyuki; Iijima, Katsuya; Nakano, Hiroshi; Oba, Kenzo; Yokono, Koichi; Sone, Hirohito; Yamada, Nobuhiro; Ako, Junya; Kozaki, Koichi; Miura, Hisayuki; Kashiwagi, Atsunori; Kikkawa, Ryuichi; Yoshimura, Yukio; Nakano, Tadasumi; Ohashi, Yasuo; Ito, Hideki

2012-04-01

To evaluate the association of low-density lipoprotein, high-density lipoprotein and non-high-density lipoprotein cholesterol with the risk of stroke, diabetes-related vascular events and mortality in elderly diabetes patients. This study was carried out as a post-hoc landmark analysis of a randomized, controlled, multicenter, prospective intervention trial. We included 1173 elderly type 2 diabetes patients (aged ≥ 65 years) from 39 Japanese institutions who were enrolled in the Japanese elderly diabetes intervention trial study and who could be followed up for 1 year. A landmark survival analysis was carried out in which follow up was set to start 1 year after the initial time of entry. During 6 years of follow up, there were 38 cardiovascular events, 50 strokes, 21 diabetes-related deaths and 113 diabetes-related events. High low-density lipoprotein cholesterol was associated with incident cardiovascular events, and high glycated hemoglobin was associated with strokes. After adjustment for possible covariables, non-high-density lipoprotein cholesterol showed a significant association with increased risk of stroke, diabetes-related mortality and total events. The adjusted hazard ratios (95% confidence intervals) of non-high-density lipoprotein cholesterol were 1.010 (1.001-1.018, P = 0.029) for stroke, 1.019 (1.007-1.031, P < 0.001) for diabetes-related death and 1.008 (1.002-1.014; P < 0.001) for total diabetes-related events. Higher non-high-density lipoprotein cholesterol was associated with an increased risk of stroke, diabetes-related mortality and total events in elderly diabetes patients. © 2012 Japan Geriatrics Society.

Automated Processing of Plasma Samples for Lipoprotein Separation by Rate-Zonal Ultracentrifugation.

PubMed

Peters, Carl N; Evans, Iain E J

2016-12-01

Plasma lipoproteins are the primary means of lipid transport among tissues. Defining alterations in lipid metabolism is critical to our understanding of disease processes. However, lipoprotein measurement is limited to specialized centers. Preparation for ultracentrifugation involves the formation of complex density gradients that is both laborious and subject to handling errors. We created a fully automated device capable of forming the required gradient. The design has been made freely available for download by the authors. It is inexpensive relative to commercial density gradient formers, which generally create linear gradients unsuitable for rate-zonal ultracentrifugation. The design can easily be modified to suit user requirements and any potential future improvements. Evaluation of the device showed reliable peristaltic pump accuracy and precision for fluid delivery. We also demonstrate accurate fluid layering with reduced mixing at the gradient layers when compared to usual practice by experienced laboratory personnel. Reduction in layer mixing is of critical importance, as it is crucial for reliable lipoprotein separation. The automated device significantly reduces laboratory staff input and reduces the likelihood of error. Overall, this device creates a simple and effective solution to formation of complex density gradients. © 2015 Society for Laboratory Automation and Screening.

Conjugation of squalene to gemcitabine as unique approach exploiting endogenous lipoproteins for drug delivery

NASA Astrophysics Data System (ADS)

Sobot, Dunja; Mura, Simona; Yesylevskyy, Semen O.; Dalbin, Laura; Cayre, Fanny; Bort, Guillaume; Mougin, Julie; Desmaële, Didier; Lepetre-Mouelhi, Sinda; Pieters, Grégory; Andreiuk, Bohdan; Klymchenko, Andrey S.; Paul, Jean-Louis; Ramseyer, Christophe; Couvreur, Patrick

2017-05-01

Once introduced in the organism, the interaction of nanoparticles with various biomolecules strongly impacts their fate. Here we show that nanoparticles made of the squalene derivative of gemcitabine (SQGem) interact with lipoproteins (LPs), indirectly enabling the targeting of cancer cells with high LP receptors expression. In vitro and in vivo experiments reveal preeminent affinity of the squalene-gemcitabine bioconjugates towards LP particles with the highest cholesterol content and in silico simulations further display their incorporation into the hydrophobic core of LPs. To the best of our knowledge, the use of squalene to induce drug insertion into LPs for indirect cancer cell targeting is a novel concept in drug delivery. Interestingly, not only SQGem but also other squalene derivatives interact similarly with lipoproteins while such interaction is not observed with liposomes. The conjugation to squalene represents a versatile platform that would enable efficient drug delivery by simply exploiting endogenous lipoproteins.

The in vitro interactions between serum lipoproteins and proteoglycans of the neointima of rabbit aorta after a single balloon catheter injury.

PubMed

Alavi, M Z; Richardson, M; Moore, S

1989-02-01

The effect of injury-induced alterations in the aortic neointimal proteoglycans on their binding with homologous serum lipoproteins was examined. Proteoglycans of the aortic intimal-medial tissues of rabbits that had undergone denudation with a balloon catheter 12 weeks earlier were isolated after homogenization of the tissues in 0.33 M sucrose, ultracentrifugation and subsequently by gel-exclusion chromatography. Lipoproteins from the plasma of healthy donors were prepared by sequential, ultracentrifugal floatation after density adjustment with KBr. To study the interactions, aliquots of electrophoretically pure very low-density lipoproteins (VLDL, d less than 1.006 g/ml), low-density lipoproteins (LDL, d = 1.019-1.063 g/ml), or high-density lipoproteins (HDL, d = 1.210 g/ml) were incubated with proteoglycans in the presence of Ca++ and Mg++ at 4 C. The amount of cholesterol found in the resulting pellet was measured as a marker of the binding capacity of the proteoglycans. Among lipoprotein fractions both VLDL and LDL showed strong binding with proteoglycans, whereas no appreciable binding was observed when incubation experiments were done with HDL. There were significant differences in the lipoprotein binding capacity of proteoglycan of control and injured animals, indicating that injury induced changes in proteoglycan composition exert profound influences on their ionic interactions.

Lipoproteins alter the catalytic behavior of the platelet-activating factor acetylhydrolase in human plasma.

PubMed Central

Stafforini, D M; Carter, M E; Zimmerman, G A; McIntyre, T M; Prescott, S M

1989-01-01

Platelet-activating factor (PAF) has been implicated as a mediator of inflammation, allergy, shock, and thrombosis. A specific degradative enzyme, PAF acetylhydrolase (EC 3.1.1.47), is found in plasma and could regulate the concentration of PAF in blood. In plasma, 70% of the PAF acetylhydrolase is found with low density lipoprotein (LDL), and the remainder is in high density lipoprotein (HDL). In previous studies we found that with subsaturating concentrations of PAF the activity in LDL seemed to be the relevant one; e.g., depletion of LDL slowed degradation of PAF, while removal of HDL accelerated the degradation slightly. We have pursued this observation by using plasma from humans with lipoprotein mutations. In abetalipoproteinemia, all of the PAF acetylhydrolase activity was in HDL, whereas in Tangier disease all of the activity was in LDL. In both conditions the total activity measured in an optimized assay was normal or increased. However, when we measured the t1/2 of PAF in plasma, we found that it was prolonged in subjects with abetalipoproteinemia compared to normal controls. Conversely, the t1/2 in Tangier plasma was shortened. We next demonstrated that the PAF acetylhydrolase in HDL was recognized by an antibody to the enzyme purified from LDL, establishing that the enzyme in the two particles is the same protein. Finally, we inactivated the PAF acetylhydrolase in isolated lipoprotein particles and then reconstituted them with enzyme from the opposite particle. The reconstituted particles were used to measure the t1/2 of PAF, and we again found that the LDL particle was more efficient. We conclude that the lipoprotein environment of the PAF acetylhydrolase markedly influences its catalytic behavior. This may be important in pathophysiology and will complicate attempts to assess the role of this enzyme in such circumstances. Images PMID:2928339

Current insights into the German Lipoprotein Apheresis Registry (GLAR) - Almost 5 years on.

PubMed

Schettler, V J J; Neumann, C L; Peter, C; Zimmermann, T; Julius, U; Roeseler, E; Heigl, F; Grützmacher, P; Blume, H

2017-11-01

In recent years the Federal Joint Committee (G-BA), a paramount decision-making body of the German health care system required a reassessment of the approval of chronic lipoprotein apheresis therapy for regular reimbursement. Since 2005 an interdisciplinary German apheresis working group has been established by members of both German Societies of Nephrology. In 2009 the working group completed the indication for lipoprotein apheresis with respect to current cardiovascular guidelines and current scientific knowledge for the registry. In 2011 the German Lipoprotein Apheresis Registry (GLAR) was launched and data acquired over nearly 5 years can now be reported. All data were collected and analyzed during the time period 2012-2015. Over this time interval, 68 German apheresis centers collected retrospective and prospective observational data of 1.283 patients undergoing lipoprotein apheresis (LA) treatment of high LDL-cholesterol (LDL-C) levels and/or high lipoprotein(a) (Lp(a)) levels suffering from progressive cardiovascular disease (CVD). A total of 15,167 documented LA treatments were investigated. All patients treated by LA exhibited a median LDL-C reduction rate of 68.6%, and a median Lp(a) reduction rate of 70.4%. Analogue to the Pro(a)LiFe pattern, patient data were analyzed and compared with respect to the incidence rate of coronary events (MACE) 1 and 2 years before the start of LA treatment (y-2 and y-1) and prospectively one year on LA treatment (y+1). During the first year of LA treatment a MACE reduction of 97% was be observed. In the years considered, LA treatment side effects occurred at a low rate (ca. 5%) and mainly comprised puncture problems. For the first time data generated by the GLAR shows that LA lowers the incidence rate of cardiovascular events in patients with high LDL-C and/or high Lp(a) levels, progressive CVD and maximally tolerated lipid lowering medication. In addition LA treatments were found to be safe, exhibiting a low rate of side

Method of assessing a lipid-related health risk based on ion mobility analysis of lipoproteins

DOEpatents

Benner, W. Henry; Krauss, Ronald M.; Blanche, Patricia J.

2010-12-14

A medical diagnostic method and instrumentation system for analyzing noncovalently bonded agglomerated biological particles is described. The method and system comprises: a method of preparation for the biological particles; an electrospray generator; an alpha particle radiation source; a differential mobility analyzer; a particle counter; and data acquisition and analysis means. The medical device is useful for the assessment of human diseases, such as cardiac disease risk and hyperlipidemia, by rapid quantitative analysis of lipoprotein fraction densities. Initially, purification procedures are described to reduce an initial blood sample to an analytical input to the instrument. The measured sizes from the analytical sample are correlated with densities, resulting in a spectrum of lipoprotein densities. The lipoprotein density distribution can then be used to characterize cardiac and other lipid-related health risks.

Changes of very low-density lipoprotein concentration in hepatic blood from cows with fasting-induced hepatic lipidosis.

PubMed

Oikawa, Shin; Mizunuma, Yuko; Iwasaki, Yukari; Tharwat, Mohamed

2010-10-01

The purpose of this study was to evaluate changes of very low-density lipoprotein (VLDL) components in hepatic blood (HB) from 5 nonlactating nonpregnant cows fasted from days 0 to 3 and subsequently refed to day 10 and, in addition, to assess those of other lipoproteins. Increased phospholipid concentrations in each lipoprotein after the start of fasting suggested their availability for the surface lipids of lipoproteins. Although the VLDL-triglyceride (TG) concentration in HB from all cows increased on day 1, the value on day 4 became similar to that on day 0. However, the concentration on day 10 was significantly increased. In all cows, the decreased ratio of the VLDL-TG concentration in HB to the non-esterified fatty acids (NEFA) concentration in portal blood (PB) on day 4 appeared to reflect relatively decreased secretion of TG as VLDL by NEFA excessively mobilized to the liver via PB. The markedly increased ratio on day 10 was considered to contribute to the improvement of hepatic lipidosis.

Lipoprotein(a) levels, genotype, and incident aortic valve stenosis: a prospective Mendelian randomization study and replication in a case-control cohort.

PubMed

Arsenault, Benoit J; Boekholdt, S Matthijs; Dubé, Marie-Pierre; Rhéaume, Eric; Wareham, Nicholas J; Khaw, Kay-Tee; Sandhu, Manjinder S; Tardif, Jean-Claude

2014-06-01

Although a previous study has suggested that a genetic variant in the LPA region was associated with the presence of aortic valve stenosis (AVS), no prospective study has suggested a role for lipoprotein(a) levels in the pathophysiology of AVS. Our objective was to determine whether lipoprotein(a) levels and a common genetic variant that is strongly associated with lipoprotein(a) levels are associated with an increased risk of developing AVS. Serum lipoprotein(a) levels were measured in 17 553 participants of the European Prospective Investigation into Cancer (EPIC)-Norfolk study. Among these study participants, 118 developed AVS during a mean follow-up of 11.7 years. The rs10455872 genetic variant in LPA was genotyped in 14 735 study participants, who simultaneously had lipoprotein(a) level measurements, and in a replication study of 379 patients with echocardiography-confirmed AVS and 404 controls. In EPIC-Norfolk, compared with participants in the bottom lipoprotein(a) tertile, those in the top lipoprotein(a) tertile had a higher risk of AVS (hazard ratio, 1.57; 95% confidence interval, 1.02-2.42) after adjusting for age, sex, and smoking. Compared with rs10455872 AA homozygotes, carriers of 1 or 2 G alleles were at increased risk of AVS (hazard ratio, 1.78; 95% confidence interval, 1.11-2.87, versus hazard ratio, 4.83; 95% confidence interval, 1.77-13.20, respectively). In the replication study, the genetic variant rs10455872 also showed a positive association with AVS (odds ratio, 1.57; 95% confidence interval, 1.10-2.26). Patients with high lipoprotein(a) levels are at increased risk for AVS. The rs10455872 variant, which is associated with higher lipoprotein(a) levels, is also associated with increased risk of AVS, suggesting that this association may be causal. © 2014 American Heart Association, Inc.

Phase 1 Development Testing of the Advanced Manufacturing Demonstrator Engine

NASA Technical Reports Server (NTRS)

Case, Nicholas L.; Eddleman, David E.; Calvert, Marty R.; Bullard, David B.; Martin, Michael A.; Wall, Thomas R.

2016-01-01

The Additive Manufacturing Development Breadboard Engine (BBE) is a pressure-fed liquid oxygen/pump-fed liquid hydrogen (LOX/LH2) expander cycle engine that was built and operated by NASA at Marshall Space Flight Center's East Test Area. The breadboard engine was conceived as a technology demonstrator for the additive manufacturing technologies for an advanced upper stage prototype engine. The components tested on the breadboard engine included an ablative chamber, injector, main fuel valve, turbine bypass valve, a main oxidizer valve, a mixer and the fuel turbopump. All parts minus the ablative chamber were additively manufactured. The BBE was successfully hot fire tested seven times. Data collected from the test series will be used for follow on demonstration tests with a liquid oxygen turbopump and a regeneratively cooled chamber and nozzle.

The Advanced Test Reactor National Scientific User Facility Advancing Nuclear Technology

DOE Office of Scientific and Technical Information (OSTI.GOV)

T. R. Allen; J. B. Benson; J. A. Foster

2009-05-01

To help ensure the long-term viability of nuclear energy through a robust and sustained research and development effort, the U.S. Department of Energy (DOE) designated the Advanced Test Reactor and associated post-irradiation examination facilities a National Scientific User Facility (ATR NSUF), allowing broader access to nuclear energy researchers. The mission of the ATR NSUF is to provide access to world-class nuclear research facilities, thereby facilitating the advancement of nuclear science and technology. The ATR NSUF seeks to create an engaged academic and industrial user community that routinely conducts reactor-based research. Cost free access to the ATR and PIE facilities ismore » granted based on technical merit to U.S. university-led experiment teams conducting non-proprietary research. Proposals are selected via independent technical peer review and relevance to DOE mission. Extensive publication of research results is expected as a condition for access. During FY 2008, the first full year of ATR NSUF operation, five university-led experiments were awarded access to the ATR and associated post-irradiation examination facilities. The ATR NSUF has awarded four new experiments in early FY 2009, and anticipates awarding additional experiments in the fall of 2009 as the results of the second 2009 proposal call. As the ATR NSUF program mature over the next two years, the capability to perform irradiation research of increasing complexity will become available. These capabilities include instrumented irradiation experiments and post-irradiation examinations on materials previously irradiated in U.S. reactor material test programs. The ATR critical facility will also be made available to researchers. An important component of the ATR NSUF an education program focused on the reactor-based tools available for resolving nuclear science and technology issues. The ATR NSUF provides education programs including a summer short course, internships, faculty

Lipoprotein particle concentration measured by nuclear magnetic resonance spectroscopy is associated with gestational age at delivery: a prospective cohort study.

PubMed

Grace, M R; Vladutiu, C J; Nethery, R C; Siega-Riz, A M; Manuck, T A; Herring, A H; Savitz, D; Thorp, J T

2018-06-01

To estimate the association between lipoprotein particle concentrations in pregnancy and gestational age at delivery. Prospective cohort study. The study was conducted in the USA at the University of North Carolina. We assessed 715 women enrolled in the Pregnancy, Infection, and Nutrition study from 2001 to 2005. Fasting blood was collected at two time points (<20 and 24-29 weeks of gestation). Nuclear magnetic resonance (NMR) quantified lipoprotein particle concentrations [low-density lipoprotein (LDL), high-density lipoprotein (HDL), very-low density lipoprotein (VLDL)] and 10 subclasses of lipoproteins. Concentrations were assessed as continuous measures, with the exception of medium HDL which was classified as any or no detectable level, given its distribution. Cox proportional hazards models estimated hazard ratios (HR) for gestational age at delivery adjusting for covariates. Gestational age at delivery, preterm birth (<37 weeks of gestation), and spontaneous preterm birth. At <20 weeks of gestation, three lipoproteins were associated with later gestational ages at delivery [large LDL NMR (HR 0.78, 95% CI 0.64-0.96), total VLDL NMR (HR 0.77, 95% CI 0.61-0.98), and small VLDL NMR (HR 0.78, 95% CI 0.62-0.98], whereas large VLDL NMR (HR 1.19, 95% CI 1.01-1.41) was associated with a greater hazard of earlier delivery. At 24-28 weeks of gestation, average VLDL NMR (HR 1.25, 95% CI 1.03-1.51) and a detectable level of medium HDL NMR (HR 1.90, 95% CI 1.19-3.02) were associated with earlier gestational ages at delivery. In this sample of pregnant women, particle concentrations of VLDL NMR , LDL NMR , IDL NMR , and HDL NMR were each independently associated with gestational age at delivery for all deliveries or spontaneous deliveries <37 weeks of gestation. These findings may help formulate hypotheses for future studies of the complex relationship between maternal lipoproteins and preterm birth. Nuclear magnetic resonance spectroscopy may identify lipoprotein

High-Density Lipoprotein, Lecithin: Cholesterol Acyltransferase, and Atherosclerosis

PubMed Central

Ossoli, Alice; Pavanello, Chiara

2016-01-01

Epidemiological data clearly show the existence of a strong inverse correlation between plasma high-density lipoprotein cholesterol (HDL-C) concentrations and the incidence of coronary heart disease. This relation is explained by a number of atheroprotective properties of HDL, first of all the ability to promote macrophage cholesterol transport. HDL are highly heterogeneous and are continuously remodeled in plasma thanks to the action of a number of proteins and enzymes. Among them, lecithin:cholesterol acyltransferase (LCAT) plays a crucial role, being the only enzyme able to esterify cholesterol within lipoproteins. LCAT is synthetized by the liver and it has been thought to play a major role in reverse cholesterol transport and in atheroprotection. However, data from animal studies, as well as human studies, have shown contradictory results. Increased LCAT concentrations are associated with increased HDL-C levels but not necessarily with atheroprotection. On the other side, decreased LCAT concentration and activity are associated with decreased HDL-C levels but not with increased atherosclerosis. These contradictory results confirm that HDL-C levels per se do not represent the functionality of the HDL system. PMID:27302716

Levels of high-density lipoprotein cholesterol (HDL-C) among children with steady-state sickle cell disease

PubMed Central

2010-01-01

Background The search for sickle cell disease (SCD) prognosis biomarkers is a challenge. These markers identification can help to establish further therapy, later severe clinical complications and with patients follow-up. We attempted to study a possible involvement of levels of high-density lipoprotein cholesterol (HDL-C) in steady-state children with SCD, once that this lipid marker has been correlated with anti-inflammatory, anti-oxidative, anti-aggregation, anti-coagulant and pro-fibrinolytic activities, important aspects to be considered in sickle cell disease pathogenesis. Methods We prospectively analyzed biochemical, inflammatory and hematological biomarkers of 152 steady-state infants with SCD and 132 healthy subjects using immunochemistry, immunoassay and electronic cell counter respectively. Clinical data were collected from patient medical records. Results Of the 152 infants investigated had a significant positive association of high-density lipoprotein cholesterol with hemoglobin (P < 0.001), hematocrit (P < 0.001) and total cholesterol (P < 0.001) and a negative significant association with reticulocytes (P = 0.046), leukocytes (P = 0.015), monocytes (P = 0.004) and platelets (P = 0.005), bilirubins [total bilirubin (P < 0.001), direct bilirubin (P < 0.001) and indirect bilirubin (P < 0.001], iron (P < 0.001), aminotransferases [aspartate aminotransferase (P = 0.004), alanine aminotransferase (P = 0.035)], lactate dehydrogenase (P < 0.001), urea (P = 0.030), alpha 1-antitrypsin (P < 0.001), very low-density lipoprotein cholesterol (P = 0.003), triglycerides (P = 0.005) and hemoglobin S (P = 0.002). Low high-density lipoprotein cholesterol concentration was associated with the history of cardiac abnormalities (P = 0.025), pneumonia (P = 0.033) and blood transfusion use (P = 0.025). Lipids and inflammatory markers were associated with the presence of cholelithiasis. Conclusions We hypothesize that some SCD patients can have a specific dyslipidemic

In-flight acoustic test results for the SR-2 and SR-3 advanced-design propellers

NASA Technical Reports Server (NTRS)

Lasagna, P. L.; Mackall, K. G.; Cohn, R. B.

1983-01-01

Several advanced-design propellers, previously tested in the wind tunnel at the Lewis Research Center, have been tested in flight at the Dryden Flight Research Facility. The flight-test propellers were mounted on a pylon on the top of the fuselage of a JetStar airplane. Acoustic data for the advanced-design SR-2 and SR-3 propellers at Mach numbers to 0.8 and helical-tip Mach numbers to 1.15 are presented; maximum blade-passage frequency sound-pressure levels are also compared.

Multi-Purpose Thermal Hydraulic Loop: Advanced Reactor Technology Integral System Test (ARTIST) Facility for Support of Advanced Reactor Technologies

DOE Office of Scientific and Technical Information (OSTI.GOV)

James E. O'Brien; Piyush Sabharwall; SuJong Yoon

2001-11-01

Effective and robust high temperature heat transfer systems are fundamental to the successful deployment of advanced reactors for both power generation and non-electric applications. Plant designs often include an intermediate heat transfer loop (IHTL) with heat exchangers at either end to deliver thermal energy to the application while providing isolation of the primary reactor system. In order to address technical feasibility concerns and challenges a new high-temperature multi-fluid, multi-loop test facility “Advanced Reactor Technology Integral System Test facility” (ARTIST) is under development at the Idaho National Laboratory. The facility will include three flow loops: high-temperature helium, molten salt, and steam/water.more » Details of some of the design aspects and challenges of this facility, which is currently in the conceptual design phase, are discussed« less

Desire for predictive testing for Alzheimer's disease and impact on advance care planning: a cross-sectional study.

PubMed

Sheffrin, Meera; Stijacic Cenzer, Irena; Steinman, Michael A

2016-12-13

It is unknown whether older adults in the United States would be willing to take a test predictive of future Alzheimer's disease, or whether testing would change behavior. Using a nationally representative sample, we explored who would take a free and definitive test predictive of Alzheimer's disease, and examined how using such a test may impact advance care planning. A cross-sectional study within the 2012 Health and Retirement Study of adults aged 65 years or older asked questions about a test predictive of Alzheimer's disease (N = 874). Subjects were asked whether they would want to take a hypothetical free and definitive test predictive of future Alzheimer's disease. Then, imagining they knew they would develop Alzheimer's disease, subjects rated the chance of completing advance care planning activities from 0 to 100. We classified a score > 50 as being likely to complete that activity. We evaluated characteristics associated with willingness to take a test for Alzheimer's disease, and how such a test would impact completing an advance directive and discussing health plans with loved ones. Overall, 75% (N = 648) of the sample would take a free and definitive test predictive of Alzheimer's disease. Older adults willing to take the test had similar race and educational levels to those who would not, but were more likely to be ≤75 years old (odds ratio 0.71 (95% CI 0.53-0.94)). Imagining they knew they would develop Alzheimer's, 81% would be likely to complete an advance directive, although only 15% had done so already. In this nationally representative sample, 75% of older adults would take a free and definitive test predictive of Alzheimer's disease. Many participants expressed intent to increase activities of advance care planning with this knowledge. This confirms high public interest in predictive testing for Alzheimer's disease and suggests this may be an opportunity to engage patients in advance care planning discussions.

The advanced receiver 2: Telemetry test results in CTA 21

NASA Technical Reports Server (NTRS)

Hinedi, S.; Bevan, R.; Marina, M.

1991-01-01

Telemetry tests with the Advanced Receiver II (ARX II) in Compatibility Test Area 21 are described. The ARX II was operated in parallel with a Block-III Receiver/baseband processor assembly combination (BLK-III/BPA) and a Block III Receiver/subcarrier demodulation assembly/symbol synchronization assembly combination (BLK-III/SDA/SSA). The telemetry simulator assembly provided the test signal for all three configurations, and the symbol signal to noise ratio as well as the symbol error rates were measured and compared. Furthermore, bit error rates were also measured by the system performance test computer for all three systems. Results indicate that the ARX-II telemetry performance is comparable and sometimes superior to the BLK-III/BPA and BLK-III/SDA/SSA combinations.

Low-Density Lipoprotein Cholesterol, Non-High-Density Lipoprotein Cholesterol, Triglycerides, and Apolipoprotein B and Cardiovascular Risk in Patients With Manifest Arterial Disease.

PubMed

van den Berg, M Johanneke; van der Graaf, Yolanda; de Borst, Gert Jan; Kappelle, L Jaap; Nathoe, Hendrik M; Visseren, Frank L J

2016-09-15

Low-density lipoprotein cholesterol (LDL-C) only partly represents the atherogenic lipid burden, and a growing body of evidence suggests that non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides, and apolipoprotein B (apoB) are more accurate in estimating lipid-related cardiovascular disease risk. Our objective was to compare the relation among LDL-C, non-HDL-C, triglycerides, and apoB and the occurrence of future vascular events and mortality in patients with manifest arterial disease. This is a prospective cohort study of 7,216 patients with clinically manifest arterial disease in the Secondary Manifestations of Arterial Disease Study. Cox proportional hazard models were used to quantify the risk of major cardiovascular events (MACE; i.e., stroke, myocardial infarction, and vascular mortality) and all-cause mortality. Interaction was tested for type of vascular disease at inclusion. MACE occurred in 1,185 subjects during a median follow-up of 6.5 years (interquartile range 3.4 to 9.9 years). Adjusted hazard ratios (HRs) of MACE per 1 SD higher were for LDL-C (HR 1.15, 95% confidence interval [CI] 1.09 to 1.22), for non-HDL-C (HR 1.17, 95% CI 1.11 to 1.23), for log(triglycerides) (HR 1.12, 95% CI 1.06 to 1.19), and for apoB HR (1.12, 95% CI 0.99 to 1.28). The relation among LDL-C, non-HDL-C, and cardiovascular events was comparable in patients with cerebrovascular disease, coronary artery disease, or polyvascular disease and absent in those with aneurysm of abdominal aorta or peripheral artery disease. In conclusion, in patients with a history of cerebrovascular, coronary artery, or polyvascular disease, but not aneurysm of abdominal aorta or peripheral artery disease, higher levels of LDL-C and non-HDL-C are related to increased risk of future MACE and of comparable magnitude. Copyright © 2016 Elsevier Inc. All rights reserved.

Apolipoprotein A-II induces acute-phase response associated AA amyloidosis in mice through conformational changes of plasma lipoprotein structure.

PubMed

Yang, Mu; Liu, Yingye; Dai, Jian; Li, Lin; Ding, Xin; Xu, Zhe; Mori, Masayuki; Miyahara, Hiroki; Sawashita, Jinko; Higuchi, Keiichi

2018-04-04

During acute-phase response (APR), there is a dramatic increase in serum amyloid A (SAA) in plasma high density lipoproteins (HDL). Elevated SAA leads to reactive AA amyloidosis in animals and humans. Herein, we employed apolipoprotein A-II (ApoA-II) deficient (Apoa2 -/- ) and transgenic (Apoa2Tg) mice to investigate the potential roles of ApoA-II in lipoprotein particle formation and progression of AA amyloidosis during APR. AA amyloid deposition was suppressed in Apoa2 -/- mice compared with wild type (WT) mice. During APR, Apoa2 -/- mice exhibited significant suppression of serum SAA levels and hepatic Saa1 and Saa2 mRNA levels. Pathological investigation showed Apoa2 -/- mice had less tissue damage and less inflammatory cell infiltration during APR. Total lipoproteins were markedly decreased in Apoa2 -/- mice, while the ratio of HDL to low density lipoprotein (LDL) was also decreased. Both WT and Apoa2 -/- mice showed increases in LDL and very large HDL during APR. SAA was distributed more widely in lipoprotein particles ranging from chylomicrons to very small HDL in Apoa2 -/- mice. Our observations uncovered the critical roles of ApoA-II in inflammation, serum lipoprotein stability and AA amyloidosis morbidity, and prompt consideration of therapies for AA and other amyloidoses, whose precursor proteins are associated with circulating HDL particles.

Advanced Control Design for Wind Turbines; Part I: Control Design, Implementation, and Initial Tests

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wright, A. D.; Fingersh, L. J.

The purpose of this report is to give wind turbine engineers information and examples of the design, testing through simulation, field implementation, and field testing of advanced wind turbine controls.

Test Hardware Design for Flight-Like Operation of Advanced Stirling Convertors

NASA Technical Reports Server (NTRS)

Oriti, Salvatore M.

2012-01-01

NASA Glenn Research Center (GRC) has been supporting development of the Advanced Stirling Radioisotope Generator (ASRG) since 2006. A key element of the ASRG project is providing life, reliability, and performance testing of the Advanced Stirling Convertor (ASC). For this purpose, the Thermal Energy Conversion branch at GRC has been conducting extended operation of a multitude of free-piston Stirling convertors. The goal of this effort is to generate long-term performance data (tens of thousands of hours) simultaneously on multiple units to build a life and reliability database. The test hardware for operation of these convertors was designed to permit in-air investigative testing, such as performance mapping over a range of environmental conditions. With this, there was no requirement to accurately emulate the flight hardware. For the upcoming ASC-E3 units, the decision has been made to assemble the convertors into a flight-like configuration. This means the convertors will be arranged in the dual-opposed configuration in a housing that represents the fit, form, and thermal function of the ASRG. The goal of this effort is to enable system level tests that could not be performed with the traditional test hardware at GRC. This offers the opportunity to perform these system-level tests much earlier in the ASRG flight development, as they would normally not be performed until fabrication of the qualification unit. This paper discusses the requirements, process, and results of this flight-like hardware design activity.

Relationship between lipoprotein subfraction cholesterol and residual risk for cardiovascular outcomes: A post hoc analysis of the AIM-HIGH trial.

PubMed

Toth, Peter P; Jones, Steven R; Slee, April; Fleg, Jerome; Marcovina, Santica M; Lacy, Megan; McBride, Ruth; Boden, William E

2018-03-09

The AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes) trial failed to demonstrate incremental clinical benefit of extended-release niacin (ERN) in 3414 statin-treated patients with established cardiovascular (CV) disease who had low baseline levels of high-density lipoprotein cholesterol (HDL-C) as compared to placebo. A previous secondary analysis suggested that ERN provided outcome benefits in ERN-treated patients with high triglycerides (TGs; >200 mg/dL) and very low HDL-C (<32 mg/dL) at baseline. The current analysis sought to ascertain how changes in TG-enriched lipoproteins and HDL subfractions impact residual risk in the comparator treatment arms. We evaluated the relationship between niacin treatment, lipoproteins and their subfractions, and CV outcomes in a non-prespecified, post hoc analysis of the AIM-HIGH trial. Lipoprotein subfraction analysis was performed with zonal ultracentrifugation in 2457 AIM-HIGH participants at baseline and 1 year of treatment. Hazard ratios were estimated using Cox proportional hazards models for relationships between lipoproteins and the composite primary endpoint of CV death, myocardial infarction, acute coronary syndrome, ischemic stroke, or symptom-driven revascularization. Analyses were performed for the entire cohort and in participants with TGs > 200 mg/dL and HDL-C < 32 mg/dL. Apoprotein B-containing lipoproteins and their subfractions decreased significantly in both treatment arms but decreased more with ERN treatment. HDL-C and its subfractions increased significantly in both treatment groups, but more so in patients treated with ERN. For the entire study population, neither apoB- nor apoA1-containing lipoprotein subfractions predicted risk at baseline or at 1 year of follow-up. In the high TG and low HDL-C subgroup treated with placebo, changes at 1 year in HDL 2 -C, total cholesterol/HDL 2 -C, and non-HDL-C/HDL 2 -C may be

Severe Hypertriglyceridemia due to a novel p.Q240H mutation in the Lipoprotein Lipase gene.

PubMed

Soto, Angela Ganan; McIntyre, Adam; Agrawal, Sungeeta; Bialo, Shara R; Hegele, Robert A; Boney, Charlotte M

2015-09-04

Lipoprotein Lipase (LPL) deficiency is a rare autosomal recessive disorder with a heterogeneous clinical presentation. Several mutations in the LPL gene have been identified to cause decreased activity of the enzyme. An 11-week-old, exclusively breastfed male presented with coffee-ground emesis, melena, xanthomas, lipemia retinalis and chylomicronemia. Genomic DNA analysis identified lipoprotein lipase deficiency due to compound heterozygosity including a novel p.Q240H mutation in exon 5 of the lipoprotein lipase (LPL) gene. His severe hypertriglyceridemia, including xanthomas, resolved with dietary long-chain fat restriction. We describe a novel mutation of the LPL gene causing severe hypertriglyceridemia and report the response to treatment. A review of the current literature regarding LPL deficiency syndrome reveals a few potential new therapies under investigation.

Pleiotropic Effect of Lipoprotein-Apheresis on the Soluble Form of Activated Leukocyte Cell Adhesion Molecule (sALCAM) in Familial Hypercholesterolaemia.

PubMed

von Bauer, Rüdiger; Oikonomou, Dimitrios; Sulaj, Alba; Kopf, Stefan; Fleming, Thomas; Rudofsky, Gottfried; Nawroth, Peter

2018-06-11

Atherosclerosis is an inflammatory disorder in which several converging immune responses modulate and induce lipid accumulation in macrophages. Activated leukocyte cell adhesion molecule (ALCAM) has been described as a structural homologue of HDL-receptor and functions as a pattern recognition receptor (PRR), while its soluble form sALCAM is involved in ALCAM-dependent and -independent immune mechanisms. The aim of this study was to investigate the effect of aggressive removal of low density lipoprotein-cholesterol (LDL-C) and lipoprotein(a) (Lp [a]) by lipoprotein-apheresis (LA) on sALCAM and blood viscosity as well as to evaluate its association with lipoproteins and serum markers of inflammation. © Georg Thieme Verlag KG Stuttgart · New York.

Raman Spectroscopic Analysis of Biochemical Changes in Individual Triglyceride-Rich Lipoproteins in the Pre- and Postprandial State

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chan, J; Motton, D; Rutledge, J

2004-09-13

Individual triglyceride-rich lipoprotein (TGRL) particles derived from human volunteers are non-destructively analyzed by laser tweezers Raman microspectroscopy and information on their composition and distribution is obtained. The Raman signature of single optically trapped very low-density lipoproteins (VLDL), a subclass of TGRL, which play an important role in cardiovascular disease, exhibits distinct peaks associated with molecular vibrations of fatty acids, proteins, lipids, and structural rearrangements of lipids. Our analysis of pre- and postprandial VLDL exhibits the signature of biochemical changes in individual lipoprotein particles following the consumption of meals. Interaction of VLDL with endothelium leads to the breakdown of complex triacylglycerolsmore » and the formation of a highly ordered core of free saturated fatty acids in the particle. A particle distribution analysis reveals trends in the degree to which this process has occurred in particles at different times during the postprandial period. Differences in particle distributions based on the different ratios of polyunsaturated to saturated fats in the consumed meals are also easily discerned. Individual lipoprotein particles hydrolyzed in-vitro through addition of lipoprotein lipase (LpL) exhibit strikingly similar changes in their Raman spectra. These results demonstrate the feasibility of monitoring the dynamics of lipid metabolism of individual TGRL particles as they interact with LpL in the endothelial cell wall using Raman spectroscopy.« less

HARP model rotor test at the DNW. [Hughes Advanced Rotor Program

NASA Technical Reports Server (NTRS)

Dawson, Seth; Jordan, David; Smith, Charles; Ekins, James; Silverthorn, Lou

1989-01-01

Data from a test of a dynamically scaled model of the Hughes Advanced Rotor Program (HARP) bearingless model main rotor and 369K tail rotor are reported. The history of the HARP program and its goals are reviewed, and the main and tail rotor models are described. The test facilities and instrumentation are described, and wind tunnel test data are presented on hover, forward flight performance, and blade-vortex interaction. Performance data, acoustic data, and dynamic data from near field/far field and shear layer studies are presented.

Mapping Atheroprotective Functions and Related Proteins/Lipoproteins in Size Fractionated Human Plasma.

PubMed

Swertfeger, Debi K; Li, Hailong; Rebholz, Sandra; Zhu, Xiaoting; Shah, Amy S; Davidson, W Sean; Lu, Long J

2017-04-01

HDL has been shown to possess a variety of cardio-protective functions, including removal of excess cholesterol from the periphery, and inhibition of lipoprotein oxidation. It has been proposed that various HDL subparticles exist, each with distinct protein and lipid compositions, which may be responsible for HDL's many functions. We hypothesized that HDL functions will co-migrate with the operational lipoprotein subspecies when separated by gel filtration chromatography. Plasma from 10 healthy male donors was fractionated and the protein composition of the phospholipid containing fractions was analyzed by mass spectrometry (MS). Each fraction was evaluated for its proteomic content as well as its ability to promote cholesterol efflux and protect low density lipoprotein (LDL) from free radical oxidation. For each function, several peaks of activity were identified across the plasma size gradient. Neither cholesterol efflux or LDL antioxidation activity correlated strongly with any single protein across the fractions. However, we identified multiple proteins that had strong correlations (r values >0.7, p < 0.01) with individual peaks of activity. These proteins fell into diverse functional categories, including those traditionally associated with lipid metabolism, as well as alternative complement cascade, innate immunity and clotting cascades and immunoglobulins. Additionally, the phospholipid and cholesterol concentration of the fractions correlated strongly with cholesterol efflux ( r = 0.95 and 0.82 respectively), whereas the total protein content of the fractions correlated best with antioxidant activity across all fractions ( r = 0.746). Furthermore, two previously postulated subspecies (apoA-I, apoA-II and apoC-1; as well as apoA-I, apoC-I and apoJ) were found to have strong correlations with both cholesterol efflux and antioxidation activity. Up till now, very little has been known about how lipoprotein composition mediates functions like cholesterol efflux

Mapping Atheroprotective Functions and Related Proteins/Lipoproteins in Size Fractionated Human Plasma *

PubMed Central

Swertfeger, Debi K.; Li, Hailong; Rebholz, Sandra; Zhu, Xiaoting; Shah, Amy S.; Davidson, W. Sean; Lu, Long J.

2017-01-01

HDL has been shown to possess a variety of cardio-protective functions, including removal of excess cholesterol from the periphery, and inhibition of lipoprotein oxidation. It has been proposed that various HDL subparticles exist, each with distinct protein and lipid compositions, which may be responsible for HDL's many functions. We hypothesized that HDL functions will co-migrate with the operational lipoprotein subspecies when separated by gel filtration chromatography. Plasma from 10 healthy male donors was fractionated and the protein composition of the phospholipid containing fractions was analyzed by mass spectrometry (MS). Each fraction was evaluated for its proteomic content as well as its ability to promote cholesterol efflux and protect low density lipoprotein (LDL) from free radical oxidation. For each function, several peaks of activity were identified across the plasma size gradient. Neither cholesterol efflux or LDL antioxidation activity correlated strongly with any single protein across the fractions. However, we identified multiple proteins that had strong correlations (r values >0.7, p < 0.01) with individual peaks of activity. These proteins fell into diverse functional categories, including those traditionally associated with lipid metabolism, as well as alternative complement cascade, innate immunity and clotting cascades and immunoglobulins. Additionally, the phospholipid and cholesterol concentration of the fractions correlated strongly with cholesterol efflux (r = 0.95 and 0.82 respectively), whereas the total protein content of the fractions correlated best with antioxidant activity across all fractions (r = 0.746). Furthermore, two previously postulated subspecies (apoA-I, apoA-II and apoC-1; as well as apoA-I, apoC-I and apoJ) were found to have strong correlations with both cholesterol efflux and antioxidation activity. Up till now, very little has been known about how lipoprotein composition mediates functions like cholesterol efflux

Behavioral versus genetic determination of lipoproteins andidentical twins discordant for exercise

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, Paul T.; Blanche, Patricia J.; Krauss, Ronald M.

Lipoprotein and weight differences between vigorously active and sedentary MZ twins are used to: (1) estimate the effects of training while controlling for genotype; (2) estimate genetic concordance in the presence of divergent lifestyles.

Validation test of advanced technology for IPV nickel-hydrogen flight cells - Update

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Hall, Stephen W.

1992-01-01

Individual pressure vessel (IPV) nickel-hydrogen technology was advanced at NASA Lewis and under Lewis contracts with the intention of improving cycle life and performance. One advancement was to use 26 percent potassium hydroxide (KOH) electrolyte to improve cycle life. Another advancement was to modify the state-of-the-art cell design to eliminate identified failure modes. The modified design is referred to as the advanced design. A breakthrough in the LEO cycle life of IPV nickel-hydrogen cells has been previously reported. The cycle life of boiler plate cells containing 26 percent KOH electrolyte was about 40,000 LEO cycles compared to 3,500 cycles for cells containing 31 percent KOH. The boiler plate test results are in the process of being validated using flight hardware and real time LEO testing. The primary function of the advanced cell is to store and deliver energy for long-term, LEO spacecraft missions. The new features of this design are: (1) use of 26 percent rather than 31 percent KOH electrolyte; (2) use of a patented catalyzed wall wick; (3) use of serrated-edge separators to facilitate gaseous oxygen and hydrogen flow within the cell, while still maintaining physical contact with the wall wick for electrolyte management; and (4) use of a floating rather than a fixed stack (state-of-the-art) to accommodate nickel electrode expansion due to charge/discharge cycling. The significant improvements resulting from these innovations are: extended cycle life; enhanced thermal, electrolyte, and oxygen management; and accommodation of nickel electrode expansion.

Lipoprotein Particle Profiles Mark Familial and Sporadic Human Longevity

PubMed Central

Heijmans, Bastiaan T; Beekman, Marian; Houwing-Duistermaat, Jeanine J; Cobain, Mark R; Powell, Jonathan; Blauw, Gerard Jan; van der Ouderaa, Frans; Westendorp, Rudi G. J; Slagboom, P. Eline

2006-01-01

Background Genetic and biochemical studies have indicated an important role for lipid metabolism in human longevity. Ashkenazi Jewish centenarians and their offspring have large low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles as compared with control individuals. This profile also coincided with a lower prevalence of disease. Here, we investigate whether this observation can be confirmed for familial longevity in an outbred European population and whether it can be extended to sporadic longevity in the general population. Methods and Findings NMR-measured lipoprotein profiles were analyzed in 165 families from the Leiden Longevity Study, consisting of 340 long-lived siblings (females >91 y, males >89 y), 511 of their offspring, and 243 partners of the offspring. Offspring had larger (21.3 versus 21.1 nm; p = 0.020) and fewer (1,470 versus 1,561 nmol/l; p = 0.011) LDL particles than their same-aged partners. This effect was even more prominent in the long-lived siblings (p < 10−3) and could be pinpointed to a reduction specifically in the concentration of small LDL particles. No differences were observed for HDL particle phenotypes. The mean LDL particle sizes in 259 90-y-old singletons from a population-based study were similar to those in the long-lived siblings and thus significantly larger than in partners of the offspring, suggesting that the relevance of this phenotype extends beyond familial longevity. A low concentration of small LDL particles was associated with better overall health among both long-lived siblings (p = 0.003) and 90-y-old singletons (p = 0.007). Conclusions Our study indicates that LDL particle profiles mark both familial and sporadic human longevity already in middle age. PMID:17194192

Test performance of immunologic fecal occult blood testing and sigmoidoscopy compared with primary colonoscopy screening for colorectal advanced adenomas.

PubMed

Khalid-de Bakker, Carolina A J; Jonkers, Daisy M A E; Sanduleanu, Silvia; de Bruïne, Adriaan P; Meijer, Gerrit A; Janssen, Jan B M J; van Engeland, Manon; Stockbrügger, Reinhold W; Masclee, Ad A M

2011-10-01

Given the current increase in colorectal cancer screening, information on performance of screening tests is needed, especially in groups with a presumed lower test performance. We compared test performance of immunologic fecal occult blood testing (FIT) and pseudosigmoidoscopy with colonoscopy for detection of advanced adenomas in an average risk screening population. In addition, we explored the influence of gender, age, and location on test performance. FIT was collected prior to colonoscopy with a 50 ng/mL cutoff point. FIT results and complete colonoscopy findings were available from 329 subjects (mean age: 54.6 ± 3.7 years, 58.4% women). Advanced adenomas were detected in 38 (11.6%) of 329 subjects. Sensitivity for advanced adenomas of FIT and sigmoidoscopy were 15.8% (95% CI: 6.0-31.3) and 73.7% (95% CI: 56.9-86.6), respectively. No sensitivity improvement was obtained using the combination of sigmoidoscopy and FIT. Mean fecal hemoglobin in FIT positives was significantly lower for participants with only proximal adenomas versus those with distal ones (P = 0.008), for women versus men (P = 0.023), and for younger (<55 years) versus older (≥55 years) subjects (P = 0.029). Sensitivities of FIT were 0.0% (95% CI: 0.0-30.9) in subjects with only proximal versus 21.4% (95% CI: 8.3-41.0) in those with distal nonadvanced adenomas; 5.3% (95% CI: 0.0-26.0) in women versus 26.3% (95% CI: 9.2-51.2) in men; 9.5% (95% CI: 1.2-30.4) in younger versus 23.5% (95% CI: 6.8-49.9) in older subjects. Sigmoidoscopy had a significantly higher sensitivity for advanced adenomas than FIT. A single FIT showed very low sensitivity, especially in subjects with only proximal nonadvanced adenomas, in women, and in younger subjects. This points to the existence of "low" FIT performance in subgroups and the need for more tailored screening strategies.

Genome-wide association studies identified novel loci for non-high-density lipoprotein cholesterol and its postprandial lipemic response

USDA-ARS?s Scientific Manuscript database

Non-high-density lipoprotein cholesterol (NHDL) is an independent and superior predictor of CVD risk as compared to low-density lipoprotein alone. It represents a spectrum of atherogenic lipid fractions with possibly a distinct genomic signature. We performed genome-wide association studies (GWAS) t...

Macular xanthophylls, lipoprotein-related genes, and age-related macular degeneration1234

PubMed Central

Koo, Euna; Neuringer, Martha; SanGiovanni, John Paul

2014-01-01

Plant-based macular xanthophylls (MXs; lutein and zeaxanthin) and the lutein metabolite meso-zeaxanthin are the major constituents of macular pigment, a compound concentrated in retinal areas that are responsible for fine-feature visual sensation. There is an unmet need to examine the genetics of factors influencing regulatory mechanisms and metabolic fates of these 3 MXs because they are linked to processes implicated in the pathogenesis of age-related macular degeneration (AMD). In this work we provide an overview of evidence supporting a molecular basis for AMD-MX associations as they may relate to DNA sequence variation in AMD- and lipoprotein-related genes. We recognize a number of emerging research opportunities, barriers, knowledge gaps, and tools offering promise for meaningful investigation and inference in the field. Overviews on AMD- and high-density lipoprotein (HDL)–related genes encoding receptors, transporters, and enzymes affecting or affected by MXs are followed with information on localization of products from these genes to retinal cell types manifesting AMD-related pathophysiology. Evidence on the relation of each gene or gene product with retinal MX response to nutrient intake is discussed. This information is followed by a review of results from mechanistic studies testing gene-disease relations. We then present findings on relations of AMD with DNA sequence variants in MX-associated genes. Our conclusion is that AMD-associated DNA variants that influence the actions and metabolic fates of HDL system constituents should be examined further for concomitant influence on MX absorption, retinal tissue responses to MX intake, and the capacity to modify MX-associated factors and processes implicated in AMD pathogenesis. PMID:24829491

Integrated System Test of the Advanced Instructional System (AIS). Final Report.

ERIC Educational Resources Information Center

Lintz, Larry M.; And Others

The integrated system test for the Advanced Instructional System (AIS) was designed to provide quantitative information regarding training time reductions resulting from certain computer managed instruction features. The reliabilities of these features and of support systems were also investigated. Basic computer managed instruction reduced…

A MARCH6 and IDOL E3 Ubiquitin Ligase Circuit Uncouples Cholesterol Synthesis from Lipoprotein Uptake in Hepatocytes

PubMed Central

Loregger, Anke; Cook, Emma Claire Laura; Nelson, Jessica Kristin; Moeton, Martina; Sharpe, Laura Jane; Engberg, Susanna; Karimova, Madina; Lambert, Gilles; Brown, Andrew John

2015-01-01

Cholesterol synthesis and lipoprotein uptake are tightly coordinated to ensure that the cellular level of cholesterol is adequately maintained. Hepatic dysregulation of these processes is associated with pathological conditions, most notably cardiovascular disease. Using a genetic approach, we have recently identified the E3 ubiquitin ligase MARCH6 as a regulator of cholesterol biosynthesis, owing to its ability to promote degradation of the rate-limiting enzymes 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR) and squalene epoxidase (SQLE). Here, we present evidence for MARCH6 playing a multifaceted role in the control of cholesterol homeostasis in hepatocytes. We identify MARCH6 as an endogenous inhibitor of the sterol regulatory element binding protein (SREBP) transcriptional program. Accordingly, loss of MARCH6 increases expression of SREBP-regulated genes involved in cholesterol biosynthesis and lipoprotein uptake. Unexpectedly, this is associated with a decrease in cellular lipoprotein uptake, induced by enhanced lysosomal degradation of the low-density lipoprotein receptor (LDLR). Finally, we provide evidence that induction of the E3 ubiquitin ligase IDOL represents the molecular mechanism underlying this MARCH6-induced phenotype. Our study thus highlights a MARCH6-dependent mechanism to direct cellular cholesterol accretion that relies on uncoupling of cholesterol synthesis from lipoprotein uptake. PMID:26527619

Testing to Characterize the Advanced Stirling Radioisotope Generator Engineering Unit

NASA Technical Reports Server (NTRS)

Lewandowski, Edward; Schreiber, Jeffrey

2010-01-01

The Advanced Stirling Radioisotope Generator (ASRG), a high efficiency generator, is being considered for space missions. Lockheed Martin designed and fabricated an engineering unit (EU), the ASRG EU, under contract to the Department of Energy. This unit is currently undergoing extended operation testing at the NASA Glenn Research Center to generate performance data and validate life and reliability predictions for the generator and the Stirling convertors. It has also undergone performance tests to characterize generator operation while varying control parameters and system inputs. This paper summarizes and explains test results in the context of designing operating strategies for the generator during a space mission and notes expected differences between the EU performance and future generators.

Analysis of human serum lipoprotein lipid composition using MALDI-TOF mass spectrometry.

PubMed

Hidaka, Hiroya; Hanyu, Noboru; Sugano, Mitsutoshi; Kawasaki, Kenji; Yamauchi, Kazuyoshi; Katsuyama, Tsutomu

2007-01-01

This study used matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS) to identify all lipid classes in human serum lipoproteins. After the major lipoproteins classes were isolated from serum by ultracentrifugation, the lipids were extracted and mixed with 2,5-dihydroxybenzoic acid (2,5-DHB) dissolved in Folch's solution (chloroform/methanol 2:1, v/v). MALDI-TOF MS analysis of the samples identified phospholipids (PLs), lysophospholipids (lysoPLs), sphingolipids (SLs), triglycerides (TGs), cholesteryl esters (CEs), and free cholesterol; it also showed the characteristics of individual fatty acid chains in serum lipids. MALDI-TOF MS allowed analysis of strongly hydrophobic and non-polar molecules such as CEs and TGs as well as hydrophilic molecules such as phospholipids. Direct analysis of fatty acids was not possible. The concentrations of lipids were not consistent with the ion peak intensities, since the extent of polarity affected the ionization characteristics of the molecules. However, lipid molecules with similar molecular structures but various fatty acid chains, such as phosphatidylcholine (PCs), were analyzed quantitatively by MALDI-TOF MS. Quantitative measurement of cholesterol was possible with the use of an internal standard. This study shows that MALDI-TOF MS can be used for direct investigation and quantitative analysis of the phospholipid composition of serum lipoproteins.

Strategies for vascular disease prevention: the role of lipids and related markers including apolipoproteins, low-density lipoproteins (LDL)-particle size, high sensitivity C-reactive protein (hs-CRP), lipoprotein-associated phospholipase A2 (Lp-PLA₂) and lipoprotein(a) (Lp(a)).

PubMed

Dallmeier, Dhayana; Koenig, Wolfgang

2014-06-01

Considerable progress has been achieved in the treatment of dyslipidemias. However, half of cardiovascular events occur in individuals with average or low cholesterol levels and there is still a considerable residual risk with 70% of patients having an event despite statin treatment. In the era of personalized medicine there is increased interest in the incorporation of individual biomarkers in risk score algorithms in order to improve cardiovascular risk stratification followed by the prompt initiation of preventive measures. Since the 2001 third report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment on High Blood Cholesterol in Adults (ATP III) several studies have evaluated the prognostic value of lipid related biomarkers such as non-HDL-cholesterol, apolipoprotein B, apolipoprotein B/apolipoprotein A1 ratio, lipoprotein(a), lipoprotein-associated phospholipase A2, and C-reactive protein. This article tries to summarize the most recent results in this area. Copyright © 2014 Elsevier Ltd. All rights reserved.

Changes of very low-density lipoprotein concentration in hepatic blood from cows with fasting-induced hepatic lipidosis

PubMed Central

Oikawa, Shin; Mizunuma, Yuko; Iwasaki, Yukari; Tharwat, Mohamed

2010-01-01

The purpose of this study was to evaluate changes of very low-density lipoprotein (VLDL) components in hepatic blood (HB) from 5 nonlactating nonpregnant cows fasted from days 0 to 3 and subsequently refed to day 10 and, in addition, to assess those of other lipoproteins. Increased phospholipid concentrations in each lipoprotein after the start of fasting suggested their availability for the surface lipids of lipoproteins. Although the VLDL-triglyceride (TG) concentration in HB from all cows increased on day 1, the value on day 4 became similar to that on day 0. However, the concentration on day 10 was significantly increased. In all cows, the decreased ratio of the VLDL-TG concentration in HB to the non-esterified fatty acids (NEFA) concentration in portal blood (PB) on day 4 appeared to reflect relatively decreased secretion of TG as VLDL by NEFA excessively mobilized to the liver via PB. The markedly increased ratio on day 10 was considered to contribute to the improvement of hepatic lipidosis. PMID:21197233

Inhibition of low-density lipoprotein oxidation and up-regulation of low-density lipoprotein receptor in HepG2 cells by tropical plant extracts.

PubMed

Salleh, Mohd Nizar; Runnie, Irine; Roach, Paul D; Mohamed, Suhaila; Abeywardena, Mahinda Y

2002-06-19

Twelve edible plant extracts rich in polyphenols were screened for their potential to inhibit oxidation of low-density lipoprotein (LDL) in vitro and to modulate LDL receptor (LDLr) activity in cultured HepG2 cells. The antioxidant activity (inhibition of LDL oxidation) was determined by measuring the formation of conjugated dienes (lag time) and thiobarbituric acid reagent substances (TBARS). Betel leaf (94%), cashew shoot (63%), Japanese mint (52%), semambu leaf (50%), palm frond (41%), sweet potato shoot, chilli fruit, papaya shoot, roselle calyx, and maman showed significantly increased lag time (>55 min, P < 0.05) and inhibition of TBARS formation (P < 0.05) compared to control. LDLr was significantly up-regulated (P < 0.05) by Japanese mint (67%), semambu (51%), cashew (50%), and noni (49%). Except for noni and betel leaf, most plant extracts studied demonstrated a positive association between antioxidant activity and the ability to up-regulate LDL receptor. Findings suggest that reported protective actions of plant polyphenols on lipoprotein metabolism might be exerted at different biochemical mechanisms.

With Home Testing, Consumers Take Charge of Their Health

MedlinePlus

... Mutation Mycophenolic Acid Mycoplasma Myoglobin Nicotine and Cotinine Non-High Density Lipoprotein Cholesterol Opioid Testing Osmolality Ova ... at the bedside," Nichols says, "but not necessarily equivalent to the quality of testing performed in a ...

The effect of polyunsaturated fatty acids on the homeostasis of yolk lipoprotein in C. elegans examined by CARS and two-photon excitation fluorescence (TPE-F) microscopy

NASA Astrophysics Data System (ADS)

Chen, Wei-Wen; Yi, Yung-Hsiang; Chien, Cheng-Hao; Hsiung, Kuei-Ching; Lin, Yi-Chun; Ma, Tian-Hsiang; Lo, Szecheng J.; Chang, Ta-Chau

2016-03-01

Yolk lipoprotein constitutes the major source of energy and the materials for synthesizing signaling factors for the development of oocytes and embryos in C. elegans. Polyunsaturated fatty acids (PUFAs) packed in yolk lipoprotein have been recently recognized as critical molecules for fertilization and reproduction.1 However, the relation between PUFAs and the homeostasis of yolk lipoprotein is not clear. Here we use coherent anti-Stokes Raman scattering (CARS) microscopy and two-photon excitation fluorescence (TPE-F) microscopy to examine the transportation of yolk lipoprotein. We demonstrate that CARS microscopy is a more sensitive method than the traditional Nile Red staining method in probing the abnormal accumulation of yolk lipoprotein in the body cavity of C. elegans. It is found that the accumulation of yolk lipoprotein is a time-dependent process. In addition, a negative correlation (r = -0.955) between reproductive aging and abnormal accumulation of yolk lipoprotein is established. We further examine wild-type, fat-1, and fat-2 worms with or without the expression of GFP-tagged yolk lipoprotein (VIT-2-GFP). Our data reveal that PUFAs have a positive effect on the synthesis and endocytosis of yolk lipoprotein, confirming the model proposed by Edmonds et al.2

Effects of progestational agents on serum lipids and lipoproteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krauss, R.M.

1982-08-01

Though progestins with relatively strong androgenic or antiestrogenic effects (e.g., levonorgestrel and norethindrone acetate) tend to have the greatest capacity to offset the major estrogen effects (e.g., on serum triglyceride and, to a greater extent, HDL-cholesterol), this association is not sufficiently strong to allow prediction of the effects of other progestins on lipid and lipoprotein metabolism.

Serum levels of lipoprotein(a) and homocysteine in patients on hemodialysis who take hydroxymethylglutaryl-CoA reductase inhibitors, vitamin B6, and folic acid.

PubMed

Shojaei, Mir Hatef; Djalali, Mamhmoud; Siassi, Fereydoun; Khatami, Mohammad Reza; Boroumand, Mohammad Ali; Eshragian, Mohammad Reza

2009-07-01

High serum levels of lipoprotein(a) and homocysteine are risk factors of cardiovascular disease which are prevalent in patients on hemodialysis. Controversy exists about the effects of hydroxymethylglutaryl-CoA reductase inhibitors on serum lipoprotein(a) levels in patients on hemodialysis. Also, deficiency of some water soluble vitamins and administration of statins may raise serum levels of homocysteine in these patients. This study was designed to investigate serum levels of lipoprotein(a) and homocysteine in patients on hemodialysis who were taking a statin, vitamin B6, and folic acid. We investigated on 152 patients with maintenance hemodialysis who were taking atorvastatin or lovastatin, vitamin B6, and folic acid for at least 6 months. Their serum levels were obtained to measure lipoprotein(a) and homocysteine levels, as well as triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The mean serum values of total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol and triglyceride were significantly less than the maximum reference values (P < .001). The mean serum level of lipoprotein(a) was also less than the reference value (P = .009), but homocysteine level was 33% higher on average than the reference value (P < .001). Our study demonstrated that in our patients on hemodialysis, the mean serum level of homocysteine was about 30% higher than the reference value although they were receiving vitamin B6 and folic acid. Hence, they were still exposed to the risk of cardiovascular disease.

Lipoprotein Profile Modifications during Gestation: A Current Approach to Cardiovascular risk surrogate markers and Maternal-fetal Unit Complications.

PubMed

Santos, Ana Paula Caires Dos; Couto, Ricardo David

2018-05-16

Several changes occur in lipid metabolism during gestation due to hormonal and metabolic changes, which are essential to satisfy the nutritional demands of the maternal-fetal unit development. The gestation shows two distinct periods that begin with fat accumulation, mainly in maternal adipose tissue, and the late phase, characterized by accelerated catabolism, with the increase of fatty acids in the circulation that causes hyperlipidemia, especially the one characterized as hypertriglyceridemia. Maternal hyperlipidemia may be associated with the development of maternal-fetal complications (preterm birth, preeclampsia, vascular complications) and the development of long-term cardiovascular disease. The cardiovascular risk may not only be related to lipoproteins cholesterol content, but also to the number and functionality of circulating lipoprotein particles. This review reports the major changes that occur in lipoprotein metabolism during pregnancy and that are associated with the development of dyslipidemias, lipoprotein atherogenic phenotype, and maternal-fetal unit complications. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

Pregnant patients' risk perception of prenatal test results with uncertain fetal clinical significance: ultrasound versus advanced genetic testing.

PubMed

Richards, Elliott G; Sangi-Haghpeykar, Haleh; McGuire, Amy L; Van den Veyver, Ignatia B; Fruhman, Gary

2015-12-01

A common concern of utilizing prenatal advanced genetic testing is that a result of uncertain clinical significance will increase patient anxiety. However, prenatal ultrasound may also yield findings of uncertain significance, such as 'soft markers' for fetal aneuploidy, or findings with variable prognosis, such as mild ventriculomegaly. In this study we compared risk perception following uncertain test results from each modality. A single survey with repeated measures design was administered to 133 pregnant women. It included 'intolerance of uncertainty' questions, two hypothetical scenarios involving prenatal ultrasound or advanced genetic testing, and response questions. The primary outcome was risk perception score. Risk perception did not vary significantly between ultrasound and genetic scenarios (p = 0.17). The genetic scenario scored a higher accuracy (p = 0.04) but lower sense of empowerment (p = 0.01). Furthermore, patients were more likely to seek additional testing after an ultrasound than after genetic testing (p = 0.05). There were no differences in other secondary outcomes including perception of life-altering consequences and hypothetical worry, anxiety, confusion, or medical care decisions. Our data suggest that uncertain findings on prenatal genetic testing do not elicit a higher perception of risk or anxiety when compared to ultrasound findings of comparable uncertainty. © 2015 John Wiley & Sons, Ltd. © 2015 John Wiley & Sons, Ltd.

Relationship Between Changes in Serum Thyrotropin and Total and Lipoprotein Cholesterol with Prolonged Antarctic Residence

DTIC Science & Technology

1993-09-01

density lipoprotein ( HDL -C) cholesterol and triglyceride changes in TSH (P < .05)1 TBG (P < .01), TT3 (P < .05), ( TG ), on the other hand, were analyzed from...total thyroxine (TT4), free T4 (FT4), total T3 (TT3), free T3 (FT3), thyroid-binding globulin (TBG), total cholesterol (T-CHOL), high - density lipoprotein ... cholesterol ( HDL -C), triglyceride ( TG ), dietary cholesterol (D-CHOL), dietary fat (D-FAT), and dietary

Design of Test Support Hardware for Advanced Space Suits

NASA Technical Reports Server (NTRS)

Watters, Jeffrey A.; Rhodes, Richard

2013-01-01

As a member of the Space Suit Assembly Development Engineering Team, I designed and built test equipment systems to support the development of the next generation of advanced space suits. During space suit testing it is critical to supply the subject with two functions: (1) cooling to remove metabolic heat, and (2) breathing air to pressurize the space suit. The objective of my first project was to design, build, and certify an improved Space Suit Cooling System for manned testing in a 1-G environment. This design had to be portable and supply a minimum cooling rate of 2500 BTU/hr. The Space Suit Cooling System is a robust, portable system that supports very high metabolic rates. It has a highly adjustable cool rate and is equipped with digital instrumentation to monitor the flowrate and critical temperatures. It can supply a variable water temperature down to 34 deg., and it can generate a maximum water flowrate of 2.5 LPM. My next project was to design and build a Breathing Air System that was capable of supply facility air to subjects wearing the Z-2 space suit. The system intakes 150 PSIG breathing air and regulates it to two operating pressures: 4.3 and 8.3 PSIG. It can also provide structural capabilities at 1.5x operating pressure: 6.6 and 13.2 PSIG, respectively. It has instrumentation to monitor flowrate, as well as inlet and outlet pressures. The system has a series of relief valves to fully protect itself in case of regulator failure. Both projects followed a similar design methodology. The first task was to perform research on existing concepts to develop a sufficient background knowledge. Then mathematical models were developed to size components and simulate system performance. Next, mechanical and electrical schematics were generated and presented at Design Reviews. After the systems were approved by the suit team, all the hardware components were specified and procured. The systems were then packaged, fabricated, and thoroughly tested. The next step

PFOS induced lipid metabolism disturbances in BALB/c mice through inhibition of low density lipoproteins excretion

NASA Astrophysics Data System (ADS)

Wang, Ling; Wang, Yu; Liang, Yong; Li, Jia; Liu, Yuchen; Zhang, Jie; Zhang, Aiqian; Fu, Jianjie; Jiang, Guibin

2014-04-01

Male BALB/c mice fed with either a regular or high fat diet were exposed to 0, 5 or 20 mg/kg perfluorooctane sulfonate (PFOS) for 14 days. Increased body weight, serum glucose, cholesterol and lipoprotein levels were observed in mice given a high fat diet. However, all PFOS-treated mice got reduced levels of serum lipid and lipoprotein. Decreasing liver glycogen content was also observed, accompanied by reduced serum glucose levels. Histological and ultrastructural examination detected more lipid droplets accumulated in hepatocytes after PFOS exposure. Moreover, transcripitonal activity of lipid metabolism related genes suggests that PFOS toxicity is probably unrelevant to PPARα's transcription. The present study demonstrates a lipid disturbance caused by PFOS and thus point to its role in inhibiting the secretion and normal function of low density lipoproteins.

Lipoprotein profile assessed by 2D-1H-NMR and subclinical atherosclerosis in children with familial hypercholesterolaemia.

PubMed

Rodríguez-Borjabad, Cèlia; Ibarretxe, Daiana; Girona, Josefa; Ferré, Raimon; Feliu, Albert; Amigó, Núria; Guijarro, Eugenio; Masana, Luis; Plana, Núria

2018-03-01

Familial hypercholesterolaemia (FH) is underdiagnosed in children. In addition to lipid concentrations, lipoprotein particle quantity and quality could influence cardiovascular risk. We aimed to perform a comprehensive plasma lipid study, including lipoprotein particle number and size assessment by two-dimensional nuclear magnetic resonance (2D-1H-NMR), in children with FH compared to non-affected children and to evaluate the clinical value of these factors as subclinical atherosclerosis biomarkers. One hundred eighty-three children participating in the broad "Hypercholesterolemia Early Detection Programme" (Decopin Project) were recruited. They were categorized as FH, if they had either a positive genetic test or clinical certainty, or as control children (CCh). Medical history, anthropometry and clinical variables were recorded. Standard biochemical measurements were performed. The lipoprotein profile was studied by 2D-1H-NMR. Carotid intima-media thickness (cIMT) was assessed by sonography in 177 children. FH children had a significant 36% increase in LDL particles. The small LDL fraction was increased by 33% compared to CCh. The relative relationship between large, medium and small LDL and the mean LDL particle size was similar between FH children and CCh. The total and small LDL particle numbers were directly associated with and contributed to the determination of the mean cIMT according to bivariate and multivariate analyses in FH children. The higher cholesterol levels of FH children are due to an overall increased number of all LDL particle subclasses, including a notable 33% increase in small LDL. Total and small LDL particle number shows a good correlation with cIMT in FH children. Copyright © 2018 Elsevier B.V. All rights reserved.

Higher high-density lipoprotein cholesterol in African-American women with polycystic ovary syndrome compared with Caucasian counterparts.

PubMed

Koval, Kathryn W; Setji, Tracy L; Reyes, Eric; Brown, Ann J

2010-09-01

Studies have demonstrated lipid differences among African-Americans and Caucasians and between women with polycystic ovary syndrome (PCOS) and normally ovulating women. However, few studies have examined racial differences in lipoprotein levels in women with PCOS. This study compared lipoprotein levels in African-American and Caucasian women with PCOS. We performed a retrospective chart review of 398 subjects seen as new patients for PCOS at the Duke University Medical Center Endocrinology Clinic in Durham, NC. We identified 126 charts appropriate for review, based on a diagnosis of PCOS (using the 1990 National Institutes of Health criteria), a self-reported race of either Caucasian or African-American, and a body mass index (BMI) higher than 25. We excluded patients taking glucophage, oral contraceptives, or lipid-lowering medications. Age, BMI, total cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol, random triglycerides (TG), and oral glucose tolerance test measurements were collected and included in the analysis. African-American women with PCOS had higher HDL cholesterol levels (52.6 vs. 47.5 mg/dl, P = 0.019), lower non-HDL cholesterol (134.1 vs. 154.6 mg/dl, P = 0.046), and lower TG levels (97.5 vs. 168.2 mg/dl, P < 0.001) than Caucasian women. These differences could not be attributed to age, BMI, or differences in insulin resistance as determined by homeostasis model assessment of insulin resistance. African-American women with PCOS appear to have a more favorable lipid profile than Caucasian women with PCOS having higher HDL cholesterol, lower non-HDL cholesterol, and lower TG when BMI and insulin resistance are equal.

Effects of peach palm oil on performance, serum lipoproteins and haemostasis in broilers.

PubMed

Baldizán, G; Oviedo, M; Michelangeli, C; Vargas, R E

2010-12-01

1. An experiment was conducted to study the comparative effects of peach palm oil (PPO, Bactris gasipaes H.B.K), crude palm oil (CPO, Elaeis guinenesis), maize oil (MO) and beef tallow (BT) on serum total and lipoprotein cholesterol levels and haemostatic factors in broiler chickens. 2. Four experimental diets were formulated to be isocaloric (14·2 MJ AME(N)/kg) and isonitrogenous (230 g CP/kg). PPO was extracted from the whole dry fruit with hexane. Each fat was added to the diet in an amount equivalent to 25% of total dietary calories. Six replicate groups of eight male broiler chicks were assigned randomly to each dietary treatment. Diets were fed on ad libitum basis. The experiment lasted 42 d. 3. At 42 d, birds were fasted overnight and three chickens/dietary treatment were utilised to draw blood for lipoprotein separation. Various haemostatic factors were determined in thrombocyte-poor plasma. Thrombocyte aggregation was assayed in whole blood. 4. No significant differences were detected in body-weight gain or feed efficiency between the chickens fed on the PPO diet and those receiving the CPO, MO or BT diets. Total serum cholesterol (TC), very low density lipoprotein cholesterol and low density lipoprotein cholesterol (LDL(C)) were not significantly affected after consuming the PPO, CPO and MO diets. Serum high density lipoprotein cholesterol (HDL(C)) was reduced only by the MO diet. Birds fed on the PPO diet had a significantly lower [corrected] LDLC/HDLC ratio compared with other dietary treatments 5. Thrombocyte count and thrombin time were not significantly affected by the experimental diets. Dietary oils significantly affected prothrombin time, fibrinogen concentration and thrombocyte aggregation. PPO and MO diets elicited the lowest fibrinogen levels compared to the CPO and BT diets. Thrombocyte aggregation in broilers fed on the PPO diet was similar to that of the CPO, MO and BT diets. 6. The results suggest that PPO might efficiently provide up to

Effect of long-term physical activity on PCSK9, high- and low-density lipoprotein cholesterol, and lipoprotein(a) levels: a prospective observational trial

PubMed