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Sample records for acute cholesterol loading

  1. Cholesterol granuloma of the right epididymis mimicking an acute scrotum

    Institute of Scientific and Technical Information of China (English)

    Borislav Spajic; Hrvoje Cupic; Goran Stimac; Ivica Brigic; Bozo Kruslin; Ognjen Kraus

    2006-01-01

    @@ Dear Sir, I am B. Spajic, the urologist from Clinical Department of Urology, Sestre Milosrdnice University Hospital,Zagreb, Croatia. Recently, we had a rare case of a cholesterol granuloma of the right epididymis at our department, showing clinical signs of acute scrotum. The case described here appears to be the second reporting cholesterol granuloma in the epididymis and the first one presenting with clinical signs of acute scrotum.

  2. Alterations in plasma lecithin : cholesterol acyltransferase and myeloperoxidase in acute myocardial infarction: Implications for cardiac outcome

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; Tietge, Uwe J. F.; Kwakernaak, Arjan J.; Dikkeschei, Bert D.; Perton, Frank; Tio, Rene A.

    2014-01-01

    Background: The cholesterol esterifying enzyme, lecithin: cholesterol acyltransferase (LCAT), plays a key role in HDL maturation and remodeling. Myeloperoxidase (MPO) may compromise LCAT enzymatic activity. We tested the extent to which plasma LCAT activity is altered in acute myocardial infarction

  3. Concentration-Dependent Diversifcation Effects of Free Cholesterol Loading on Macrophage Viability and Polarization

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    Xiaoyang Xu

    2015-08-01

    Full Text Available Background/Aims: The accumulation of free cholesterol in atherosclerotic lesions has been well documented in both animals and humans. In studying the relevance of free cholesterol buildup in atherosclerosis, contradictory results have been generated, indicating that free cholesterol produces both pro- and anti-atherosclerosis effects in macrophages. This inconsistency might stem from the examination of only select concentrations of free cholesterol. In the present study, we sought to investigate the implication of excess free cholesterol loading in the pathophysiology of atherosclerosis across a broad concentration range from (in µg/ml 0 to 60. Methods: Macrophage viability was determined by measuring formazan formation and flow cytometry viable cell counting. The polarization of M1 and M2 macrophages was differentiated by FACS (Fluorescence-Activated Cell Sorting assay. The secretion of IL-1β in macrophage culture medium was measured by ELISA kit. Macrophage apoptosis was detected by flow cytometry using a TUNEL kit. Results: Macrophage viability was increased at the treatment of lower concentrations of free cholesterol from (in µg/ml 0 to 20, but gradually decreased at higher concentrations from 20 to 60. Lower free cholesterol loading induced anti-inflammatory M2 macrophage polarization. The activation of the PPARγ (Peroxisome Proliferator-Activated Receptor gamma nuclear factor underscored the stimulation of this M2 phenotype. Nevertheless, higher levels of free cholesterol resulted in pro-inflammatory M1 activation. Moreover, with the application of higher free cholesterol concentrations, macrophage apoptosis and secretion of the inflammatory cytokine IL-1β increased significantly. Conclusion: These results for the first time demonstrate that free cholesterol could render concentration-dependent diversification effects on macrophage viability, polarization, apoptosis and inflammatory cytokine secretions, thereby reconciling the pros

  4. Cholesterol loaded cyclodextrin increases freezability of buffalo bull (Bubalus bubalis spermatozoa by increasing cholesterol to phospholipid ratio

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    J. S. Rajoriya

    2014-09-01

    Full Text Available Aim: The study was conducted to investigate the effect of cholesterol loaded cyclodextrin (CLC on freezability of buffalo spermatozoa. Materials and Methods: Murrah buffalo bull semen samples with progressive motility of 70% and greater were used. After the evaluation of motility and livability, four equal fractions of semen samples were made. Group I was kept as control and diluted with Tris, whereas Group II, III and IV were treated with CLC solution at the rate of 2.0, 3.0 and 4.0 mg/ml respectively to obtain 120 × 106 sperm/ml as final spermatozoa concentration. The aliquots of all the groups were incubated for action of CLC, followed by dilution and freezing. Evaluation at pre-freeze and post-thaw stage of progressive motility, viability and level of cholesterol and phospholipid was done. Results: The mean cholesterol content (μg/100 × 106 spermatozoa of Group I, II, III and IV at pre-freeze stage was 21.55±0.63, 49.56±1.38, 55.67±0.45 and 47.79±1.01 and at post-thaw stage were 13.18±0.45, 34.27±0.71, 36.21±0.48 and 33.68±0.56, respectively. At pre-freeze stage, cholesterol content was significantly (p<0.01 higher in Group III in comparison to other groups. The mean cholesterol and phospholipids content of fresh sperm was 24.14±0.58 and 51.13±0.66 μg/100 × 106 sperm cells, respectively, and C/P ratio of spermatozoa at fresh stage was 0.47±0.067. Conclusion: CLC treatment maintains the C/P ratio and plays an important role in maintaining membrane architecture of spermatozoa. Hence, addition of CLC may be helpful in increasing freezability of buffalo spermatozoa by increasing the C/P ratio of spermatozoa.

  5. The Structural Basis of Cholesterol Accessibility in Membranes

    OpenAIRE

    Olsen, Brett N.; Bielska, Agata A.; Lee, Tiffany; Daily, Michael D.; Covey, Douglas F.; Schlesinger, Paul H.; Baker, Nathan A.; Ory, Daniel S.

    2013-01-01

    Although the majority of free cellular cholesterol is present in the plasma membrane, cholesterol homeostasis is principally regulated through sterol-sensing proteins that reside in the cholesterol-poor endoplasmic reticulum (ER). In response to acute cholesterol loading or depletion, there is rapid equilibration between the ER and plasma membrane cholesterol pools, suggesting a biophysical model in which the availability of plasma membrane cholesterol for trafficking to internal membranes mo...

  6. Phospholipid liposomes acquire apolipoprotein E in atherogenic plasma and block cholesterol loading of cultured macrophages.

    OpenAIRE

    Williams, K J; Tall, A.R.; Bisgaier, C; Brocia, R

    1987-01-01

    A single infusion of phospholipid liposomes promptly and persistently abolished the ability of hypercholesterolemic rabbit plasma to cause cholesteryl ester loading in cultured macrophages. This phospholipid enrichment of plasma caused moderate stimulation of cellular cholesterol efflux and, unexpectedly, almost complete inhibition of cellular uptake of beta-very low density lipoprotein (beta-VLDL), the major cholesteryl ester-rich particle in hypercholesterolemic rabbit plasma. Cell viabilit...

  7. Effect of Cholesterol on the Properties of Spray-Dried Lysozyme-Loaded Liposomal Powders

    OpenAIRE

    Charnvanich, Dusadee; Vardhanabhuti, Nontima; Kulvanich, Poj

    2010-01-01

    The influence of cholesterol (Chol) in the liposomal bilayer on the properties of inhalable protein-loaded liposomal powders prepared by spray-drying technique was investigated. Lysozyme (LSZ) was used as a model protein. Feed solution for spray drying was prepared by direct mixing of aqueous solution of LSZ with mannitol solution and empty liposome dispersions composed of hydrogenated phosphatidylcholine and Chol at various molar ratios. The spray-dried powders were characterized with respec...

  8. Retinoid regulated macrophage cholesterol efflux involves the steroidogenic acute regulatory protein

    OpenAIRE

    Manna, Pulak R.

    2016-01-01

    Elimination of excess cholesteryl esters from macrophage-derived foam cells is known to be a key process in limiting plaque stability and progression of atherosclerotic lesions. We have recently demonstrated that regulation of retinoid mediated cholesterol efflux is influenced by liver X receptor (LXR) signaling in mouse macrophages (Manna, P.R. et al., 2015, Biochem. Biophys. Res. Commun., 464:312-317). The data presented in this article evaluate the importance of the steroidogenic acute reg...

  9. Phosphatidylcholine: Greasing the Cholesterol Transport Machinery

    Science.gov (United States)

    Lagace, Thomas A.

    2015-01-01

    Negative feedback regulation of cholesterol metabolism in mammalian cells ensures a proper balance of cholesterol with other membrane lipids, principal among these being the major phospholipid phosphatidylcholine (PC). Processes such as cholesterol biosynthesis and efflux, cholesteryl ester storage in lipid droplets, and uptake of plasma lipoproteins are tuned to the cholesterol/PC ratio. Cholesterol-loaded macrophages in atherosclerotic lesions display increased PC biosynthesis that buffers against elevated cholesterol levels and may also facilitate cholesterol trafficking to enhance cholesterol sensing and efflux. These same mechanisms could play a generic role in homeostatic responses to acute changes in membrane free cholesterol levels. Here, I discuss the established and emerging roles of PC metabolism in promoting intracellular cholesterol trafficking and membrane lipid homeostasis. PMID:27081313

  10. Free-cholesterol loading does not trigger phase separation of the fluorescent sterol dehydroergosterol in the plasma membrane of macrophages

    DEFF Research Database (Denmark)

    Wüstner, Daniel

    2008-01-01

    membrane distribution of the fluorescent cholesterol-mimicking sterol dehydroergosterol (DHE) was investigated in FC-loaded J774 macrophages. Wide field fluorescence and deconvolution microscopy were combined with quantitative assessment of sterol distribution in straightened plasma membrane image segments....... DHE's surface distribution matched exactly large ruffles and membrane protrusions which were pronounced in FC-loaded cells. Plasma membrane blebs, however, formed in FC-loaded J774 cells had a homogenous staining along the membrane bilayer at 20 degrees C. The results show that even in FC-loaded cells...... with increased membrane cholesterol content, sterols do not form a separate phase in the plasma membrane....

  11. Retinoid regulated macrophage cholesterol efflux involves the steroidogenic acute regulatory protein.

    Science.gov (United States)

    Manna, Pulak R

    2016-06-01

    Elimination of excess cholesteryl esters from macrophage-derived foam cells is known to be a key process in limiting plaque stability and progression of atherosclerotic lesions. We have recently demonstrated that regulation of retinoid mediated cholesterol efflux is influenced by liver X receptor (LXR) signaling in mouse macrophages (Manna, P.R. et al., 2015, Biochem. Biophys. Res. Commun., 464:312-317). The data presented in this article evaluate the importance of the steroidogenic acute regulatory protein (StAR) in retinoid mediated macrophage cholesterol efflux. Overexpression of StAR in mouse RAW 264.7 macrophages increased the effects of both all-trans retinoic acid (atRA) and 9-cis RA on cholesterol efflux, suggesting StAR enhances the efficacy of retinoic acid receptor (RAR) and/or retinoid X receptor (RXR) ligands. Additional data revealed that atRA enhances (Bu)2cAMP induced StAR and ATP-binding cassette transporter A1 protein levels. Treatment of macrophages transfected with an LXRE reporter plasmid (pLXREx3-Luc) was found to induce the effects of RAR and RXR analogs on LXR activity. PMID:27081671

  12. Effect of cholesterol-loaded-cyclodextrin on sperm viability and acrosome reaction in boar semen cryopreservation.

    Science.gov (United States)

    Lee, Yong-Seung; Lee, Seunghyung; Lee, Sang-Hee; Yang, Boo-Keun; Park, Choon-Keun

    2015-08-01

    This study was undertaken to examine the effect of cholesterol-loaded-cyclodextrin (CLC) on boar sperm viability and spermatozoa cryosurvival during boar semen cryopreservation, and methyl-β-cyclodextrin (MBCD) was treated for comparing with CLC. Boar semen treated with CLC and MBCD before freezing process to monitor the effect on survival and capacitation status by flow cytometry with appropriate fluorescent probes. Sperm viability was higher in 1.5mg CLC-treated sperm (76.9±1.01%, Psemen, in which CLC treatment prior to freezing and thawing increased the development of oocytes to blastocyst stage in vitro. In conclusion, CLC could protect the viability of spermatozoa from cryodamage prior to cryopreservation in boar semen. PMID:26091957

  13. Clinical Factors and Viral Load Influencing Severity of Acute Hepatitis A.

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    Hyun Woong Lee

    Full Text Available Clinical manifestations of hepatitis A virus (HAV infection vary from mild to fulminant hepatic failure (FHF in adults. We investigated the relationship between laboratory findings, including viral load, and clinical outcomes in patients with acute hepatitis A (AHA and evaluated predictive factors for severe acute hepatitis (s-AH.We analyzed the clinical manifestations of AHA in 770 patients. Patients with a prothrombin time (PT of less than 40% of normal were classified as s-AH and included 4 patients with FHF, 11 patients with acute renal failure, and 3 patients with prolonged jaundice (n = 128. Other patients were defined as mild acute hepatitis (m-AH (n = 642. Serum samples were obtained from 48 patients with acute hepatitis A. Among them, 20 with s-AH, and 28 with m-AH, were tested for HAV RNA titer.In a multivariate analysis, age (HR = 1.042, P = 0.041, peak creatinine (HR = 4.014, P = 0.001, bilirubin (HR = 1.153, P = 0.003, alanine aminotransferase (ALT (HR = 1.001, P < 0.001, initial lactate dehydrogenase (LDH (HR = 1.000, P = 0.045 and total cholesterol (HR = 0.978, P < 0.001 were independent factors for s-AH. Serum HAV RNA was detected in 20/20 (100% patients with s-AH and 22/28 (78.6% patients with m-AH. In a multivariate analysis of the 48 patients who were tested for HAV RNA, peak ALT (HR = 1.001, P = 0.004 and HAV RNA titer (HR = 2.076, P = 0.012 were independent factors for s-AH.Clinical factors including age, peak creatinine, bilirubin, ALT, initial LDH and total cholesterol were independent factors for s-AH in a multivariate analysis. In particular, HAV load strongly correlated with the severity of hepatitis A.

  14. Concentration-dependent Diversification Effects of Free Cholesterol Loading on Macrophage Viability and Polarization

    OpenAIRE

    Xu, Xiaoyang; Zhang, Aolin; Li, Ningjun; Li, Pin-Lan; Zhang, Fan

    2015-01-01

    The accumulation of free cholesterol in atherosclerotic lesions has been well documented in both animals and humans. In studying the relevance of free cholesterol buildup in atherosclerosis, contradictory results have been generated, indicating that free cholesterol produces both pro- and anti-atherosclerosis effects in macrophages. This inconsistency might stem from the examination of only select concentrations of free cholesterol. In the present study, we sought to investigate the implicati...

  15. Myeloperoxidase and serum amyloid A contribute to impaired in vivo reverse cholesterol transport during the acute phase response but not group IIA secretory phospholipase A(2)

    NARCIS (Netherlands)

    Annema, Wijtske; Nijstad, Niels; Toelle, Markus; de Boer, Jan Freark; Buijs, Ruben V. C.; Heeringa, Peter; van der Giet, Markus; Tietge, Uwe J. F.

    2010-01-01

    Atherosclerosis is linked to inflammation. HDL protects against atherosclerotic cardiovascular disease, mainly by mediating cholesterol efflux and reverse cholesterol transport (RCT). The present study aimed to test the impact of acute inflammation as well as selected acute phase proteins on RCT wit

  16. Addition of cholesterol-loaded cyclodextrins to the thawing extender: effects on boar sperm quality.

    Science.gov (United States)

    Tomás, C; Gómez-Fernández, J; Gómez-Izquierdo, E; Mocé, E; de Mercado, E

    2014-06-01

    The aim of the present study was to evaluate the effect that the addition of cholesterol-loaded cyclodextrins (CLC) to the thawing extender has on the quality of frozen-thawed boar sperm. Pooled semen (n = 5) from three boars was used for the experiments. The semen was cryopreserved with an egg-yolk-based extender, it was diluted after thawing in Beltsville thawing solution (BTS) supplemented with different concentrations of CLC (0, 12.5, 25, 50 or 100 mg/500 × 10(6) sperm), and these samples were incubated at 37°C for 150 min. The following parameters of sperm quality were evaluated 30 and 150 min after incubation: sperm with intact plasma membrane (SIPM; %), sperm with normal acrosomal ridge (NAR; %), total motile sperm (TMS; %), progressively motile sperm (PMS; %) and kinetic parameters. Both SIPM and NAR increased (p < 0.05) when the thawing extender was supplemented with 12.5, 25 and 50 mg CLC/500 × 10(6) sperm. Nevertheless, motility decreased (p < 0.05) when the concentration of CLC exceeded 12.5 mg CLC/500 × 10(6) sperm. In conclusion, our results suggest that the supplementation of thawing extenders with CLC improves sperm viability and reduces acrosome damage after freezing/thawing.

  17. Cognitive Load Undermines Thought Suppression in Acute Stress Disorder.

    Science.gov (United States)

    Nixon, Reginald D V; Rackebrandt, Julie

    2016-05-01

    Thought suppression studies demonstrate that attempts to suppress can be undermined by cognitive load. We report the first instance in which this has been tested experimentally in a sample of recently traumatized individuals. Individuals with and without acute stress disorder (ASD) were recruited following recent trauma and randomized to load or no load conditions (N=56). They monitored intrusive memories during baseline, suppression, and think anything phases. The impact of suppression and load on self-reported intrusions, attention bias (dot-probe), and memory priming (word-stem task) was assessed. The ASD load group were less able to suppress memories (d=0.32, CI95 [-0.15, 0.83], p=.088) than the ASD no load group (d=0.63, CI95 [0.08, 1.24], panything phase, the ASD load group reported more intrusions than the ASD no load or non-ASD groups (with and without load). No consistent findings were observed in relation to attentional bias. ASD load individuals exhibited stronger priming responses for motor vehicle accident and assault words than all other groups (ds between 0.35-0.73). Working memory did not moderate any outcomes of interest. The findings indicate that cognitive load interferes with suppression and may enhance access to trauma memories and associated material. The study extends previous research by demonstrating these effects for the first time in a clinical sample of recent survivors of trauma. PMID:27157032

  18. Effect of incubation on freezability of cholesterol-loaded cyclodextrin treated buffalo (Bubalus bubalis spermatozoa

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    S. A. Lone

    2016-02-01

    Full Text Available Aim: The aim of this study was to investigate the effect of incubation on freezability of cholesterol loaded cyclodextrin (CLC treated buffalo spermatozoa. Materials and Methods: Semen samples with mass motility of 3+ and greater, collected from Murrah buffalo bulls were utilized. Immediately after collection, four equal groups of semen sample were made. Group I was kept as control and diluted with Tris upto concentration of 60×106 sperm/ml, where as Groups II, III, and IV were treated with CLC at 3 mg/120× 106 spermatozoa, incubated at 37°C for action of CLC for 10, 15 and 20 min, respectively, and diluted with tris upto concentration of 60×106 sperm/ml. All groups were subjected to equilibration and freezing. The evaluation of semen samples from all groups was carried out at fresh, pre-freeze and post-thaw stage for progressive motility, viability and hypo-osmotic swelling response (HOS response. Results: At the pre-freeze stage, significantly (p<0.05 higher percentage of progressive motility and viability was observed in treatment groups as compared to control with no significant difference among treatment groups. HOS response was significantly (p<0.05 higher in treatment groups as compared to control at pre-freeze stage. At post-thaw stage, significantly (p<0.05 higher percentage of progressive motility, viability and HOS response was recorded in Group II as compared to control and other treatment groups (III and IV. Group II retained significant post-thaw motility and viability at various post-thaw incubation periods. Conclusion: Incubation period of 10 min for CLC treated buffalo spermatozoa yielded significantly higher results in terms of freezability as compared to incubation for 15 and 20 min.

  19. Roles of High-Density Lipoprotein Cholesterol in Patients With Acute Myocardial Infarction.

    Science.gov (United States)

    Lee, Cheol Hyun; Woo, Jong Shin; Park, Chang Bum; Cho, Jin Man; Ahn, Young Keun; Kim, Chong Jin; Jeong, Myung Ho; Kim, Weon

    2016-05-01

    Many observational studies showed hogh-density lipoprotein cholesterol (HDL-C) is a strong inverse predictor of cardiovascular (CV) outcome. However, recent large clinical trials evaluating therapies to raise HDL-C level in those already on statin therapy have been discouraging. This complexity is not well-known.A total of 28,357 acute myocardial infarction (AMI) patients were enrolled in the Korea Acute Myocardial Infarction Registry (KAMIR), which was a prospective, multicenter, nationwide, web-based database of AMI in Korea. From this registry, we evaluated 3574 patients with AMI who have follow-up HDL-C level to investigate its association with clinical outcomes. The primary endpoint was the relationship between follow-up change in HDL-C and a 12-month composite of major adverse cardiac events (MACEs).Patients with initial HDL-C ≥ 40 mg/dL showed significantly lower rates of 12-month MACEs, especially cardiac and all-cause mortalities (P < 0.001). When patients were stratified into 4 groups according to the change of HDL-C, patients with decreasing HDL-C showed significantly higher rates of 12-month MACEs as comparable with patients with increasing HLD-C. A multivariate analysis indicated that HDL-C level was a significant predictor of CV events (hazard ratio, 1.38; 95% confidence interval, 1.12-1.71) after correcting for confounding variables.The follow-up change in HDL-C level was significantly related with CV outcomes in patients with AMI. PMID:27149442

  20. The Structural Basis of Cholesterol Activity in Membranes

    Energy Technology Data Exchange (ETDEWEB)

    Olsen, Brett N.; Bielska, Agata; Lee, Tiffany; Daily, Michael D.; Covey, Douglas F.; Schlesinger, Paul H.; Baker, Nathan A.; Ory, Daniel S.

    2013-10-15

    Although the majority of free cellular cholesterol is present in the plasma membrane, cholesterol homeostasis is principally regulated through sterol-sensing proteins that reside in the cholesterol-poor endoplasmic reticulum (ER). In response to acute cholesterol loading or depletion, there is rapid equilibration between the ER and plasma membrane cholesterol pools, suggesting a biophysical model in which the availability of plasma membrane cholesterol for trafficking to internal membranes modulates ER membrane behavior. Previous studies have predominantly examined cholesterol availability in terms of binding to extramembrane acceptors, but have provided limited insight into the structural changes underlying cholesterol activation. In this study, we use both molecular dynamics simulations and experimental membrane systems to examine the behavior of cholesterol in membrane bilayers. We find that cholesterol depth within the bilayer provides a reasonable structural metric for cholesterol availability and that this is correlated with cholesterol-acceptor binding. Further, the distribution of cholesterol availability in our simulations is continuous rather than divided into distinct available and unavailable pools. This data provide support for a revised cholesterol activation model in which activation is driven not by saturation of membrane-cholesterol interactions but rather by bulk membrane remodeling that reduces membrane-cholesterol affinity.

  1. Adjuvant Effect of Cationic Liposomes for Subunit Influenza Vaccine: Influence of Antigen Loading Method, Cholesterol and Immune Modulators

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    Alexander Kros

    2013-07-01

    Full Text Available Cationic liposomes are potential adjuvants for influenza vaccines. In a previous study we reported that among a panel of cationic liposomes loaded with influenza hemagglutinin (HA, DC-Chol:DPPC (1:1 molar ratio liposomes induced the strongest immune response. However, it is not clear whether the cholesterol (Chol backbone or the tertiary amine head group of DC-Chol was responsible for this. Therefore, in the present work we studied the influence of Chol in the lipid bilayer of cationic liposomes. Moreover, we investigated the effect of the HA loading method (adsorption versus encapsulation and the encapsulation of immune modulators in DC-Chol liposomes on the immunogenicity of HA. Liposomes consisting of a neutral lipid (DPPC or Chol and a cationic compound (DC-Chol, DDA, or eDPPC were produced by film hydration-extrusion with/without an encapsulated immune modulator (CpG or imiquimod. The liposomes generally showed comparable size distribution, zeta potential and HA loading. In vitro studies with monocyte-derived human dendritic cells and immunization studies in C57Bl/6 mice showed that: (1 liposome-adsorbed HA is more immunogenic than encapsulated HA; (2 the incorporation of Chol in the bilayer of cationic liposomes enhances their adjuvant effect; and (3 CpG loaded liposomes are more efficient at enhancing HA-specific humoral responses than plain liposomes or Alhydrogel.

  2. Accelerated decline in renal function after acute myocardial infarction in patients with high low-density lipoprotein-cholesterol to high-density lipoprotein-cholesterol ratio.

    Science.gov (United States)

    Okumura, Satoshi; Sakakibara, Masaki; Hayashida, Ryo; Jinno, Yasushi; Tanaka, Akihito; Okada, Koji; Hayashi, Mutsuharu; Ishii, Hideki; Murohara, Toyoaki

    2014-01-01

    High low-density lipoprotein-cholesterol to high-density lipoprotein-cholesterol (L/H) ratio is associated with progressions of coronary arteriosclerosis and chronic kidney disease. On the other hand, renal function markedly declined after acute myocardial infarction (AMI). The aims of the present study were (1) to identify what type of patients with AMI would have high L/H ratio at follow-up and (2) to evaluate whether decline in renal function after AMI had accelerated or not in patients with high L/H ratio. The 190 eligible AMI patients who underwent primary percutaneous coronary intervention (PCI) and received atorvastatin (10 mg) were divided into one of two groups according to the L/H ratio at 6-month follow-up: L/H >2 group (n = 81) or L/H ≤2 group (n = 109). The characteristics on admission in the two groups were examined. Furthermore, changes in serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) during 1- and 6-month follow-up were compared between the two groups. L/H >2 group were significantly younger and had greater body mass index (BMI) and worse lipid profile on admission compared with L/H ≤2 group. Percentage increase in sCr and percentage decrease in eGFR during 1-month follow-up in L/H >2 group tended to be greater than in L/H ≤2 group, and those during 6-month follow-up were significantly greater (16.5 ± 2.77 vs. 9.79 ± 2.23 %, p = 0.03 and 11.8 ± 1.93 vs. 2.75 ± 3.85 %, p = 0.04, respectively). In AMI patients undergoing primary PCI, those who were young and had large BMI and poor lipid profile on admission were likely to have a high L/H ratio at follow-up despite statin therapy. In addition, the decline in renal function after AMI had significantly accelerated in patients with high L/H ratio.

  3. Fecal loading in the cecum as a new radiological sign of acute appendicitis

    Institute of Scientific and Technical Information of China (English)

    Andy Petroianu; Luiz Ronaldo Alberti; Renata Indelicato Zac

    2005-01-01

    AIM: Although the radiological features of acute appendicitis have been well documented, the value of plain radiography has not been fully appreciated. The aim of this study was to determine the frequency of the association of acute appendicitis with images of fecal loading in the cecum.METHODS: Plain abdominal radiographs of 400 patients operated upon for acute appendicitis (n = 100), acute cholecystitis (n = 100), right acute pelvic inflammatory disease (n = 100) and right nephrolithiasis (n = 100)were assessed. The presence of fecal loading was recorded and the sensitivity and specificity of this sign for acute appendicitis were calculated.RESULTS: The presence of fecal loading in the cecum occurred in 97 patients with acute appendicitis, 13 patients with acute cholecystitis, 12 patients with acute inflammatory pelvic disease and 19 patients with nephrolithiasis. The sensitivity of this sign for appendicitis was 97% and its specificity to this disease was 85.3%. Its positive predictive value for appendicitis was 68.7%; however, its negative predictive value for appendicitis was 98.8%.CONCLUSION: The present study suggests that the presence of radiological images of fecal loading in the cecum may be a useful sign of acute appendicitis, and the absence of this sign probably excludes this disease.This is the first description of fecal loading as a radiological sign for acute appendicitis.

  4. Associations between COX-2 polymorphisms, blood cholesterol and risk of acute coronary syndrome

    DEFF Research Database (Denmark)

    Vogel, Ulla Birgitte; Segel, Stine; Dethlefsen, Claus;

    2010-01-01

    Background: The use of specific COX-2 inhibitors in cancer prevention has been associated with higher risk of acute coronary syndrome (ACS) and myocardial infarction. The aim of this study was to investigate if the polymorphisms COX2 T8473C (rs5275), and COX2 A-1195G (rs689466), which modify the ...

  5. Protective effect of cholesterol-loaded cyclodextrin pretreatment against hydrogen peroxide induced oxidative damage in ram sperm.

    Science.gov (United States)

    Naseer, Zahid; Ahmad, Ejaz; Aksoy, Melih; Küçük, Niyazi; Serin, İlker; Ceylan, Ahmet; Boyacıoğlu, Murat; Kum, Cavit

    2015-08-01

    Three experiments were conducted to determine the protective effect of cholesterol-loaded cyclodextrin (CLC) against hydrogen peroxide (H2O2) or cryo-induced damage in ram sperm. In Experiment 1, the fresh ejaculates were either treated with CLC or remained untreated. Both CLC treated and untreated samples were then incubated with 0, 250 or 500 μM H2O2 at 35°C for 12 h. After incubation period of 12 h, the motility, viability and membrane integrity remained higher in CLC treated sperm even in the presence of 250 or 500 μM H2O2. The H2O2 treatment affected all the sperm parameters adversely (P0.05) in MDA level was observed among the groups at any stage of incubation. In conclusion, the CLC incorporation in ram sperm membrane may protects it against H2O2 or cryo-induced oxidative damage. The cryoprotective influence of CLC on ram sperm might be resulted from, at least partly, its antioxidative property.

  6. Lipoprotein Cholesterol and the Analysis of the Acute Cerebral Infarction%脂蛋白胆固醇与发生急性脑梗死的分析

    Institute of Scientific and Technical Information of China (English)

    赵彦坡

    2015-01-01

    Objective To observe the relationships between non-high-density lipoprotein cholesterol and acute cerebral infaction. Methods 88 patients were divided into 2 groups: cerebral infaction group, non-cerebral infaction group group. Al zhe patients were taken the blood with fasting after admission, the total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c),triglyceride (TG) were measured and non-high-density lipoprotein cholesterol (non-HDL-c) calculated.The date were analysed with SPSS 3.0. Results There were no significant dif erences in the total cholesterol(TC), low density lipoprotein cholesterol(LDL-c), non-high-density lipoprotein cholesterol(non-HDL-c) between the two groups(>0.05).Conclusion The abnormal metabolism of lipoprotein cholesterol are important risk factors of cerebrovascular disease, acute cerebral infarction group and nonacute cerebral infarction groups have no significant dif erence, indicate that acute cerebral infarction occurs eventual y may have other more risk factors involved in.%目的探讨脂蛋白胆固醇与急性脑梗死的关系。方法88例患者分为急性脑梗死组和非急性脑梗死组,均在入院后采集空腹血清,检测总胆固醇(TC),甘油三酯(TG),低密度脂蛋白胆固醇(LDL-c),高密度脂蛋白胆固醇(HDL-c),计算非高密度脂蛋白胆固醇(non-HDL-c),对数据均采用SPSS13.0进行分析。结果两组的总胆固醇,甘油三酯及低密度脂蛋白胆固醇及非高密度脂蛋白胆固醇比较及统计学分析,差异无显著统计学意义(跃0.05)。结论脂蛋白胆固醇代谢异常是脑血管病的重要危险因素,急性脑梗死组与非急性脑梗死组差别不明显,表明急性脑梗死发生可能有其它更多危险因素参与有关。

  7. Acute and chronic effects of a 24-hour intravenous triglyceride emulsion challenge on plasma lecithin : cholesterol acyltransferase, phospholipid transfer protein, and cholesteryl ester transfer protein activities

    NARCIS (Netherlands)

    Riemens, SC; Van Tol, A; Sluiter, WJ; Dullaart, RPF

    1999-01-01

    Lecithin:cholesterol acyltransferase (LCAT), phospholipid transfer protein (PLTP), and cholesteryl ester transfer protein (CETP) are key factors in remodeling of high density lipoproteins (HDL) and triglyceride-rich lipoproteins. We examined the effect of a large, 24 h intravenous fat load on plasma

  8. What's Cholesterol?

    Science.gov (United States)

    ... Skiing, Snowboarding, Skating Crushes What's a Booger? What's Cholesterol? KidsHealth > For Kids > What's Cholesterol? Print A A ... thing for food to be low in it? Cholesterol and Your Body Cholesterol (say: kuh-LES-tuh- ...

  9. Impaired homeostatic mechanism of potassium handling after acute oral potassium load in diabetes mellitus.

    OpenAIRE

    H.J. Kim; Ahn, Y. H.; Park, C H; Kang, C M; Park, H C; Bae, H. Y.; Choi, S. D.

    1993-01-01

    Chronic stable diabetic patients (n = 6) were compared with healthy control subjects (n = 5) after acute oral intake of 50 mEq of potassium chloride (KCl) to investigate for possible derangements of homeostatic responses for acute term (3 hrs) to acute potassium load. Plasma renin activity (PRA), plasma aldosterone (PA), and transtubular potassium concentration gradient (TTKG) known as a useful semiquantative index of distal nephron potassium secretion were measured. All the baseline paramete...

  10. Low-density lipoprotein cholesterol target goal attainment rate and related factors in patients with acute coronary syndrome after percutaneous coronary intervention

    Institute of Scientific and Technical Information of China (English)

    张波

    2014-01-01

    Objective To observe the low-density lipoprotein cholesterol(LDL-C)target goal attainment rate and related factors in patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods From March 2011 to March 2012,a total of832 ACS patients were retrospectively evaluated in the Cardiology Department of the First Affiliated Hospital of Dalian Medical University.The target goal attainment

  11. Effect of acute acid loading on acid-base and calcium metabolism

    DEFF Research Database (Denmark)

    Osther, Palle J

    2006-01-01

    OBJECTIVE: To investigate the acid-base and calcium metabolic responses to acute non-carbonic acid loading in idiopathic calcium stone-formers and healthy males using a quantitative organ physiological approach. MATERIAL AND METHODS: Five-h ammonium chloride loading studies were performed in 12 m...

  12. About Cholesterol

    Science.gov (United States)

    ... High Blood Pressure Tools & Resources Stroke More About Cholesterol Updated:Aug 10,2016 It may surprise you ... our bodies to keep us healthy. What is cholesterol and where does it come from? Cholesterol is ...

  13. Validated HPLC Method for the Determination of Paclitaxel-related Substances in an Intravenous Emulsion Loaded with a Paclitaxel–Cholesterol Complex

    OpenAIRE

    Xia, X. J.; Peng, J.; Zhang, P. X.; D J Jin; Liu, Y L

    2013-01-01

    A high-performance liquid chromatography method was developed for the determination of related substances in an intravenous emulsion loaded with a paclitaxel-cholesterol complex. The separation was achieved using Agilent Eclipse XDB-C18 column (150×4.6 mm, 3.5 μm), which was kept at 40°. The gradient mobile phase consisted of acetonitrile and water with a flow rate of 1.2 ml/min. The ultraviolet detection wavelength was set at 227 nm. The preparation of the sample solution began with the addi...

  14. Efficacy of antibacterial-loaded coating in an in vivo model of acutely highly contaminated implant

    OpenAIRE

    Giavaresi, Gianluca; Meani, Enzo; Sartori, Maria; Ferrari, Andrea; BELLINI, Davide; Sacchetta, Anna C.; Meraner, Joachim; Sambri, Andrea; Vocale, Caterina; Sambri, Vittorio; Fini, Milena; Romanò, Carlo L.

    2013-01-01

    Purpose The purpose of this study was to test the ability of DAC®, a fast resorbable, antibacterial-loaded hydrogel coating, to prevent acute bacterial colonization in an in vivo model of an intra-operatively highly contaminated implant. Methods A histocompatibility study was performed in 10 adult New Zealand rabbits. Then, methicillin-resistant Staph. aureus were inoculated in the femur of 30 adult New Zealand rabbits at the time of intra-medullary nailing; vancomycin-loaded DAC® coated nail...

  15. THE RATE OF CLINICAL RESPONSE OF ORAL LOADING SODIUM VALPROATE IN ACUTELY MANLC PATIENT

    OpenAIRE

    K SHAFIEE; M BAREKATEYN; N BASHARDOOST; Mahmoudi, J

    2003-01-01

    Introduction: Acheiving accelerated clinical response is desirable in patients with acute manic episode. We conducted a prospective study to compare the rate of clinical response of oral loading sodium valproate versus standard dose titration. Methods: Fourty - two patients who met DSM - IV critevia for current manic episode and who had a "Young mania rating scale "score between 20 and 50 were randomly assigned on a double blind basis to recieve valproate oral "loading"(N = 21) at a dose...

  16. Standardization of formulations for the acute amino acid depletion and loading tests.

    Science.gov (United States)

    Badawy, Abdulla A-B; Dougherty, Donald M

    2015-04-01

    The acute tryptophan depletion and loading and the acute tyrosine plus phenylalanine depletion tests are powerful tools for studying the roles of cerebral monoamines in behaviour and symptoms related to various disorders. The tests use either amino acid mixtures or proteins. Current amino acid mixtures lack specificity in humans, but not in rodents, because of the faster disposal of branched-chain amino acids (BCAAs) by the latter. The high content of BCAA (30-60%) is responsible for the poor specificity in humans and we recommend, in a 50g dose, a control formulation with a lowered BCAA content (18%) as a common control for the above tests. With protein-based formulations, α-lactalbumin is specific for acute tryptophan loading, whereas gelatine is only partially effective for acute tryptophan depletion. We recommend the use of the whey protein fraction glycomacropeptide as an alternative protein. Its BCAA content is ideal for specificity and the absence of tryptophan, tyrosine and phenylalanine render it suitable as a template for seven formulations (separate and combined depletion or loading and a truly balanced control). We invite the research community to participate in standardization of the depletion and loading methodologies by using our recommended amino acid formulation and developing those based on glycomacropeptide.

  17. Acute cholesterol depletion leads to net loss of the organic osmolyte taurine in Ehrlich Lettré tumor cells

    DEFF Research Database (Denmark)

    Villumsen, Kasper Rømer; Duelund, Lars; Lambert, Ian Henry

    2010-01-01

    In mammalian cells, the organic osmolyte taurine is accumulated by the Na-dependent taurine transporter TauT and released though the volume- and DIDS-sensitive organic anion channel. Incubating Ehrlich Lettré tumor cells with methyl-ß-cyclodextrin (5 mM, 1 h) reduces the total cholesterol pool to...

  18. Long distance running and acute effects on plantar foot sensitivity and plantar foot loading.

    Science.gov (United States)

    Alfuth, Martin; Rosenbaum, Dieter

    2011-09-26

    The plantar surface of the foot senses local pressures during stance and locomotion. These foot loading characteristics may be affected by long distance running. Little is known about the physiological effects of sports-related loading on plantar sensitivity and their relationship with plantar foot loading. The purpose of this study was to investigate the acute effects of long distance running on plantar sensitivity to touch and their relationship with foot loading characteristics. It was hypothesized that plantar sensation would decrease after long distance running and may be related to foot loading characteristics. In 15 middle-aged runners, sensory detection thresholds to light touch and plantar pressures were measured before and after a 10 km run. After the run, no significant changes in sensory perception thresholds were observed so that correlations between foot sensitivity and foot loading could not be calculated. A significant decrease of force-time integrals and maximum forces was demonstrated in the whole foot (-6.2%, p=0.003; -3.9%, p=0.001) and the heel (-10.5%, p=0.003; -8.5%, p=0.002). Furthermore, maximum force was significantly reduced in the lateral midfoot (-6.4%, p=0.002). In conclusion, a sub-maximal 10 km running exercise appears to have no significant acute effects on plantar sensitivity, plantar pressure distribution and peak forces. PMID:21871535

  19. Safety and Efficacy of Acute Clopidogrel Load in Patients with Moderate and Severe Ischemic Strokes

    Science.gov (United States)

    Monlezun, Dominique J.; Rincon, Natalia; Tiu, Jonathan; Valmoria, Melisa

    2016-01-01

    Objective. To study the safety and efficacy of a clopidogrel loading dose in patients with moderate and severe acute ischemic strokes. Background. The safety of clopidogrel loading has been extensively investigated in patients with minor strokes and transient ischemic attacks. Methods. Acute ischemic stroke patients presenting consecutively to our center from 07/01/08 to 07/31/13 were screened. Clopidogrel loading was defined as at least 300 mg dose (with or without aspirin) given within 6 hours of admission. We compared outcomes in patients with baseline NIHSS > 3 with and without clopidogrel loading. Results. Inclusion criteria were met for 1011 patients (43.6% females, 69.1% black, median age 63). Patients with clopidogrel loading had lower baseline NIHSS than patients who were not loaded (8 versus 9, p = 0.005). The two groups had similar risk for hemorrhagic transformation (p = 0.918) and symptomatic hemorrhage (p = 0.599). Patients who were loaded had a lower rate of neurological worsening (38.9% versus 48.3%, p = 0.031) and less in-hospital mortality (4.3% versus 13.4%, p = 0.001) compared to those who were not loaded. The likelihood of having a poor functional outcome did not differ between the two groups after adjusting for NIHSS on admission (OR = 0.71, 95% CI 0.4633–1.0906, p = 0.118). Conclusion. Clopidogrel loading dose was not associated with increased risk for hemorrhagic transformation or symptomatic intracranial hemorrhage in our retrospective study and was associated with reduced rates of neuroworsening following moderate and severe stroke.

  20. Cholesterol (image)

    Science.gov (United States)

    Cholesterol is a soft, waxy substance that is present in all parts of the body including the ... and obtained from animal products in the diet. Cholesterol is manufactured in the liver and is needed ...

  1. Reduced natriuretic response to acute sodium loading in COMT Gene deleted mice

    Directory of Open Access Journals (Sweden)

    Uhlén Staffan

    2002-08-01

    Full Text Available Abstract Background The intrarenal natriuretic hormone dopamine (DA is metabolised by catechol-O-methyltransferase (COMT and monoamine oxidase (MAO. Inhibition of COMT, as opposed to MAO, results in a potent natriuretic response in the rat. The present study in anaesthetized homozygous and heterozygous COMT gene deleted mice attempted to further elucidate the importance of COMT in renal DA and sodium handling. After acute intravenous isotonic sodium loading, renal function was followed. Results COMT activity in heterozygous mice was about half of that in wild type mice and was zero in the homozygous mice. MAO activity did not differ between the genotypes. Urinary sodium excretion increased 10-fold after sodium loading in wild type mice. In heterozygous and homozygous mice, the natriuretic effects of sodium loading were only 29 % and 39 %, respectively, of that in wild type mice. Arterial pressure and glomerular filtration rate did not differ between genotypes. Baseline norepinephrine and DA excretions in urine were elevated in the homozygous, but not in heterozygous, COMT gene deleted mice. Urinary DA excretion increased after isotonic sodium loading in the wild type mice but not in the COMT gene deleted mice. Conclusions Mice with reduced or absent COMT activity have altered metabolism of catecholamines and are unable to increase renal DA activity and produce normal natriuresis in response to acute sodium loading. The results support the hypothesis that COMT has an important role in the DA-mediated regulation of renal sodium excretion.

  2. THE RATE OF CLINICAL RESPONSE OF ORAL LOADING SODIUM VALPROATE IN ACUTELY MANLC PATIENT

    Directory of Open Access Journals (Sweden)

    K SHAFIEE

    2003-12-01

    Full Text Available Introduction: Acheiving accelerated clinical response is desirable in patients with acute manic episode. We conducted a prospective study to compare the rate of clinical response of oral loading sodium valproate versus standard dose titration. Methods: Fourty - two patients who met DSM - IV critevia for current manic episode and who had a "Young mania rating scale "score between 20 and 50 were randomly assigned on a double blind basis to recieve valproate oral "loading"(N = 21 at a dose of 20 mg/kg in divided doses for 7 days and valproate "non -loading" at a starting dose of 10 mg/kg followed by standard titration which at day 6 , they recieved 20 mg/kg valproate. Patients were scored at day 0, 3, 5 and 7 by a blindraterusing YMRS. Results: There was no significat differences between the groups in advers events and useing of adjunctive tranquilizer .The efficacy of valproate in both two groups was similar but " the rate of improvement on YMRS" over the first 3 days was significantly greater in loading group. Conclusion: Valproate oral loading with sodium valproate can induced a more rapid clinical response in acutely manic patient.

  3. Ethanol Extract of Fructus Schisandrae Decreases Hepatic Triglyceride Level in Mice Fed with a High Fat/Cholesterol Diet, with Attention to Acute Toxicity

    Directory of Open Access Journals (Sweden)

    Si-Yuan Pan

    2011-01-01

    Full Text Available Effects of the ethanol extract of Fructus Schisandrae (EtFSC on serum and liver lipid contents were investigated in mice fed with high fat/cholesterol (HFC diet for 8 or 15 days. The induction of hypercholesterolemia by HFC diet caused significant increases in serum and hepatic total cholesterol (TC levels (up to 62% and 165%, resp. and hepatic triglyceride (TG levels (up to 528% in mice. EtFSC treatment (1 or 5 g/kg/day for 7 days; from Day 1 to 7 or from Day 8 to 14, i.g. significantly decreased the hepatic TG level (down to 35% and slightly increased the hepatic index (by 8% in hypercholesterolemic mice. Whereas fenofibrate treatment (0.1 g/kg/day for 7 days, i.g. significantly lowered the hepatic TG level (by 61%, it elevated the hepatic index (by 77% in hypercholesterolemic mice. Acute toxicity test showed that EtFSC was relatively non-toxic, with an LD50 value of 35.63 ± 6.46 g/kg in mice. The results indicate that EtFSC treatment can invariably decrease hepatic TG in hypercholesterolemic mice, as assessed by both preventive and therapeutic protocols, suggesting its potential use for fatty liver treatment.

  4. Ethanol Extract of Fructus Schisandrae Decreases Hepatic Triglyceride Level in Mice Fed with a High Fat/Cholesterol Diet, with Attention to Acute Toxicity

    Science.gov (United States)

    Pan, Si-Yuan; Yu, Zhi-Ling; Dong, Hang; Xiang, Chun-Jing; Fong, Wang-Fun; Ko, Kam-Ming

    2011-01-01

    Effects of the ethanol extract of Fructus Schisandrae (EtFSC) on serum and liver lipid contents were investigated in mice fed with high fat/cholesterol (HFC) diet for 8 or 15 days. The induction of hypercholesterolemia by HFC diet caused significant increases in serum and hepatic total cholesterol (TC) levels (up to 62% and 165%, resp.) and hepatic triglyceride (TG) levels (up to 528%) in mice. EtFSC treatment (1 or 5 g/kg/day for 7 days; from Day 1 to 7 or from Day 8 to 14, i.g.) significantly decreased the hepatic TG level (down to 35%) and slightly increased the hepatic index (by 8%) in hypercholesterolemic mice. Whereas fenofibrate treatment (0.1 g/kg/day for 7 days, i.g.) significantly lowered the hepatic TG level (by 61%), it elevated the hepatic index (by 77%) in hypercholesterolemic mice. Acute toxicity test showed that EtFSC was relatively non-toxic, with an LD50 value of 35.63 ± 6.46 g/kg in mice. The results indicate that EtFSC treatment can invariably decrease hepatic TG in hypercholesterolemic mice, as assessed by both preventive and therapeutic protocols, suggesting its potential use for fatty liver treatment. PMID:19592476

  5. Good vs. Bad Cholesterol

    Science.gov (United States)

    ... Pressure Tools & Resources Stroke More Good vs. Bad Cholesterol Updated:Mar 23,2016 Cholesterol can't dissolve ... test . View an animation of cholesterol . LDL (Bad) Cholesterol LDL cholesterol is considered the “bad” cholesterol because ...

  6. Renal response to acute acid loading--an organ physiological approach

    DEFF Research Database (Denmark)

    Osther, P J; Engel, K; Kildeberg, P

    2004-01-01

    , as the extracellular acid-base status would be expected to be the key physiological trigger for renal NAE. The object of this study was to investigate the renal response to acute non-carbonic acid loading using a quantitative organ physiological approach. MATERIAL AND METHODS: Five-h NH4Cl loading studies were...... calculated from measured concentrations of non-metabolizable ions according to Kildeberg. RESULTS: In the steady state (placebo) the rate of renal excretion of NA (=-NB) was close to zero, indicating that the net extrarenal input of NA (endogeneous production, gastrointestinal absorption. skeletal release...... from bone contributed substantially to the current net extrarenal NA input. CONCLUSION: From a physiological point of view, NB can be regarded as the actual substrate for renal acid-base control, and measurement of renal turnover of NB may give a more precise description of renal acid-base metabolism...

  7. Validated HPLC method for the determination of paclitaxel-related substances in an intravenous emulsion loaded with a paclitaxel-cholesterol complex

    Directory of Open Access Journals (Sweden)

    X J Xia

    2013-01-01

    Full Text Available A high-performance liquid chromatography method was developed for the determination of related substances in an intravenous emulsion loaded with a paclitaxel-cholesterol complex. The separation was achieved using Agilent Eclipse XDB-C18 column (150×4.6 mm, 3.5 μm, which was kept at 40°. The gradient mobile phase consisted of acetonitrile and water with a flow rate of 1.2 ml/min. The ultraviolet detection wavelength was set at 227 nm. The preparation of the sample solution began with the addition of anhydrous sodium sulphate to break the emulsion. Then, methanol and ethyl ether were added to pick up the drug and remove the accessories of the emulsion by extraction and centrifugation. Finally, paclitaxel was enriched by a nitrogen blow method and resolved with a mixture of methanol:glacial acetic acid (200:1. The method was proven to be selective, sensitive, robust, linear, repeatable, accurate and suitable for the determination of paclitaxel-related substances in the emulsion formulations, and the major degradation products in the potential pharmaceutical product were 7-epipaclitaxel and 10-deacetylpaclitaxel.

  8. Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease

    Energy Technology Data Exchange (ETDEWEB)

    Poulsen, Sarah S., E-mail: spo@nrcwe.dk [National Research Centre for the Working Environment, DK-2100 Copenhagen (Denmark); Department of Science, Systems and Models, Roskilde University, DK-4000 Roskilde (Denmark); Saber, Anne T., E-mail: ats@nrcwe.dk [National Research Centre for the Working Environment, DK-2100 Copenhagen (Denmark); Mortensen, Alicja, E-mail: almo@food.dtu.dk [National Food Institute, Technical University of Denmark, Søborg (Denmark); Szarek, Józef, E-mail: szarek@uwm.edu.pl [Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn (Poland); Wu, Dongmei, E-mail: dongmei.wu@hc-sc.gc.ca [Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Williams, Andrew, E-mail: andrew.williams@hc-sc.gc.ca [Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Andersen, Ole, E-mail: oa@ruc.dk [Department of Science, Systems and Models, Roskilde University, DK-4000 Roskilde (Denmark); Jacobsen, Nicklas R., E-mail: nrj@nrcwe.dk [National Research Centre for the Working Environment, DK-2100 Copenhagen (Denmark); Yauk, Carole L., E-mail: carole.yauk@hc-sc.gc.ca [Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Wallin, Håkan, E-mail: hwa@nrcwe.dk [National Research Centre for the Working Environment, DK-2100 Copenhagen (Denmark); Department of Public Health, University of Copenhagen, DK-1014 Copenhagen K (Denmark); Halappanavar, Sabina, E-mail: sabina.halappanavar@hc-sc.gc.ca [Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Vogel, Ulla, E-mail: ubv@nrcwe.dk [National Research Centre for the Working Environment, DK-2100 Copenhagen (Denmark); Department of Micro- and Nanotechnology, Technical University of Denmark, DK-2800 Kgs. Lyngby (Denmark)

    2015-03-15

    Adverse lung effects following pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) are well documented in rodents. However, systemic effects are less understood. Epidemiological studies have shown increased cardiovascular disease risk after pulmonary exposure to airborne particles, which has led to concerns that inhalation exposure to MWCNTs might pose similar risks. We analyzed parameters related to cardiovascular disease, including plasma acute phase response (APR) proteins and plasma lipids, in female C57BL/6 mice exposed to a single intratracheal instillation of 0, 18, 54 or 162 μg/mouse of small, entangled (CNT{sub Small}, 0.8 ± 0.1 μm long) or large, thick MWCNTs (CNT{sub Large}, 4 ± 0.4 μm long). Liver tissues and plasma were harvested 1, 3 and 28 days post-exposure. In addition, global hepatic gene expression, hepatic cholesterol content and liver histology were used to assess hepatic effects. The two MWCNTs induced similar systemic responses despite their different physicochemical properties. APR proteins SAA3 and haptoglobin, plasma total cholesterol and low-density/very low-density lipoprotein were significantly increased following exposure to either MWCNTs. Plasma SAA3 levels correlated strongly with pulmonary Saa3 levels. Analysis of global gene expression revealed perturbation of the same biological processes and pathways in liver, including the HMG-CoA reductase pathway. Both MWCNTs induced similar histological hepatic changes, with a tendency towards greater response following CNT{sub Large} exposure. Overall, we show that pulmonary exposure to two different MWCNTs induces similar systemic and hepatic responses, including changes in plasma APR, lipid composition, hepatic gene expression and liver morphology. The results link pulmonary exposure to MWCNTs with risk of cardiovascular disease. - Highlights: • Systemic and hepatic alterations were evaluated in female mice following MWCNT instillation. • Despite being physicochemically

  9. Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease

    International Nuclear Information System (INIS)

    Adverse lung effects following pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) are well documented in rodents. However, systemic effects are less understood. Epidemiological studies have shown increased cardiovascular disease risk after pulmonary exposure to airborne particles, which has led to concerns that inhalation exposure to MWCNTs might pose similar risks. We analyzed parameters related to cardiovascular disease, including plasma acute phase response (APR) proteins and plasma lipids, in female C57BL/6 mice exposed to a single intratracheal instillation of 0, 18, 54 or 162 μg/mouse of small, entangled (CNTSmall, 0.8 ± 0.1 μm long) or large, thick MWCNTs (CNTLarge, 4 ± 0.4 μm long). Liver tissues and plasma were harvested 1, 3 and 28 days post-exposure. In addition, global hepatic gene expression, hepatic cholesterol content and liver histology were used to assess hepatic effects. The two MWCNTs induced similar systemic responses despite their different physicochemical properties. APR proteins SAA3 and haptoglobin, plasma total cholesterol and low-density/very low-density lipoprotein were significantly increased following exposure to either MWCNTs. Plasma SAA3 levels correlated strongly with pulmonary Saa3 levels. Analysis of global gene expression revealed perturbation of the same biological processes and pathways in liver, including the HMG-CoA reductase pathway. Both MWCNTs induced similar histological hepatic changes, with a tendency towards greater response following CNTLarge exposure. Overall, we show that pulmonary exposure to two different MWCNTs induces similar systemic and hepatic responses, including changes in plasma APR, lipid composition, hepatic gene expression and liver morphology. The results link pulmonary exposure to MWCNTs with risk of cardiovascular disease. - Highlights: • Systemic and hepatic alterations were evaluated in female mice following MWCNT instillation. • Despite being physicochemically different, the two

  10. Are acute effects of maximal dynamic contractions on upper-body ballistic performance load specific?

    Science.gov (United States)

    Markovic, Goran; Simek, Sanja; Bradic, Asim

    2008-11-01

    This study investigated the acute effects of upper-body maximal dynamic contractions on maximal throwing speed with 0.55- and 4-kg medicine balls. It was hypothesized that heavy preloading would transiently improve throwing performance only when overcoming the heavier of the two loads. Twenty-three male volunteers were randomly allocated into experimental (n = 11) and control (n = 12) groups. Both groups performed initial and final seated medicine ball throws from the chest, and the maximal medicine ball speed was measured by means of a radar gun. Between the two measurements, the control group rested passively for 15 minutes, and the experimental group performed three sets of three-repetition maximum bench presses. For the 0.55-kg load, a 2 x 2 repeated-measures analysis of variance revealed no significant effect of time x group interaction (p = 0.22), as well as no significant time (p = 0.22) or group (p = 0.72) effects. In contrast, for the 4-kg load, a significant time x group interaction (p = 0.004) and a significant time (p = 0.035) but not group (p = 0.77) effect were observed. Analysis of simple main effects revealed that the experimental group significantly (8.3%; p ballistic performance might be load specific. In a practical sense, our findings suggest that the use of upper-body heavy resistance exercise before ballistic throwing movements against moderate external loads might be an efficient training strategy for improving an athlete's upper-body explosive performance.

  11. REDUCTION DEGREE OF LOW-DENSITY LIPOPROTEINS CHOLESTEROL LEVELS ACCORDING TO DIFFERENT DOSES OF STATINS; ITS EFFECT ON THE RISK OF ISCHEMIC HEART DISEASE ACUTE EPISODES DEPENDING ON TREATMENT DURATION; AND RISK OF ISCHEMIC AND THROMBOEMBOLIC STROKE. COMMENT ON THE PAPER OF LAW M.R., WALD N.J., RUDNICKA A.R. QUANTIFYING EFFECT OF STATINS ON LOW DENSITY LIPOPROTEIN CHOLESTEROL, ISCHAEMIC HEART DISEASE, AND STROKE: SYSTEMATIC REVIEW AND META-ANALYSIS. BMJ 2003; 326:1423-1427

    Directory of Open Access Journals (Sweden)

    N. V. Perova

    2016-01-01

    Full Text Available Comparative dose-dependent ability of different statins to lower serum low-density lipoproteins (LDL cholesterol was determined in three large meta-analysis. Besides, it was found that standardized decrease in LDL cholesterol levels on 1.0 or 1.8 mmol/l leads to rate reduction in ischemic heart disease acute episodes as well as stroke depending on treatment duration. Effect of LDL cholesterol reduction on stroke occurrence was more significant in studies, which included a major share of patients with vascular disease, because these patients have a higher risk of thromboembolic stroke (rather than haemorrhagic stroke in comparison with the general population.

  12. Cholesterol Test

    Science.gov (United States)

    ... seen when there is an existing problem like malnutrition , liver disease , or cancer . However there is no ... cholesterol levels include anabolic steroids, beta blockers , epinephrine, oral contraceptives, and vitamin D. ^ Back to top ... Health Professionals Get the Mobile App iTunes | Android | Kindle ...

  13. Improved Coarse-Grained Modeling of Cholesterol-Containing Lipid Bilayers

    Energy Technology Data Exchange (ETDEWEB)

    Daily, Michael D.; Olsen, Brett N.; Schlesinger, Paul H.; Ory, Daniel S.; Baker, Nathan A.

    2014-03-24

    In mammalian cells cholesterol is essential for membrane function, but in excess can be cytototoxic. The cellular response to acute cholesterol loading involves biophysical-based mechanisms that regulate cholesterol levels, through modulation of the “activity” or accessibility of cholesterol to extra-membrane acceptors. Experiments and united atom (UA) simulations show that at high concentrations of cholesterol, lipid bilayers thin significantly and cholesterol availability to external acceptors increases substantially. Such cholesterol activation is critical to its trafficking within cells. Here we aim to reduce the computational cost to enable simulation of large and complex systems involved in cholesterol regulation, such as those including oxysterols and cholesterol-sensing proteins. To accomplish this, we have modified the published MARTINI coarse-grained force field to improve its predictions of cholesterol-induced changes in both macroscopic and microscopic properties of membranes. Most notably, MARTINI fails to capture both the (macroscopic) area condensation and membrane thickening seen at less than 30% cholesterol and the thinning seen above 40% cholesterol. The thinning at high concentration is critical to cholesterol activation. Microscopic properties of interest include cholesterol-cholesterol radial distribution functions (RDFs), tilt angle, and accessible surface area. First, we develop an “angle-corrected” model wherein we modify the coarse-grained bond angle potentials based on atomistic simulations. This modification significantly improves prediction of macroscopic properties, most notably the thickening/thinning behavior, and also slightly improves microscopic property prediction relative to MARTINI. Second, we add to the angle correction a “volume correction” by also adjusting phospholipid bond lengths to achieve a more accurate volume per molecule. The angle + volume correction substantially further improves the quantitative

  14. The Predictive Role of Serum Triglyceride to High-Density Lipoprotein Cholesterol Ratio According to Renal Function in Patients with Acute Myocardial Infarction

    Science.gov (United States)

    Woo, Jong Shin; Lee, Tae Won; Ihm, Chun Gyoo; Kim, Yang Gyoon; Moon, Joo Young; Lee, Sang Ho; Jeong, Myung Ho; Jeong, Kyung Hwan

    2016-01-01

    Objective A high serum triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been reported as an independent predictor for cardiovascular events in the general population. However, the prognostic value of this ratio in patients with renal dysfunction is unclear. We examined the association of the TG/HDL-C ratio with major adverse cardiovascular events (MACEs) according to renal function in patients with acute myocardial infarction (AMI). Method This study was based on the Korea Acute Myocardial Infarction Registry database. Of 13,897 patients who were diagnosed with AMI, the study population included the 7,016 patients with available TG/HDL-C ratio data. Patients were stratified into three groups according to their estimated glomerular filtration rate (eGFR), and the TG/HDL-C ratio was categorized into tertiles. We investigated 12-month MACEs, which included cardiac death, myocardial infarction, and repeated percutaneous coronary intervention or coronary artery bypass grafting. Results During the 12-month follow up period, 593 patients experienced MACEs. There was a significant association between the TG/HDL-C ratio and MACEs (p<0.001) in the entire study cohort. Having a TG/HDL-C ratio value in the highest tertile of TG/HDL-C ratio was an independent factor associated with increased risk of MACEs (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.26–1.93; p<0.001). Then we performed subgroup analyses according to renal function. In patients with normal renal function (eGFR ≥ 90 ml/min/1.73m2) and mild renal dysfunction (eGFR ≥ 60 to < 90ml/min/1.73m2), a higher TG/HDL-C ratio was significantly associated with increased risk of MACEs (HR, 1.64; 95% CI, 1.04–2.60; p = 0.035; and HR, 1.56; 95% CI, 1.14–2.12; p = 0.005, respectively). However, in patients with moderate renal dysfunction (eGFR < 60 ml/min/1.73m2), TG/HDL-C ratio lost its predictive value on the risk of MACEs (HR, 1.23; 95% CI, 0.82–1.83; p = 0.317). Conclusions In

  15. Daily spinal mechanical loading as a risk factor for acute non-specific low back pain: A case-control study using the 24-Hour Schedule

    NARCIS (Netherlands)

    E.W.P. Bakker (Eric); A.P. Verhagen (Arianne); C. Lucas (Cees); H.J.C.M.F. Koning (Hans); R.J. de Haan (Rob); B.W. Koes (Bart)

    2007-01-01

    textabstractA case-control study was conducted to assess the daily loading of the spine as a risk factor for acute non-specific low back pain (acute LBP). Acute LBP is a benign, self-limiting disease, with a recovery rate of 80-90% within 6 weeks irrespective of the treatment type. Unfortunately, re

  16. Cholesterol and Your Child

    Science.gov (United States)

    ... Tropical Delight: Melon Smoothie Pregnant? Your Baby's Growth Cholesterol and Your Child KidsHealth > For Parents > Cholesterol and ... child's risk of developing heart disease later. About Cholesterol Cholesterol is a waxy substance produced by the ...

  17. Women and Cholesterol

    Science.gov (United States)

    ... Blood Pressure Tools & Resources Stroke More Women and Cholesterol Updated:Apr 1,2016 The female sex hormone ... Glossary Related Sites Nutrition Center My Life Check Cholesterol • Home • About Cholesterol • Why Cholesterol Matters • Understand Your ...

  18. HDL Cholesterol Test

    Science.gov (United States)

    ... limited. Home Visit Global Sites Search Help? HDL Cholesterol Share this page: Was this page helpful? Also ... HDL; HDL-C Formal name: High-density Lipoprotein Cholesterol Related tests: Cholesterol ; LDL Cholesterol ; Triglycerides ; Lipid Profile ; ...

  19. LDL Cholesterol Test

    Science.gov (United States)

    ... limited. Home Visit Global Sites Search Help? LDL Cholesterol Share this page: Was this page helpful? Also ... LDL; LDL-C Formal name: Low-Density Lipoprotein Cholesterol Related tests: Cholesterol ; HDL Cholesterol ; Triglycerides ; Lipid Profile ; ...

  20. Cholesterol IQ Quiz

    Science.gov (United States)

    ... Pressure High Blood Pressure Tools & Resources Stroke More Cholesterol IQ Quiz Updated:Feb 2,2015 Begin the quiz Cholesterol • Home • About Cholesterol Introduction Good vs. Bad Cholesterol ...

  1. Acute acetaminophen intoxication leads to hepatic iron loading by decreased hepcidin synthesis.

    Science.gov (United States)

    van Swelm, Rachel P L; Laarakkers, Coby M M; Blous, Linda; Peters, Janny G P; Blaney Davidson, Esmeralda N; van der Kraan, Peter M; Swinkels, Dorine W; Masereeuw, Rosalinde; Russel, Frans G M

    2012-09-01

    Acetaminophen (APAP), a major cause of acute liver injury in the Western world, is mediated by metabolism and oxidative stress. Recent studies have suggested a role for iron in potentiating APAP-induced liver injury although its regulatory mechanism is not completely understood. The current study was designed to unravel the iron-regulating pathways in mice after APAP-induced hepatotoxicity. Mice with severe injury showed a significant increase in liver iron concentration and oxidative stress. Concurrently, the plasma concentration of hepcidin, the key regulator in iron metabolism, and hepatic hepcidin antimicrobial peptide (Hamp) mRNA expression levels were significantly reduced. We showed that hepcidin transcription was inhibited via several hepcidin-regulating factors, including the bone morphogenetic protein/small mother against decapentaplegic (BMP/SMAD) pathway, CCAAT/enhancer-binding protein α (C/EBPα), and possibly also via erythropoietin (EPO). Downregulation of the BMP/SMAD signaling pathway was most likely caused by hypoxia-inducible factor 1α (HIF-1α), which was increased in mice with severe APAP-induced liver injury. HIF-1α stimulates cleaving of hemojuvelin, the cofactor of the BMP receptor, thereby blocking BMP-induced signaling. In addition, gene expression levels of C/ebpα were significantly reduced, and Epo mRNA expression levels were significantly increased after APAP intoxication. These factors are regulated through HIF-1α during oxidative stress and suggest that HIF-1α is a key modulator in reduced hepcidin transcription after APAP-induced hepatotoxicity. In conclusion, acute APAP-induced liver injury leads to activation of HIF-1α, which results in a downregulation in hepcidin expression through a BMP/SMAD signaling pathway and through C/EBPα inhibition. Eventually, this leads to hepatic iron loading associated with APAP cytotoxicity. PMID:22610607

  2. Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles

    Directory of Open Access Journals (Sweden)

    Xie Shuyu

    2011-11-01

    Full Text Available Abstract Background Our previous studies demonstrated that tilmicosin-loaded hydrogenated castor oil solid lipid nanoparticles (Til-HCO-SLN are a promising formulation for enhanced pharmacological activity and therapeutic efficacy in veterinary use. The purpose of this work was to evaluate the acute toxicity of Til-HCO-SLN. Methods Two nanoparticle doses were used for the study in ICR mice. The low dose (766 mg/kg.bw with tilmicosin 7.5 times of the clinic dosage and below the median lethal dose (LD50 was subcutaneously administered twice on the first and 7th day. The single high dose (5 g/kg.bw was the practical upper limit in an acute toxicity study and was administered subcutaneously on the first day. Blank HCO-SLN, native tilmicosin, and saline solution were included as controls. After medication, animals were monitored over 14 days, and then necropsied. Signs of toxicity were evaluated via mortality, symptoms of treatment effect, gross and microscopic pathology, and hematologic and biochemical parameters. Results After administration of native tilmicosin, all mice died within 2 h in the high dose group, in the low dose group 3 died after the first and 2 died after the second injections. The surviving mice in the tilmicosin low dose group showed hypoactivity, accelerated breath, gloomy spirit and lethargy. In contrast, all mice in Til-HCO-SLN and blank HCO-SLN groups survived at both low and high doses. The high nanoparticle dose induced transient clinical symptoms of treatment effect such as transient reversible action retardation, anorexy and gloomy spirit, increased spleen and liver coefficients and decreased heart coefficients, microscopic pathological changes of liver, spleen and heart, and minor changes in hematologic and biochemical parameters, but no adverse effects were observed in the nanoparticle low dose group. Conclusions The results revealed that the LD50 of Til-HCO-SLN and blank HCO-SLN exceeded 5 g/kg.bw and thus the

  3. Effect of saline loading on uranium-induced acute renal failure in rats

    Energy Technology Data Exchange (ETDEWEB)

    Hishida, A.; Yonemura, K.; Ohishi, K.; Yamada, M.; Honda, N.

    1988-05-01

    Studies were performed to examine the effect of saline loading on uranium-induced acute renal failure (ARF) in rats. Forty-eight hours after the i.v. injection of uranyl acetate (UA, 5 mg/kg), inulin clearance rate (Cin) decreased to approximately 43% of the control value in water drinking rats (P less than 0.005). Animals receiving continuous isotonic saline infusion following UA showed higher urine flow and Cin (60% of control, P less than 0.01), and lessened intratubular cast formation when compared with water-drinking ARF rats. A short-term saline infusion following UA did not attenuate the decline in Cin (43% of control). An inverse relationship was found between Cin and the number of casts (r = -0.75, P less than 0.01). Multiple regression analysis showed that standardized partial regression coefficient is statistically significant between Cin and cast formation (-0.69, P less than 0.05), but not between Cin and tubular necrosis (-0.07, P greater than 0.05). Renin depletion caused by DOCA plus saline drinking did not attenuate the decline in Cin in ARF (47% of control). No significant difference was found in urinary uranium excretion between water-drinking and saline-infused ARF rats. The findings suggest that continuous saline infusion following UA attenuates the decline in Cin in ARF rats; and that this beneficial effect of saline loading is associated with lessened cast formation rather than with suppressed renin-angiotensin activity or enhanced urinary-uranium excretion.

  4. Acute Toxicity Study of Zerumbone-Loaded Nanostructured Lipid Carrier on BALB/c Mice Model

    Directory of Open Access Journals (Sweden)

    Heshu Sulaiman Rahman

    2014-01-01

    Full Text Available Zerumbone- (ZER- loaded nanostructure lipid carrier (NLC (ZER-NLC prepared for its antileukemia effect in vitro was evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50 of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration.

  5. Load dependence of changes in forearm and peripheral vascular resistance after acute leg exercise in man.

    Science.gov (United States)

    Piepoli, M; Isea, J E; Pannarale, G; Adamopoulos, S; Sleight, P; Coats, A J

    1994-07-15

    1. It is known that acute exercise is often followed by a reduction in arterial blood pressure. Little is known about the time course of the recovery of the blood pressure or the influence of the intensity of the exercise on this response. Controversy exists, in particular, concerning the changes in peripheral resistance that occur during this period. 2. Eight normal volunteers performed, in random order on separate days, voluntary upright bicycle exercise of three different intensities (maximal, moderate and minimal load) and, on another day, a control period of sitting on a bicycle. They were monitored for 60 min after each test. 3. Diastolic pressure fell after maximal exercise at 5 min (-15.45 mmHg) and 60 min (-9.45 mmHg), compared with the control day. Systolic and mean pressure also fell (non-significantly) after 45 min; heart rate was significantly elevated for the whole hour of recovery (at 60 min, +7.23 beats min-1). No changes in post-exercise blood pressure and heart rate were observed on the days of moderate and minimal exercises. 4. An increase in cardiac index was observed after maximal exercise compared with control (at 60 min, 2.6 +/- 0.3 vs. 1.9 +/- 0.2 l min-1 m-2). This was entirely accounted for by the persistent increase in heart rate, with no significant alteration in stroke volume after exercise on any day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7965851

  6. Acute Inflammatory Response to Low-, Moderate-, and High-Load Resistance Exercise in Women With Breast Cancer-Related Lymphedema.

    Science.gov (United States)

    Cormie, Prue; Singh, Benjamin; Hayes, Sandi; Peake, Jonathan M; Galvão, Daniel A; Taaffe, Dennis R; Spry, Nigel; Nosaka, Kazunori; Cornish, Bruce; Schmitz, Kathryn H; Newton, Robert U

    2016-09-01

    Background Resistance exercise is emerging as a potential adjunct therapy to aid in the management of breast cancer-related lymphedema (BCRL). However, the mechanisms underlying the relationships between the acute and long-term benefits of resistance exercise on BCRL are not well understood. Purpose To examine the acute inflammatory response to upper-body resistance exercise in women with BCRL and to compare these effects between resistance exercises involving low, moderate, and high loads. The impact on lymphedema status and associated symptoms was also compared. Methods A total of 21 women, 62 ± 10 years old, with BCRL participated in the study. Participants completed low-load (15-20 repetition maximum [RM]), moderate-load (10-12 RM), and high-load (6-8 RM) exercise sessions consisting of 3 sets of 6 upper-body resistance exercises. Sessions were completed in a randomized order separated by a 7- to 10-day wash-out period. Venous blood samples were obtained to assess markers of exercise-induced muscle damage and inflammation. Lymphedema status was assessed using bioimpedance spectroscopy and arm circumferences, and associated symptoms were assessed using Visual Analogue Scales for pain, heaviness, and tightness. Measurements were conducted before and 24 hours after the exercise sessions. Results No significant changes in creatine kinase, C-reactive protein, interleukin-6, and tumor necrosis factor-α were observed following the 3 resistance exercise sessions. There were no significant changes in arm swelling or symptom severity scores across the 3 resistance exercise conditions. Conclusions The magnitude of acute exercise-induced inflammation following upper-body resistance exercise in women with BCRL does not vary between resistance exercise loads. PMID:26582633

  7. What Is Cholesterol?

    Science.gov (United States)

    ... How Can I Help a Friend Who Cuts? Cholesterol KidsHealth > For Teens > Cholesterol Print A A A ... High Cholesterol? en español ¿Qué es el colesterol? Cholesterol Is a Fat in the Blood Cholesterol (kuh- ...

  8. Ethanol Extract of Fructus Schisandrae Decreases Hepatic Triglyceride Level in Mice Fed with a High Fat/Cholesterol Diet, with Attention to Acute Toxicity

    OpenAIRE

    Si-Yuan Pan; Zhi-Ling Yu; Hang Dong; Chun-Jing Xiang; Wang-Fun Fong; Kam-Ming Ko

    2011-01-01

    Effects of the ethanol extract of Fructus Schisandrae (EtFSC) on serum and liver lipid contents were investigated in mice fed with high fat/cholesterol (HFC) diet for 8 or 15 days. The induction of hypercholesterolemia by HFC diet caused significant increases in serum and hepatic total cholesterol (TC) levels (up to 62% and 165%, resp.) and hepatic triglyceride (TG) levels (up to 528%) in mice. EtFSC treatment (1 or 5 g/kg/day for 7 days; from Day 1 to 7 or from Day 8 to 14, i.g.) significant...

  9. Effects of acute creatine loading with or without carbohydrate on repeated bouts of maximal swimming in high-performance swimmers.

    Science.gov (United States)

    Theodorou, Apostolos S; Havenetidis, Konstantinos; Zanker, Cathy L; O'Hara, John P; King, Roderick F G J; Hood, Colin; Paradisis, Giorgios; Cooke, Carlton B

    2005-05-01

    The addition of carbohydrate (CHO) to an acute creatine (Cr) loading regimen has been shown to increase muscle total creatine content significantly beyond that achieved through creatine loading alone. However, the potential ergogenic effects of combined Cr and CHO loading have not been assessed. The purpose of this study was to compare swimming performance, assessed as mean swimming velocity over repeated maximal intervals, in high-performance swimmers before and after an acute loading regimen of either creatine alone (Cr) or combined creatine and carbohydrate (Cr + CHO). Ten swimmers (mean +/- SD of age and body mass: 17.8 +/- 1.8 years and 72.3 +/- 6.8 kg, respectively) of international caliber were recruited and were randomized to 1 of 2 groups. Each swimmer ingested five 5 g doses of creatine for 4 days, with the Cr + CHO group also ingesting approximately 100 g of simple CHO 30 minutes after each dose of creatine. Performance was measured on 5 separate occasions: twice at "baseline" (prior to intervention, to assess the repeatability of the performance test), within 48 hours after intervention, and then 2 and 4 weeks later. All subjects swam faster after either dietary loading regimen (p < 0.01, both regimens); however, there was no difference in the extent of improvement of performance between groups. In addition, all swimmers continued to produce faster swim times for up to 4 weeks after intervention. Our findings suggest that no performance advantage was gained from the addition of carbohydrate to a creatine-loading regimen in these high-caliber swimmers.

  10. Acute hormonal and force responses to combined strength and endurance loadings in men and women: the "order effect".

    Directory of Open Access Journals (Sweden)

    Ritva S Taipale

    Full Text Available PURPOSE: To examine acute responses and recovery of serum hormones and muscle force following combined strength (S and endurance (E loading sessions in which the order of exercises is reversed (ES vs. SE. METHODS: This cross-over study design included recreationally endurance trained men and women (age 21-45 years, n = 12 men n = 10 women who performed both loadings. Maximal bilateral isometric strength (MVC, isometric rate of force development (RFD and serum concentrations of testosterone (T, cortisol (C, growth hormone (GH, insulin-like growth factor 1 (IGF-1, binding protein 3 (IGFBP3 and sex hormone binding globulin (SHBG were measured during and after both loadings. RESULTS: Both of the present combined (ES and SE loadings led to a greater acute decrease in MVC in men than in women, while RFD was slightly affected only in men. Recovery of MVC and RFD to baseline was complete at 24 h regardless of the order of exercises. In men, neuromuscular fatigue was accompanied by increased C concentrations observed post SE. This was followed by decreased concentrations of T at 24 h and 48 h that were significantly lower than those observed following ES. GH response in men also differed significantly post loadings. In women, only a significant difference in T between ES and SE loadings was observed at post. CONCLUSION: These observed differences in hormonal responses despite similarities in neuromuscular fatigue in men indicate the presence of an order effect as the body was not fully recovered at 48 h following SE. These findings may be applicable in training prescription in order to optimize specific training adaptations.

  11. Cholesterol and lifestyle

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000099.htm Cholesterol and lifestyle To use the sharing features on ... Stroke Serious heart or blood vessel disease Your Cholesterol Numbers All men should have their blood cholesterol ...

  12. Cholesterol testing and results

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000386.htm Cholesterol testing and results To use the sharing features ... can tell you what your goal should be. Cholesterol Tests Some cholesterol is considered good and some ...

  13. Cholesterol Facts and Statistics

    Science.gov (United States)

    ... Blood Pressure Salt Million Hearts® WISEWOMAN Program High Cholesterol Facts Recommend on Facebook Tweet Share Compartir As ... the facts about high cholesterol [PDF-281K] . High Cholesterol in the United States 73.5 million adults ( ...

  14. Influence factors of salt-sensitive hypertension and responses of blood pressure and urinary sodium and potassium excretion to acute oral saline loading among essential hypertensive patients

    Institute of Scientific and Technical Information of China (English)

    刘叶舟

    2014-01-01

    Objective To explore the influence factors of saltsensitive hypertension and to observe changes of blood pressures and urinary sodium and potassium excretion in response to acute oral saline loading among essential hypertensive patients in China.Methods Essential hypertensive patients from Beijing Jinzhan second community were included in this study.Salt-sensitivity was determined via the improved Sullivan’s acute oral saline loading

  15. Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease

    DEFF Research Database (Denmark)

    Poulsen, Sarah S.; Saber, Anne T.; Mortensen, Alicja;

    2015-01-01

    Adverse lung effects following pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) are well documented in rodents. However, systemic effects are less understood. Epidemiological studies have shown increased cardiovascular disease risk after pulmonary exposure to airborne particles, which...... hepatic effects. The two MWCNTs induced similar systemic responses despite their different physicochemical properties. APR proteins SAA3 and haptoglobin, plasma total cholesterol and low-density/very low-density lipoprotein were significantly increased following exposure to either MWCNTs. Plasma SAA3...

  16. The effect of acute magnesium loading on the maximal exercise performance of stable chronic obstructive pulmonary disease patients

    Directory of Open Access Journals (Sweden)

    Angélica Florípedes do Amaral

    2012-01-01

    Full Text Available OBJECTIVE: The potential influence of magnesium on exercise performance is a subject of increasing interest. Magnesium has been shown to have bronchodilatatory properties in asthma and chronic obstructive pulmonary disease patients. The aim of this study was to investigate the effects of acute magnesium IV loading on the aerobic exercise performance of stable chronic obstructive pulmonary disease patients. METHODS: Twenty male chronic obstructive pulmonary disease patients (66.2 + 8.3 years old, FEV1: 49.3+19.8% received an IV infusion of 2 g of either magnesium sulfate or saline on two randomly assigned occasions approximately two days apart. Spirometry was performed both before and 45 minutes after the infusions. A symptom-limited incremental maximal cardiopulmonary test was performed on a cycle ergometer at approximately 100 minutes after the end of the infusion. ClinicalTrials.gov: NCT00500864 RESULTS: Magnesium infusion was associated with significant reductions in the functional residual capacity (-0.41 l and residual volume (-0.47 l, the mean arterial blood pressure (-5.6 mmHg and the cardiac double product (734.8 mmHg.bpm at rest. Magnesium treatment led to significant increases in the maximal load reached (+8 w and the respiratory exchange ratio (0.06 at peak exercise. The subgroup of patients who showed increases in the work load equal to or greater than 5 w also exhibited significantly greater improvements in inspiratory capacity (0.29 l. CONCLUSIONS: The acute IV loading of magnesium promotes a reduction in static lung hyperinflation and improves the exercise performance in stable chronic obstructive pulmonary disease patients. Improvements in respiratory mechanics appear to be responsible for the latter finding.

  17. Reverse cholesterol transport revisited

    Institute of Scientific and Technical Information of China (English)

    Astrid; E; van; der; Velde

    2010-01-01

    Reverse cholesterol transport was originally described as the high-density lipoprotein-mediated cholesterol flux from the periphery via the hepatobiliary tract to the intestinal lumen, leading to fecal excretion. Since the introduction of reverse cholesterol transport in the 1970s, this pathway has been intensively investigated. In this topic highlight, the classical reverse cholesterol transport concepts are discussed and the subject reverse cholesterol transport is revisited.

  18. Acute acetaminophen intoxication leads to hepatic iron loading by decreased hepcidin synthesis.

    NARCIS (Netherlands)

    Swelm, R.P.L. van; Laarakkers, J.M.M.; Blous, L.; Peters, J.G.P.; Blaney Davidson, E.N.; Kraan, P.M. van der; Swinkels, D.W.; Masereeuw, R.; Russel, F.G.M.

    2012-01-01

    Acetaminophen (APAP), a major cause of acute liver injury in the Western world, is mediated by metabolism and oxidative stress. Recent studies have suggested a role for iron in potentiating APAP-induced liver injury although its regulatory mechanism is not completely understood. The current study wa

  19. Acute Effects of Loaded Half-Squat Jumps on Sprint Running Speed in Track and Field Athletes and Soccer Players.

    Science.gov (United States)

    Vanderka, Marián; Krčmár, Matúš; Longová, Katarína; Walker, Simon

    2016-06-01

    Vanderka, M, Krčmár, M, Longová, K, and Walker, S. Acute effects of loaded half-squat jumps on sprint running speed in track and field athletes and soccer players. J Strength Cond Res 30(6): 1540-1546, 2016-The purpose of the study was to determine the acute responses to a jump squat protocol designed to induce postactivation potentiation on sprint running performance in experienced track and field athletes and soccer players. Twenty-five regional level athletes (12 track and field: ∼17 years; ∼177 cm; ∼73 kg and 13 soccer: ∼18 years; ∼175 cm; ∼72 kg) performed 2 test sessions assessing 40-m sprint running performance in a balanced, crossover design. Dual-beam light timing gates measured 0-20 and 20-40 m sprint times before and after either 9 minutes of sitting (control) or 2 sets of 6 repetition half-squat jump with the load eliciting maximum power (experimental) conditions. Sprint performance was significantly enhanced over both 0-20 m (3.09 ± 0.07 to 3.04 ± 0.08 seconds; Δ ∼1.5%; p ≤ 0.05) and 20-40 m (2.42 ± 0.09 to 2.39 ± 0.09 seconds; Δ ∼1%; p ≤ 0.05) in track and field athletes only. Also, the magnitude of enhanced sprint performance was related to baseline 0-20 m sprint performance (r = 0.44; p = 0.028; n = 25). It seems that using loaded half-squat jumps to enhance sprint performance could be used in training of high-level young athletes.

  20. Acute Effects of Loaded Half-Squat Jumps on Sprint Running Speed in Track and Field Athletes and Soccer Players.

    Science.gov (United States)

    Vanderka, Marián; Krčmár, Matúš; Longová, Katarína; Walker, Simon

    2016-06-01

    Vanderka, M, Krčmár, M, Longová, K, and Walker, S. Acute effects of loaded half-squat jumps on sprint running speed in track and field athletes and soccer players. J Strength Cond Res 30(6): 1540-1546, 2016-The purpose of the study was to determine the acute responses to a jump squat protocol designed to induce postactivation potentiation on sprint running performance in experienced track and field athletes and soccer players. Twenty-five regional level athletes (12 track and field: ∼17 years; ∼177 cm; ∼73 kg and 13 soccer: ∼18 years; ∼175 cm; ∼72 kg) performed 2 test sessions assessing 40-m sprint running performance in a balanced, crossover design. Dual-beam light timing gates measured 0-20 and 20-40 m sprint times before and after either 9 minutes of sitting (control) or 2 sets of 6 repetition half-squat jump with the load eliciting maximum power (experimental) conditions. Sprint performance was significantly enhanced over both 0-20 m (3.09 ± 0.07 to 3.04 ± 0.08 seconds; Δ ∼1.5%; p ≤ 0.05) and 20-40 m (2.42 ± 0.09 to 2.39 ± 0.09 seconds; Δ ∼1%; p ≤ 0.05) in track and field athletes only. Also, the magnitude of enhanced sprint performance was related to baseline 0-20 m sprint performance (r = 0.44; p = 0.028; n = 25). It seems that using loaded half-squat jumps to enhance sprint performance could be used in training of high-level young athletes. PMID:26562707

  1. Loading of acute myeloid leukemia cells with poly(I:C) by electroporation

    NARCIS (Netherlands)

    Lion, E.; Winde, C.M. de; Tendeloo, V.F. Van; Smits, E.L.

    2014-01-01

    In this chapter, we describe the technique of electroporation as an efficient method to load primary leukemic cells with the double-stranded RNA (dsRNA) analogue, polyriboinosinic polyribocytidylic acid (poly(I:C)), and detail on the delicate freezing and thawing procedure of primary leukemic cells.

  2. Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease

    DEFF Research Database (Denmark)

    Poulsen, Sarah S.; Saber, Anne T.; Mortensen, Alicja;

    2015-01-01

    g/mouse of small, entangled (CNTsmall, 0.8 +/- 0.1 pm long) or large, thick MWCNTs (CNTLarge, 4 +/- 0.4 mu m long). Liver tissues and plasma were harvested 1,3 and 28 days post-exposure. In addition, global hepatic gene expression, hepatic cholesterol content and liver histology were used to assess...... levels correlated strongly with pulmonary Saa3 levels. Analysis of global gene expression revealed perturbation of the same biological processes and pathways in liver, including the HMG-CoA reductase pathway. Both MWCNTs induced similar histological hepatic changes, with a tendency towards greater...... response following CNTLarge exposure. Overall, we show that pulmonary exposure to two different MWCNTs induces similar systemic and hepatic responses, including changes in plasma APR, lipid composition, hepatic gene expression and liver morphology. The results link pulmonary exposure to MWCNTs with risk...

  3. Get Your Cholesterol Checked

    Science.gov (United States)

    ... You also get cholesterol by eating foods like egg yolks, fatty meats, and regular cheese. If you have too much cholesterol in your body, it can build up inside your blood vessels and make it hard for blood to ...

  4. Cholesterol - drug treatment

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000314.htm Cholesterol - drug treatment To use the sharing features on ... treatment; Hardening of the arteries - statin Statins for Cholesterol Statins reduce your risk of heart disease, stroke, ...

  5. Acute Consumption of Walnuts and Walnut Components Differentially Affect Postprandial Lipemia, Endothelial Function, Oxidative Stress, and Cholesterol Efflux in Humans with Mild Hypercholesterolemia.

    Science.gov (United States)

    Walnut consumption improves cardiovascular disease risk; however, to our knowledge, the contribution of individual walnut components has not been assessed. This study evaluated the acute consumption of whole walnuts (85 g), separated nut skins (5.6 g), de-fatted nutmeat (34 g), and nut oil (51 g) on...

  6. Common Misconceptions about Cholesterol

    Science.gov (United States)

    ... your doctor recommends. Learn more about eating a healthy diet. Thin people don't have to worry about high cholesterol. A person with any body type can have high cholesterol. Overweight people are more likely to have ... heart-healthy. Have your cholesterol checked regularly regardless of your ...

  7. Home-Use Tests - Cholesterol

    Science.gov (United States)

    ... Medical Procedures In Vitro Diagnostics Home Use Tests Cholesterol Share Tweet Linkedin Pin it More sharing options ... a home-use test kit to measure total cholesterol. What cholesterol is: Cholesterol is a fat (lipid) ...

  8. Complement lysis activity in autologous plasma is associated with lower viral loads during the acute phase of HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Michael Huber

    2006-11-01

    Full Text Available BACKGROUND: To explore the possibility that antibody-mediated complement lysis contributes to viremia control in HIV-1 infection, we measured the activity of patient plasma in mediating complement lysis of autologous primary virus. METHODS AND FINDINGS: Sera from two groups of patients-25 with acute HIV-1 infection and 31 with chronic infection-were used in this study. We developed a novel real-time PCR-based assay strategy that allows reliable and sensitive quantification of virus lysis by complement. Plasma derived at the time of virus isolation induced complement lysis of the autologous virus isolate in the majority of patients. Overall lysis activity against the autologous virus and the heterologous primary virus strain JR-FL was higher at chronic disease stages than during the acute phase. Most strikingly, we found that plasma virus load levels during the acute but not the chronic infection phase correlated inversely with the autologous complement lysis activity. Antibody reactivity to the envelope (Env proteins gp120 and gp41 were positively correlated with the lysis activity against JR-FL, indicating that anti-Env responses mediated complement lysis. Neutralization and complement lysis activity against autologous viruses were not associated, suggesting that complement lysis is predominantly caused by non-neutralizing antibodies. CONCLUSIONS: Collectively our data provide evidence that antibody-mediated complement virion lysis develops rapidly and is effective early in the course of infection; thus it should be considered a parameter that, in concert with other immune functions, steers viremia control in vivo.

  9. Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease

    OpenAIRE

    Poulsen, Sarah S.; Saber, Anne T.; Mortensen, Alicja; Szarek, Jozef; Wu, Dongmei; Williams, Andrew; Andersen, Ole; Nicklas R. Jacobsen; Yauk, Carole L.; Wallin, Hakan; Halappanavar, Sabina; Vogel, Ulla Birgitte

    2015-01-01

    Adverse lung effects following pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) are well documented in rodents. However, systemic effects are less understood. Epidemiological studies have shown increased cardiovascular disease risk after pulmonary exposure to airborne particles, which has led to concerns that inhalation exposure to MWCNTs might pose similar risks. We analyzed parameters related to cardiovascular disease, including plasma acute phase response (APR) proteins and pla...

  10. Statin-induced chronic cholesterol depletion inhibits Leishmania donovani infection: Relevance of optimum host membrane cholesterol.

    Science.gov (United States)

    Kumar, G Aditya; Roy, Saptarshi; Jafurulla, Md; Mandal, Chitra; Chattopadhyay, Amitabha

    2016-09-01

    Leishmania are obligate intracellular protozoan parasites that invade and survive within host macrophages leading to leishmaniasis, a major cause of mortality and morbidity worldwide, particularly among economically weaker sections in tropical and subtropical regions. Visceral leishmaniasis is a potent disease caused by Leishmania donovani. The detailed mechanism of internalization of Leishmania is poorly understood. A basic step in the entry of Leishmania involves interaction of the parasite with the host plasma membrane. In this work, we have explored the effect of chronic metabolic cholesterol depletion using lovastatin on the entry and survival of Leishmania donovani in host macrophages. We show here that chronic cholesterol depletion of host macrophages results in reduction in the attachment of Leishmania promastigotes, along with a concomitant reduction in the intracellular amastigote load. These results assume further relevance since chronic cholesterol depletion is believed to mimic physiological cholesterol modulation. Interestingly, the reduction in the ability of Leishmania to enter host macrophages could be reversed upon metabolic replenishment of cholesterol. Importantly, enrichment of host membrane cholesterol resulted in reduction in the entry and survival of Leishmania in host macrophages. As a control, the binding of Escherichia coli to host macrophages remained invariant under these conditions, thereby implying specificity of cholesterol requirement for effective leishmanial infection. To the best of our knowledge, these results constitute the first comprehensive demonstration that an optimum content of host membrane cholesterol is necessary for leishmanial infection. Our results assume relevance in the context of developing novel therapeutic strategies targeting cholesterol-mediated leishmanial infection. PMID:27319380

  11. Effect of a pre-freezing treatment with cholesterol-loaded cyclodextrins on boar sperm longevity, capacitation dynamics, ability to adhere to porcine oviductal epithelial cells in vitro and DNA fragmentation dynamics.

    Science.gov (United States)

    Tomás, C; Blanch, E; Fazeli, A; Mocé, E

    2013-01-01

    The aim of this work was to examine how a pre-freezing treatment with cholesterol-loaded cyclodextrins (CLC) affects boar sperm longevity, capacitation dynamics, ability to bind to a porcine telomerase-immortalised oviductal epithelial cell line (TERT-OPEC) in vitro and DNA integrity dynamics after freeze-thawing. Although the samples treated with CLC exhibited lower sperm quality than the control samples (P0.05) after long-term incubation (26h at 37 or 16°C). Additionally, the CLC-treated spermatozoa underwent similar capacitation and DNA fragmentation dynamics as the control spermatozoa (P>0.05). However, CLC-treated spermatozoa were better able to bind to TERT-OPEC in vitro (POPEC in vitro, which could have an effect on the establishment of the sperm reservoir in the ampullary--isthmic junction in vivo. Additionally, frozen-thawed spermatozoa can be stored at 16°C for at least 6h without a significant observable decline in sperm quality, which could be beneficial for the transport of thawed diluted doses of spermatozoa from the laboratory to the farm. PMID:23036662

  12. Relationship between changes in mRNAs of the genes encoding steroidogenic acute regulatory protein and P450 cholesterol side chain cleavage in head kidney and plasma levels of cortisol in response to different kinds of acute stress in the rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Geslin, Malika; Auperin, Benoit

    2004-01-01

    In this study, the expression of several genes involved in cortisol synthesis in head kidneys, the site of cortisol production, and in the rainbow trout (Oncorhynchus mykiss) was examined in response to two different acute stressors and an acute ACTH treatment. mRNAs levels of the "steroidogenic acute regulatory" (StAR) sterol transport protein, which transports cholesterol to the inner mitochondrial membrane as well as cytochrome P450 cholesterol side chain cleavage (P450(SCC)) were determined in head kidney (containing the interrenal tissue). In one experiment, we also quantified 3-beta-hydroxysteroid dehydrogenase (3B-HSD) and cytochrome P450(11beta) (11B-H) mRNAs. The presence of these four transcripts in the head kidney was confirmed by Northern blot analysis. For each stress condition, mRNA levels were quantified by quantitative or real-time RT-PCR. The results of these two methods were highly correlated. An acute stress induced by capture, short confinement (2min), and anesthesia (3min) resulted in significant elevation of plasma cortisol (30-fold higher than controls) and an increase in levels of StAR and P450(SCC) mRNAs 3h post-stress. When fish were submitted to an acute stress caused by 5min of chase with a net in a tank, plasma cortisol reached a peak within 1h, but after 3h, levels were only 5-fold higher in stressed trout than in controls and no variations in the expression of StAR, P450(SCC), 3B-HSD, and 11B-H were observed whatever the time post-stress. One hour after acute ACTH stimulation (5IU/kg), plasma cortisol level was 4-fold higher than in control trout and no changes in StAR and P450(SCC) mRNAs levels were detected. The data suggest that the high levels of cortisol after stress need an activation of genes involved in cortisol synthesis, but lower levels do not. Futhermore, under these three test conditions, we always found a strong positive correlation between mRNA levels of StAR and P450(SCC), in contrast to what has been described in

  13. Relationships between static foot alignment and dynamic plantar loads in runners with acute and chronic stages of plantar fasciitis: a cross-sectional study

    Science.gov (United States)

    Ribeiro, Ana P.; Sacco, Isabel C. N.; Dinato, Roberto C.; João, Silvia M. A.

    2016-01-01

    BACKGROUND: The risk factors for the development of plantar fasciitis (PF) have been associated with the medial longitudinal arch (MLA), rearfoot alignment and calcaneal overload. However, the relationships between the biomechanical variables have yet to be determined. OBJECTIVE: The goal of this study was to investigate the relationships between the MLA, rearfoot alignment, and dynamic plantar loads in runners with unilateral PF in acute and chronic phases. METHOD: Cross-sectional study which thirty-five runners with unilateral PF were evaluated: 20 in the acute phase (with pain) and 15 with previous chronic PF (without pain). The MLA index and rearfoot alignment were calculated using digital images. The contact area, maximum force, peak pressure, and force-time integral over three plantar areas were acquired with Pedar X insoles while running at 12 km/h, and the loading rates were calculated from the vertical forces. RESULTS: The multiple regression analyses indicated that both the force-time integral (R 2=0.15 for acute phase PF; R 2=0.17 for chronic PF) and maximum force (R 2=0.35 for chronic PF) over the forefoot were predicted by an elevated MLA index. The rearfoot valgus alignment predicted the maximum force over the rearfoot in both PF groups: acute (R 2=0.18) and chronic (R 2=0.45). The rearfoot valgus alignment also predicted higher loading rates in the PF groups: acute (R 2=0.19) and chronic (R 2=0.40). CONCLUSION: The MLA index and the rearfoot alignment were good predictors of plantar loads over the forefoot and rearfoot areas in runners with PF. However, rearfoot valgus was demonstrated to be an important clinical measure, since it was able to predict the maximum force and both loading rates over the rearfoot. PMID:26786073

  14. Relationships between static foot alignment and dynamic plantar loads in runners with acute and chronic stages of plantar fasciitis: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Ana P. Ribeiro

    2016-02-01

    Full Text Available BACKGROUND: The risk factors for the development of plantar fasciitis (PF have been associated with the medial longitudinal arch (MLA, rearfoot alignment and calcaneal overload. However, the relationships between the biomechanical variables have yet to be determined. OBJECTIVE: The goal of this study was to investigate the relationships between the MLA, rearfoot alignment, and dynamic plantar loads in runners with unilateral PF in acute and chronic phases. METHOD: Cross-sectional study which thirty-five runners with unilateral PF were evaluated: 20 in the acute phase (with pain and 15 with previous chronic PF (without pain. The MLA index and rearfoot alignment were calculated using digital images. The contact area, maximum force, peak pressure, and force-time integral over three plantar areas were acquired with Pedar X insoles while running at 12 km/h, and the loading rates were calculated from the vertical forces. RESULTS: The multiple regression analyses indicated that both the force-time integral (R2=0.15 for acute phase PF; R2=0.17 for chronic PF and maximum force (R2=0.35 for chronic PF over the forefoot were predicted by an elevated MLA index. The rearfoot valgus alignment predicted the maximum force over the rearfoot in both PF groups: acute (R2=0.18 and chronic (R2=0.45. The rearfoot valgus alignment also predicted higher loading rates in the PF groups: acute (R2=0.19 and chronic (R2=0.40. CONCLUSION: The MLA index and the rearfoot alignment were good predictors of plantar loads over the forefoot and rearfoot areas in runners with PF. However, rearfoot valgus was demonstrated to be an important clinical measure, since it was able to predict the maximum force and both loading rates over the rearfoot.

  15. SUPPRESSION OF ANGⅡ AFTER ACUTE SALINE LOAD ASSOCIATED WITH THE CHANGES OF PLASMA ANP AND SODIUM METABOLISM IN SALT-SENSITIVE HYPERTENSION PATIENTS

    Institute of Scientific and Technical Information of China (English)

    王永兴; 刘治全; 刘艳; 侯嵘; 叶涛

    2003-01-01

    Objective To observe the changes of plasma AngⅡ,ANP and their relationship with urine sodium excretion in salt sensitive hypertension. Methods The salt sensitivity was determined by acute saline loading test in 173 primary hypertensives of Stage Ⅰ or Stage Ⅱ. Plasma AngⅡand ANP was determined by radioimmunoassay. Results After acute salt load, AngⅡ was suppressed inadequately. The plasma ANP secretion was not increased. The urine sodiun excretion was delayed, Na+ in RBC was increased in salt sensitive subjects. The plasma ANP was decreased in the salt sensitive subjects without AngⅡ suppressed. The 24 hours urine sodium excretion was lower than those AngⅡ suppressed.Conclusion The changes of plasma RAS are not homogeneous after salt load. Those without the plasma AngⅡ suppressed have more severe sodium metabolism abnormalities and the endogenous ANP secretion is impaired in salt sensitive patients.

  16. The characteristics of high density lipoprotein cholesterol and the relationship between high density lipoprotein cholesterol and the severity of coronary artery lesions in young men with acute myocardial infarction%青年男性心肌梗死的高密度脂蛋白胆固醇特点及其与冠状动脉病变的关系

    Institute of Scientific and Technical Information of China (English)

    李昭; 陶英; 黄觊; 王茜; 张冬花; 吴翔宇

    2013-01-01

    .784)、高血压(OR =7.782)、早发冠心病家族史(OR =4.613)、LDL-C(OR=2.496)、吸烟(OR=2.241)、Hb(OR=1.042)及UA(OR=1.005)是心梗的独立危险因素(均P<0.05),HDL-C(OR=0.147,P<0.05)是心梗的保护性因素;在青年男性心梗人群中,LDL-C(OR=2.095)及高血压(OR=1.042)(均P<0.05)是冠脉多支病变的独立危险因素,HDL-C(OR=0.071,P<0.05)是冠脉多支病变的保护性因素.结论 高密度脂蛋白胆固醇是青年男性急性心梗和冠脉多支病变的保护性因素.%Objective To investigate the characteristics of high density lipoprotein cholesterol and the relationship between high density lipoprotein cholesterol and the severity of coronary artery lesions in young men with acute myocardial infarction (AMI).Methods We retrospectively studied 278 young men with acute myocardial infarction and compared with 208 non-CHD young men,137 old men with AMI.All patients were admitted to hospital from Jan 2009 to Dec 2011 and undergone coronary angiography,and the clinic and coronary angiographic features were assessed.According to the result of coronary angiography,the patients were divided into three groups:the single,double and triple vessel lesions.The relation between systolic body mass index (BMI),hemoglobin (Hb),serum uric acid (UA),total cholesterol (TC),triglyceride (TG),high density lipoprotein cholesterol (HDL-C),low density lipoprotein cholesterol (LDLC),smoking history,essential hypertension,type 2 diabetes mellitus,familial history of early coronary artery disease with acute myocardial infarction and severity of coronary artery disease are observed.And observe the characteristics of HDL-C in the obesity group and the smoking group in young men based on body mass index and smoking history.Results (1) In young men with AMI group,the HDL-C levels was significantly lower than those in non-CHD young men group ((1.00 ± 0.28) mmol/L vs (1.05 ± 0.23)mmol/L,P < 0.05).In young men with AMI group,the HDL-C levels was

  17. The acute effect of lower-body training on average power output measured by loaded half-squat jump exercise

    Directory of Open Access Journals (Sweden)

    Matúš Krčmár

    2015-09-01

    Full Text Available Background: High muscular power output is required in many athletic endeavors in order for success to be achieved. In the scientific community postactivation potentiation and its effect on performance are often discussed. There are many studies where the effect of resistance exercise on motor performance (such as vertical jump performance and running speed has been investigated but only a few of them studied power output. Objective: The purpose of this study was to determine the acute responses to a 2 set loaded half-squat jumps and 2 set loaded back half-squat protocols designed to induce the acute maximum average power output during loaded half-squat jumps. Methods: A randomized cross-over design was used. 11 participants of this study performed 3 trials in randomized order separated by at least 48 hours where maximum average power output was measured. The specific conditioning activities were comprised of 2 sets and 4 repetitions of half-squat jumps, 2 sets and 4 repetitions of back half-squat exercises and a control protocol without an intervention by specific a conditioning activity. Participants were strength trained athletes with different sport specializations (e.g. ice-hockey, volleyball. Mean age of the athletes was 22 ± 1.8 years, body mass 80 ± 7.1 kg and body height 185 ± 6.5 cm. Analysis of variance with repeated measures was used to determine differences between pre- and post-condition in each protocol, as well as between conditioning protocols, and also effect size was used to evaluate practical significance. Results: Maximum average power was significantly enhanced after application of the half-squat jump condition protocol (1496.2 ± 194.5 to 1552 ± 196.1 W, Δ ~ 3.72%, p < .001 and after application of the back half-squat protocol (1500.7 ± 193.2 to 1556 ± 191.2 W, Δ ~ 3.68%, p < .001 after 10 min of rest. Power output after control protocol was

  18. 急性冠脉综合征肥胖及非肥胖患者血清LDL-C/HDL-C比值与冠状动脉病变严重程度的相关性%Correlation between LDL cholesterol/HDL cholesterol ratio and severity of coronary disease in obese and non-obese patients with acute coronary syndrome

    Institute of Scientific and Technical Information of China (English)

    宋艳; 王亚萍; 索萌; 卢群; 田刚

    2013-01-01

    Objective To investigate the correlation between low-density lipoprotein cholesterol (LDL-C)/ high-density lipoprotein cholesterol (HDL-C) ratio and severity of coronary disease in obese and non-obese patients with acute coronary syndrome (ACS). Methods Totally 394 patients with ACS were divided into two groups: obesity with ACS [n = 78, BMI≥28 kg/m2 or WHR>0.9 (male) or >0.85 (female)] and non-obesity with ACS (n = 316). Another 101 healthy individuals served as controls. According to results of coronary angiography. Gensini scores were calculated to quantize the severity of coronary arterial stenosis, and blood lipid indices were determined. Gensini scores and blood lipid indices were compared between the first two groups, and linear correlation analysis was made of Gensini scores and blood lipid indices. Results LDL-C/HDL-C ratio was positively correlated with Gensini scores in obese patients with ACS. Gensini scores, total cholesterol (TC) and ApoB were significantly higher in high LDL-C/HDL-C value sub-group than in low LDL-C/HDL-C value sub-group (P0.05). Conclusion Gensini score in obese patients with ACS is significantly correlated with LDL-C/HDL-C ratio. LDL-C/HDL-C ratio may be a better index to estimate the severity of coronary lesion than LDL-C.%目的 探讨急性冠脉综合征(ACS)肥胖及非肥胖患者血清低密度脂蛋白胆固醇(LDL-C)/高密度脂蛋白胆固醇(HDL-C)比值与冠状动脉病变严重程度的相关性.方法 收集ACS患者394例,以BMI≥28.0 kg/m2,或WHR男性>0.9,女性>0.85为肥胖标准,分为ACS肥胖组(n=78)和ACS非肥胖组(n=316),体检健康者作为对照组(n=101).根据1984年美国心脏病协会规定的冠脉血管图像分段评价标准和Gensini积分系统对每支血管狭窄程度进行定量分析.比较ACS肥胖组和非肥胖组肥胖指标、血脂指标及Gensini积分水平变化,相关性分析肥胖组Gensini积分与各指标的相关性.结果 ACS肥胖患者LDL-C/HDL-C比值

  19. National Cholesterol Education Month

    Centers for Disease Control (CDC) Podcasts

    2009-09-01

    Do you know your cholesterol numbers? Your doctor can do a simple test to check your cholesterol levels and help you make choices that lower your risk for heart disease and stroke.  Created: 9/1/2009 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 9/9/2009.

  20. Bile acid sequestrants for cholesterol

    Science.gov (United States)

    ... ency/patientinstructions/000787.htm Bile acid sequestrants for cholesterol To use the sharing features on this page, ... are medicines that help lower your LDL (bad) cholesterol . Too much cholesterol in your blood can stick ...

  1. What Causes High Blood Cholesterol?

    Science.gov (United States)

    ... the NHLBI on Twitter. What Causes High Blood Cholesterol? Many factors can affect the cholesterol levels in your blood. You can control some ... but not others. Factors You Can Control Diet Cholesterol is found in foods that come from animal ...

  2. The Impairment of Macrophage-to-Feces Reverse Cholesterol Transport during Inflammation Does Not Depend on Serum Amyloid A

    Directory of Open Access Journals (Sweden)

    Maria C. de Beer

    2013-01-01

    Full Text Available Studies suggest that inflammation impairs reverse cholesterol transport (RCT. We investigated whether serum amyloid A (SAA contributes to this impairment using an established macrophage-to-feces RCT model. Wild-type (WT mice and mice deficient in SAA1.1 and SAA2.1 (SAAKO were injected intraperitoneally with 3H-cholesterol-labeled J774 macrophages 4 hr after administration of LPS or buffered saline. 3H-cholesterol in plasma 4 hr after macrophage injection was significantly reduced in both WT and SAAKO mice injected with LPS, but this was not associated with a reduced capacity of serum from LPS-injected mice to promote macrophage cholesterol efflux in vitro. Hepatic accumulation of 3H-cholesterol was unaltered in either WT or SAAKO mice by LPS treatment. Radioactivity present in bile and feces of LPS-injected WT mice 24 hr after macrophage injection was reduced by 36%   (P<0.05 and 80%   (P<0.001, respectively. In contrast, in SAAKO mice, LPS did not significantly reduce macrophage-derived 3H-cholesterol in bile, and fecal excretion was reduced by only 45%   (P<0.05. Injection of cholesterol-loaded allogeneic J774 cells, but not syngeneic bone-marrow-derived macrophages, transiently induced SAA in C57BL/6 mice. Our study confirms reports that acute inflammation impairs steps in the RCT pathway and establishes that SAA plays only a minor role in this impairment.

  3. Clinical Impact of Rapid Reduction of Low-Density Lipoprotein Cholesterol Level on Long-Term Outcome of Acute Myocardial Infarction in the Statin Era: Subanalysis of the ALPS-AMI Study.

    Directory of Open Access Journals (Sweden)

    Takashi Miura

    Full Text Available The optimal period to achieve target percent reduction of low-density lipoprotein cholesterol (LDL-C level for secondary prevention of acute myocardial infarction (AMI is not well established.The Assessment of Lipophilic vs. Hydrophilic Statin Therapy in AMI (ALPS-AMI study enrolled 508 patients (mean age, 66.0± 11.6 years; 80.6% male who were hospitalized for AMI and underwent percutaneous coronary intervention (PCI. Of these patients, 81 were excluded because of the absence of LDL-C measurements at 4 weeks after randomization. In the remaining 427 patients, the target LDL-C level reduction of ≥30% was achieved and not reached within 4 weeks after randomization in 204 cases (early reduction group and 223 cases (late reduction group. The groups were formed prospectively and analyzed with regard to the composite end point (major adverse cardiovascular event [MACE]: all-cause death, myocardial infarction, and stroke and clinical outcomes.MACE were significantly more frequent in the late reduction group compared to the early reduction group (9.4% vs. 3.4%, P = 0.013. The incidence of cardiac deaths was also significantly higher in the late reduction group (3.1% vs. 0.5%, P = 0.044. On age-adjusted Cox proportional hazards analysis in statin-naïve patients, percent reduction of LDL-C level during the initial 4 weeks (HR, 0.98; 95% CI: 0.97-0.99, P = 0.042 and baseline LDL-C level (HR, 0.98; 95% CI: 0.97-0.99, P = 0.033 predicted adverse events.Rapid reduction of LDL-C level is strongly associated with favorable outcome in patients with AMI.

  4. Lifestyle Changes and Cholesterol

    Science.gov (United States)

    ... Pressure High Blood Pressure Tools & Resources Stroke More Lifestyle Changes and Cholesterol Updated:Oct 26,2015 As ... disease and stroke, your doctor may suggest some lifestyle changes. Regardless of whether your plan includes drug ...

  5. Impact of acute vivax malaria on the immune system and viral load of HIV-positive subjects

    Institute of Scientific and Technical Information of China (English)

    陈小平; 肖斌权; 施文钧; 徐慧芳; 高凯; 饶纪礼; 张周斌

    2003-01-01

    Objective To explore the mechanisms of malariotherapy for human immunodeficiency virus (HIV)-infected patients and to identify which stage(s) of HIV infection is suitable for the treatment of malariotherapy.Methods Therapeutic acute vivax malaria was induced and terminated after 10 fever episodes in 12 HIV-1-infected subjects: Group 1 (G1) had 5 patients with CD4 T-cell counts500/μl at baseline, Group 2 (G2) had 5 patients with CD4 at 499-200/μl and Group 3 had 2 patients with CD4<200/μl (not included in statistical analysis). Enzyme-Linked-Immuno-Sorbent Assay (ELISA) was used to measure plasma levels of cytokines and soluble activation markers. Flow cytometry was used to measure levels of lymphocyte subsets and phenotypes and CD4 cell apoptosis. Bayer bDNA assay was used to test plasma levels of HIV-1 RNA (viral load). Samples were taken and tested twice before malaria (baselines), three times during malaria and seven times after termination of malaria (at day 10 and 1, 3, 6, 12, 18 and 24 months). Results Levels of plasma tumor necrosis factor-α (TNF-α), soluble TNF-α receptor-2 (sTNF-RII), neopterin (NPT) and soluble IL-2 receptor (sIL-2R) significantly increased during malaria and sharply reduced to baselines post malaria in all groups. Stronger responses of the aforementioned factors were seen in G2 than in G1 during malaria (P=0.081, 0.001, 0.013, 0.020). CD4 count and percentage; CD4/CD8 ratio and CD25+ and CD4+CD25+ percentages increased but HLA DR+ percentage decreased either during or post malaria in G2. Most G2 patients experienced sustained increase but most G1 patients underwent natural history decline of CD4 counts and percentages during 2-year follow-up. Percentage of apoptotic CD4 cells decreased post malaria in all groups. G3 patients had weaker immune responses, however, one advanced AIDS patient in this group experienced clinical improvement after malariotherapy. Most of the 12 patients experienced increase of HIV viral load during

  6. Cholesterol in unusual places

    Energy Technology Data Exchange (ETDEWEB)

    Kucerka, N; Nieh, M P; Marquardt, D; Harroun, T A; Wassail, S R; Katsaras, J, E-mail: John.Katsaras@nrc.gc.ca, E-mail: Norbert.Kucerka@nrc.gc.ca

    2010-11-01

    Cholesterol is an essential component of mammalian cells, and is required for building and maintaining cell membranes, regulating their fluidity, and possibly acting as an antioxidant. Cholesterol has also been implicated in cell signaling processes, where it has been suggested that it triggers the formation of lipid rafts in the plasma membrane. Aside from cholesterol's physiological roles, what is also becoming clear is its poor affinity for lipids with unsaturated fatty acids as opposed to saturated lipids, such as sphingomyelin with which it forms rafts. We previously reported the location of cholesterol in membranes with varying degrees of acyl chain unsaturation as determined by neutron diffraction studies (Harroun et al 2006 Biochemistry 45, 1227; Harroun et al 2008 Biochemistry 47, 7090). In bilayers composed of phosphatidylcholine (PC) molecules with a saturated acyl chain at the sn-1 position or a monounsaturated acyl chain at both sn-1 and sn-2 positions, cholesterol was found in its much-accepted 'upright' position. However, in dipolyunsaturated 1,2-diarachidonyl phosphatidylcholine (20:4-20:4PC) membranes the molecule was found sequestered in the center of the bilayers. In further experiments, mixing l-palmitoyl-2-oleoyl phosphatidylcholine (16:0-18:1 PC) with 20:4-20:4PC resulted in cholesterol reverting to its upright orientation at approximately 40 mol% 16:0-18:1 PC. Interestingly, the same effect was achieved with only 5 mol% 1,2-dimyristoyl phosphatidylchoile (14:0-14:0PC).

  7. Hubungan Kadar Low-Density Lipoprotein Cholesterol dengan Kejadian dan Keparahan Stroke Akut

    OpenAIRE

    Hasibuan, Azwita Effrina

    2016-01-01

    Introduction : The role of serum cholesterol as the stroke etiology is still uncertain. Studies that focused on the association between low-density lipoprotein cholesterol (LDLC) and acute stroke was still rare, with inconsistent results. The aim of this study is to evaluate the correlation between LDL-C level and the acute stroke occurance and severity. Methods : We conducted a cross-sectional study of 51-acute stroke patients in Adam Malik General Hospital, Medan. Subjects...

  8. Relationship between serum cholesterol and low dense lipoprotein receptor activity of patients with acute myelogenous leukemia%急性髓性白血病患者血清胆固醇水平变化 与低密度脂蛋白受体活性的关系研究

    Institute of Scientific and Technical Information of China (English)

    李蔚; 彭军; 张茂宏; 徐松德

    2001-01-01

    测定了52例初发未治急性髓性白血病(AML)患者血清胆固醇浓度及其外周血白血病细胞对125I-低密度脂蛋白(125I-LDL)的降解率,结果显示两者呈负相关,白细胞数及125I-LDL降解率较高者血清胆固醇浓度较低,化疗后,随着外周血白血病细胞消失,血清胆固醇及LDL胆固醇水平升高。据此推测AML患者的低胆固醇血症可能归因于白血病细胞的LDL受体活性增高,白血病细胞对LDL的高摄取及降解为利用LDL作为化疗药物的载体靶向治疗白血病提供了新思路。%The serum cholesterol concentration and the rates of degradationof 125 I-low density lipoprotein(125I-LDL)by isolated leukemic cells of 52 patients with acute myeloblastic leukemia at diagnosis were assayed.The results showed that the lowest serum cholesterol concentrations were found in the patients with very high rates of cellular degradation of 125 I-LDL.After chemotherapy,both LDL cholesterol and total serum cholesterol levels rosed concomitantly with the fall in white blood cell counts.This suggests that a high receptor-mediated uptake and degradation of LDL by the leukemic cells may be the cause of hypocholesterolaemia in acute myeloblastic leukemia.LDL-receptor activity in leukemic cells may provide a basis for therapeutic approaches.

  9. Low-density lipoprotein cholesterol of less than 70 mg/dL is associated with fewer cardiovascular events in acute coronary syndrome patients: a real-life cohort in Thailand

    Directory of Open Access Journals (Sweden)

    Chinwong D

    2015-04-01

    Full Text Available Dujrudee Chinwong,1,2 Jayanton Patumanond,3 Surarong Chinwong,1 Khanchai Siriwattana,4 Siriluck Gunaparn,5 John Joseph Hall,6 Arintaya Phrommintikul5 1Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand; 2Clinical Epidemiology Program, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 3Center of Excellence in Applied Epidemiology, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand; 4Division of Medicine, Nakornping Hospital, Chiang Mai, Thailand; 5Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 6Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, Faculty of Health, University of Newcastle, Callaghan, NSW, Australia Background: Elevated low-density lipoprotein cholesterol (LDL-C is associated with an increased risk of cardiovascular disease or mortality; however, the LDL-C goal for therapy in acute coronary syndrome (ACS patients is controversial and varies among guidelines. This study aimed to assess the effect of reaching an LDL-C goal of <70 mg/dL (<1.8 mmol/L on first composite cardiovascular outcomes in routine clinical practice in Thailand.Methods: A retrospective cohort study was conducted using medical charts and the electronic hospital database of patients diagnosed with ACS and treated with statins at a tertiary care hospital in Thailand between 2009 and 2012. After admission, patients were followed from the date of LDL-C goal assessment until the first event of composite cardiovascular outcomes (nonfatal ACS, nonfatal stroke, or all-cause death. Cox proportional hazard models adjusted for potential confounders were used.Results: Of 405 patients, mean age was 65 years (60% males. Twenty-seven percent of the patients attained an LDL-C goal of <70 mg/dL, 38% had LDL-C between 70 and 99 mg/dL, and 35% had LDL-C ≥100 mg/dL. Forty-six patients experienced a composite

  10. CHOLESTEROL AND CHOLESTEROL ESTER CONTENT OF BOVINE COLOSTRUM

    Science.gov (United States)

    Shope, Richard E.; Gowen, John W.

    1928-01-01

    The total amount of cholesterol found in colostrum and milk is comparatively low. The amount of cholesterol found in colostrum declines at an ever decreasing rate as milk secretion develops until at 48 hours the cholesterol is nearly the same as that found in milk 3 months or 7 months after parturition. The morning milk differs from the evening milk in that the cholesterol bound as ester is greater in amount. PMID:19869468

  11. Transintestinal cholesterol efflux

    NARCIS (Netherlands)

    van der Velde, Astrid E.; Brufau, Gemma; Groen, Albert K.

    2010-01-01

    Purpose of review Regulation of cholesterol homeostasis is a complex interplay of a multitude of metabolic pathways situated in different organs. The liver plays a central role and has received most attention of the research community. In this review, we discuss recent progress in the understanding

  12. Regulation of cholesterol homeostasis

    NARCIS (Netherlands)

    van der Wulp, Mariette Y. M.; Verkade, Henkjan J.; Groen, Albert K.

    2013-01-01

    Hypercholesterolemia is an important risk factor for cardiovascular disease. It is caused by a disturbed balance between cholesterol secretion into the blood versus uptake. The pathways involved are regulated via a complex interplay of enzymes, transport proteins, transcription factors and non-codin

  13. Cholesterol transport in model membranes

    Science.gov (United States)

    Garg, Sumit; Porcar, Lionel; Butler, Paul; Perez-Salas, Ursula

    2010-03-01

    Physiological processes distribute cholesterol unevenly within the cell. The levels of cholesterol are maintained by intracellular transport and a disruption in the cell's ability to keep these normal levels will lead to disease. Exchange rates of cholesterol are generally studied in model systems using labeled lipid vesicles. Initially donor vesicles have all the cholesterol and acceptor vesicles are devoid of it. They are mixed and after some time the vesicles are separated and cholesterol is traced in each vesicle. The studies performed up to date have significant scatter indicating that the methodologies are not consistent. The present work shows in-situ Time-Resolved SANS studies of cholesterol exchange rates in unsaturated PC lipid vesicles. Molecular dynamics simulations were done to investigate the energetic and kinetic behavior of cholesterol in this system. This synergistic approach will provide insight into our efforts to understand cholesterol traffic.

  14. What Your Cholesterol Levels Mean

    Science.gov (United States)

    ... Blood Pressure Tools & Resources Stroke More What Your Cholesterol Levels Mean Updated:Aug 9,2016 How’s your ... the Terms and Conditions and Privacy Policy Interactive Cholesterol Guide Find videos, trackers and more with our ...

  15. Acute Pancreatitis Associated with Pegylated Interferon and Ribavirin Treatment of Chronic Hepatitis C, Genotype 1b with High Viral Load

    Directory of Open Access Journals (Sweden)

    Kenji Ando

    2009-11-01

    Full Text Available Acute pancreatitis, an uncommon side effect of pegylated interferon α (PEG-IFN α and ribavirin (RBV combination therapy, has rarely been reported in the English language literature. Here, acute pancreatitis associated with PEG-IFN plus RBV treatment is described in three patients with chronic hepatitis C, genotype 1b with high serum hepatitis C virus RNA levels. The patients had been started on weekly subcutaneous injections of PEG-IFN α (60, 80, and 90 μg plus a daily oral dose of RBV (600 mg. The therapy was discontinued, however, because of the onset of acute pancreatitis (after 15 weeks, 48 weeks, and 3 weeks respectively. The drug-induced pancreatitis was diagnosed on the basis of elevated levels of amylase and lipase and the absence of other identifiable causes. High tumor necrosis factor-α was found in one patient and high interleukin-6 in the other two. The immune system stimulated by PEG-IFN and RBV combination therapy might have caused the acute pancreatitis. Further study is needed to clarify the mechanism of the onset of drug-induced pancreatitis by PEG-IFN and RBV combination therapy.

  16. Mitochondria, cholesterol and cancer cell metabolism.

    Science.gov (United States)

    Ribas, Vicent; García-Ruiz, Carmen; Fernández-Checa, José C

    2016-12-01

    Given the role of mitochondria in oxygen consumption, metabolism and cell death regulation, alterations in mitochondrial function or dysregulation of cell death pathways contribute to the genesis and progression of cancer. Cancer cells exhibit an array of metabolic transformations induced by mutations leading to gain-of-function of oncogenes and loss-of-function of tumor suppressor genes that include increased glucose consumption, reduced mitochondrial respiration, increased reactive oxygen species generation and cell death resistance, all of which ensure cancer progression. Cholesterol metabolism is disturbed in cancer cells and supports uncontrolled cell growth. In particular, the accumulation of cholesterol in mitochondria emerges as a molecular component that orchestrates some of these metabolic alterations in cancer cells by impairing mitochondrial function. As a consequence, mitochondrial cholesterol loading in cancer cells may contribute, in part, to the Warburg effect stimulating aerobic glycolysis to meet the energetic demand of proliferating cells, while protecting cancer cells against mitochondrial apoptosis due to changes in mitochondrial membrane dynamics. Further understanding the complexity in the metabolic alterations of cancer cells, mediated largely through alterations in mitochondrial function, may pave the way to identify more efficient strategies for cancer treatment involving the use of small molecules targeting mitochondria, cholesterol homeostasis/trafficking and specific metabolic pathways. PMID:27455839

  17. Reduction in total recurrent cardiovascular events in acute coronary syndrome patients with low-density lipoprotein cholesterol goal <70 mg/dL: a real-life cohort in a developing country

    Directory of Open Access Journals (Sweden)

    Chinwong S

    2016-03-01

    Full Text Available Surarong Chinwong,1 Jayanton Patumanond,2 Dujrudee Chinwong,1 John Joseph Hall,3 Arintaya Phrommintikul4 1Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand; 2Center of Excellence in Applied Epidemiology, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand; 3Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, Faculty of Health, University of Newcastle, Callaghan, NSW, Australia; 4Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Background: For investigations into cardiovascular disease, the first problematic event (ie, nonfatal acute coronary syndrome (ACS, nonfatal stroke, or all-cause mortality generally was considered as the primary end point; however, ACS patients often experience subsequent events, which are rarely considered. This study reports an investigation into whether achieving a low-density lipoprotein cholesterol (LDL-C goal of <70 mg/dL (1.8 mmol/L is associated with a reduction in total recurrent cardiovascular events in a cohort of ACS patients hospitalized in northern Thailand.Methods: The medical charts and the electronic hospital database of ACS patients treated with statins at a tertiary hospital in Thailand between 2009 and 2012 were reviewed. Patients were checked for their LDL-C goal attainment, and then were followed for subsequent events until the last follow-up date, or to December 31, 2012. The Wei–Lin–Weissfeld method was used for multiple time-to-events data to investigate the association between achieving an LDL-C goal of <70 mg/dL and total recurrent cardiovascular events.Results: Of 405 eligible patients, 110 patients attained an LDL-C goal of <70 mg/dL. During a median follow-up of 1.94 years, the majority of patients (88.6% had no subsequent cardiovascular events, while 46 patients experienced at least one recurrent cardiovascular event: 36 with one event, six

  18. Effects of dietary cholesterol on cholesterol and bile acid homeostasis in patients with cholesterol gallstones.

    OpenAIRE

    Kern, F

    1994-01-01

    We examined changes in cholesterol and bile acid metabolism produced by dietary cholesterol in gallstone subjects and matched controls. Healthy women were recruited and, after confirming the presence or absence of radiolucent gallstones, they were studied on regular diets and again on the same diet supplemented with five eggs daily for 15-18 d. Studies included plasma lipids, lipoproteins and apolipoproteins, dietary records, cholesterol absorption, cholesterol synthesis, plasma clearance of ...

  19. The production and characterization of drug-loaded liposomal and PLGA nanocarriers for targeted treatment of acute myeloid leukemia

    OpenAIRE

    Gundersen, Edvin Tang

    2016-01-01

    While some progress has been made lately in developing transplantation therapy against acute myeloid leukemia (AML), it remains a problematic and aggressive disease, associated with both poor survival, as well as treatments with high toxicity. The field of nanomedicine is however aiming to improve treatment therapies by using dedicated nanocarriers to deliver therapeutics. Such drug delivery systems may provide benefits like more targeted drug delivery, as wel...

  20. HDL: More Than Just Cholesterol

    Directory of Open Access Journals (Sweden)

    Anna Meilina

    2010-12-01

    Full Text Available BACKGROUND: Plasma concentration of high density lipoprotein cholesterol (HDL-C are strongly, consistenly, and independently inversely associated with risk of atheroschlerotic cardiovascular disease (CVD. However, the last decade has seen several observations that do not follow this simple script. CONTENT: A proteomic analysis of HDL has given us an intriguing glimpse into novel components of HDL. HDL isolated from normal humans contains several classes of proteins, including not only apolipoproteins, but also complement regulatory proteins, endopeptidase inhibitors, hemopexin, and acute phase response proteins. These observations raise the possibility of unsuspected roles for HDL. HDL delivery of complement proteins would implicate HDL in innate immunity. Serine proteinase inhibitors would enable HDL to modulate proteolysis of the vessel wall. HDL from patients with coronary artery disease was enriched in apoE, apoC-IV, apoA-IV, Paraoxonase (PON, and complement factor C3. Highlighted additional mechanisms through which HDL protects the vessel wall are: HDL improves vascular function, decreases vascular inflammation, detoxifies radicals, and limits thrombosis. SUMMARY: Both inter- and intra-organ desynchrony may be involved in the pathogenesis of cardiometabolic disease attributable to effects in brain and multiple metabolic tissues including heart, liver, fat, muscle, pancreas, and gut. Efforts to dissect the molecular mediators that coordinate circadian, metabolic, and cardiovascular systems may ultimately lead to both improved therapeutics and preventive interventions. KEYWORDS: HDL, Apo–A1, RCT, inflammation, HDL dysfunction, HDL proteome, HDL & Apo-A1 mimetics.

  1. Specificity of the Acute Tryptophan and Tyrosine Plus Phenylalanine Depletion and Loading Tests I. Review of Biochemical Aspects and Poor Specificity of Current Amino Acid Formulations

    Directory of Open Access Journals (Sweden)

    Abdulla A.-B. Badawy

    2010-06-01

    Full Text Available The acute tryptophan or tyrosine plus phenylalanine depletion and loading tests are powerful tools for studying the roles of serotonin, dopamine and noradrenaline in normal subjects and those with behavioural disorders. The current amino acid formulations for these tests, however, are associated with undesirable decreases in ratios of tryptophan or tyrosine plus phenylalanine to competing amino acids resulting in loss of specificity. This could confound biochemical and behavioural findings. Compositions of current formulations are reviewed, the biochemical principles underpinning the tests are revisited and examples of unintended changes in the above ratios and their impact on monoamine function and behaviour will be demonstrated from data in the literature. The presence of excessive amounts of the 3 branched-chain amino acids Leu, Ile and Val is responsible for these unintended decreases and the consequent loss of specificity. Strategies for enhancing the specificity of the different formulations are proposed.

  2. Importance of macrophage cholesterol content on the flux of cholesterol mass

    OpenAIRE

    Sankaranarayanan, Sandhya; de la Llera-Moya, Margarita; Drazul-Schrader, Denise; Asztalos, Bela F.; Weibel, Ginny L.; Rothblat, George H.

    2010-01-01

    Net flux of cholesterol represents the difference between efflux and influx and can result in net cell-cholesterol accumulation, net cell-cholesterol depletion, or no change in cellular cholesterol content. We measured radiolabeled cell-cholesterol efflux and cell-cholesterol mass using cholesterol-normal and -enriched J774 and elicited mouse peritoneal macrophage cells. Net cell-cholesterol effluxes were observed when cholesterol-enriched J774 cells were incubated with 3.5% apolipoprotein (a...

  3. Data on respiratory variables in critically ill patients with acute respiratory failure placed on proportional assist ventilation with load adjustable gain factors (PAV+).

    Science.gov (United States)

    Georgopoulos, Dimitris; Xirouchaki, Nectaria; Tzanakis, Nikolaos; Younes, Magdy

    2016-09-01

    The data show respiratory variables in 108 critically ill patients with acute respiratory failure placed on proportional assist ventilation with load adjustable gain factors (PAV+) after at least 36 h on passive mechanical ventilation. PAV+ was continued for 48 h until the patients met pre-defined criteria either for switching to controlled modes or for breathing without ventilator assistance. Data during passive mechanical ventilation and during PAV+ are reported. Data are acquired from the whole population, as well as from patients with and without acute respiratory distress syndrome. The reported variables are tidal volume, driving pressure (ΔP, the difference between static end-inspiratory plateau pressure and positive end-expiratory airway pressure), respiratory system compliance and resistance, and arterial blood gasses. The data are supplemental to our original research article, which described individual ΔP in these patients and examined how it related to ΔP when the same patients were ventilated with passive mechanical ventilation using the currently accepted lung-protective strategy "Driving pressure during assisted mechanical ventilation. Is it controlled by patient brain?" [1]. PMID:27358909

  4. Data on respiratory variables in critically ill patients with acute respiratory failure placed on proportional assist ventilation with load adjustable gain factors (PAV+

    Directory of Open Access Journals (Sweden)

    Dimitris Georgopoulos

    2016-09-01

    Full Text Available The data show respiratory variables in 108 critically ill patients with acute respiratory failure placed on proportional assist ventilation with load adjustable gain factors (PAV+ after at least 36 h on passive mechanical ventilation. PAV+ was continued for 48 h until the patients met pre-defined criteria either for switching to controlled modes or for breathing without ventilator assistance. Data during passive mechanical ventilation and during PAV+ are reported. Data are acquired from the whole population, as well as from patients with and without acute respiratory distress syndrome. The reported variables are tidal volume, driving pressure (ΔP, the difference between static end-inspiratory plateau pressure and positive end-expiratory airway pressure, respiratory system compliance and resistance, and arterial blood gasses. The data are supplemental to our original research article, which described individual ΔP in these patients and examined how it related to ΔP when the same patients were ventilated with passive mechanical ventilation using the currently accepted lung-protective strategy “Driving pressure during assisted mechanical ventilation. Is it controlled by patient brain?” [1].

  5. Data on respiratory variables in critically ill patients with acute respiratory failure placed on proportional assist ventilation with load adjustable gain factors (PAV+).

    Science.gov (United States)

    Georgopoulos, Dimitris; Xirouchaki, Nectaria; Tzanakis, Nikolaos; Younes, Magdy

    2016-09-01

    The data show respiratory variables in 108 critically ill patients with acute respiratory failure placed on proportional assist ventilation with load adjustable gain factors (PAV+) after at least 36 h on passive mechanical ventilation. PAV+ was continued for 48 h until the patients met pre-defined criteria either for switching to controlled modes or for breathing without ventilator assistance. Data during passive mechanical ventilation and during PAV+ are reported. Data are acquired from the whole population, as well as from patients with and without acute respiratory distress syndrome. The reported variables are tidal volume, driving pressure (ΔP, the difference between static end-inspiratory plateau pressure and positive end-expiratory airway pressure), respiratory system compliance and resistance, and arterial blood gasses. The data are supplemental to our original research article, which described individual ΔP in these patients and examined how it related to ΔP when the same patients were ventilated with passive mechanical ventilation using the currently accepted lung-protective strategy "Driving pressure during assisted mechanical ventilation. Is it controlled by patient brain?" [1].

  6. Effects of acute and chronic attenuation of postprandial hyperglycemia on postglucose-load endothelial function in insulin resistant individuals: is stimulation of first phase insulin secretion beneficial for the endothelial function?

    DEFF Research Database (Denmark)

    Major-Pedersen, A; Ihlemann, N; Hermann, T S;

    2008-01-01

    The aim of the study is to determine if attenuation of postprandial hyperglycemia, by acutely and chronically enhancing postprandial insulin secretion in insulin-resistant individuals, improves the endothelial dysfunction. We assessed postoral glucose-load endothelial function in 56 insulin....... We found no relationship between postprandial hyperglycemia and post-OGL FMD....

  7. Food combinations for cholesterol lowering.

    Science.gov (United States)

    Harland, Janice I

    2012-12-01

    Reducing elevated LDL-cholesterol is a key public health challenge. There is substantial evidence from randomised controlled trials (RCT) that a number of foods and food components can significantly reduce LDL-cholesterol. Data from RCT have been reviewed to determine whether effects are additive when two or more of these components are consumed together. Typically components, such as plant stanols and sterols, soya protein, β-glucans and tree nuts, when consumed individually at their target rate, reduce LDL-cholesterol by 3-9 %. Improved dietary fat quality, achieved by replacing SFA with unsaturated fat, reduces LDL-cholesterol and can increase HDL-cholesterol, further improving blood lipid profile. It appears that the effect of combining these interventions is largely additive; however, compliance with multiple changes may reduce over time. Food combinations used in ten 'portfolio diet' studies have been reviewed. In clinical efficacy studies of about 1 month where all foods were provided, LDL-cholesterol is reduced by 22-30 %, whereas in community-based studies of >6 months' duration, where dietary advice is the basis of the intervention, reduction in LDL-cholesterol is about 15 %. Inclusion of MUFA into 'portfolio diets' increases HDL-cholesterol, in addition to LDL-cholesterol effects. Compliance with some of these dietary changes can be achieved more easily compared with others. By careful food component selection, appropriate to the individual, the effect of including only two components in the diet with good compliance could be a sustainable 10 % reduction in LDL-cholesterol; this is sufficient to make a substantial impact on cholesterol management and reduce the need for pharmaceutical intervention.

  8. Reducing Cholesterol Intake: Are the recommendations valid?

    OpenAIRE

    Chan, Joanna K.; McDonald, Bruce E.

    1991-01-01

    The authors question dietary recommendations for the general public calling for reduced cholesterol intake. Metabolic studies have shown that dietary cholesterol normally induces only small increases in blood cholesterol level. There is evidence that only a portion of the population responds to a change in cholesterol intake; hence lowering dietary cholesterol will be effective for only some.

  9. Epigenetic Regulation of Cholesterol Homeostasis

    Directory of Open Access Journals (Sweden)

    Steve eMeaney

    2014-09-01

    Full Text Available Although best known as a risk factor for cardiovascular disease, cholesterol is a vital component of all mammalian cells. In addition to key structural roles, cholesterol is a vital biochemical precursor for numerous biologically important compounds including oxysterols and bile acids, as well as acting as an activator of critical morphogenic systems (e.g. the Hedgehog system. A variety of sophisticated regulatory mechanisms interact to coordinate the overall level of cholesterol in cells, tissues and the entire organism. Accumulating evidence indicates that in additional to the more ‘traditional’ regulatory schemes, cholesterol homeostasis is also under the control of epigenetic mechanisms such as histone acetylation and DNA methylation. The available evidence supporting a role for these mechanisms in the control of cholesterol synthesis, elimination, transport and storage are the focus of this review.

  10. Inhibition of pancreatic cholesterol esterase reduces cholesterol absorption in the hamster

    OpenAIRE

    Heidrich, John E.; Contos, Linda M; Hunsaker, Lucy A; Deck, Lorraine M.; Vander Jagt, David L.

    2004-01-01

    Background Pancreatic cholesterol esterase has three proposed functions in the intestine: 1) to control the bioavailability of cholesterol from dietary cholesterol esters; 2) to contribute to incorporation of cholesterol into mixed micelles; and 3) to aid in transport of free cholesterol to the enterocyte. Inhibitors of cholesterol esterase are anticipated to limit the absorption of dietary cholesterol. Results The selective and potent cholesterol esterase inhibitor 6-chloro-3-(1-ethyl-2-cycl...

  11. Bacterial load of pneumococcal serotypes correlates with their prevalence and multiple serotypes is associated with acute respiratory infections among children less than 5 years of age.

    Directory of Open Access Journals (Sweden)

    Bhim Gopal Dhoubhadel

    Full Text Available BACKGROUND: Among pneumococcal serotypes, some serotypes are more prevalent in the nasopharynx than others; determining factors for higher prevalence remain to be fully explored. As non-vaccine serotypes have emerged after the introduction of 7-valent conjugate vaccines, study of serotype specific epidemiology is in need. When two or more serotypes co-colonize, they evolve rapidly to defend host's immune responses; however, a clear association of co-colonization with a clinical outcome is lacking. METHODS: Children less than 5 years old who were admitted to hospital due to acute respiratory infections (ARI (n = 595 and healthy children (n = 350 were recruited. Carriage of pneumococcus was determined by culture and lytA PCR in the nasopharyngeal samples. Serotype/serogroup detection and its quantification were done by the nanofluidic real time PCR system. Spearman's correlation and logistic regression were used to examine a correlation of serotype/serogroup specific bacterial load with its prevalence and an association of co-colonization with ARI respectively. RESULTS: Serotype/serogroup specific bacterial load was correlated with its prevalence, both in ARI cases (Spearman's rho = 0.44, n = 186; P<0.0001 and healthy children (Spearman's rho = 0.41, n = 115; P<0.0001. The prevalence of multiple serotypes was more common in ARI cases than in healthy children (18.5% vs 7.1%; aOR 2.92, 95% CI: 1.27-6.71; P = 0.01. The dominant serotype in the co-colonization had a 2 log10 higher bacterial load than the subdominant serotype, both in ARI cases (P<0.001 and healthy children (P<0.05. CONCLUSIONS: High bacterial load in the nasopharynx may help transmit pneumococci among hosts, and increase the chance of successful acquisition and colonization. Co-colonization of multiple serotypes of pneumococci is linked with ARI, which infers the interactions of multiple serotypes may increase their pathogenicity; however, they may compete

  12. Understand Your Risk for High Cholesterol

    Science.gov (United States)

    ... Resources Stroke More Understand Your Risk for High Cholesterol Updated:Apr 1,2016 LDL (bad) cholesterol is ... content was last reviewed on 04/21/2014. Cholesterol Guidelines: Putting the pieces together Myth vs. Truth – ...

  13. Overview of Cholesterol and Lipid Disorders

    Science.gov (United States)

    ... Medical Dictionary Additional Content Medical News Overview of Cholesterol and Lipid Disorders By Anne Carol Goldberg, MD ... Version. DOCTORS: Click here for the Professional Version Cholesterol Disorders Overview of Cholesterol and Lipid Disorders Dyslipidemia ...

  14. Cholesterol - what to ask your doctor

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000211.htm Cholesterol - what to ask your doctor To use the ... this page, please enable JavaScript. Your body needs cholesterol to work properly. When you have extra cholesterol ...

  15. [Structure of allostatic load in railway workers].

    Science.gov (United States)

    Gorokhova, S G; Pfaf, V F; Muraseyeva, E V; Akhsanova, E R; Prigorovskaya, T S; At'kov, O Yu

    2016-01-01

    The authors studied allostatic load in railway workers, as an indicator of stress effect. Analysis covered biomarkers that form allostatic load index, and their ratio for variable allostatic load index levels. Moderate allostatic load appeared to prevail in the examinees group. Findings are that systolic and diastolic blood pressure, general cholesterol and hemoglobin make major contribution into allostatic load index. Comparison covered models of allostatic load index calculation for variable biomarkers sets.

  16. Characterization of placental cholesterol transport

    DEFF Research Database (Denmark)

    Lindegaard, Marie L; Wassif, Christopher A; Vaisman, Boris;

    2008-01-01

    circulation might attenuate congenital malformations. The cholesterol transporters Abca1, Abcg1, and Sr-b1 are present in placenta; however, their potential role in placental transport remains undetermined. In mice, expression analyses showed that Abca1 and Abcg1 transcripts increased 2-3-fold between...... embryonic days 13.5 and 18.5 in placental tissue; whereas, Sr-b1 expression decreased. To examine the functional role of Abca1, Abcg1 and Sr-b1 we measured the maternal-fetal transfer of (14)C-cholesterol in corresponding mutant embryos. Disruption of either Abca1 or Sr-b1 decreased cholesterol transfer...

  17. Increased cardiovascular reactivity to acute stress and salt-loading in adult male offspring of fat fed non-obese rats.

    Science.gov (United States)

    Rudyk, Olena; Makra, Péter; Jansen, Eugene; Shattock, Michael J; Poston, Lucilla; Taylor, Paul D

    2011-01-01

    Diet-induced obesity in rat pregnancy has been shown previously to be associated with consistently raised blood pressure in the offspring, attributed to sympathetic over-activation, but the relative contributions to this phenotype of maternal obesity versus raised dietary fat is unknown. Sprague-Dawley female rats were fed either a control (4.3% fat, n = 11) or lard-enriched (23.6% fat, n = 16) chow 10 days prior to mating, throughout pregnancy and lactation. In conscious adult (9-month-old) offspring cardiovascular parameters were measured (radiotelemetry). The short period of fat-feeding did not increase maternal weight versus controls and the baseline blood pressure was similar in offspring of fat fed dams (OF) and controls (OC). However, adult male OF showed heightened cardiovascular reactivity to acute restraint stress (pprolonged recovery time compared to male OC. α1/β-adrenergic receptor blockade normalised the response. Also, after dietary salt-loading (8%-NaCl ad libitum for 1 week) male OF demonstrated higher SBP (pobesity in pregnant rats leads to altered sympathetic control of cardiovascular function in adult male offspring, and hypertension in response to stressor stimuli.

  18. Efficacy and safety of single-bolus tenecteplase compared with front-loaded alteplase in Chinese patients with acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Background and Objective Previous study showed tenecteplase and alteplaxe were equovalent for 30-day mortality in the treatment of acute myocardial infarction. The purpose of this open-label, randomized, multi-center, angiographic trial was to assess the efficacy and safety of tenecteplase compared with alteplase in Chinese patients with acute myocardial infarction. Methods We recruited patients with acute ST-elevation myocardial infarction presenting within 6 hours of symptom onset from October, 2002 to March,2004, in 5 hospitals in Beijing. After giving informed consent, patients were randomly assigned a single-bolus injection of tenecteplase (30-50 mg according to body weight) or front loaded alteplase (100 mg), and underwent coronary angiography at 90 min after starting the study drug. All patients received aspirin and heparin (target activated partial thromboplastin time 50-70 s). The primary efficacy end point was the rate of TIMI grade 3 flow at 90 minutes. Other efficacy end points included TIMI grade 2/3 flow at 90 minutes. Safety end points included all stroke, intracranial hemorrhage (ICH), moderate/severe hemorrhage (except for ICH), all-cause mortality at 30-days, and major non-fatal cardiac events at 30 days. Results Overall 110 patients were eligible for statistical analysis, with 58 patients assigned to receive tenecteplase and 52 patients to alteplase. Tenecteplase produced a rate of TIMI grade 3 flow at 90 minutes after the start of thrombolysis(68.4%) similar to that of alteplase (66.7%, P=1.0); the rates of TIMI grade 2 or 3 were similar for patients treated with tenecteplase versus alteplase (89.5% versus 80.4%, respectively, P=0.278). At 30 days, rates for all strokes were similar for the two groups (5.17% for tenecteplase and 1.92% for alteplase, P=0.62); rates of ICH were 3.45% and 1.92% (tenecteplase and rt-PA,P=1.00) respectively. The rate of moderate/severe hemorrhage was 8.62% with tenecteplase and 5.77% with alteplase (P=0.72); total

  19. Clinically used selective estrogen receptor modulators affect different steps of macrophage-specific reverse cholesterol transport.

    Science.gov (United States)

    Fernández-Suárez, María E; Escolà-Gil, Joan C; Pastor, Oscar; Dávalos, Alberto; Blanco-Vaca, Francisco; Lasunción, Miguel A; Martínez-Botas, Javier; Gómez-Coronado, Diego

    2016-01-01

    Selective estrogen receptor modulators (SERMs) are widely prescribed drugs that alter cellular and whole-body cholesterol homeostasis. Here we evaluate the effect of SERMs on the macrophage-specific reverse cholesterol transport (M-RCT) pathway, which is mediated by HDL. Treatment of human and mouse macrophages with tamoxifen, raloxifene or toremifene induced the accumulation of cytoplasmic vesicles of acetyl-LDL-derived free cholesterol. The SERMs impaired cholesterol efflux to apolipoprotein A-I and HDL, and lowered ABCA1 and ABCG1 expression. These effects were not altered by the antiestrogen ICI 182,780 nor were they reproduced by 17β-estradiol. The treatment of mice with tamoxifen or raloxifene accelerated HDL-cholesteryl ester catabolism, thereby reducing HDL-cholesterol concentrations in serum. When [(3)H]cholesterol-loaded macrophages were injected into mice intraperitoneally, tamoxifen, but not raloxifene, decreased the [(3)H]cholesterol levels in serum, liver and feces. Both SERMs downregulated liver ABCG5 and ABCG8 protein expression, but tamoxifen reduced the capacity of HDL and plasma to promote macrophage cholesterol efflux to a greater extent than raloxifene. We conclude that SERMs interfere with intracellular cholesterol trafficking and efflux from macrophages. Tamoxifen, but not raloxifene, impair M-RCT in vivo. This effect is primarily attributable to the tamoxifen-mediated reduction of the capacity of HDL to promote cholesterol mobilization from macrophages. PMID:27601313

  20. Successful topical dissolution of cholesterol gallbladder stones using ethyl propionate.

    Science.gov (United States)

    Hofmann, A F; Amelsberg, A; Esch, O; Schteingart, C D; Lyche, K; Jinich, H; Vansonnenberg, E; D'Agostino, H B

    1997-06-01

    Topical dissolution of cholesterol gallbladder stones using methyl tert-butyl ether (MTBE) is useful in symptomatic patients judged too ill for surgery. Previous studies showed that ethyl propionate (EP), a C5 ester, dissolves cholesterol gallstones rapidly in vitro, but differs from MTBE in being eliminated so rapidly by the liver that blood levels remain undetectable. Our aim was to test EP as a topical dissolution agent for cholesterol gallbladder stones. Five high-risk patients underwent topical dissolution of gallbladder stones by EP. In three patients, the solvent was instilled via a cholecystostomy tube placed previously to treat acute cholecystitis; in two patients, a percutaneous transhepatic catheter was placed in the gallbladder electively. Gallstone dissolution was assessed by chromatography, by gravimetry, and by catheter cholecystography. Total dissolution of gallstones was obtained in four patients after 6-10 hr of lavage; in the fifth patient, partial gallstone dissolution facilitated basketing of the stones. In two patients, cholesterol dissolution was measured and averaged 30 mg/min. Side effects were limited to one episode of transient hypotension and pain at the infusion site; no patient developed somnolence or nausea. Gallstone elimination was associated with relief of symptoms. EP is an acceptable alternative to MTBE for topical dissolution of cholesterol gallbladder stones in high-risk patients. The lower volatility and rapid hepatic extraction of EP suggest that it may be preferable to MTBE in this investigational procedure.

  1. Imaging appearances of cholesterol pneumonia

    International Nuclear Information System (INIS)

    Objection: To analyze the imaging appearances of cholesterol pneumonia. Methods We retrospectively analyzed the X-ray and CT findings of 3 patients with cholesterol pneumonia confirmed pathologically and reviewed correlative literature. Results: Lesions similar to mass were found in X-ray and CT imaging of three cases. Two of them appeared cavity with fluid-level and one showed multiple ring enhancement after CT contrast. The course of disease was very. long and it had no respond to antibiotic therapy. Amounts of foam cells rich in cholesterol crystal were detected in pathological examination. Conclusions: Cholesterol pneumonia is a rare chronic pulmonary idiopathic disease, and the radiological findings can do some help to its diagnosis. (authors)

  2. Cholesterol testing on a smartphone.

    Science.gov (United States)

    Oncescu, Vlad; Mancuso, Matthew; Erickson, David

    2014-02-21

    Home self-diagnostic tools for blood cholesterol monitoring have been around for over a decade but their widespread adoption has been limited by the relatively high cost of acquiring a quantitative test-strip reader, complicated procedure for operating the device, and inability to easily store and process results. To address this we have developed a smartphone accessory and software application that allows for the quantification of cholesterol levels in blood. Through a series of human trials we demonstrate that the system can accurately quantify total cholesterol levels in blood within 60 s by imaging standard test strips. In addition, we demonstrate how our accessory is optimized to improve measurement sensitivity and reproducibility across different individual smartphones. With the widespread adoption of smartphones and increasingly sophisticated image processing technology, accessories such as the one presented here will allow cholesterol monitoring to become more accurate and widespread, greatly improving preventive care for cardiovascular disease.

  3. Cholesterol's location in lipid bilayers.

    Science.gov (United States)

    Marquardt, Drew; Kučerka, Norbert; Wassall, Stephen R; Harroun, Thad A; Katsaras, John

    2016-09-01

    It is well known that cholesterol modifies the physical properties of lipid bilayers. For example, the much studied liquid-ordered Lo phase contains rapidly diffusing lipids with their acyl chains in the all trans configuration, similar to gel phase bilayers. Moreover, the Lo phase is commonly associated with cholesterol-enriched lipid rafts, which are thought to serve as platforms for signaling proteins in the plasma membrane. Cholesterol's location in lipid bilayers has been studied extensively, and it has been shown - at least in some bilayers - to align differently from its canonical upright orientation, where its hydroxyl group is in the vicinity of the lipid-water interface. In this article we review recent works describing cholesterol's location in different model membrane systems with emphasis on results obtained from scattering, spectroscopic and molecular dynamics studies. PMID:27056099

  4. Formation of cholesterol bilayer domains precedes formation of cholesterol crystals in cholesterol/dimyristoylphosphatidylcholine membranes: EPR and DSC studies.

    Science.gov (United States)

    Mainali, Laxman; Raguz, Marija; Subczynski, Witold K

    2013-08-01

    Saturation-recovery EPR along with DSC were used to determine the cholesterol content at which pure cholesterol bilayer domains (CBDs) and cholesterol crystals begin to form in dimyristoylphosphatidylcholine (DMPC) membranes. To preserve compositional homogeneity throughout the membrane suspension, lipid multilamellar dispersions were prepared using a rapid solvent exchange method. The cholesterol content increased from 0 to 75 mol %. With spin-labeled cholesterol analogues, it was shown that the CBDs begin to form at ~50 mol % cholesterol. It was confirmed by DSC that the cholesterol solubility threshold for DMPC membranes is detected at ~66 mol % cholesterol. At levels above this cholesterol content, monohydrate cholesterol crystals start to form. The major finding is that the formation of CBDs precedes formation of cholesterol crystals. The region of the phase diagram for cholesterol contents between 50 and 66 mol % is described as a structured one-phase region in which CBDs have to be supported by the surrounding DMPC bilayer saturated with cholesterol. Thus, the phase boundary located at 66 mol % cholesterol separates the structured one-phase region (liquid-ordered phase of DMPC with CBDs) from the two-phase region where the structured liquid-ordered phase of DMPC coexists with cholesterol crystals. It is likely that CBDs are precursors of monohydrate cholesterol crystals.

  5. Cholesterol Worships a New Idol

    Institute of Scientific and Technical Information of China (English)

    Ira G. Schulman

    2009-01-01

    The growing worldwide epidemic of cardiovascular disease suggests that new therapeutic strategies are needed to complement statins in the lowering of cholesterol levels. In a recent paper in Science, Tontonoz and colleagues have identified Idol as a protein that can control cholesterol levels by regulating the stability of the low-density lipoprotein receptor; inhibiting the activity of Idol could provide novel approaches for the treatment of cardiovascular disease.

  6. A relation between high-density-lipoprotein cholesterol and bile cholesterol saturation.

    OpenAIRE

    Thornton, J R; Heaton, K. W.; Macfarlane, D G

    1981-01-01

    The association of cholesterol gall stones with coronary artery disease is controversial. To investigate this possible relation at the biochemical level, bile cholesterol saturation and the plasma concentrations of triglycerides, total cholesterol, and high-density-lipoprotein cholesterol (HDL cholesterol) were measured in 25 healthy, middle-aged women. Bile cholesterol saturation index was negatively correlated with HDL cholesterol. It was positively correlated with plasma triglycerides and ...

  7. Formation of Cholesterol Bilayer Domains Precedes Formation of Cholesterol Crystals in Cholesterol/Dimyristoylphosphatidylcholine Membranes: EPR and DSC Studies

    OpenAIRE

    Mainali, Laxman; Raguz, Marija; Subczynski, Witold K.

    2013-01-01

    Saturation-recovery EPR along with DSC were used to determine the cholesterol content at which pure cholesterol bilayer domains (CBDs) and cholesterol crystals begin to form in dimyristoylphosphatidylcholine (DMPC) membranes. To preserve compositional homogeneity throughout the membrane suspension, lipid multilamellar dispersions were prepared using a rapid solvent exchange method. The cholesterol content increased from 0 to 75 mol%. With spin-labeled cholesterol analogs it was shown that the...

  8. Facts about...Blood Cholesterol. Revised.

    Science.gov (United States)

    National Heart, Lung, and Blood Inst. (DHHS/NIH), Bethesda, MD.

    This fact sheet on blood cholesterol examines the connection between cholesterol and heart disease, lists risk factors for heart disease that can and cannot be controlled, points out who can benefit from lowering blood cholesterol, distinguishes between blood and dietary cholesterol, describes low density lipoprotein and high density lipoprotein…

  9. Effect of rosuvastatin dose-loading on serum sLox-1, hs-CRP, and postoperative prognosis in diabetic patients with acute coronary syndromes undergoing selected percutaneous coronary intervention (PCI)

    OpenAIRE

    Jiao, Yungen; Hu, Feng; Zhang, Zhengang; Gong, Kaizheng; Sun, Xiaoning; Li, Aihua; Liu, Naifeng

    2015-01-01

    Objective: To investigate the effect of rosuvastatin dose-loading on serum levels of lectin-like oxidized low-density lipoprotein receptor-1 (Lox-1) and high-sensitivity c-reactive protein (hs-CRP) and postoperative prognosis in patients with diabetes and non-ST segment elevation acute coronary syndromes (NSTEACS) undergoing selected percutaneous coronary intervention (PCI). Methods: A total of 72 patients with diabetes and NSTEACS were randomized to either the group treated with 20 mg rosuva...

  10. Endometrial Cholesterol Granuloma Associated with Prolapsed Uterus- A Rare Case Report with Unusual Clinical Presentation.

    Science.gov (United States)

    Sumathi, S

    2016-03-01

    Cholesterol granuloma is a chronic inflammatory reaction to cholesterol deposition. It may develop in variety of sites including middle ear, mastoid process, para nasal sinuses, mediastinum, breast, testis and kidney. But endometrial cholesterol granuloma is a rarely reported case and is usually presented clinically as pyometra. This article reports a case of cholesterol granuloma in the endometrium associated with prolapsed uterus. In this case the patient clinically presented with urinary retention and overflow incontinence of urine. The reason of acute urinary retention in this case was pelvic fibrosis and adhesion secondary to this chronic inflammatory reaction. This was supported by the presence of pus like yellowish material over the uterine surface and pelvic adhesion, noted during surgery. Endometrial biopsy revealed cholesterol granuloma that confirmed the source of chronic inflammatory reaction and pelvic fibrosis. PMID:27134881

  11. Increased cardiovascular reactivity to acute stress and salt-loading in adult male offspring of fat fed non-obese rats.

    Directory of Open Access Journals (Sweden)

    Olena Rudyk

    Full Text Available Diet-induced obesity in rat pregnancy has been shown previously to be associated with consistently raised blood pressure in the offspring, attributed to sympathetic over-activation, but the relative contributions to this phenotype of maternal obesity versus raised dietary fat is unknown. Sprague-Dawley female rats were fed either a control (4.3% fat, n = 11 or lard-enriched (23.6% fat, n = 16 chow 10 days prior to mating, throughout pregnancy and lactation. In conscious adult (9-month-old offspring cardiovascular parameters were measured (radiotelemetry. The short period of fat-feeding did not increase maternal weight versus controls and the baseline blood pressure was similar in offspring of fat fed dams (OF and controls (OC. However, adult male OF showed heightened cardiovascular reactivity to acute restraint stress (p<0.01; Δ systolic blood pressure (SBP and Δheart rate (HR with a prolonged recovery time compared to male OC. α1/β-adrenergic receptor blockade normalised the response. Also, after dietary salt-loading (8%-NaCl ad libitum for 1 week male OF demonstrated higher SBP (p<0.05 in the awake phase (night-time and increased low/high frequency ratio of power spectral density of HR variability versus OC. Baroreflex gain and basal power spectral density components of the heart rate or blood pressure were similar in male OF and OC. Minor abnormalities were evident in female OF. Fat feeding in the absence of maternal obesity in pregnant rats leads to altered sympathetic control of cardiovascular function in adult male offspring, and hypertension in response to stressor stimuli.

  12. Cholesterol-Modified Amino-Pullulan Nanoparticles as a Drug Carrier: Comparative Study of Cholesterol-Modified Carboxyethyl Pullulan and Pullulan Nanoparticles

    Directory of Open Access Journals (Sweden)

    Xiaojun Tao

    2016-09-01

    Full Text Available To search for nano-drug preparations with high efficiency in tumor treatment, we evaluated the drug-loading capacity and cell-uptake toxicity of three kinds of nanoparticles (NPs. Pullulan was grafted with ethylenediamine and hydrophobic groups to form hydrophobic cholesterol-modified amino-pullulan (CHAP conjugates. Fourier transform infrared spectroscopy and nuclear magnetic resonance were used to identify the CHAP structure and calculate the degree of substitution of the cholesterol group. We compared three types of NPs with close cholesterol hydrophobic properties: CHAP, cholesterol-modified pullulan (CHP, and cholesterol-modified carboxylethylpullulan (CHCP, with the degree of substitution of cholesterol of 2.92%, 3.11%, and 3.46%, respectively. As compared with the two other NPs, CHAP NPs were larger, 263.9 nm, and had a positive surface charge of 7.22 mV by dynamic light-scattering measurement. CHAP NPs showed low drug-loading capacity, 12.3%, and encapsulation efficiency of 70.8%, which depended on NP hydrophobicity and was affected by surface charge. The drug release amounts of all NPs increased in the acid media, with CHAP NPs showing drug-release sensitivity with acid change. Cytotoxicity of HeLa cells was highest with mitoxantrone-loaded CHAP NPs on MTT assay. CHAP NPs may have potential as a high-efficiency drug carrier for tumor treatment.

  13. Free cholesterol-induced macrophage apoptosis is mediated by inositol-requiring enzyme 1 alpha-regulated activation of Jun N-terminal kinase

    Institute of Scientific and Technical Information of China (English)

    Fangming Li; Yi Guo; Shenggang Sun; Xin Jiang; Bingshan Tang; Qizhang Wang; Ling Wang

    2008-01-01

    Macrophage death in advanced atherosclerotic lesions leads to iesional necrosis, possible plaque rupture, and acute vascular occlusion. A likely cause of macrophage death is the accumulation of free cholesterol (FC) leading to activation of endoplasmic reticulum (ER) stress-induced apoptosis.Inositol-requiring enzyme 1 alpha (IRE1α) is an integral membrane protein of the ER that is a key signaling step in cholesterol-induced apoptosis in macrophages, activated by stress in the ER. However, the role of IRE1α in the regulation of ER stress-induced macrophage death and the mechanism for this process are largely unclear.In this study,a cell culture model was used to explore the mechanisms involved in the ER stress pathway of FC-induced macrophage death.The results herein showed that FC loading of macrophages leads to an apoptotic response that is partially dependent on initiation by activation of IRE1α.Taken together,these results showed that the IRE1-apoptosis-signaling kinase 1-c-Jun NH2-terminal kinase cascade pathway was required in this process.Moreover,the data suggested a novel cellular mechanism for cholesterol-induced macrophage death in advanced atherosclerotic lesions.The critical function of this signaling cascade is indicated by prevention of ER stress-induced apoptosis after inhibition of IRE1α,or c-Jun NH2-terminal kinase.

  14. Cholesterol confusion and statin controversy

    Institute of Scientific and Technical Information of China (English)

    Robert; Du; Broff; Michel; de; Lorgeril

    2015-01-01

    The role of blood cholesterol levels in coronary heart disease(CHD) and the true effect of cholesterollowering statin drugs are debatable. In particular,whether statins actually decrease cardiac mortality and increase life expectancy is controversial. Concurrently,the Mediterranean diet model has been shown to prolong life and reduce the risk of diabetes,cancer,and CHD. We herein review current data related to both statins and the Mediterranean diet. We conclude that the expectation that CHD could be prevented or eliminated by simply reducing cholesterol appears unfounded. On the contrary,we should acknowledge the inconsistencies of the cholesterol theory and recognize the proven benefits of a healthy lifestyle incorporating a Mediterranean diet to prevent CHD.

  15. Polarizable multipolar electrostatics for cholesterol

    Science.gov (United States)

    Fletcher, Timothy L.; Popelier, Paul L. A.

    2016-08-01

    FFLUX is a novel force field under development for biomolecular modelling, and is based on topological atoms and the machine learning method kriging. Successful kriging models have been obtained for realistic electrostatics of amino acids, small peptides, and some carbohydrates but here, for the first time, we construct kriging models for a sizeable ligand of great importance, which is cholesterol. Cholesterol's mean total (internal) electrostatic energy prediction error amounts to 3.9 kJ mol-1, which pleasingly falls below the threshold of 1 kcal mol-1 often cited for accurate biomolecular modelling. We present a detailed analysis of the error distributions.

  16. Regulation of biliary cholesterol secretion and reverse cholesterol transport

    NARCIS (Netherlands)

    Dikkers, Arne

    2016-01-01

    According to the World Health Organization the number one cause of death throughout the world is cardiovascular disease. Therefore, there is an urgent need for new therapeutic strategies to prevent and treat cardiovascular disease. One possible way is to target the HDL-driven reverse cholesterol tra

  17. Membrane Cholesterol Modulates Superwarfarin Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Marangoni, M. Natalia; Martynowycz, Michael W.; Kuzmenko, Ivan; Braun, David; Polak, Paul E.; Weinberg, Guy; Rubinstein, Israel; Gidalevitz, David; Feinstein, Douglas L.

    2016-04-26

    Superwarfarins are modified analogs of warfarin with additional lipophilic aromatic rings, up to 100-fold greater potency, and longer biological half-lives. We hypothesized that increased hydrophobicity allowed interactions with amphiphilic membranes and modulation of biological responses. We find that superwarfarins brodifacoum and difenacoum increase lactate production and cell death in neuroblastoma cells. In contrast, neither causes changes in glioma cells that have higher cholesterol content. After choleterol depletion, lactate production was increased and cell viability was reduced. Drug-membrane interactions were examined by surface X-ray scattering using Langmuir monolayers of dipalmitoylphosphatidylcholine and/or cholesterol. Specular X-ray reflectivity data revealed that superwarfarins, but not warfarin, intercalate between dipalmitoylphosphatidylcholine molecules, whereas grazing incidence X-ray diffraction demonstrated changes in lateral crystalline order of the film. Neither agent showed significant interactions with monolayers containing >20% cholesterol. These findings demonstrate an affinity of superwarfarins to biomembranes and suggest that cellular responses to these agents are regulated by cholesterol content.

  18. The ABC of cholesterol transport

    NARCIS (Netherlands)

    Plösch, Torsten

    2004-01-01

    Cholesterol fulfills an indispensable role in mammalian physiology. It is an important constituent of all cell membranes. Furthermore, it is the precursor of steroid hormones, which regulate a variety of physiological functions, and of bile salts, which are necessary for the generation of bile flow

  19. Membrane Cholesterol Modulates Superwarfarin Toxicity.

    Science.gov (United States)

    Marangoni, M Natalia; Martynowycz, Michael W; Kuzmenko, Ivan; Braun, David; Polak, Paul E; Weinberg, Guy; Rubinstein, Israel; Gidalevitz, David; Feinstein, Douglas L

    2016-04-26

    Superwarfarins are modified analogs of warfarin with additional lipophilic aromatic rings, up to 100-fold greater potency, and longer biological half-lives. We hypothesized that increased hydrophobicity allowed interactions with amphiphilic membranes and modulation of biological responses. We find that superwarfarins brodifacoum and difenacoum increase lactate production and cell death in neuroblastoma cells. In contrast, neither causes changes in glioma cells that have higher cholesterol content. After choleterol depletion, lactate production was increased and cell viability was reduced. Drug-membrane interactions were examined by surface X-ray scattering using Langmuir monolayers of dipalmitoylphosphatidylcholine and/or cholesterol. Specular X-ray reflectivity data revealed that superwarfarins, but not warfarin, intercalate between dipalmitoylphosphatidylcholine molecules, whereas grazing incidence X-ray diffraction demonstrated changes in lateral crystalline order of the film. Neither agent showed significant interactions with monolayers containing >20% cholesterol. These findings demonstrate an affinity of superwarfarins to biomembranes and suggest that cellular responses to these agents are regulated by cholesterol content. PMID:27119638

  20. Mechanical modeling of cholesterol crystallization in atherosclerotic plaques base on Micro-OCT images (Conference Presentation)

    Science.gov (United States)

    Luo, Yuemei; Liu, Xinyu; Chen, Si; Cui, Dongyao; Wang, Xianghong; Liu, Linbo

    2016-02-01

    Plaque rupture is the critical cause of cardiovascular thrombosis but this process is still under discussion. Recent studies show that, during crystallization, cholesterol crystals in atheromatous plaques accumulate rapidly in a limited space and may result in plaque rupture. However, the actual role of cholesterol crystals on plaque rupture remains unclear due to the lack of detailed morphological information of cholesterol crystals. In this study, we used a Micro-optical coherence tomography (µOCT) setup with 1-2 µm spatial resolution to extract the geometry of cholesterol crystals from human atherosclerotic artery ex vivo firstly. With measured dimensions of cholesterol crystals by this µOCT system (the average length and thickness of 269.1±80.16 µm and 3.0±0.33 µm), we developed a two-dimensional mechanical model in which rectangular shaped cholesterol crystals distribute at different locations spatially. We predicted the stress on the thin cap induced by the expansion of cholesterol crystals by use of finite-element method. Since a large portion of plaques (58%) rupture at points of peak circumferential stress (PCS), we used PCS as the primary indicator of plaque stability with blood pressure of 14.6 kPa on the lumen. The results demonstrate that loading of the concentrated crystals especially at the cap shoulder destabilize the plaque by proportionally increasing the PCS, while evenly distributed crystals loading along the cap might impose less PCS to the plaque than the concentrated case.

  1. Active membrane cholesterol as a physiological effector.

    Science.gov (United States)

    Lange, Yvonne; Steck, Theodore L

    2016-09-01

    Sterols associate preferentially with plasma membrane sphingolipids and saturated phospholipids to form stoichiometric complexes. Cholesterol in molar excess of the capacity of these polar bilayer lipids has a high accessibility and fugacity; we call this fraction active cholesterol. This review first considers how active cholesterol serves as an upstream regulator of cellular sterol homeostasis. The mechanism appears to utilize the redistribution of active cholesterol down its diffusional gradient to the endoplasmic reticulum and mitochondria, where it binds multiple effectors and directs their feedback activity. We have also reviewed a broad literature in search of a role for active cholesterol (as opposed to bulk cholesterol or lipid domains such as rafts) in the activity of diverse membrane proteins. Several systems provide such evidence, implicating, in particular, caveolin-1, various kinds of ABC-type cholesterol transporters, solute transporters, receptors and ion channels. We suggest that this larger role for active cholesterol warrants close attention and can be tested easily. PMID:26874289

  2. Do You Know Your Cholesterol Levels?

    Science.gov (United States)

    ... The Health Information Center Do You Know Your Cholesterol Levels? Print-friendly Version (PDF, 6.1 MB) ... Eat Smart Did you know that high blood cholesterol is a serious problem among Latinos? About one ...

  3. Analysis of Cholesterol Trafficking with Fluorescent Probes

    DEFF Research Database (Denmark)

    Maxfield, Frederick R.; Wustner, Daniel

    2012-01-01

    Cholesterol plays an important role in determining the biophysical properties of biological membranes, and its concentration is tightly controlled by homeostatic processes. The intracellular transport of cholesterol among organelles is a key part of the homeostatic mechanism, but sterol transport...... that can bind to cholesterol to reveal its distribution in cells. We also discuss the use of intrinsically fluorescent sterols that closely mimic cholesterol, as well as some minimally modified fluorophore-labeled sterols. Methods for imaging these sterols by conventional fluorescence microscopy...

  4. Cerebral cholesterol granuloma in homozygous familial hypercholesterolemia

    OpenAIRE

    Francis, Gordon A; Johnson, Royce L.; Findlay, J. Max; Wang, Jian; Hegele, Robert A.

    2005-01-01

    Familial hypercholesterolemia (FH) is characterized by the accumulation of excess cholesterol in tissues including the artery wall and tendons. We describe a patient with homozygous FH who presented with asymptomatic cholesterol granuloma of the brain. The patient's plasma low-density lipoprotein cholesterol level was remarkably responsive to combination hypolipidemic therapy with statin plus ezetimibe. This case illustrates another potential complication of whole-body cholesterol excess and ...

  5. Intracellular cholesterol transport proteins: roles in health and disease.

    Science.gov (United States)

    Soffientini, Ugo; Graham, Annette

    2016-11-01

    Effective cholesterol homoeostasis is essential in maintaining cellular function, and this is achieved by a network of lipid-responsive nuclear transcription factors, and enzymes, receptors and transporters subject to post-transcriptional and post-translational regulation, whereas loss of these elegant, tightly regulated homoeostatic responses is integral to disease pathologies. Recent data suggest that sterol-binding sensors, exchangers and transporters contribute to regulation of cellular cholesterol homoeostasis and that genetic overexpression or deletion, or mutations, in a number of these proteins are linked with diseases, including atherosclerosis, dyslipidaemia, diabetes, congenital lipoid adrenal hyperplasia, cancer, autosomal dominant hearing loss and male infertility. This review focuses on current evidence exploring the function of members of the 'START' (steroidogenic acute regulatory protein-related lipid transfer) and 'ORP' (oxysterol-binding protein-related proteins) families of sterol-binding proteins in sterol homoeostasis in eukaryotic cells, and the evidence that they represent valid therapeutic targets to alleviate human disease. PMID:27660308

  6. Intestinal cholesterol secretion : future clinical implications

    NARCIS (Netherlands)

    Jakulj, L.; Besseling, J.; Stroes, E. S. G.; Groen, A. K.

    2013-01-01

    Together with the liver, the intestine serves as a homeostatic organ in cholesterol metabolism. Recent evidence has substantiated the pivotal role of the intestine in reverse cholesterol transport (RCT). RCT is a fundamental antiatherogenic pathway, mediating the removal of cholesterol from tissues

  7. Isolation of Cholesterol from an Egg Yolk

    Science.gov (United States)

    Taber, Douglass F.; Li, Rui; Anson, Cory M.

    2011-01-01

    A simple procedure for the isolation of the cholesterol, by hydrolysis and extraction followed by column chromatography, is described. The cholesterol can be further purified by complexation with oxalic acid. It can also be oxidized and conjugated to cholestenone. The source of the cholesterol is one egg yolk, which contains about 200 mg of…

  8. Public health aspects of serum cholesterol

    NARCIS (Netherlands)

    S. Houterman (Saskia)

    2001-01-01

    textabstractIn the beginning of this century Anitschkow and De Langen started pioneering work concerning the relation between cholesterol and coronary heart disease. Both showed that there was a possible relation between cholesterol in the diet, blood cholesterol levels and atherosclerosis. It took

  9. Remnant cholesterol and ischemic heart disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Nordestgaard, Børge G

    2014-01-01

    PURPOSE OF REVIEW: To review recent advances in the field of remnant cholesterol as a contributor to the development of ischemic heart disease (IHD). RECENT FINDINGS: Epidemiologic, mechanistic, and genetic studies all support a role for elevated remnant cholesterol (=cholesterol in triglyceride...

  10. High Cholesterol: Medicines to Help You

    Science.gov (United States)

    ... risks of taking these medicines. Talk to your doctor or pharmacist about all of the risks of taking your ... 20 should have their cholesterol checked by a doctor. Most people do not show ... Good vs. Bad Cholesterol Not all cholesterol in your blood ...

  11. Cholesterol Screening: A Practical Guide to Implementation.

    Science.gov (United States)

    Kingery, Paul M.

    1995-01-01

    Dry-chemistry cholesterol analysis has made screening feasible in a variety of settings. The article provides practical tips for the implementation of mass cholesterol screening using a portable dry-chemistry analyzer and discusses issues involved in conducting effective cholesterol screening programs from start to finish. (SM)

  12. Non-cholesterol sterols and cholesterol metabolism in sitosterolemia.

    Science.gov (United States)

    Othman, Rgia A; Myrie, Semone B; Jones, Peter J H

    2013-12-01

    Sitosterolemia (STSL) is a rare autosomal recessive disease, manifested by extremely elevated plant sterols (PS) in plasma and tissue, leading to xanthoma and premature atherosclerotic disease. Therapeutic approaches include limiting PS intake, interrupting enterohepatic circulation of bile acid using bile acid binding resins such as cholestyramine, and/or ileal bypass, and inhibiting intestinal sterol absorption by ezetimibe (EZE). The objective of this review is to evaluate sterol metabolism in STSL and the impact of the currently available treatments on sterol trafficking in this disease. The role of PS in initiation of xanthomas and premature atherosclerosis is also discussed. Blocking sterols absorption with EZE has revolutionized STSL patient treatment as it reduces circulating levels of non-cholesterol sterols in STSL. However, none of the available treatments including EZE have normalized plasma PS concentrations. Future studies are needed to: (i) explore where cholesterol and non-cholesterol sterols accumulate, (ii) assess to what extent these sterols in tissues can be mobilized after blocking their absorption, and (iii) define the factors governing sterol flux.

  13. Effect of cholesterol supplementation on cryosurvival of goat spermatozoa

    Directory of Open Access Journals (Sweden)

    Sunita Behera

    2015-12-01

    Full Text Available Aim: Sperm membrane cholesterol influences cryodamage during cryopreservation. The present study was carried out to evaluate the effect of varying cholesterol levels in Tris based extenders on the freezability of sexually healthy Malabari buck semen. Materials and Methods: A total of 48 ejaculates from two adults healthy sexually healthy Malabari bucks were utilized for the study. The collected and pooled ejaculates were divided into four groups with Group I serving as Control - I, Group II and III were treated with 1 mg and 2 mg of cholesterol-loaded-cyclodextrin (CLC/120 × 106 spermatozoa, respectively, and Group IV treated with 1 mg methyl-β-cyclodextrin (MβCD served as Control - II. Manual freezing was carried out to cryopreserve the treated and control spermatozoa. Results: Treatment of semen samples with CLC resulted in improved maintenance of sperm motility at pre-freeze and post-thaw stages of cryopreservation without affecting hypo-osmotic swelling response. Treatment of semen with 1 mg of CLC/120 × 106 spermatozoa was observed to be better than treatment with 2 mg of CLC/120 × 106 spermatozoa. In general, MβCD treatment was found to result in significantly lower sperm characteristics than those of Control - I and CLC treatment at pre-feeze and post-thaw stages and when incubated up to 4 h. Conclusion: Cholesterol treatment of sexually healthy Malabari buck semen was found to hold promise for improving cryopreser-vability of spermatozoa.

  14. Treating ram sperm with cholesterol-loaded cyclodextrins improves cryosurvival

    Science.gov (United States)

    Diluted ram sperm can be held for 24 h at 5º C prior to cryopreservation without impacting cryosurvival rates, however, the effects this storage has on subsequent fertility is unknown. These studies were conducted to evaluate the fertility of semen held for 24 h (to mimic shipping semen to a cryopr...

  15. Cholesterol Depletion from a Ceramide/Cholesterol Mixed Monolayer: A Brewster Angle Microscope Study

    KAUST Repository

    Mandal, Pritam

    2016-06-01

    Cholesterol is crucial to the mechanical properties of cell membranes that are important to cells’ behavior. Its depletion from the cell membranes could be dramatic. Among cyclodextrins (CDs), methyl beta cyclodextrin (MβCD) is the most efficient to deplete cholesterol (Chol) from biomembranes. Here, we focus on the depletion of cholesterol from a C16 ceramide/cholesterol (C16-Cer/Chol) mixed monolayer using MβCD. While the removal of cholesterol by MβCD depends on the cholesterol concentration in most mixed lipid monolayers, it does not depend very much on the concentration of cholesterol in C16-Cer/Chol monolayers. The surface pressure decay during depletion were described by a stretched exponential that suggested that the cholesterol molecules are unable to diffuse laterally and behave like static traps for the MβCD molecules. Cholesterol depletion causes morphology changes of domains but these disrupted monolayers domains seem to reform even when cholesterol level was low.

  16. Relationship between plasma cholesterol levels and cholesterol esterification in isolated human mononuclear cells

    Energy Technology Data Exchange (ETDEWEB)

    Dallongeville, J.; Davignon, J.; Lussier-Cacan, S. (Clinical Research Institute of Montreal, Quebec (Canada))

    1990-01-01

    The authors studied the relationship between plasma lipoprotein concentrations and cholesterol esterification in freshly isolated human mononuclear cells from 27 normolipidemic and 32 hyperlipidemic individuals. Cells were either incubated for 5 hours with radiolabeled oleate immediately after isolation or were preincubated for 18 hours in the presence of exogenous cholesterol, and then incubated with ({sup 14}C)sodium-oleate-albumin complex. In the absence of exogenous cholesterol, control and hypercholesterolemic subjects had similarly low values of intracellular cholesterol esterification. In the presence of exogenous cholesterol, both hypertriglyceridemic and hypercholesterolemic subjects had higher cholesterol esterification than controls. There was a significant correlation between the rate of cholesterol esterification and plasma total cholesterol. These results suggest that plasma cholesterol levels may regulate mononuclear cell intra-cellular cholesterol esterification in humans.

  17. Biliary cholesterol secretion : More than a simple ABC

    NARCIS (Netherlands)

    Dikkers, Arne; Tietge, Uwe J. F.

    2010-01-01

    Biliary cholesterol secretion is a process important for 2 major disease complexes, atherosclerotic cardiovascular disease and cholesterol gallstone disease With respect to cardiovascular disease, biliary cholesterol secretion is regarded as the final step for the elimination of cholesterol originat

  18. Fish protein hydrolysates affect cholesterol metabolism in rats fed non-cholesterol and high-cholesterol diets.

    Science.gov (United States)

    Hosomi, Ryota; Fukunaga, Kenji; Arai, Hirofumi; Kanda, Seiji; Nishiyama, Toshimasa; Yoshida, Munehiro

    2012-03-01

    Fish consumption is well known to provide health benefits in both experimental animals and human subjects. Numerous studies have demonstrated the beneficial effects of various protein hydrolysates on lipid metabolism. In this context, this study examined the effect of fish protein hydrolysates (FPH) on cholesterol metabolism compared with the effect of casein. FPHs were prepared from Alaska pollock meat using papain as a protease. Male Wistar rats were divided into the following four dietary groups of seven rats each: either casein (20%) or FPH (10%) + casein (10%), with or without 0.5% cholesterol and 0.1% sodium cholate. Serum and liver lipid levels, fecal cholesterol and bile acid excretions, and the hepatic expression of genes encoding proteins involved in cholesterol homeostasis were examined. In rats fed the FPH diets compared with casein diets with or without cholesterol and sodium cholate, the indexes of cholesterol metabolism-namely, serum cholesterol, triglyceride, and low-density lipoprotein-cholesterol levels-were significantly lower, whereas fecal cholesterol and bile acid excretions were higher. Rats fed the FPH diets compared with casein with cholesterol exhibited a lower liver cholesterol level via an increased liver cholesterol 7α-hydroxylase (CYP7A1) expression level. This study demonstrates that the intake of FPH has hypocholesterolemic effects through the enhancement of fecal cholesterol and bile acid excretions and CYP7A1 expression levels. Therefore, fish peptides prepared by papain digestion might provide health benefits by decreasing the cholesterol content in the blood, which would contribute to the prevention of circulatory system diseases such as arteriosclerosis. PMID:22181072

  19. How cholesterol homeostasis is regulated by plasma membrane cholesterol in excess of phospholipids

    OpenAIRE

    Lange, Yvonne; Ye, Jin; Steck, Theodore L.

    2004-01-01

    How do cells sense and control their cholesterol levels? Whereas most of the cell cholesterol is located in the plasma membrane, the effectors of its abundance are regulated by a small pool of cholesterol in the endoplasmic reticulum (ER). The size of the ER compartment responds rapidly and dramatically to small changes in plasma membrane cholesterol around the normal level. Consequently, increasing plasma membrane cholesterol in vivo from just below to just above the basal level evoked an ac...

  20. Peptide mediators of cholesterol efflux

    Energy Technology Data Exchange (ETDEWEB)

    Bielicki, John K.; Johansson, Jan

    2013-04-09

    The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABAC1 that parallels that of full-length apolipoproteins. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.

  1. Epididymis cholesterol homeostasis and sperm fertilizing ability

    Institute of Scientific and Technical Information of China (English)

    Fabrice Saez; Aurélia Ouvrier; Jo(e)l R Drevet

    2011-01-01

    Cholesterol, being the starting point of steroid hormone synthesis, is a long known modulator of both female and male reproductive physiology especially at the level of the gonads and the impact cholesterol has on gametogenesis. Less is known about the effects cholesterol homeostasis may have on postgonadic reproductive functions. Lately, several data have been reported showing how imbalanced cholesterol levels may particularly affect the post-testicular events of sperm maturation that lead to fully fertile male gametes. This review will focus on that aspect and essentially centers on how cholesterol is important for the physiology of the mammalian epididymis and spermatozoa.

  2. Poly(amidoamine-Cholesterol Conjugate Nanoparticles Obtained by Electrospraying as Novel Tamoxifen Delivery System

    Directory of Open Access Journals (Sweden)

    R. Cavalli

    2011-01-01

    Full Text Available A new poly(amidoamine-cholesterol (PAA-cholesterol conjugate was synthesized, characterized and used to produce nanoparticles by the electrospraying technique. The electrospraying is a method of liquid atomization that consists in the dispersion of a solution into small charged droplets by an electric field. Tuning the electrospraying process parameters spherical PAA-chol nanoparticles formed. The PAA-cholesterol nanoparticles showed sizes lower than 500 nm and spherical shape. The drug incorporation capacity was investigated using tamoxifen, a lipophilic anticancer drug, as model drug. The incorporation of the tamoxifen did not affect the shape and sizes of nanoparticles showing a drug loading of 40%. Tamoxifen-loaded nanoparticles exhibited a higher dose-dependent cytotoxicity than free tamoxifen, while blank nanoparticles did not show any cytotoxic effect at the same concentrations. The electrospray technique might be proposed to produce tamoxifen-loaded PAA-chol nanoparticle in powder form without any excipient in a single step.

  3. Poly(amidoamine)-Cholesterol Conjugate Nanoparticles Obtained by Electrospraying as Novel Tamoxifen Delivery System.

    Science.gov (United States)

    Cavalli, R; Bisazza, A; Bussano, R; Trotta, M; Civra, A; Lembo, D; Ranucci, E; Ferruti, P

    2011-01-01

    A new poly(amidoamine)-cholesterol (PAA-cholesterol) conjugate was synthesized, characterized and used to produce nanoparticles by the electrospraying technique. The electrospraying is a method of liquid atomization that consists in the dispersion of a solution into small charged droplets by an electric field. Tuning the electrospraying process parameters spherical PAA-chol nanoparticles formed. The PAA-cholesterol nanoparticles showed sizes lower than 500 nm and spherical shape. The drug incorporation capacity was investigated using tamoxifen, a lipophilic anticancer drug, as model drug. The incorporation of the tamoxifen did not affect the shape and sizes of nanoparticles showing a drug loading of 40%. Tamoxifen-loaded nanoparticles exhibited a higher dose-dependent cytotoxicity than free tamoxifen, while blank nanoparticles did not show any cytotoxic effect at the same concentrations. The electrospray technique might be proposed to produce tamoxifen-loaded PAA-chol nanoparticle in powder form without any excipient in a single step. PMID:21785731

  4. Endogenous cholesterol synthesis, fecal steroid excretion and serum lanosterol in subjects with high or low response of serum cholesterol to dietary cholesterol

    OpenAIRE

    A. C. Beynen; Katan, M B; Gent, van, H.

    1986-01-01

    In this study we addressed the question whether hypo- and hyper-responders to dietary cholesterol differ with regard to the flexibility of endogenous cholesterol synthesis after changes in cholesterol intake. Whole-body cholesterol synthesis was measured as faecal excretion of neutral steroids and bile acids minus cholesterol intake. In addition, we determined serum concentrations of lanosterol, a precursor of cholesterol and a possible indicator of cholesterol biosynthetic activity. The stud...

  5. SIGNIFICANCE OF LIPID PROFILE ESTIMATION IN PATIENT WITH ACUTE MYOCARDIAL INFARCTION

    OpenAIRE

    Santhosh Kumar N; Mohammad Anwar; Balu Mahendran.K; Kalaivanam. K N

    2013-01-01

    Acute myocardial infarction is one of the important reasons of death and unhealthiness in the world. The present study was undertaken to investigate the changes in serum lipids and lipoproteins in patients with acute myocardial infarction. The levels of lipid profile were significantly changed in the acute myocardial infarction patients. Acute myocardial infarction patients had significantly higher levels of total cholesterol, LDL-cholesterol, TG, Lipoprotein and lower level of HDL-cholestero...

  6. Boots for Achilles: progesterone's reduction of cholesterol is a second-order adaptation.

    Science.gov (United States)

    Amir, Dorsa; Fessler, Daniel M T

    2013-06-01

    Progesterone and cholesterol are both vital to pregnancy. Among other functions, progesterone downregulates inflammatory responses, allowing for maternal immune tolerance of the fetal allograft. Cholesterol a key component of cell membranes, is important in intracellular transport, cell signaling, nerve conduction, and metabolism Despite the importance of each substance in pregnancy, one exercises an antagonistic effect on the other, as periods of peak progesterone correspond with reductions in cholesterol availability, a consequence of progesterone's negative effects on cholesterol biosynthesis. This arrangement is understandable in light of the threat posed by pathogens early in pregnancy. Progesterone-induced immunomodulation entails increased vulnerability to infection, an acute problem in the first trimester, when fetal development is highly susceptible to insult. Many pathogens rely on cholesterol for cell entry, egress, and replication. Progesterone's antagonistic effects on cholesterol thus partially compensate for the costs entailed by progesterone-induced immunomodulation. Among pathogens to which the host's vulnerability is increased by progesterone's effects, approximately 90% utilize cholesterol, and this is notably true of pathogens that pose a risk during pregnancy. In addition to having a number of possible clinical applications, our approach highlights the potential importance of second-order adaptations, themselves a consequence of the lack of teleology in evolutionary processes. PMID:23909226

  7. Intracellular transport of cholesterol in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Brasaemle, D.L.

    1989-01-01

    The erythrocyte was selected as a simple cell for the study of transbilayer movement of cholesterol. Cholesterol oxidase was used to measure the distribution of ({sup 3}H)cholesterol across the erythrocyte membrane. Cholesterol oxidase was also used to estimate the rate of transport of low density lipoprotein (LDL) cholesterol to the plasma membrane of cultured Chinese hamster ovary (CHO) fibroblasts; the half-time of this process was 42 minutes. The rate of transport of LDL cholesterol to the plasma membrane was confirmed by a second procedure using amphotericin B. Amphotericin B was also used to estimate the rate of transport of endogenously synthesized cholesterol to the plasma membrane of CHO cells. New methodology was developed including improvements of the previously published cholesterol oxidase assay for plasma membrane cholesterol. A new method for detecting transport of cholesterol to the plasma membrane in cultured cells was developed using amphotericin B. Preliminary studies investigated the use of fluorescent polyenes, pimaricin and etruscomycin, as probes for plasma membrane cholesterol in transport studies. Finally, a modification of a previously published cell staining protocol yielded a simple, quantitative assay for cell growth.

  8. Enriching membrane cholesterol improves stability and cryosurvival of buffalo spermatozoa.

    Science.gov (United States)

    Rajoriya, J S; Prasad, J K; Ramteke, S S; Perumal, P; Ghosh, S K; Singh, M; Pande, Megha; Srivastava, N

    2016-01-01

    Buffalo spermatozoa are comparatively more susceptible to freezing hazards than cattle spermatozoa. In recent times incubation of spermatozoa with cholesterol-loaded-cyclodextrins (CLC) has shown improvements in semen quality in several species. Therefore, this study was undertaken to evaluate the incubation level of CLC at which maximum benefit is derived for the buffalo spermatozoa. For the study, 120 million spermatozoa were incubated in 2, 3 and 4 mg/mL of CLC (Gr II, III and IV, respectively) and cholesterol and phospholipids content, their ratio, flow cytometric evaluation of plasma membrane integrity (PMI), plasma membrane fluidity and extent of cryoinjury (Chlortetracycline, CTC assay) were compared with an untreated control (Gr I). Additionally the ability of cholesterol-loaded-spermatozoa to undergo induced acrosome reaction (IAR) using ionophore calcium (A23187) was evaluated in frozen-thaw samples. Data show a significant and linear increase (CV=0.88) in cholesterol content of spermatozoa in Gr II, III and IV and a significant decrease in phospholipids content at frozen-thaw stage in Gr IV than Gr III spermatozoa. The study revealed a significant improvement in PMI and significant reduction in plasma membrane fluidity and cryoinjury of CLC treated spermatozoa at progressive stages in three groups compared to control. Nevertheless, spermatozoa of Gr II, III and IV were significantly less responsive to ionophore calcium (A23187) than Gr I. This study shows for the first time that incubation of buffalo bull spermatozoa with CLC (3mg/120×10(6)) prior to processing permits greater numbers of sperm to survive cryopreservation while allowing spermatozoa to capacitate and the acrosome to react to AR inducer ionophore calcium (A23187). PMID:26619942

  9. The Role of Cholesterol in Cancer.

    Science.gov (United States)

    Kuzu, Omer F; Noory, Mohammad A; Robertson, Gavin P

    2016-04-15

    The roles played by cholesterol in cancer development and the potential of therapeutically targeting cholesterol homeostasis is a controversial area in the cancer community. Several epidemiologic studies report an association between cancer and serum cholesterol levels or statin use, while others suggest that there is not one. Furthermore, the Cancer Genome Atlas (TCGA) project using next-generation sequencing has profiled the mutational status and expression levels of all the genes in diverse cancers, including those involved in cholesterol metabolism, providing correlative support for a role of the cholesterol pathway in cancer development. Finally, preclinical studies tend to more consistently support the role of cholesterol in cancer, with several demonstrating that cholesterol homeostasis genes can modulate development. Because of space limitations, this review provides selected examples of the epidemiologic, TCGA, and preclinical data, focusing on alterations in cholesterol homeostasis and its consequent effect on patient survival. In melanoma, this focused analysis demonstrated that enhanced expression of cholesterol synthesis genes was associated with decreased patient survival. Collectively, the studies in melanoma and other cancer types suggested a potential role of disrupted cholesterol homeostasis in cancer development but additional studies are needed to link population-based epidemiological data, the TCGA database results, and preclinical mechanistic evidence to concretely resolve this controversy. Cancer Res; 76(8); 2063-70. ©2016 AACR. PMID:27197250

  10. 血清低密度脂蛋白与急性出血性卒中患者病情的相关性分析%Analysis of relation between serum low density lipoprotein cholesterol and the pathogenetic condition of pa-tients with acute hemorrhagic stroke

    Institute of Scientific and Technical Information of China (English)

    邬莹

    2015-01-01

    Objective To investigate the relation between serum low density lipoprotein cholesterol(LDL‐C)and the patho‐genetic condition of patients with acute hemorrhagic stroke. Methods The clinical data of 100 cases of patients with acute hem‐orrhagic stroke in our hospital from January 2010 to January 2013 were analyzed retrospectively. All the patients were divided into 43 cases of LDL‐C0.05).The incidence of hematoma enlargement of LDL‐C<2.49 mmol/L group was significantly increased, compared with LDL‐C≥2.49 mmol/L group, the difference was statistically significant(P<0.05), and the level of LDL‐C in patients with hematoma enlargement was significantly lower than that of patients without hematoma enlargement, the difference was statistically signifi‐cant(P<0.05). Conclusion The pathogenetic condition of patients with acute hemorrhagic stroke is related with the serum LDL‐C level, patients with LDL‐C<2.49 mmol/L are prone to occur hematoma enlargement. It should pay much attention to the detection of serum LDL‐C on admission, w hich is helpful to predict the pathogenetic condition.%目的探讨血清低密度脂蛋白(LDL‐C)和急性出血性卒中患者病情的关系。方法100例急性出血性卒中患者按照入院时LDL‐C水平分成LDL‐C<2.49 mmol/L组43例与LDL‐C≥2.49 mmol/L组57例,分析急性出血性卒中患者病情程度与LDL‐C水平的相关性。结果2组患者在凝血酶原时间、收缩压、舒张压、血肿大小、纤维蛋白原、部分活化凝血酶时间、血小板数量以及血糖等生化指标水平比较差异无统计学意义(P>0.05);LDL‐C<2.49 mmol/L组血肿扩大发生率显著上升,与LDL‐C≥2.49 mmol/L组相比,差异有统计学意义(P<0.05),且血肿扩大患者的LDL‐C水平显著低于无血肿扩大患者,差异有统计学意义(P<0.05)。结论急性出血性卒中患者病情与血清LDL‐C水平有关,LDL‐C<2.49 mmol

  11. Biliary cholesterol secretion: More than a simple ABC

    Institute of Scientific and Technical Information of China (English)

    Arne; Dikkers; Uwe; JF; Tietge

    2010-01-01

    Biliary cholesterol secretion is a process important for 2 major disease complexes, atherosclerotic cardiovascular disease and cholesterol gallstone disease. With respect to cardiovascular disease, biliary cholesterol secretion is regarded as the f inal step for the elimination of cholesterol originating from cholesterol-laden macrophage foam cells in the vessel wall in a pathway named reverse cholesterol transport. On the other hand, cholesterol hypersecretion into the bile is considered the main pathophys...

  12. Raising HDL cholesterol in women

    Directory of Open Access Journals (Sweden)

    Danny J Eapen

    2009-11-01

    Full Text Available Danny J Eapen1, Girish L Kalra1, Luay Rifai1, Christina A Eapen2, Nadya Merchant1, Bobby V Khan11Emory University School of Medicine, Atlanta, GA, USA; 2University of South Florida School of Medicine, Tampa, FL, USAAbstract: High-density lipoprotein cholesterol (HDL-C concentration is essential in the determination of coronary heart disease (CHD risk in women. This is especially true in the postmenopausal state, where lipid profiles and CHD risk mimic that of age-matched men. Thus, interventions designed to reduce CHD risk by raising HDL-C levels may have particular significance during the transition to menopause. This review discusses HDL-C-raising therapies and the role of HDL in the primary prevention of CHD in women. Lifestyle-based interventions such as dietary change, aerobic exercise regimens, and smoking cessation are initial steps that are effective in raising HDL-C, and available data suggest women respond similarly to men with these interventions. When combined with pharmacotherapy, the effects of these lifestyle alterations are further amplified. Though studies demonstrating gender-specific differences in therapy are limited, niacin continues to be the most effective agent in raising HDL-C levels, especially when used in combination with fibrate or statin therapy. Emerging treatments such as HDL mimetic therapy show much promise in further raising HDL-C levels and improving cardiovascular outcomes.Keywords: high-density lipoprotein, HDL, women, cholesterol, heart disease

  13. Structure of Cholesterol in Lipid Rafts

    Science.gov (United States)

    Toppozini, Laura; Meinhardt, Sebastian; Armstrong, Clare L.; Yamani, Zahra; Kučerka, Norbert; Schmid, Friederike; Rheinstädter, Maikel C.

    2014-11-01

    Rafts, or functional domains, are transient nano-or mesoscopic structures in the plasma membrane and are thought to be essential for many cellular processes such as signal transduction, adhesion, trafficking, and lipid or protein sorting. Observations of these membrane heterogeneities have proven challenging, as they are thought to be both small and short lived. With a combination of coarse-grained molecular dynamics simulations and neutron diffraction using deuterium labeled cholesterol molecules, we observe raftlike structures and determine the ordering of the cholesterol molecules in binary cholesterol-containing lipid membranes. From coarse-grained computer simulations, heterogenous membranes structures were observed and characterized as small, ordered domains. Neutron diffraction was used to study the lateral structure of the cholesterol molecules. We find pairs of strongly bound cholesterol molecules in the liquid-disordered phase, in accordance with the umbrella model. Bragg peaks corresponding to ordering of the cholesterol molecules in the raftlike structures were observed and indexed by two different structures: a monoclinic structure of ordered cholesterol pairs of alternating direction in equilibrium with cholesterol plaques, i.e., triclinic cholesterol bilayers.

  14. Black pepper and piperine reduce cholesterol uptake and enhance translocation of cholesterol transporter proteins.

    Science.gov (United States)

    Duangjai, Acharaporn; Ingkaninan, Kornkanok; Praputbut, Sakonwun; Limpeanchob, Nanteetip

    2013-04-01

    Black pepper (Piper nigrum L.) lowers blood lipids in vivo and inhibits cholesterol uptake in vitro, and piperine may mediate these effects. To test this, the present study aimed to compare actions of black pepper extract and piperine on (1) cholesterol uptake and efflux in Caco-2 cells, (2) the membrane/cytosol distribution of cholesterol transport proteins in these cells, and (3) the physicochemical properties of cholesterol micelles. Piperine or black pepper extract (containing the same amount of piperine) dose-dependently reduced cholesterol uptake into Caco-2 cells in a similar manner. Both preparations reduced the membrane levels of NPC1L1 and SR-BI proteins but not their overall cellular expression. Micellar cholesterol solubility of lipid micelles was unaffected except by 1 mg/mL concentration of black pepper extract. These data suggest that piperine is the active compound in black pepper and reduces cholesterol uptake by internalizing the cholesterol transporter proteins.

  15. Potential of BODIPY-cholesterol for analysis of cholesterol transport and diffusion in living cells

    DEFF Research Database (Denmark)

    Wüstner, Daniel; Lund, Frederik Wendelboe; Röhrl, Clemens;

    2016-01-01

    Cholesterol is an abundant and important lipid component of cellular membranes. Analysis of cholesterol transport and diffusion in living cells is hampered by the technical challenge of designing suitable cholesterol probes which can be detected for example by optical microscopy. One strategy...... is to use intrinsically fluorescent sterols, as dehydroergosterol (DHE), having minimal chemical alteration compared to cholesterol but giving low fluorescence signals in the UV region of the spectrum. Alternatively, one can use dye-tagged cholesterol analogs and in particular BODIPY-cholesterol (BChol......), whose synthesis and initial characterization was pioneered by Robert Bittman. Here, we give a general overview of the properties and applications but also limitations of BODIPY-tagged cholesterol probes for analyzing intracellular cholesterol trafficking. We describe our own experiences...

  16. Arctigenin promotes cholesterol efflux from THP-1 macrophages through PPAR-γ/LXR-α signaling pathway

    International Nuclear Information System (INIS)

    Highlights: •Arctigenin enhanced cholesterol efflux in oxLDL-loaded THP-1 macrophages. •The expression of ABCA1, ABCG1 and apoE was upregulated in arctigenin-treated cells. •Arctigenin promoted the expression of PPAR-γ and LXR-α. •Inhibition of PPAR-γ or LXR-α reversed arctigenin-mediated biological effects. •Arctigenin promotes cholesterol efflux via activation of PPAR-γ/LXR-α/ABCA1 pathway. -- Abstract: Cholesterol efflux from macrophages is a critical mechanism to prevent the development of atherosclerosis. Here, we sought to investigate the effects of arctigenin, a bioactive component of Arctium lappa, on the cholesterol efflux in oxidized low-density lipoprotein (oxLDL)-loaded THP-1 macrophages. Our data showed that arctigenin significantly accelerated apolipoprotein A-I- and high-density lipoprotein-induced cholesterol efflux in both dose- and time-dependent manners. Moreover, arctigenin treatment enhanced the expression of ATP binding cassette transporter A1 (ABCA1), ABCG1, and apoE, all of which are key molecules in the initial step of cholesterol efflux, at both mRNA and protein levels. Arctigenin also caused a concentration-dependent elevation in the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and liver X receptor-alpha (LXR-α). The arctigenin-mediated induction of ABCA1, ABCG1, and apoE was abolished by specific inhibition of PPAR-γ or LXR-α using small interfering RNA technology. Our results collectively indicate that arctigenin promotes cholesterol efflux in oxLDL-loaded THP-1 macrophages through upregulation of ABCA1, ABCG1 and apoE, which is dependent on the enhanced expression of PPAR-γ and LXR-α

  17. Arctigenin promotes cholesterol efflux from THP-1 macrophages through PPAR-γ/LXR-α signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Xiaolin [Department of Cardiothoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200032 (China); Li, Qian [Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai (China); Pang, Liewen; Huang, Guoqian; Huang, Jiechun; Shi, Meng; Sun, Xiaotian [Department of Cardiothoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200032 (China); Wang, Yiqing, E-mail: yiqingwangbiopaper@163.com [Department of Cardiothoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200032 (China)

    2013-11-15

    Highlights: •Arctigenin enhanced cholesterol efflux in oxLDL-loaded THP-1 macrophages. •The expression of ABCA1, ABCG1 and apoE was upregulated in arctigenin-treated cells. •Arctigenin promoted the expression of PPAR-γ and LXR-α. •Inhibition of PPAR-γ or LXR-α reversed arctigenin-mediated biological effects. •Arctigenin promotes cholesterol efflux via activation of PPAR-γ/LXR-α/ABCA1 pathway. -- Abstract: Cholesterol efflux from macrophages is a critical mechanism to prevent the development of atherosclerosis. Here, we sought to investigate the effects of arctigenin, a bioactive component of Arctium lappa, on the cholesterol efflux in oxidized low-density lipoprotein (oxLDL)-loaded THP-1 macrophages. Our data showed that arctigenin significantly accelerated apolipoprotein A-I- and high-density lipoprotein-induced cholesterol efflux in both dose- and time-dependent manners. Moreover, arctigenin treatment enhanced the expression of ATP binding cassette transporter A1 (ABCA1), ABCG1, and apoE, all of which are key molecules in the initial step of cholesterol efflux, at both mRNA and protein levels. Arctigenin also caused a concentration-dependent elevation in the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and liver X receptor-alpha (LXR-α). The arctigenin-mediated induction of ABCA1, ABCG1, and apoE was abolished by specific inhibition of PPAR-γ or LXR-α using small interfering RNA technology. Our results collectively indicate that arctigenin promotes cholesterol efflux in oxLDL-loaded THP-1 macrophages through upregulation of ABCA1, ABCG1 and apoE, which is dependent on the enhanced expression of PPAR-γ and LXR-α.

  18. Intracellular cholesterol-binding proteins enhance HDL-mediated cholesterol uptake in cultured primary mouse hepatocytes

    OpenAIRE

    Storey, Stephen M.; McIntosh, Avery L.; Huang, Huan; Landrock, Kerstin K.; Martin, Gregory G.; Landrock, Danilo; Payne, H. Ross; Atshaves, Barbara P.; Kier, Ann B.; Schroeder, Friedhelm

    2012-01-01

    A major gap in our knowledge of rapid hepatic HDL cholesterol clearance is the role of key intracellular factors that influence this process. Although the reverse cholesterol transport pathway targets HDL to the liver for net elimination of free cholesterol from the body, molecular details governing cholesterol uptake into hepatocytes are not completely understood. Therefore, the effects of sterol carrier protein (SCP)-2 and liver fatty acid-binding protein (L-FABP), high-af...

  19. Oxidised LDL, HDL cholesterol, LDL cholesterol levels in patients of coronary artery disease

    OpenAIRE

    Ghosh, Joya; T K Mishra; Rao, Y. N.; Aggarwal, S. K.

    2006-01-01

    Coronary artery disease is a major cause of morbidity and has various risk factors. Lipid profile i.e. low HDL-cholesterol, high LDL cholesterol, high total cholesterol, high triglycerides playing important role in its causation. Recently interest has been shown in the oxidized fraction of LDL as one of the risk factors. In the present study 60 age and sex matched normal healthy individuals were taken as controls and 60 patients of CAD were taken. Cholesterol was measured by enzymatic method,...

  20. Mast Cells and HDL Studies on Cholesterol Efflux and Reverse Cholesterol Transport

    OpenAIRE

    Kareinen, Ilona

    2015-01-01

    Atherosclerosis is an inflammatory disease characterized by the accumulation of cholesterol in the arterial intima and consequently the formation of atherosclerotic plaques. Formation of these plaques is initiated by the appearance of macrophage foam cell in the arterial intima. Foam cells are formed as excessive cholesterol accumulates in the cytosol of macrophages and finally the net influx exceeds the efflux of cholesterol. Excessive accumulation of chemically modified cholesterol in foam ...

  1. Treating patients with low high-density lipoprotein cholesterol: choices, issues and opportunities

    Directory of Open Access Journals (Sweden)

    Watts Gerald F

    2001-05-01

    Full Text Available Abstract Three clinical trials have recently focused on the benefits of lipid-regulating therapy in populations with normocholesterolaemia and low high-density lipoprotein (HDL-cholesterol. Two secondary prevention studies (Veterans Affairs HDL-Cholesterol Intervention Trial [VA-HIT] and Bezafibrate Infarction Prevention [BIP] trial testified to the efficacy of fibrates in decreasing cardiovascular events, particularly in patients with coexisting risk factors, including hypertriglyceridaemia. The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS demonstrated that a statin could decrease acute coronary events in patients with isolated low HDL-cholesterol in a primary prevention setting. The absolute risk reduction in coronary events in the VA-HIT study compares favourably with those reported from the statin-based Cholesterol and Recurrent Events (CARE and Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID trials. The absolute risk reduction in AFCAPS-TexCAPS is similar to that in West of Scotland Coronary Pravastatin Study (WOSCOPS. Recommendations are given concerning lifestyle and pharmacological management of low HDL-cholesterol. Optimal management also requires review of current treatment targets for HDL-cholesterol and triglycerides levels.

  2. Dietary cholesterol and fats at a young age : do they influence cholesterol metabolism in adult life?

    NARCIS (Netherlands)

    Temmerman, A M; Vonk, R J; Niezen-Koning, K; Berger, R.; Fernandes, J

    1989-01-01

    The effects of dietary cholesterol and fats on cholesterol metabolism later in life were studied in Mongolian gerbils. Three groups were given a basic diet with soybean oil, palm kernel oil amounting to 8.75% (w/w), or the basic diet only. In three other groups, cholesterol (0.05%) was added to the

  3. From blood to gut : Direct secretion of cholesterol via transintestinal cholesterol efflux

    NARCIS (Netherlands)

    Vrins, Carlos L. J.

    2010-01-01

    The reverse cholesterol transport pathway (RCT) is the focus of many cholesterol lowering therapies By way of this pathway, excess cholesterol is collected from peripheral tissues and delivered back to the liver and gastrointestinal tract for excretion from the body For a long time this removal via

  4. Statins increase hepatic cholesterol synthesis and stimulate fecal cholesterol elimination in mice

    NARCIS (Netherlands)

    Schonewille, Marleen; de Boer, Jan Freark; Mele, Laura; Wolters, Henk; Bloks, Vincent W; Wolters, Justina C; Kuivenhoven, Jan Albert; Tietge, Uwe J.F.; Brufau Dones, Gemma; Groen, Albert K

    2016-01-01

    Statins are competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol synthesis. Statins reduce plasma cholesterol levels, but whether this is actually caused by inhibition of de novo cholesterol synthesis has not been clearly established. Using three different statins we

  5. C57Bl/6 N mice on a western diet display reduced intestinal and hepatic cholesterol levels despite a plasma hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Desmarchelier Charles

    2012-03-01

    Full Text Available Abstract Background Small intestine and liver greatly contribute to whole body lipid, cholesterol and phospholipid metabolism but to which extent cholesterol and phospholipid handling in these tissues is affected by high fat Western-style obesogenic diets remains to be determined. Methods We therefore measured cholesterol and phospholipid concentration in intestine and liver and quantified fecal neutral sterol and bile acid excretion in C57Bl/6 N mice fed for 12 weeks either a cholesterol-free high carbohydrate control diet or a high fat Western diet containing 0.03% (w/w cholesterol. To identify the underlying mechanisms of dietary adaptations in intestine and liver, changes in gene expression were assessed by microarray and qPCR profiling, respectively. Results Mice on Western diet showed increased plasma cholesterol levels, associated with the higher dietary cholesterol supply, yet, significantly reduced cholesterol levels were found in intestine and liver. Transcript profiling revealed evidence that expression of numerous genes involved in cholesterol synthesis and uptake via LDL, but also in phospholipid metabolism, underwent compensatory regulations in both tissues. Alterations in glycerophospholipid metabolism were confirmed at the metabolite level by phospolipid profiling via mass spectrometry. Conclusions Our findings suggest that intestine and liver react to a high dietary fat intake by an activation of de novo cholesterol synthesis and other cholesterol-saving mechanisms, as well as with major changes in phospholipid metabolism, to accommodate to the fat load.

  6. Inherited Cholesterol Disorder Significantly Boosts Heart Risks

    Science.gov (United States)

    ... leaves her cholesterol untreated, her risk of coronary heart disease death or nonfatal heart attack would be comparable to ... Recent Health News Related MedlinePlus Health Topics Cholesterol Heart Diseases--Prevention ... Us Get email updates Subscribe to RSS Follow us ...

  7. Computational model for monitoring cholesterol metabolism.

    Science.gov (United States)

    Selvakumar, R; Rashith Muhammad, M; Poornima Devi, G

    2014-12-01

    A non-deterministic finite automaton is designed to observe the cholesterol metabolism with the states of acceptance and rejection. The acceptance state of the automaton depicts the normal level of metabolism and production of good cholesterol as an end product. The rejection state of this machine shows the inhibition of enzymatic activity in cholesterol synthesis and removal of free fatty acids. The deficiency in human cholesterol metabolism pathway results in abnormal accumulation of cholesterol in plasma, arterial tissues leading to diseases such as hypercholesterolemia, atherosclerosis respectively and formation of gallstones. The designed machine can be used to monitor the cholesterol metabolism at molecular level through regulation of enzymes involved in the biosynthesis and metabolism of cholesterol for the treatment of diseases incident due to the respective metabolic disorder. In addition, an algorithm for this machine has been developed to compare the programmed string with the given string. This study demonstrates the construction of a machine that is used for the development of molecular targeted therapy for the disorders in cholesterol metabolism. PMID:26396654

  8. Cholesterol, the central lipid of mammalian cells

    NARCIS (Netherlands)

    Maxfield, F. R.; van Meer, G.

    2010-01-01

    Despite its importance for mammalian cell biology and human health, there are many basic aspects of cholesterol homeostasis that are not well understood. Even for the well-characterized delivery of cholesterol to cells via lipoproteins, a novel regulatory mechanism has been discovered recently, invo

  9. Cholesterol modulates bitter taste receptor function.

    Science.gov (United States)

    Pydi, Sai Prasad; Jafurulla, Md; Wai, Lisa; Bhullar, Rajinder P; Chelikani, Prashen; Chattopadhyay, Amitabha

    2016-09-01

    Bitter taste perception in humans is believed to act as a defense mechanism against ingestion of potential toxic substances. Bitter taste is perceived by 25 distinct bitter taste receptors (T2Rs) which belong to the family of G protein-coupled receptors (GPCRs). In the overall context of the role of membrane lipids in GPCR function, we show here that T2R4, a representative member of the bitter taste receptor family, displays cholesterol sensitivity in its signaling function. In order to gain further insight into cholesterol sensitivity of T2R4, we mutated two residues Tyr114(3.59) and Lys117(3.62) present in the cholesterol recognition amino acid consensus (CRAC) motif in T2R4 with alanines. We carried out functional characterization of the mutants by calcium mobilization, followed by cholesterol depletion and replenishment. CRAC motifs in GPCRs have previously been implicated in preferential cholesterol association. Our analysis shows that the CRAC motif represents an intrinsic feature of bitter taste receptors and is conserved in 22 out of 25 human T2Rs. We further demonstrate that Lys117, an important CRAC residue, is crucial in the reported cholesterol sensitivity of T2R4. Interestingly, cholesterol sensitivity of T2R4 was observed at quinine concentrations in the lower mM range. To the best of our knowledge, our results represent the first report addressing the molecular basis of cholesterol sensitivity in the function of taste receptors. PMID:27288892

  10. Mitochondrial function is involved in regulation of cholesterol efflux to apolipoprotein (apoA-I from murine RAW 264.7 macrophages

    Directory of Open Access Journals (Sweden)

    Allen Anne Marie

    2012-12-01

    Full Text Available Abstract Background Mitochondrial DNA damage, increased production of reactive oxygen species and progressive respiratory chain dysfunction, together with increased deposition of cholesterol and cholesteryl esters, are hallmarks of atherosclerosis. This study investigated the role of mitochondrial function in regulation of macrophage cholesterol efflux to apolipoprotein A-I, by the addition of established pharmacological modulators of mitochondrial function. Methods Murine RAW 264.7 macrophages were treated with a range of concentrations of resveratrol, antimycin, dinitrophenol, nigericin and oligomycin, and changes in viability, cytotoxicity, membrane potential and ATP, compared with efflux of [3H]cholesterol to apolipoprotein (apo A-I. The effect of oligomycin treatment on expression of genes implicated in macrophage cholesterol homeostasis were determined by quantitative polymerase chain reaction, and immunoblotting, relative to the housekeeping enzyme, Gapdh, and combined with studies of this molecule on cholesterol esterification, de novo lipid biosynthesis, and induction of apoptosis. Significant differences were determined using analysis of variance, and Dunnett’s or Bonferroni post t-tests, as appropriate. Results The positive control, resveratrol (24 h, significantly enhanced cholesterol efflux to apoA-I at concentrations ≥30 μM. By contrast, cholesterol efflux to apoA-I was significantly inhibited by nigericin (45%; ppAbca1 mRNA. Oligomycin treatment did not affect cholesterol biosynthesis, but significantly inhibited cholesterol esterification following exposure to acetylated LDL, and induced apoptosis at ≥30 μM. Finally, oligomycin induced the expression of genes implicated in both cholesterol efflux (Abca1, Abcg4, Stard1 and cholesterol biosynthesis (Hmgr, Mvk, Scap, Srebf2, indicating profound dysregulation of cholesterol homeostasis. Conclusions Acute loss of mitochondrial function, and in particular Δψm, reduces

  11. Prosopis farcta beans increase HDL cholesterol and decrease LDL cholesterol in ostriches (Struthio camelus).

    Science.gov (United States)

    Omidi, Arash; Ansari nik, Hossein; Ghazaghi, Mahmood

    2013-02-01

    Ten blue-neck male ostriches (Struthio camelus) were fed Prosopis farcta beans throughout a 30-day experiment. Blood samples were collected from ostriches on days 0 and 30 to measure levels of high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride, total serum protein, albumin, globulin, cholesterol, calcium, inorganic phosphorus, the activity of aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transferase (γ-GT). From days 0 to 30, HDL cholesterol, total protein, and globulins levels increased significantly whereas LDL cholesterol, inorganic phosphorus, and γ-GT activity decreased significantly.

  12. Biliary cholesterol excretion: A novel mechanism that regulates dietary cholesterol absorption

    OpenAIRE

    Sehayek, Ephraim; Ono, Jennie G.; Shefer, Sarah; Nguyen, Lien B.; Wang, Nan; Batta, Ashok K.; Salen, Gerald; Smith, Jonathan D.; Tall, Alan R.; Breslow, Jan L.

    1998-01-01

    The regulation of dietary cholesterol absorption was examined in C57BL/6 and transgenic mice with liver overexpression of the scavenger receptor BI (SR-BI Tg). In C57BL/6 animals, feeding 0.02 to 1% (wt/wt) dietary cholesterol resulted in a dose-dependent decrease in the percentage of dietary cholesterol absorbed. A plot of total daily mass of dietary cholesterol absorbed versus the percentage by weight of cholesterol in the diet yielded a curve suggesting a saturable process with a Km of 0.4...

  13. Protective effects of alginate–chitosan microspheres loaded with alkaloids from Coptis chinensis Franch. and Evodia rutaecarpa (Juss. Benth. (Zuojin Pill against ethanol-induced acute gastric mucosal injury in rats

    Directory of Open Access Journals (Sweden)

    Wang QS

    2015-11-01

    Full Text Available Qiang-Song Wang,1,2,* Xiao-Ning Zhu,1,* Heng-Li Jiang,1,* Gui-Fang Wang,3 Yuan-Lu Cui1 1Tianjin State Key Laboratory of Modern Chinese Medicine, Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 2Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, 3Pharmacy Department, Baokang Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: Zuojin Pill (ZJP, a traditional Chinese medicine formula, consists of Coptis chinensis Franch. and Evodia rutaecarpa (Juss. Benth. in a ratio of 6:1 (w/w and was first recorded in “Danxi’s experiential therapy” for treating gastrointestinal disorders in the 15th century. However, the poor solubility of alkaloids from ZJP restricted the protective effect in treating gastritis and gastric ulcer. The aim of the study was to investigate the protective mechanism of mucoadhesive microspheres loaded with alkaloids from C. chinensis Franch. and E. rutaecarpa (Juss. Benth. on ethanol-induced acute gastric mucosal injury in rats. Surface morphology, particle size, drug loading, encapsulation efficiency, in vitro drug release, mucoadhesiveness, and fluorescent imaging of the microspheres in gastrointestinal tract were studied. The results showed that the mucoadhesive microspheres loaded with alkaloids could sustain the release of drugs beyond 12 hours and had gastric mucoadhesive property with 82.63% retention rate in vitro. The fluorescence tracer indicated high retention of mucoadhesive microspheres within 12 hours in vivo. The mucoadhesive microspheres loaded with alkaloids could reduce the gastric injury by decreasing the mucosal lesion index, increasing the percentage of inhibition and increasing the amount of mucus in the gastric mucosa in an ethanol-induced gastric mucosal injury rat model. Moreover, the

  14. The Structure of Cholesterol in Lipid Rafts

    CERN Document Server

    Toppozini, Laura; Armstrong, Clare L; Yamani, Zahra; Kucerka, Norbert; Schmid, Friederike; Rheinstaedter, Maikel C

    2014-01-01

    Rafts, or functional domains, are transient nano- or mesoscopic structures in the plasma membrane and are thought to be essential for many cellular processes such as signal transduction, adhesion, trafficking and lipid/protein sorting. Observations of these membrane heterogeneities have proven challenging, as they are thought to be both small and short-lived. With a combination of coarse-grained molecular dynamics simulations and neutron diffraction using deuterium labeled cholesterol molecules we observe raft-like structures and determine the ordering of the cholesterol molecules in binary cholesterol-containing lipid membranes. From coarse-grained computer simulations, heterogenous membranes structures were observed and characterized as small, ordered domains. Neutron diffraction was used to study the lateral structure of the cholesterol molecules. We find pairs of strongly bound cholesterol molecules in the liquid-disordered phase, in accordance with the umbrella model. Bragg peaks corresponding to orderin...

  15. Trapping crystal nucleation of cholesterol monohydrate

    DEFF Research Database (Denmark)

    Solomonov, I.; Weygand, M.J.; Kjær, K.;

    2005-01-01

    Crystalline nucleation of cholesterol at the air-water interface has been studied via grazing incidence x-ray diffraction using synchrotron radiation. The various stages of cholesterol molecular assembly from monolayer to three bilayers incorporating interleaving hydrogen-bonded water layers...... in a monoclinic cholesterol . H2O phase, has been monitored and their structures characterized to near atomic resolution. Crystallographic evidence is presented that this multilayer phase is similar to that of a reported metastable cholesterol phase of undetermined structure obtained from bile before...... transformation to the triclinic phase of cholesterol . H2O, the thermodynamically stable macroscopic form. According to grazing incidence x-ray diffraction measurements and crystallographic data, a transformation from the monoclinic film structure to a multilayer of the stable monohydrate phase involves...

  16. Major Risk Factors for Heart Disease: High Blood Cholesterol

    Science.gov (United States)

    ... Major Risk Factors for Heart Disease High Blood Cholesterol High blood cholesterol is another major risk factor for heart disease ... can do something about. The higher your blood cholesterol level, the greater your risk for developing heart ...

  17. High Blood Cholesterol: What You Need to Know

    Science.gov (United States)

    ... Audiences Contact The Health Information Center High Blood Cholesterol: What You Need To Know Table of Contents ... Lifestyle Changes (TLC) Drug Treatment Resources Why Is Cholesterol Important? Your blood cholesterol level has a lot ...

  18. Arctigenin promotes cholesterol efflux from THP-1 macrophages through PPAR-γ/LXR-α signaling pathway.

    Science.gov (United States)

    Xu, Xiaolin; Li, Qian; Pang, Liewen; Huang, Guoqian; Huang, Jiechun; Shi, Meng; Sun, Xiaotian; Wang, Yiqing

    2013-11-15

    Cholesterol efflux from macrophages is a critical mechanism to prevent the development of atherosclerosis. Here, we sought to investigate the effects of arctigenin, a bioactive component of Arctium lappa, on the cholesterol efflux in oxidized low-density lipoprotein (oxLDL)-loaded THP-1 macrophages. Our data showed that arctigenin significantly accelerated apolipoprotein A-I- and high-density lipoprotein-induced cholesterol efflux in both dose- and time-dependent manners. Moreover, arctigenin treatment enhanced the expression of ATP binding cassette transporter A1 (ABCA1), ABCG1, and apoE, all of which are key molecules in the initial step of cholesterol efflux, at both mRNA and protein levels. Arctigenin also caused a concentration-dependent elevation in the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and liver X receptor-alpha (LXR-α). The arctigenin-mediated induction of ABCA1, ABCG1, and apoE was abolished by specific inhibition of PPAR-γ or LXR-α using small interfering RNA technology. Our results collectively indicate that arctigenin promotes cholesterol efflux in oxLDL-loaded THP-1 macrophages through upregulation of ABCA1, ABCG1 and apoE, which is dependent on the enhanced expression of PPAR-γ and LXR-α. PMID:24140409

  19. SIRT2 ablation has no effect on tubulin acetylation in brain, cholesterol biosynthesis or the progression of Huntington's disease phenotypes in vivo.

    Directory of Open Access Journals (Sweden)

    Anna Bobrowska

    Full Text Available Huntington's disease (HD is a devastating neurodegenerative disorder for which there are no disease-modifying treatments. The molecular pathogenesis of HD is complex and many mechanisms and cellular processes have been proposed as potential sites of therapeutic intervention. However, prior to embarking on drug development initiatives, it is essential that therapeutic targets can be validated in mammalian models of HD. Previous studies in invertebrate and cell culture HD models have suggested that inhibition of SIRT2 could have beneficial consequences on disease progression. SIRT2 is a NAD(+-dependent deacetylase that has been proposed to deacetylate α-tubulin, histone H4 K16 and to regulate cholesterol biogenesis - a pathway which is dysregulated in HD patients and HD mouse models. We have utilized mice in which SIRT2 has been reduced or ablated to further explore the function of SIRT2 and to assess whether SIRT2 loss has a beneficial impact on disease progression in the R6/2 mouse model of HD. Surprisingly we found that reduction or loss of SIRT2 had no effect on the acetylation of α-tubulin or H4K16 or on cholesterol biosynthesis in the brains of wild type mice. Equally, genetic reduction or ablation of SIRT2 had no effect on HD progression as assessed by a battery of physiological and behavioural tests. Furthermore, we observed no change in aggregate load or levels of soluble mutant huntingtin transprotein. Intriguingly, neither the constitutive genetic loss nor acute pharmacological inhibition of SIRT2 affected the expression of cholesterol biosynthesis enzymes in the context of HD. Therefore, we conclude that SIRT2 inhibition does not modify disease progression in the R6/2 mouse model of HD and SIRT2 inhibition should not be prioritised as a therapeutic option for HD.

  20. Endogenous cholesterol synthesis, fecal steroid excretion and serum lanosterol in subjects with high or low response of serum cholesterol to dietary cholesterol

    NARCIS (Netherlands)

    Beynen, A.C.; Katan, M.B.; Gent, van C.M.

    1986-01-01

    In this study we addressed the question whether hypo- and hyper-responders to dietary cholesterol differ with regard to the flexibility of endogenous cholesterol synthesis after changes in cholesterol intake. Whole-body cholesterol synthesis was measured as faecal excretion of neutral steroids and b

  1. Perturbed cholesterol homeostasis in aging spinal cord.

    Science.gov (United States)

    Parkinson, Gemma M; Dayas, Christopher V; Smith, Doug W

    2016-09-01

    The spinal cord is vital for the processing of sensorimotor information and for its propagation to and from both the brain and the periphery. Spinal cord function is affected by aging, however, the mechanisms involved are not well-understood. To characterize molecular mechanisms of spinal cord aging, microarray analyses of gene expression were performed on cervical spinal cords of aging rats. Of the metabolic and signaling pathways affected, cholesterol-associated pathways were the most comprehensively altered, including significant downregulation of cholesterol synthesis-related genes and upregulation of cholesterol transport and metabolism genes. Paradoxically, a significant increase in total cholesterol content was observed-likely associated with cholesterol ester accumulation. To investigate potential mechanisms for the perturbed cholesterol homeostasis, we quantified the expression of myelin and neuroinflammation-associated genes and proteins. Although there was minimal change in myelin-related expression, there was an increase in phagocytic microglial and astrogliosis markers, particularly in the white matter. Together, these results suggest that perturbed cholesterol homeostasis, possibly as a result of increased inflammatory activation in spinal cord white matter, may contribute to impaired spinal cord function with aging. PMID:27459933

  2. Physiological and pathological implications of cholesterol.

    Science.gov (United States)

    Cortes, Victor A; Busso, Dolores; Maiz, Alberto; Arteaga, Antonio; Nervi, Flavio; Rigotti, Attilio

    2014-01-01

    Cholesterol has evolved to fulfill sophisticated biophysical, cell signaling and endocrine requirements of animal systems. At a cellular level, cholesterol is found in membranes, where it increases both bilayer stiffness and impermeability to water and ions. Furthermore, cholesterol is integrated into specialized lipid-protein membrane microdomains with critical topographical and signaling functions. At an organismal level, cholesterol is the precursor for all steroid hormones, including gluco- and mineralo-corticoids, sex hormones and vitamin D, all of which regulate carbohydrate, sodium, reproductive and bone homeostasis, respectively. This sterol is also the precursor for bile acids, which are important for intestinal absorption of dietary lipids as well as energy and glucose metabolic regulation. Importantly, complex mechanisms maintain cholesterol within physiological ranges and the disregulation of these mechanisms results in embryonic or adult diseases, caused by either excessive or reduced tissue cholesterol levels. The causative role of cholesterol in these diseases has been demonstrated by diverse genetic and pharmacologic animal models that are commented in this review. PMID:24389193

  3. Diet serum cholesterol and coronary diseases

    Directory of Open Access Journals (Sweden)

    Narindar Nath

    1961-07-01

    Full Text Available The probable sequence of events leading to atherosclerotic disease of the coronary artery and heart attack are briefly described. Blood cholesterol as a casual agent in atherosclerosis and how blood cholesterol can be modified are discussed. The effects of various dietary components particularly quality and quantity of fat and protein on the blood cholesterol concentration are discussed and it is emphasized that more work needs to be done to ascertain the role of individual components of the diet and their relative importance in atherogenesis.

  4. The role of cholesterol in membrane fusion.

    Science.gov (United States)

    Yang, Sung-Tae; Kreutzberger, Alex J B; Lee, Jinwoo; Kiessling, Volker; Tamm, Lukas K

    2016-09-01

    Cholesterol modulates the bilayer structure of biological membranes in multiple ways. It changes the fluidity, thickness, compressibility, water penetration and intrinsic curvature of lipid bilayers. In multi-component lipid mixtures, cholesterol induces phase separations, partitions selectively between different coexisting lipid phases, and causes integral membrane proteins to respond by changing conformation or redistribution in the membrane. But, which of these often overlapping properties are important for membrane fusion?-Here we review a range of recent experiments that elucidate the multiple roles that cholesterol plays in SNARE-mediated and viral envelope glycoprotein-mediated membrane fusion. PMID:27179407

  5. Novel role of a triglyceride-synthesizing enzyme: DGAT1 at the crossroad between triglyceride and cholesterol metabolism

    Science.gov (United States)

    Sachdev, Vinay; Leopold, Christina; Bauer, Raimund; Patankar, Jay V.; Iqbal, Jahangir; Obrowsky, Sascha; Boverhof, Renze; Doktorova, Marcela; Scheicher, Bernhard; Goeritzer, Madeleine; Kolb, Dagmar; Turnbull, Andrew V.; Zimmer, Andreas; Hoefler, Gerald; Hussain, M. Mahmood; Groen, Albert K.; Kratky, Dagmar

    2016-01-01

    Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) is a key enzyme in triacylglycerol (TG) biosynthesis. Here we show that genetic deficiency and pharmacological inhibition of DGAT1 in mice alters cholesterol metabolism. Cholesterol absorption, as assessed by acute cholesterol uptake, was significantly decreased in the small intestine and liver upon DGAT1 deficiency/inhibition. Ablation of DGAT1 in the intestine (I-DGAT1−/−) alone is sufficient to cause these effects. Consequences of I-DGAT1 deficiency phenocopy findings in whole-body DGAT1−/− and DGAT1 inhibitor-treated mice. We show that deficiency/inhibition of DGAT1 affects cholesterol metabolism via reduced chylomicron size and increased trans-intestinal cholesterol excretion. These effects are independent of cholesterol uptake at the apical surface of enterocytes but mediated through altered dietary fatty acid metabolism. Our findings provide insight into a novel role of DGAT1 and identify a pathway by which intestinal DGAT1 deficiency affects whole-body cholesterol homeostasis in mice. Targeting intestinal DGAT1 may represent a novel approach for treating hypercholesterolemia. PMID:27344248

  6. Novel role of a triglyceride-synthesizing enzyme: DGAT1 at the crossroad between triglyceride and cholesterol metabolism.

    Science.gov (United States)

    Sachdev, Vinay; Leopold, Christina; Bauer, Raimund; Patankar, Jay V; Iqbal, Jahangir; Obrowsky, Sascha; Boverhof, Renze; Doktorova, Marcela; Scheicher, Bernhard; Goeritzer, Madeleine; Kolb, Dagmar; Turnbull, Andrew V; Zimmer, Andreas; Hoefler, Gerald; Hussain, M Mahmood; Groen, Albert K; Kratky, Dagmar

    2016-09-01

    Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) is a key enzyme in triacylglycerol (TG) biosynthesis. Here we show that genetic deficiency and pharmacological inhibition of DGAT1 in mice alters cholesterol metabolism. Cholesterol absorption, as assessed by acute cholesterol uptake, was significantly decreased in the small intestine and liver upon DGAT1 deficiency/inhibition. Ablation of DGAT1 in the intestine (I-DGAT1(-/-)) alone is sufficient to cause these effects. Consequences of I-DGAT1 deficiency phenocopy findings in whole-body DGAT1(-/-) and DGAT1 inhibitor-treated mice. We show that deficiency/inhibition of DGAT1 affects cholesterol metabolism via reduced chylomicron size and increased trans-intestinal cholesterol excretion. These effects are independent of cholesterol uptake at the apical surface of enterocytes but mediated through altered dietary fatty acid metabolism. Our findings provide insight into a novel role of DGAT1 and identify a pathway by which intestinal DGAT1 deficiency affects whole-body cholesterol homeostasis in mice. Targeting intestinal DGAT1 may represent a novel approach for treating hypercholesterolemia. PMID:27344248

  7. Cyclosporine A impairs the macrophage reverse cholesterol transport in mice by reducing sterol fecal excretion.

    Directory of Open Access Journals (Sweden)

    Ilaria Zanotti

    Full Text Available Despite the efficacy in reducing acute rejection events in organ transplanted subjects, long term therapy with cyclosporine A is associated with increased atherosclerotic cardiovascular morbidity. We studied whether this drug affects the antiatherogenic process of the reverse cholesterol transport from macrophages in vivo. Cyclosporine A 50 mg/kg/d was administered to C57BL/6 mice by subcutaneous injection for 14 days. Macrophage reverse cholesterol transport was assessed by following [(3H]-cholesterol mobilization from pre-labeled intraperitoneally injected macrophages, expressing or not apolipoprotein E, to plasma, liver and feces. The pharmacological treatment significantly reduced the amount of radioactive sterols in the feces, independently on the expression of apolipoprotein E in the macrophages injected into recipient mice and in absence of changes of plasma levels of high density lipoprotein-cholesterol. Gene expression analysis revealed that cyclosporine A inhibited the hepatic levels of cholesterol 7-alpha-hydroxylase, concomitantly with the increase in hepatic and intestinal expression of ATP Binding Cassette G5. However, the in vivo relevance of the last observation was challenged by the demonstration that mice treated or not with cyclosporine A showed the same levels of circulating beta-sitosterol. These results indicate that treatment of mice with cyclosporine A impaired the macrophage reverse cholesterol transport by reducing fecal sterol excretion, possibly through the inhibition of cholesterol 7-alpha-hydroxylase expression. The current observation may provide a potential mechanism for the high incidence of atherosclerotic coronary artery disease following the immunosuppressant therapy in organ transplanted recipients.

  8. Polyunsaturated fatty acyl-coenzyme As are inhibitors of cholesterol biosynthesis in zebrafish and mice

    Directory of Open Access Journals (Sweden)

    Santhosh Karanth

    2013-11-01

    Lipid disorders pose therapeutic challenges. Previously we discovered that mutation of the hepatocyte β-hydroxybutyrate transporter Slc16a6a in zebrafish causes hepatic steatosis during fasting, marked by increased hepatic triacylglycerol, but not cholesterol. This selective diversion of trapped ketogenic carbon atoms is surprising because acetate and acetoacetate can exit mitochondria and can be incorporated into both fatty acids and cholesterol in normal hepatocytes. To elucidate the mechanism of this selective diversion of carbon atoms to fatty acids, we fed wild-type and slc16a6a mutant animals high-protein ketogenic diets. We find that slc16a6a mutants have decreased activity of the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr, despite increased Hmgcr protein abundance and relative incorporation of mevalonate into cholesterol. These observations suggest the presence of an endogenous Hmgcr inhibitor. We took a candidate approach to identify such inhibitors. First, we found that mutant livers accumulate multiple polyunsaturated fatty acids (PUFAs and PUFA-CoAs, and we showed that human HMGCR is inhibited by PUFA-CoAs in vitro. Second, we injected mice with an ethyl ester of the PUFA eicosapentaenoic acid and observed an acute decrease in hepatic Hmgcr activity, without alteration in Hmgcr protein abundance. These results elucidate a mechanism for PUFA-mediated cholesterol lowering through direct inhibition of Hmgcr.

  9. What Do My Cholesterol Levels Mean?

    Science.gov (United States)

    ... goes beyond cholesterol levels alone and considers overall risk assessment and reduction. It's still important to know your numbers, but work with your healthcare provider to treat your risk. What numbers do ...

  10. How to Get Your Cholesterol Tested

    Science.gov (United States)

    ... six years as part of a cardiovascular risk assessment. You may need to have your cholesterol and other risk factors assessed more often if your risk is elevated. Your healthcare provider will talk with you about what your ...

  11. Cholesterol oxidation products and their biological importance.

    Science.gov (United States)

    Kulig, Waldemar; Cwiklik, Lukasz; Jurkiewicz, Piotr; Rog, Tomasz; Vattulainen, Ilpo

    2016-09-01

    The main biological cause of oxysterols is the oxidation of cholesterol. They differ from cholesterol by the presence of additional polar groups that are typically hydroxyl, keto, hydroperoxy, epoxy, or carboxyl moieties. Under typical conditions, oxysterol concentration is maintained at a very low and precisely regulated level, with an excess of cholesterol. Like cholesterol, many oxysterols are hydrophobic and hence confined to cell membranes. However, small chemical differences between the sterols can significantly affect how they interact with other membrane components, and this in turn can have a substantial effect on membrane properties. In this spirit, this review describes the biological importance and the roles of oxysterols in the human body. We focus primarily on the effect of oxysterols on lipid membranes, but we also consider other issues such as enzymatic and nonenzymatic synthesis processes of oxysterols as well as pathological conditions induced by oxysterols. PMID:26956952

  12. SIGNIFICANCE OF LIPID PROFILE ESTIMATION IN PATIENT WITH ACUTE MYOCARDIAL INFARCTION

    Directory of Open Access Journals (Sweden)

    Santhosh Kumar .N

    2013-06-01

    Full Text Available Acute myocardial infarction is one of the important reasons of death and unhealthiness in the world. The present study was undertaken to investigate the changes in serum lipids and lipoproteins in patients with acute myocardial infarction. The levels of lipid profile were significantly changed in the acute myocardial infarction patients. Acute myocardial infarction patients had significantly higher levels of total cholesterol, LDL-cholesterol, TG, Lipoprotein and lower level of HDL-cholesterol, as compared to the control subjects. We found a significant association of lipid profiles with acute myocardial infarction. Reduced serum HDL-cholesterol and increased Serum LDL, Serum TG, Lipoprotein (a, in our study subjects may be the effective reasonable lipid disorders in AMI patients.

  13. A new framework for reverse cholesterol transport: Non-biliary contributions to reverse cholesterol transport

    Institute of Scientific and Technical Information of China (English)

    Ryan; E; Temel; J; Mark; Brown

    2010-01-01

    Reduction of low-density lipoprotein-cholesterol through statin therapy has only modestly decreased coronary heart disease (CHD)-associated mortality in developed countries, which has prompted the search for alternative therapeutic strategies for CHD. Major efforts are now focused on therapies that augment high-density lipoprotein (HDL)-mediated reverse cholesterol transport (RCT), and ultimately increase the fecal disposal of cholesterol. The process of RCT has long been thought to simply involve HDL-media...

  14. From blood to gut: Direct secretion of cholesterol via transintestinal cholesterol efflux

    Institute of Scientific and Technical Information of China (English)

    Carlos; LJ; Vrins

    2010-01-01

    The reverse cholesterol transport pathway (RCT) is the focus of many cholesterol-lowering therapies. By way of this pathway, excess cholesterol is collected from peripheral tissues and delivered back to the liver and gastrointestinal tract for excretion from the body. For a long time this removal via the hepatobiliary secretion was considered to be the sole route involved in the RCT. However, observations from early studies in animals and humans already pointed towards the possibility of another route. In t...

  15. Assessing possible hazards of reducing serum cholesterol.

    OpenAIRE

    Law, M. R.; Thompson, S. G.; Wald, N J

    1994-01-01

    OBJECTIVE--To assess whether low serum cholesterol concentration increases mortality from any cause. DESIGN--Systematic review of published data on mortality from causes other than ischaemic heart disease derived from the 10 largest cohort studies, two international studies, and 28 randomised trials, supplemented by unpublished data on causes of death obtained when necessary. MAIN OUTCOME MEASURES--Excess cause specific mortality associated with low or lowered serum cholesterol concentration....

  16. Dietary Phospholipids and Intestinal Cholesterol Absorption

    OpenAIRE

    Sally Tandy; Chung, Rosanna W. S.; Elaine Wat; Alvin Kamili; Cohn, Jeffrey S.

    2010-01-01

    Experiments carried out with cultured cells and in experimental animals have consistently shown that phospholipids (PLs) can inhibit intestinal cholesterol absorption. Limited evidence from clinical studies suggests that dietary PL supplementation has a similar effect in man. A number of biological mechanisms have been proposed in order to explain how PL in the gut lumen is able to affect cholesterol uptake by the gut mucosa. Further research is however required to establish whether the abili...

  17. Cholesterol suppresses antimicrobial effect of statins

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Haeri

    2015-12-01

    Full Text Available Objective(s:Isoprenoid biosynthesis is a key metabolic pathway to produce a wide variety of biomolecules such as cholesterol and carotenoids, which target cell membranes. On the other hand, it has been reported that statins known as inhibitors of isoprenoid biosynthesis and cholesterol lowering agents, may have a direct antimicrobial effect on the some bacteria. The exact action of statins in microbial metabolism is not clearly understood. It is possible that statins inhibit synthesis or utilization of some sterol precursor necessary for bacterial membrane integrity. Accordingly, this study was designed in order to examine if statins inhibit the production of a compound, which can be used in the membrane, and whether cholesterol would replace it and rescue bacteria from toxic effects of statins. Materials and Methods: To examine the possibility we assessed antibacterial effect of statins with different classes; lovastatin, simvastatin, and atorvastatin, alone and in combination with cholesterol on two Gram-positive (Staphylococcus aureus and Enterococcus faecalis and two Gram-negative (Pseudomonas aeruginosa and Escherichia coli bacteria using gel diffusion assay. Results: Our results showed that all of the statins except for lovastatin had significant antibacterial property in S. aureus, E. coli, and Enter. faecalis. Surprisingly, cholesterol nullified the antimicrobial action of effective statins in statin-sensitive bacteria. Conclusion: It is concluded that statins may deprive bacteria from a metabolite responsible for membrane stability, which is effectively substituted by cholesterol.

  18. Dietary cholesterol modulates pathogen blocking by Wolbachia.

    Directory of Open Access Journals (Sweden)

    Eric P Caragata

    Full Text Available The bacterial endosymbiont Wolbachia pipientis protects its hosts from a range of pathogens by limiting their ability to form infections inside the insect. This "pathogen blocking" could be explained by innate immune priming by the symbiont, competition for host-derived resources between pathogens and Wolbachia, or the direct modification of the cell or cellular environment by Wolbachia. Recent comparative work in Drosophila and the mosquito Aedes aegypti has shown that an immune response is not required for pathogen blocking, implying that there must be an additional component to the mechanism. Here we have examined the involvement of cholesterol in pathogen blocking using a system of dietary manipulation in Drosophila melanogaster in combination with challenge by Drosophila C virus (DCV, a common fly pathogen. We observed that flies reared on cholesterol-enriched diets infected with the Wolbachia strains wMelPop and wMelCS exhibited reduced pathogen blocking, with viral-induced mortality occurring 2-5 days earlier than flies reared on Standard diet. This shift toward greater virulence in the presence of cholesterol also corresponded to higher viral copy numbers in the host. Interestingly, an increase in dietary cholesterol did not have an effect on Wolbachia density except in one case, but this did not directly affect the strength of pathogen blocking. Our results indicate that host cholesterol levels are involved with the ability of Wolbachia-infected flies to resist DCV infections, suggesting that cholesterol contributes to the underlying mechanism of pathogen blocking.

  19. CHOLESTEROL ASSIMILATION BY COMMERCIAL YOGHURT STARTER CULTURES

    Directory of Open Access Journals (Sweden)

    Małgorzata Ziarno

    2007-03-01

    Full Text Available The ability to in vitro cholesterol level reduction in laboratory media has been shown for numerous strains of lactic acid bacteria, but not for all strains of lactic bacteria used in the dairy industry. The aim of this work was the determination of the ability of selected thermophilic lactic acid bacteria to cholesterol assimilation during 24 h culture in MRS broth. Commercial starter cultures showed various ability to cholesterol assimilation from laboratory medium. In case of starter cultures used for production of traditional yoghurt, consisting of Streptococcus salivarius subsp. thermophilus and Lactobacillus delbrueckii subsp. bulgaricus, the quantity of assimilated cholesterol did not exceed 27% of its initial contents (0.7 g in 1 dm3. Starter cultures used for bioyoghurt production, containing also probiotic strains (came from Lactobacillus acidophilus species or Bifidobacterium genus assimilated from almost 18% to over 38% of cholesterol. For one monoculture of Lb. acidophilus, cholesterol assimilation ability of 49-55% was observed, despite that the number of bacterial cells in this culture was not different from number of bacteria in other cultures.

  20. Chromatographic separation of cholesterol in foods.

    Science.gov (United States)

    Fenton, M

    1992-10-30

    Based on the current literature and on experience gained in the laboratory, a simplified procedure using direct saponification (0.4 M potassium hydroxide in ethanol and heating at 60 degrees C for 1 h) is the most appropriate method for the determination of total cholesterol in foods. Extraction of the unsaponifiable matter with hexane is efficient and no extra clean-up is required before quantification. An internal standard, 5 alpha-cholestane or epicoprostanol, should be added to the sample prior to saponification and, together with reference standards, carried through the entire procedure to ensure accurate results. A significant improvement in cholesterol methodology has been achieved by decreasing the sample size and performing all the sample preparation steps in a single tube. The method has the advantages of elimination of an initial solvent extraction for total lipids and errors resulting from multiple extractions, transfers, filtration and wash steps after saponification. The resulting hexane extract, which contains a variety of sterols and fat soluble vitamins, requires an efficient capillary column for complete resolution of cholesterol from the other compounds present. The development of fused-silica capillary columns using cross-linked and bonded liquid phases has provided high thermal stability, inertness and separation efficiency and, together with automated cold on-column gas chromatographic injection systems, has resulted in reproducible cholesterol determinations in either underivatized or derivatized form. If free cholesterol and its esters need to be determined separately, they are initially extracted with other lipids with chloroform-methanol followed by their separation by column or thin-layer chromatography and subsequently analysed by gas or liquid chromatography. Although capillary gas chromatography offers superior efficiency in separation, the inherent benefits of liquid chromatography makes it a potential alternative. Isotope dilution

  1. Dairy products and plasma cholesterol levels

    Directory of Open Access Journals (Sweden)

    Lena Ohlsson

    2010-08-01

    Full Text Available Cholesterol synthesized in the body or ingested is an essential lipid component for human survival from our earliest life. Newborns ingest about 3–4 times the amount per body weight through mother's milk compared to the dietary intake of adults. A birth level of 1.7 mmol/L plasma total cholesterol will increase to 4–4.5 mmol/L during the nursing period and continue to increase from adulthood around 40% throughout life. Coronary artery disease and other metabolic disorders are strongly associated with low-density lipoprotein (LDL and high-density lipoprotein (HDL cholesterol as well as triacylglycerol concentration. Milk fat contains a broad range of fatty acids and some have a negative impact on the cholesterol rich lipoproteins. The saturated fatty acids (SFAs, such as palmitic acid (C16:0, myristic acid (C14:0, and lauric acid (C12:0, increase total plasma cholesterol, especially LDL, and constitute 11.3 g/L of bovine milk, which is 44.8% of total fatty acid in milk fat. Replacement of dairy SFA and trans-fatty acids with polyunsaturated fatty acids decreases plasma cholesterol, especially LDL cholesterol, and is associated with a reduced risk of cardiovascular disease. Available data shows different effects on lipoproteins for different dairy products and there is uncertainty as to the impact a reasonable intake amount of dairy items has on cardiovascular risk. The aim of this review is to elucidate the effect of milk components and dairy products on total cholesterol, LDL, HDL, and the LDL/HDL quotients. Based on eight recent randomized controlled trials of parallel or cross-over design and recent reviews it can be concluded that replacement of saturated fat mainly (but not exclusively derived from high-fat dairy products with low-fat dairy products lowers LDL/HDL cholesterol and total/HDL cholesterol ratios. Whey, dairy fractions enriched in polar lipids, and techniques such as fermentation, or fortification of cows feeding can be used

  2. Cholesterol and ocular pathologies: focus on the role of cholesterol-24S-hydroxylase in cholesterol homeostasis

    Directory of Open Access Journals (Sweden)

    Fourgeux Cynthia

    2015-03-01

    Full Text Available The retina is responsible for coding the light stimulus into a nervous signal that is transferred to the brain via the optic nerve. The retina is formed by the association of the neurosensory retina and the retinal pigment epithelium that is supported by Bruch’s membrane. Both the physical and metabolic associations between these partners are crucial for the functioning of the retina, by means of nutrient intake and removal of the cell and metabolic debris from the retina. Dysequilibrium are involved in the aging processes and pathologies such as age-related macular degeneration, the leading cause of visual loss after the age of 50 years in Western countries. The retina is composed of several populations of cells including glia that is involved in cholesterol biosynthesis. Cholesterol is the main sterol in the retina. It is present as free form in cells and as esters in Bruch’s membrane. Accumulation of cholesteryl esters has been associated with aging of the retina and impairment of the retinal function. Under dietary influence and in situ synthesized, the metabolism of cholesterol is regulated by cell interactions, including neurons and glia via cholesterol-24S-hydroxylase. Several pathophysiological associations with cholesterol and its metabolism can be suggested, especially in relation to glaucoma and age-related macular degeneration.

  3. Clinic application of serum low-density lipoprotein cholesterol level in predicting expansion hematoma in elderly male patients with acute hypertensive intracerebral hemorrhage%血清LDL-C水平对老年男性高血压性脑出血血肿扩大的预测作用

    Institute of Scientific and Technical Information of China (English)

    周红霞; 刘首峰; 李玉旺; 王欣; 徐小林

    2015-01-01

    Objective To investigate whether serum level of low-density lipoprotein cholesterol can predict the expan⁃sion of hemorrhage growth in elderly male patients with acute hypertensive intracerebral hemorrhage. Methods Patients (n=108) who visited our hospital with from June 2012 until May 2014 spontaneous hypertensive intracerebral hemorrhage with⁃in 6 hours of onset which is confirmed by initial computed tomography (CT) were sent to repeated CT within 24 hours of on⁃set. All selected patients were divided into the LDL-C≥2.49 mmol/L group and LDL-C<2.49 mmol/L group. Clinical data of these 2 groups were compared and the relationships of hematoma growth and its risk factors were analyzed. Results Baseline blood pressure, the level of blood glucose, PT, APTT, FIB, PLT and hemorrhage volume did not differ significantly between the LDL-C≥2.49 mmol/L group and LDL-C<2.49 mmol/L group. The ratio of hemorrhage growth in LDL-C<2.49 mmol/L group was significantly higher than that in LDL-C≥2.49 mmol/L group (34.21%vs 11.43%). Multiple logistic regres⁃sion analysis showed that LDL-C<2.49 mmol/L was the only risk factor contribute to hemorrhage growth. Conclusion Pa⁃tients with LDL-C<2.49 mmol/L in acute intracerebral hemorrhage are of high risk of hemorrhage growth so early attention and appropriate procedure are needed to prevent or slow its growth.%目的:探讨血清低密度脂蛋白胆固醇(LDL-C)水平对老年男性高血压性脑出血急性期血肿扩大有无预测作用。方法收集我院2012年6月—2014年5月发病6 h以内的老年男性高血压性脑出血患者108例,按发病时LDL-C水平分为LDL-C<2.49 mmol/L组和LDL-C≥2.49 mmol/L组,对2组患者入院时的收缩压(SBP)、舒张压(DBP)、血糖水平、凝血酶原时间(PT)、部分活化凝血酶时间(APTT)、纤维蛋白原(FIB)、血小板计数、血肿体积进行对比分析,并于发病24 h复查头CT了解2组血肿扩大情况并进

  4. Load Measurements

    DEFF Research Database (Denmark)

    Kock, Carsten Weber; Vesth, Allan

    The report describes Load measurements carried out on a given wind turbine. The aim of the measurement program regarding the loads on the turbine is to verify the basic characteristics of the wind turbine and loads on the blades, the rotor and the tower, using [Ref 1], [Ref2] and [Ref 3]. Regarding...... the fatigue loads, the rotor, blades and tower moments are presented. The fatigue loads are evaluated using rainflow counting described in detail in Ref. [1]. The 1Hz equivalent load ranges are calculated at different wind speeds. All information regarding the instrumentation is collected in [ref 4] and [ref...

  5. Cholesterol efflux analyses using stable isotopes and mass spectrometry

    OpenAIRE

    Robert J Brown; Shao, Fei; Baldán, Ángel; Albert, Carolyn J.; Ford, David A.

    2012-01-01

    Cholesterol efflux from macrophages and the vascular wall is the initial step of the cardiovascular protective reverse cholesterol transport process. This study demonstrates a mass spectrometry based assay to measure the cellular and media content of [d7]-cholesterol and unlabeled cholesterol that can be used to measure cholesterol efflux from cell lines. Using a triple quadrupole ESI-MS instrument in direct infusion mode, product ion scanning for m/z 83, neutral loss (NL) 375.5 scanning and ...

  6. A novel alkyne cholesterol to trace cellular cholesterol metabolism and localization.

    Science.gov (United States)

    Hofmann, Kristina; Thiele, Christoph; Schött, Hans-Frieder; Gaebler, Anne; Schoene, Mario; Kiver, Yuriy; Friedrichs, Silvia; Lütjohann, Dieter; Kuerschner, Lars

    2014-03-01

    Cholesterol is an important lipid of mammalian cells and plays a fundamental role in many biological processes. Its concentration in the various cellular membranes differs and is tightly regulated. Here, we present a novel alkyne cholesterol analog suitable for tracing both cholesterol metabolism and localization. This probe can be detected by click chemistry employing various reporter azides. Alkyne cholesterol is accepted by cellular enzymes from different biological species (Brevibacterium, yeast, rat, human) and these enzymes include cholesterol oxidases, hydroxylases, and acyl transferases that generate the expected metabolites in in vitro and in vivo assays. Using fluorescence microscopy, we studied the distribution of cholesterol at subcellular resolution, detecting the lipid in the Golgi and at the plasma membrane, but also in the endoplasmic reticulum and mitochondria. In summary, alkyne cholesterol represents a versatile, sensitive, and easy-to-use tool for tracking cellular cholesterol metabolism and localization as it allows for manifold detection methods including mass spectrometry, thin-layer chromatography/fluorography, and fluorescence microscopy. PMID:24334219

  7. Emerging roles of the intestine in control of cholesterol metabolism

    Institute of Scientific and Technical Information of China (English)

    Janine K Kruit; Albert K Groen; Theo J van Berkel; Folkert Kuipers

    2006-01-01

    The liver is considered the major "control center" for maintenance of whole body cholesterol homeostasis. This organ is the main site for de novo cholesterol synthesis,clears cholesterol-containing chylomicron remnants and low density lipoprotein particles from plasma and is the major contributor to high density lipoprotein (HDL; good cholesterol) formation. The liver has a central position in the classical definition of the reverse cholesterol transport pathway by taking up peripheryderived cholesterol from lipoprotein particles followed by conversion into bile acids or its direct secretion into bile for eventual removal via the feces. During the past couple of years, however, an additional important role of the intestine in maintenance of cholesterol homeostasis and regulation of plasma cholesterol levels has become apparent. Firstly, molecular mechanisms of cholesterol absorption have been elucidated and novel pharmacological compounds have been identified that interfere with the process and positively impact plasma cholesterol levels. Secondly, it is now evident that the intestine itself contributes to fecal neutral sterol loss as a cholesterol-secreting organ. Finally, very recent work has unequivocally demonstrated that the intestine contributes significantly to plasma HDL cholesterol levels.Thus, the intestine is a potential target for novel antiatherosclerotic treatment strategies that, in addition to interference with cholesterol absorption, modulate direct cholesterol excretion and plasma HDL cholesterol levels.

  8. [Trans-intestinal cholesterol excretion (TICE): a new route for cholesterol excretion].

    Science.gov (United States)

    Blanchard, Claire; Moreau, François; Cariou, Bertrand; Le May, Cédric

    2014-10-01

    The small intestine plays a crucial role in dietary and biliary cholesterol absorption, as well as its lymphatic secretion as chylomicrons (lipoprotein exogenous way). Recently, a new metabolic pathway called TICE (trans-intestinal excretion of cholesterol) that plays a central role in cholesterol metabolism has emerged. TICE is an inducible way, complementary to the hepatobiliary pathway, allowing the elimination of the plasma cholesterol directly into the intestine lumen through the enterocytes. This pathway is poorly characterized but several molecular actors of TICE have been recently identified. Although it is a matter of debate, two independent studies suggest that TICE is involved in the anti-atherogenic reverse cholesterol transport pathway. Thus, TICE is an innovative drug target to reduce -cardiovascular diseases.

  9. Lipoproteins, cholesterol homeostasis and cardiac health

    Directory of Open Access Journals (Sweden)

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

    2009-01-01

    Full Text Available 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.

  10. LDL cholesterol: controversies and future therapeutic directions.

    Science.gov (United States)

    Ridker, Paul M

    2014-08-16

    Lifelong exposure to raised concentrations of LDL cholesterol increases cardiovascular event rates, and the use of statin therapy as an adjunct to diet, exercise, and smoking cessation has proven highly effective in reducing the population burden associated with hyperlipidaemia. Yet, despite consistent biological, genetic, and epidemiological data, and evidence from randomised trials, there is controversy among national guidelines and clinical practice with regard to LDL cholesterol, its measurement, the usefulness of population-based screening, the net benefit-to-risk ratio for different LDL-lowering drugs, the benefit of treatment targets, and whether aggressive lowering of LDL is safe. Several novel therapies have been introduced for the treatment of people with genetic defects that result in loss of function within the LDL receptor, a major determinant of inherited hyperlipidaemias. Moreover, the usefulness of monoclonal antibodies that extend the LDL-receptor lifecycle (and thus result in substantial lowering of LDL cholesterol below the levels achieved with statins alone) is being assessed in phase 3 trials that will enrol more than 60,000 at-risk patients worldwide. These trials represent an exceptionally rapid translation of genetic observations into clinical practice and will address core questions of how low LDL cholesterol can be safely reduced, whether the mechanism of LDL-cholesterol lowering matters, and whether ever more aggressive lipid-lowering provides a safe, long-term mechanism to prevent atherothrombotic complications.

  11. Estatinas para el Síndrome Coronario Agudo Medicina basada en evidencia sobre la administración temprana con dosis de carga Statins in Acute Coronary Syndrome Use of an Early Loading Dose

    Directory of Open Access Journals (Sweden)

    Carlos Fonseca-Gamboa

    2011-09-01

    Full Text Available Objetivo: En algunos Servicios de Emergencias de la CCSS, a los pacientes con infarto agudo de miocardio se les administra una dosis alta -aunque variable- de lovastatina en las primeras horas de evolución de los síndromes coronarios agudos, con la expectativa de lograr efectos pleiotrópicos, un resultado positivo sobre el endotelio y la disminución de mediadores inflamatorios. Analizar la evidencia científica que sustenta el beneficio de esta intervención farmacológica y clarificar la posible dosis oral y el potencial intervalo idóneo. Búsqueda vía electrónica en sistemas secundarios de información científica y análisis de fuentes primarias, con énfasis en ensayos clínicos aleatorizados que evalúen la eficacia de las estatinas en los eventos coronarios agudos; también de fuentes terciarias, específicamente revisiones sistemáticas y guías de consenso para práctica clínica basadas en evidencia y revisiones por instancias evaluadoras de tecnologías con reconocimiento internacional. Resultados: Cuatro ensayos clínicos aleatorizados controlados con placebo, no demostraron diferencias significativas ni clínicamente relevantes en la variable primaria combinada: evento cardiaco mayor, muerte, IAM recurrente fatal, AVC fatal u otra causa de muerte cardiovascular, ninguno usó dosis de carga, ni se inició la administración en las 24 hs del inicio de la sintomatología. Conclusión: Ante la falta de evidencia que permita proyectar con claridad un papel beneficioso para las estatinas en el manejo inicial del síndrome coronario agudo, esta práctica desequilibra la relación beneficio/riesgo y se aleja de los principios del uso racional de medicamentos y la aplicación del paradigma de la medicina basada en evidencia.Aim: It has been observed that in some emergency services it has become a common practice to prescribe a high but variable loading dose of statins to patients with acute myocardial infarction within the first few

  12. Increased plasma membrane cholesterol in cystic fibrosis cells correlates with CFTR genotype and depends on de novo cholesterol synthesis

    OpenAIRE

    Sonawane Nitin D; Previs Stephen F; Jiang Dechen; Ruddy Jennifer; Manson Mary E; West Richard H; Fang Danjun; Burgess James D; Kelley Thomas J

    2010-01-01

    Abstract Background Previous observations demonstrate that Cftr-null cells and tissues exhibit alterations in cholesterol processing including perinuclear cholesterol accumulation, increased de novo synthesis, and an increase in plasma membrane cholesterol accessibility compared to wild type controls. The hypothesis of this study is that membrane cholesterol accessibility correlates with CFTR genotype and is in part influenced by de novo cholesterol synthesis. Methods Electrochemical detectio...

  13. Acute Bronchitis

    Science.gov (United States)

    ... of bronchitis: acute and chronic. Most cases of acute bronchitis get better within several days. But your cough ... that cause colds and the flu often cause acute bronchitis. These viruses spread through the air when people ...

  14. An unusual case of a patient who lost his native kidneys and renal allograft from cholesterol crystal emboli.

    Science.gov (United States)

    Ahmed, Wasim; Al Garni, Abdulkareem; Abdelgadir, Elbadri; Khamees, Khamess Obeid; Ellouly, Mohammed Ali Ahmed; Haleem, Abdul

    2015-09-01

    Cholesterol crystal emboli (CCE) syndrome involving native kidneys is an underdiagnosed condition. CCE is rare in renal allografts. It may present with acute kidney injury, but usually not acute graft loss. CCE should be considered in patients with a history of atherosclerosis and an invasive arterial procedure who present with acute or chronic renal allograft dysfunction. Therapy for CCE is mainly supportive and carries a high rate of mortality. To the best of our knowledge, this is the first reported case of a patient who lost his native kidneys and renal allograft due to CCE arising from his own vasculature.

  15. Load Measurements

    DEFF Research Database (Denmark)

    Vesth, Allan; Kock, Carsten Weber

    The report describes Load measurements carried out on a given wind turbine. The aim of the measurement program regarding the loads on the turbine is to verify the basic characteristics of the wind turbine and loads on the blades, the rotor and the tower, using [Ref 1], [Ref2] and [Ref 3]. Regardi...

  16. Load Measurements

    DEFF Research Database (Denmark)

    Kock, Carsten Weber; Vesth, Allan

    The report describes Load measurements carried out on a given wind turbine. The aim of the measurement program regarding the loads on the turbine is to verify the basic characteristics of the wind turbine and loads on the blades, the rotor and the tower, using [Ref 1], [Ref2] and [Ref 3]. Regarding...

  17. Elevated Remnant Cholesterol Causes Both Low-Grade Inflammation and Ischemic Heart Disease, Whereas Elevated Low-Density Lipoprotein Cholesterol Causes Ischemic Heart Disease Without Inflammation

    DEFF Research Database (Denmark)

    Varbo, Anette; Tybjærg-Hansen, Anne; Nordestgaard, Børge G;

    2013-01-01

    Elevated nonfasting remnant cholesterol and low-density lipoprotein (LDL) cholesterol are causally associated with ischemic heart disease (IHD), but whether elevated nonfasting remnant cholesterol and LDL cholesterol both cause low-grade inflammation is currently unknown....

  18. Dietary cholesterol from eggs increases the ratio of total cholesterol to high-density lipoprotein cholesterol in humans : a meta-analysis

    NARCIS (Netherlands)

    Weggemans, R.M.; Zock, P.L.; Katan, M.B.

    2001-01-01

    Several epidemiologic studies found no effect of egg consumption on the risk of coronary heart disease. It is possible that the adverse effect of eggs on LDL-cholesterol is offset by their favorable effect on HDL cholesterol. Objective: The objective was to review the effect of dietary cholesterol o

  19. CHOBIMALT: A Cholesterol-Based Detergent†

    Science.gov (United States)

    Howell, Stanley C.; Mittal, Ritesh; Huang, Lijun; Travis, Benjamin; Breyer, Richard M.; Sanders, Charles R.

    2010-01-01

    Cholesterol and its hemisuccinate and sulfate derivatives are widely used in studies of purified membrane proteins, but are difficult to solubilize in aqueous solution, even in the presence of detergent micelles. Other cholesterol derivatives do not form conventional micelles and lead to viscous solutions. To address these problems a cholesterol-based detergent, CHOBIMALT, has been synthesized and characterized. At concentrations above 3–4μM, CHOBIMALT forms micelles without the need for elevated temperatures or sonic disruption. Diffusion and fluorescence measurements indicated that CHOBIMALT micelles are large (210 ± 30 kDa). The ability to solubilize a functional membrane protein was explored using a G-protein coupled receptor, the human kappa opioid receptor type 1 (hKOR1). While CHOBIMALT alone was not found to be effective as a surfactant for membrane extraction, when added to classical detergent micelles CHOBIMALT was observed to dramatically enhance the thermal stability of solubilized hKOR1. PMID:20919740

  20. CHOBIMALT: a cholesterol-based detergent.

    Science.gov (United States)

    Howell, Stanley C; Mittal, Ritesh; Huang, Lijun; Travis, Benjamin; Breyer, Richard M; Sanders, Charles R

    2010-11-01

    Cholesterol and its hemisuccinate and sulfate derivatives are widely used in studies of purified membrane proteins but are difficult to solubilize in aqueous solution, even in the presence of detergent micelles. Other cholesterol derivatives do not form conventional micelles and lead to viscous solutions. To address these problems, a cholesterol-based detergent, CHOBIMALT, has been synthesized and characterized. At concentrations above 3−4 μM, CHOBIMALT forms micelles without the need for elevated temperatures or sonic disruption. Diffusion and fluorescence measurements indicated that CHOBIMALT micelles are large (210±30 kDa). The ability to solubilize a functional membrane protein was explored using a G-protein coupled receptor, the human kappa opioid receptor type 1 (hKOR1). While CHOBIMALT alone was not found to be effective as a surfactant for membrane extraction, when added to classical detergent micelles CHOBIMALT was observed to dramatically enhance the thermal stability of solubilized hKOR1.

  1. Aspirin Increases the Solubility of Cholesterol in Lipid Membranes

    Science.gov (United States)

    Alsop, Richard; Barrett, Matthew; Zheng, Sonbo; Dies, Hannah; Rheinstadter, Maikel

    2014-03-01

    Aspirin (ASA) is often prescribed for patients with high levels of cholesterol for the secondary prevention of myocardial events, a regimen known as the Low-Dose Aspirin Therapy. We have recently shown that Aspirin partitions in lipid bilayers. However, a direct interplay between ASA and cholesterol has not been investigated. Cholesterol is known to insert itself into the membrane in a dispersed state at moderate concentrations (under ~37.5%) and decrease fluidity of membranes. We prepared model lipid membranes containing varying amounts of both ASA and cholesterol molecules. The structure of the bilayers as a function of ASA and cholesterol concentration was determined using high-resolution X-ray diffraction. At cholesterol levels of more than 40mol%, immiscible cholesterol plaques formed. Adding ASA to the membranes was found to dissolve the cholesterol plaques, leading to a fluid lipid bilayer structure. We present first direct evidence for an interaction between ASA and cholesterol on the level of the cell membrane.

  2. Increased plasma membrane cholesterol in cystic fibrosis cells correlates with CFTR genotype and depends on de novo cholesterol synthesis

    Directory of Open Access Journals (Sweden)

    Sonawane Nitin D

    2010-05-01

    Full Text Available Abstract Background Previous observations demonstrate that Cftr-null cells and tissues exhibit alterations in cholesterol processing including perinuclear cholesterol accumulation, increased de novo synthesis, and an increase in plasma membrane cholesterol accessibility compared to wild type controls. The hypothesis of this study is that membrane cholesterol accessibility correlates with CFTR genotype and is in part influenced by de novo cholesterol synthesis. Methods Electrochemical detection of cholesterol at the plasma membrane is achieved with capillary microelectrodes with a modified platinum coil that accepts covalent attachment of cholesterol oxidase. Modified electrodes absent cholesterol oxidase serves as a baseline control. Cholesterol synthesis is determined by deuterium incorporation into lipids over time. Incorporation into cholesterol specifically is determined by mass spectrometry analysis. All mice used in the study are on a C57Bl/6 background and are between 6 and 8 weeks of age. Results Membrane cholesterol measurements are elevated in both R117H and ΔF508 mouse nasal epithelium compared to age-matched sibling wt controls demonstrating a genotype correlation to membrane cholesterol detection. Expression of wt CFTR in CF epithelial cells reverts membrane cholesterol to WT levels further demonstrating the impact of CFTR on these processes. In wt epithelial cell, the addition of the CFTR inhibitors, Gly H101 or CFTRinh-172, for 24 h surprisingly results in an initial drop in membrane cholesterol measurement followed by a rebound at 72 h suggesting a feedback mechanism may be driving the increase in membrane cholesterol. De novo cholesterol synthesis contributes to membrane cholesterol accessibility. Conclusions The data in this study suggest that CFTR influences cholesterol trafficking to the plasma membrane, which when depleted, leads to an increase in de novo cholesterol synthesis to restore membrane content.

  3. The cholesterol system of the swine

    International Nuclear Information System (INIS)

    The purpose of this work was to characterize the dynamic system of adult female Large White swine. The content of this system and its relationships with both the external environment and between the different parts of the system were explained. The analysis of these results in terms of compared physiology showed that the structure of the cholesterol system was the same in man and in the swine. Consequently, the swine constitutes a good biological tool to study human cholesterol indirectly and to foresee the changes that might be induced in various physio-pathological cases. (author)

  4. Ordering effects of cholesterol and its analogues

    DEFF Research Database (Denmark)

    Róg, Tomasz; Pasenkiewicz-Gierula, Marta; Vattulainen, Ilpo;

    2009-01-01

    . In this review, we discuss the biophysical effects of cholesterol on the lipid bilayer, in particular the ordering and condensing effects, concentrating on the molecular level or inter-atomic interactions perspective, starting from two-component systems and proceeding to many-component ones e.g., modeling lipid...... rafts. Particular attention is paid to the roles of the methyl groups in the cholesterol ring system, and their possible biological function. Although our main research methodology is computer modeling, in this review we make extensive comparisons between experiments and different modeling approaches....

  5. Electron Transfer Pathways in Cholesterol Synthesis.

    Science.gov (United States)

    Porter, Todd D

    2015-10-01

    Cholesterol synthesis in the endoplasmic reticulum requires electron input at multiple steps and utilizes both NADH and NADPH as the electron source. Four enzymes catalyzing five steps in the pathway require electron input: squalene monooxygenase, lanosterol demethylase, sterol 4α-methyl oxidase, and sterol C5-desaturase. The electron-donor proteins for these enzymes include cytochrome P450 reductase and the cytochrome b5 pathway. Here I review the evidence for electron donor protein requirements with these enzymes, the evidence for additional electron donor pathways, and the effect of deletion of these redox enzymes on cholesterol and lipid metabolism. PMID:26344922

  6. Acute acalculous cholecystitis.

    Science.gov (United States)

    Barie, Philip S; Eachempati, Soumitra R

    2003-08-01

    Acute cholecystitis can develop without gallstones in critically ill or injured patients. However, the development of acute acalculous cholecystitis is not limited to surgical or injured patients, or even to the intensive care unit. Diabetes, malignant disease, abdominal vasculitis, congestive heart failure, cholesterol embolization, and shock or cardiac arrest have been associated with acute acalculous cholecystitis. Children may also be affected, especially after a viral illness. The pathogenesis of acute acalculous cholecystitis is a paradigm of complexity. Ischemia and reperfusion injury, or the effects of eicosanoid proinflammatory mediators, appear to be the central mechanisms, but bile stasis, opioid therapy, positive-pressure ventilation, and total parenteral nutrition have all been implicated. Ultrasound of the gallbladder is the most accurate diagnostic modality in the critically ill patient, with gallbladder wall thickness of 3.5 mm or greater and pericholecystic fluid being the two most reliable criteria. The historical treatment of choice for acute acalculous cholecystitis has been cholecystectomy, but percutaneous cholecystostomy is now the mainstay of therapy, controlling the disease in about 85% of patients. Rapid improvement can be expected when the procedure is performed properly. The mortality rates (historically about 30%) for percutaneous and open cholecystostomy appear to be similar, reflecting the severity of illness, but improved resuscitation and critical care may portend a decreased risk of death. Interval cholecystectomy is usually not indicated after acute acalculous cholecystitis in survivors; if the absence of gallstones is confirmed and the precipitating disorder has been controlled, the cholecystostomy tube can be pulled out after the patient has recovered. PMID:12864960

  7. Intestinal SR-BI does not impact cholesterol absorption or transintestinal cholesterol efflux in mice.

    Science.gov (United States)

    Bura, Kanwardeep S; Lord, Caleb; Marshall, Stephanie; McDaniel, Allison; Thomas, Gwyn; Warrier, Manya; Zhang, Jun; Davis, Matthew A; Sawyer, Janet K; Shah, Ramesh; Wilson, Martha D; Dikkers, Arne; Tietge, Uwe J F; Collet, Xavier; Rudel, Lawrence L; Temel, Ryan E; Brown, J Mark

    2013-06-01

    Reverse cholesterol transport (RCT) can proceed through the classic hepatobiliary route or through the nonbiliary transintestinal cholesterol efflux (TICE) pathway. Scavenger receptor class B type I (SR-BI) plays a critical role in the classic hepatobiliary route of RCT. However, the role of SR-BI in TICE has not been studied. To examine the role of intestinal SR-BI in TICE, sterol balance was measured in control mice and mice transgenically overexpressing SR-BI in the proximal small intestine (SR-BI(hApoCIII-ApoAIV-Tg)). SR-BI(hApoCIII-ApoAIV-Tg) mice had significantly lower plasma cholesterol levels compared with wild-type controls, yet SR-BI(hApoCIII-ApoAIV-Tg) mice had normal fractional cholesterol absorption and fecal neutral sterol excretion. Both in the absence or presence of ezetimibe, intestinal SR-BI overexpression had no impact on the amount of cholesterol excreted in the feces. To specifically study effects of intestinal SR-BI on TICE we crossed SR-BI(hApoCIII-ApoAIV-Tg) mice into a mouse model that preferentially utilized the TICE pathway for RCT (Niemann-Pick C1-like 1 liver transgenic), and likewise found no alterations in cholesterol absorption or fecal sterol excretion. Finally, mice lacking SR-BI in all tissues also exhibited normal cholesterol absorption and fecal cholesterol disposal. Collectively, these results suggest that SR-BI is not rate limiting for intestinal cholesterol absorption or for fecal neutral sterol loss through the TICE pathway.

  8. Cholesterol homeostasis: How do cells sense sterol excess?

    Science.gov (United States)

    Howe, Vicky; Sharpe, Laura J; Alexopoulos, Stephanie J; Kunze, Sarah V; Chua, Ngee Kiat; Li, Dianfan; Brown, Andrew J

    2016-09-01

    Cholesterol is vital in mammals, but toxic in excess. Consequently, elaborate molecular mechanisms have evolved to maintain this sterol within narrow limits. How cells sense excess cholesterol is an intriguing area of research. Cells sense cholesterol, and other related sterols such as oxysterols or cholesterol synthesis intermediates, and respond to changing levels through several elegant mechanisms of feedback regulation. Cholesterol sensing involves both direct binding of sterols to the homeostatic machinery located in the endoplasmic reticulum (ER), and indirect effects elicited by sterol-dependent alteration of the physical properties of membranes. Here, we examine the mechanisms employed by cells to maintain cholesterol homeostasis. PMID:26993747

  9. Remnant cholesterol as a cause of ischemic heart disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Nordestgaard, Børge G

    2014-01-01

    levels of remnant cholesterol may cause atherosclerosis same way as elevated levels of low-density lipoprotein (LDL) cholesterol, by cholesterol accumulation in the arterial wall. Genetic studies of variants associated with elevated remnant cholesterol levels show that an increment of 1mmol/L (39mg....... However, elevated levels of LDL cholesterol are associated with IHD, but not with low-grade inflammation. Such results indicate that elevated LDL cholesterol levels cause atherosclerosis without a major inflammatory component, whereas an inflammatory component of atherosclerosis is driven by elevated...

  10. Histone deacetylase inhibition decreases cholesterol levels in neuronal cells by modulating key genes in cholesterol synthesis, uptake and efflux.

    Directory of Open Access Journals (Sweden)

    Maria João Nunes

    Full Text Available Cholesterol is an essential component of the central nervous system and increasing evidence suggests an association between brain cholesterol metabolism dysfunction and the onset of neurodegenerative disorders. Interestingly, histone deacetylase inhibitors (HDACi such as trichostatin A (TSA are emerging as promising therapeutic approaches in neurodegenerative diseases, but their effect on brain cholesterol metabolism is poorly understood. We have previously demonstrated that HDACi up-regulate CYP46A1 gene transcription, a key enzyme in neuronal cholesterol homeostasis. In this study, TSA was shown to modulate the transcription of other genes involved in cholesterol metabolism in human neuroblastoma cells, namely by up-regulating genes that control cholesterol efflux and down-regulating genes involved in cholesterol synthesis and uptake, thus leading to an overall decrease in total cholesterol content. Furthermore, co-treatment with the amphipathic drug U18666A that can mimic the intracellular cholesterol accumulation observed in cells of Niemman-Pick type C patients, revealed that TSA can ameliorate the phenotype induced by pathological cholesterol accumulation, by restoring the expression of key genes involved in cholesterol synthesis, uptake and efflux and promoting lysosomal cholesterol redistribution. These results clarify the role of TSA in the modulation of neuronal cholesterol metabolism at the transcriptional level, and emphasize the idea of HDAC inhibition as a promising therapeutic tool in neurodegenerative disorders with impaired cholesterol metabolism.

  11. The Success Story of LDL Cholesterol Lowering.

    Science.gov (United States)

    Pedersen, Terje R

    2016-02-19

    We can look back at >100 years of cholesterol research that has brought medicine to a stage where people at risk of severe or fatal coronary heart disease have a much better prognosis than before. This progress has not come about without resistance. Perhaps one of the most debated topics in medicine, the cholesterol controversy, could only be brought to rest through the development of new clinical research methods that were capable of taking advantage of the amazing achievements in basic and pharmacological science after the second World War. It was only after understanding the biochemistry and physiology of cholesterol synthesis, transport and clearance from the blood that medicine could take advantage of drugs and diets to reduce the risk of atherosclerotic diseases. This review points to the highlights of the history of low-density lipoprotein-cholesterol lowering, with the discovery of the low-density lipoprotein receptor and its physiology and not only the development of statins as the stellar moments but also the development of clinical trial methodology as an effective tool to provide scientifically convincing evidence. PMID:26892969

  12. [Giant cholesterol cysts of the petrous apex].

    Science.gov (United States)

    Pellet, W; Valenzuela, S; Malca, S; Cannoni, M; Perez-Castillo, A M

    1992-01-01

    In connection with their two own cases, the authors deal about the giant cholesterol cysts of the petrous apex. The lesions which are to be differentiated from epidermoid cysts are cholesterol granulomas. Their petrous apex location explains their characteristic large appearance. As each cholesterol granuloma, they occur when a bony cell is obstructed. This chronic obstruction induces mucosal edema then bleedings which lead to the formation and, by the lack of drainage, to the accumulation of cholesterol crystals. These crystals initiate a non specific reaction to foreign bodies, a granuloma, which also can bleed. Thus, a continuous cycle perpetuates the growth of the lesion. This lesion, when it is localized in the petrous apex, can reach a big size before the appearance of some signs. Usually, these are otologic (sensorineural hearing loss, tinnitus, vertigo) and/or cranial nerve palsies (V, VI, VII). C.T. scan (well defined, sharply marginated bony expansible lesion with isodense to the brain central part) and M.R.I. (central region of increased intensity on both T1 and T2 weighted images and peripheral rim of markedly decreased signal intensity in all instances) features are characteristic enough to allow diagnose with other petrous apex lesions (cholesteatoma, mucocele, epithelial cyst, histiocytosis X, ...). Surgical treatment must try to evacuate and to aerate the cavity or perhaps to obliterate it with fatty pieces in order to prevent the recurrence. PMID:1299772

  13. Fluorimetric determination of cholesterol in hypercholesterolemia serum

    Science.gov (United States)

    Lan, Xiufeng; Liu, Jiangang; Liu, Ying; Luo, Xiaosen; Lu, Jian; Ni, Xiaowu

    2005-01-01

    With the increase of people"s living standard and the changes of living form, the number of people who suffer from hypercholesterolemia is increasing. It is not only harmful to heart and blood vessel, but also leading to obstruction of cognition. The conventional blood detection technology has weakness such as complex operation, long detecting period, and bad visibility. In order to develop a new detection method that can checkout hypercholesterolemia conveniently, spectroscopy of cholesterol in hypercholesterolemia serum is obtained by the multifunctional grating spectrograph. The experiment results indicate that, under the excitation of light-emitting diode (LED) with the wavelength at 407 nm, the serum from normal human and the hypercholesterolemia serum emit different fluorescence spectra. The former can emit one fluorescence region with the peak locating at 516 nm while the latter can emit two more regions with peaks locating at 560 nm and 588 nm. Moreover, the fluorescence intensity of serum is non-linear increasing with the concentration of cholesterol increases when the concentration of cholesterol is lower than 13.8 mmol/L, and then, with the concentration of cholesterol increase, the fluorescence intensity decreases. However, the fluorescence intensity is still much higher than that of serum from normal human. Conclusions can be educed from the experiments: the intensity and the shape of fluorescence spectra of hypercholesterolemia serum are different of those of normal serum, from which the cholesterol abnormal in blood can be judged. The consequences in this paper may offer an experimental reference for the diagnosis of the hypercholesterolemia.

  14. Enzymatic Quantification of Cholesterol and Cholesterol Esters from Silicone Hydrogel Contact Lenses

    OpenAIRE

    Pucker, Andrew D.; Thangavelu, Mirunalni; Nichols, Jason J.

    2010-01-01

    There is significant interest in lipid deposition associated with current silicone hydrogel contact lens materials. This work describes the application of a cholesterol assay used to examine this question.

  15. Hearing Outcomes after Surgical Drainage of Petrous Apex Cholesterol Granuloma

    OpenAIRE

    Rihani, Jordan; Kutz, J. Walter; Isaacson, Brandon

    2014-01-01

    Objective This study aims to assess the hearing outcomes of patients undergoing surgical management of petrous apex cholesterol granuloma and to discuss the role of otic capsule–sparing approaches in drainage of petrous apex cholesterol granulomas.

  16. Plasma Ubiquinone, Alpha-Tocopherol and Cholesterol in Man

    DEFF Research Database (Denmark)

    Karlsson, Jan; Diamant, Bertil; Edlund, Per Olof;

    1992-01-01

    Farmakologi, Coenzyme Q10, free cholesterol, vitamin E, antioxidants, Alpha-Tocopherol, vitamin Q, plasma, LDL-particle......Farmakologi, Coenzyme Q10, free cholesterol, vitamin E, antioxidants, Alpha-Tocopherol, vitamin Q, plasma, LDL-particle...

  17. Nonfasting triglycerides, cholesterol, and ischemic stroke in the general population

    DEFF Research Database (Denmark)

    Varbo, Anette; Nordestgaard, Børge G; Tybjaerg-Hansen, Anne;

    2011-01-01

    Current guidelines on stroke prevention have recommendations on desirable cholesterol levels, but not on nonfasting triglycerides. We compared stepwise increasing levels of nonfasting triglycerides and cholesterol for their association with risk of ischemic stroke in the general population....

  18. Trans Fat Now Listed With Saturated Fat and Cholesterol

    Science.gov (United States)

    ... Trans Fat Now Listed With Saturated Fat and Cholesterol Share Tweet Linkedin Pin it More sharing options ... I Do About Saturated Fat, Trans Fat, and Cholesterol? When comparing foods, look at the Nutrition Facts ...

  19. Talk with Your Health Care Provider about High Cholesterol

    Science.gov (United States)

    ... you do? Always ask your provider what your cholesterol numbers are and write them down. Discuss these ... provider may prescribe medicine to help lower your cholesterol. y y Take your medicine every day, or ...

  20. Genetic evidence implicates the immune system and cholesterol metabolism in the aetiology of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Lesley Jones

    Full Text Available BACKGROUND: Late Onset Alzheimer's disease (LOAD is the leading cause of dementia. Recent large genome-wide association studies (GWAS identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes. METHODOLOGY: We applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset. PRINCIPAL FINDINGS: We found a significant overrepresentation of association signals in pathways related to cholesterol metabolism and the immune response in both of the two largest genome-wide association studies for LOAD. SIGNIFICANCE: Processes related to cholesterol metabolism and the innate immune response have previously been implicated by pathological and epidemiological studies of Alzheimer's disease, but it has been unclear whether those findings reflected primary aetiological events or consequences of the disease process. Our independent evidence from two large studies now demonstrates that these processes are aetiologically relevant, and suggests that they may be suitable targets for novel and existing therapeutic approaches.

  1. Ezetimibe and Simvastatin Reduce Cholesterol Levels in Zebrafish Larvae Fed a High-Cholesterol Diet

    Directory of Open Access Journals (Sweden)

    Ji Sun Baek

    2012-01-01

    Full Text Available Cholesterol-fed zebrafish is an emerging animal model to study metabolic, oxidative, and inflammatory vascular processes relevant to pathogenesis of human atherosclerosis. Zebrafish fed a high-cholesterol diet (HCD develop hypercholesterolemia and are characterized by profound lipoprotein oxidation and vascular lipid accumulation. Using optically translucent zebrafish larvae has the advantage of monitoring vascular pathology and assessing the efficacy of drug candidates in live animals. Thus, we investigated whether simvastatin and ezetimibe, the principal drugs used in management of hypercholesterolemia in humans, would also reduce cholesterol levels in HCD-fed zebrafish larvae. We found that ezetimibe was well tolerated by zebrafish and effectively reduced cholesterol levels in HCD-fed larvae. In contrast, simvastatin added to water was poorly tolerated by zebrafish larvae and, when added to food, had little effect on cholesterol levels in HCD-fed larvae. Combination of low doses of ezetimibe and simvastatin had an additive effect in reducing cholesterol levels in zebrafish. These results suggest that ezetimibe exerts in zebrafish a therapeutic effect similar to that in humans and that the hypercholesterolemic zebrafish can be used as a low-cost and informative model for testing new drug candidates and for investigating mechanisms of action for existing drugs targeting dyslipidemia.

  2. Polymer sorbent with the properties of an artificial cholesterol receptor

    Science.gov (United States)

    Polyakova, I. V.; Ezhova, N. M.; Osipenko, A. A.; Pisarev, O. A.

    2015-02-01

    A cholesterol-imprinted polymer sorbent and the corresponding reticular control copolymer were synthesized from hydroxyethyl methacrylate and ethyleneglycol dimethacrylate. The sorption isotherms of cholesterol were analyzed using the generalized Langmuir and Freundlich equations. In the case of the imprinted reticular polymer, cholesterol sorption occurred on the energetically homogeneous binding centers, forming one monolayer, while the nonspecific sorption of cholesterol on the control copolymer occurred with energetically nonhomogeneous binding of the sorbate and depended on the physicochemical conditions of sorption.

  3. Structure and function of lysosomal phospholipase A2 and lecithin:cholesterol acyltransferase

    Science.gov (United States)

    Glukhova, Alisa; Hinkovska-Galcheva, Vania; Kelly, Robert; Abe, Akira; Shayman, James A.; Tesmer, John J. G.

    2015-03-01

    Lysosomal phospholipase A2 (LPLA2) and lecithin:cholesterol acyltransferase (LCAT) belong to a structurally uncharacterized family of key lipid-metabolizing enzymes responsible for lung surfactant catabolism and for reverse cholesterol transport, respectively. Whereas LPLA2 is predicted to underlie the development of drug-induced phospholipidosis, somatic mutations in LCAT cause fish eye disease and familial LCAT deficiency. Here we describe several high-resolution crystal structures of human LPLA2 and a low-resolution structure of LCAT that confirms its close structural relationship to LPLA2. Insertions in the α/β hydrolase core of LPLA2 form domains that are responsible for membrane interaction and binding the acyl chains and head groups of phospholipid substrates. The LCAT structure suggests the molecular basis underlying human disease for most of the known LCAT missense mutations, and paves the way for rational development of new therapeutics to treat LCAT deficiency, atherosclerosis and acute coronary syndrome.

  4. Immobilization of cholesterol esterase and cholesterol oxidase onto sol-gel films for application to cholesterol biosensor

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Suman [Central Mechanical Engineering Research Institute, G. Avenue, Durgapur 713209, West Bengal (India); Singhal, Rahul [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K.S. Krishnan Marg, New Delhi 110012 (India); Malhotra, B.D. [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K.S. Krishnan Marg, New Delhi 110012 (India)]. E-mail: bansi.malhotra@gmail.com

    2007-01-23

    Cholesterol oxidase (ChOx) and cholesterol esterase (ChEt) have been covalently immobilized onto tetraethylorthosilicate (TEOS) sol-gel films. The tetraethylorthosilicate sol-gel/ChEt/ChOx enzyme films thus prepared have been characterized using scanning electron microscopic (SEM), UV-vis spectroscopic, Fourier-transform-infrared (FTIR) spectroscopic and amperometric techniques, respectively. The results of photometric measurements carried out on tetraethylorthosilicate sol-gel/ChEt/ChOx reveal thermal stability up to 55 deg. C, response time as 180 s, linearity up to 780 mg dL{sup -1} (12 mM), shelf life of 1 month, detection limit of 12 mg dL{sup -1} and sensitivity as 5.4 x 10{sup -5} Abs. mg{sup -1} dL{sup -1}.

  5. Moderate alcohol consumption increases cholesterol efflux mediated by ABCA1

    NARCIS (Netherlands)

    Beulens, J.W.J.; Sierksma, A.; Tol, van A.; Fournier, C.

    2004-01-01

    Moderate alcohol consumption increases HDL cholesterol, which is involved in reverse cholesterol transport (RCT). The aim of this study was to investigate the effect of moderate alcohol consumption on cholesterol efflux, using J774 mouse macrophages and Fu5AH cells, and on other parameters in the RC

  6. Emerging roles of the intestine in control of cholesterol metabolism

    NARCIS (Netherlands)

    Kruit, Janine K.; Groen, Albert K.; van Berkel, Theo J.; Kuipers, Folkert

    2006-01-01

    The liver is considered the major "control center" for maintenance of whole body cholesterol homeostasis. This organ is the main site for de novo cholesterol synthesis, clears cholesterol-containing chylomicron remnants and low density lipoprotein particles from plasma and is the major contributor t

  7. Understanding Lipoproteins as Transporters of Cholesterol and Other Lipids

    Science.gov (United States)

    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…

  8. Cholesterol Assimilation by Lactobacillus Probiotic Bacteria: An In Vitro Investigation

    OpenAIRE

    Catherine Tomaro-Duchesneau; Mitchell L. Jones; Divya Shah; Poonam Jain; Shyamali Saha; Satya Prakash

    2014-01-01

    Excess cholesterol is associated with cardiovascular diseases (CVD), an important cause of mortality worldwide. Current CVD therapeutic measures, lifestyle and dietary interventions, and pharmaceutical agents for regulating cholesterol levels are inadequate. Probiotic bacteria have demonstrated potential to lower cholesterol levels by different mechanisms, including bile salt hydrolase activity, production of compounds that inhibit enzymes such as 3-hydroxy-3-methylglutaryl coenzyme A, and ch...

  9. Hypercholesterolemia: The Role of Schools in Cholesterol Screening.

    Science.gov (United States)

    Price, James H.; Casler, Suzanne M.

    1997-01-01

    Examines the prevalence of cardiovascular disease risk factors among children and adolescents, the pros and cons of cholesterol screening among youth, cholesterol assessments of at-risk youth, and the role of schools in cholesterol education and screening (focusing on comprehensive school health education and services). (SM)

  10. CHROMATOGRAPHIC METHODS IN THE ANALYSIS OF CHOLESTEROL AND RELATED LIPIDS

    NARCIS (Netherlands)

    HOVING, EB

    1995-01-01

    Methods using thin-layer chromatography, solid-phase extraction, gas chromatography, high-performance liquid chromatography and supercritical fluid chromatography are described for the analysis of single cholesterol, esterified and sulfated cholesterol, and for cholesterol in the context of other li

  11. HDL Cholesterol and Risk of Type 2 Diabetes

    DEFF Research Database (Denmark)

    Haase, Christiane L; Tybjærg-Hansen, Anne; Nordestgaard, Børge G;

    2015-01-01

    Observationally, low levels of HDL cholesterol are consistently associated with increased risk of type 2 diabetes. Therefore, plasma HDL cholesterol increasing has been suggested as a novel therapeutic option to reduce the risk of type 2 diabetes. Whether levels of HDL cholesterol are causally as...

  12. Carbon Inverse Opal Rods for Nonenzymatic Cholesterol Detection.

    Science.gov (United States)

    Zhong, Qifeng; Xie, Zhuoying; Ding, Haibo; Zhu, Cun; Yang, Zixue; Gu, Zhongze

    2015-11-18

    Carbon inverse opal rods made from silica photonic crystal rods are used for nonenzymatic cholesterol sensing. The characteristic reflection peak originating from the physical periodic structure works as sensing signals for quantitatively estimating cholesterol concentrations. Carbon inverse opal rods work both in cholesterol standard solutions and human serum. They are suitable for practical use in clinical diagnose.

  13. Porcine artery elastin preparation reduces serum cholesterol level in rats

    OpenAIRE

    Liyanage, Ruvini; Nakamura, Yumi; Shimada, Ken-ichiro; SEKIKAWA, Mitsuo; Jayawardana, Barana Chaminda; HAN, Kyu-Ho; Tomoko, Okada; Ohba, Kiyoshi; Takahata, Yoshihisa; Morimatsu, Fumiki; FUKUSHIMA, Michihiro; 福島, 道広; 島田, 謙一郎; 関川, 三男; 韓, 圭鎬

    2009-01-01

    The effect of porcine artery elastin on serum cholesterol level was investigated in rats fed a cholesterol-free diet. Rats were fed for 4 weeks, with a diet (ED) containing 15% casein and 5% of porcine artery elastin in comparison with a diet (CD) containing 20% casein. The total serum and non-HDL-cholesterol concentrations were lower (P

  14. 25-Hydroxycholesterol Increases the Availability of Cholesterol in Phospholipid Membranes

    Energy Technology Data Exchange (ETDEWEB)

    Olsen, Brett N.; Schlesinger, Paul H.; Ory, Daniel S.; Baker, Nathan A.

    2011-02-01

    Side-chain oxysterols are enzymatically generated oxidation products of cholesterol that serve a central role in mediating cholesterol homeostasis. Recent work has shown that side-chain oxysterols, such as 25-hydroxycholesterol (25-HC), alter membrane structure in very different ways from cholesterol, suggesting a possible mechanism for how these oxysterols regulate cholesterol homeostasis. Here we extend our previous work, using molecular dynamics simulations of 25-HC and cholesterol mixtures in 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) bilayers to examine interactions between 25-HC and cholesterol in the same bilayer. When added to cholesterol-containing membranes, 25-HC causes larger changes in membrane structure than when added to cholesterol-free membranes, demonstrating interactions between the two sterols. We also find that the presence of 25-HC changes the position, orientation, and solvent accessibility of cholesterol, shifting it into the water interface and therefore its availability to external acceptors. This is consistent with experimental results showing that oxysterols can trigger cholesterol trafficking from the plasma membrane to the endoplasmic reticulum. These interactions provide a potential mechanism for 25-HC-mediated regulation of cholesterol trafficking and homeostasis through direct modulation of cholesterol availability.

  15. On the puzzling distribution of cholesterol in the plasma membrane.

    Science.gov (United States)

    Giang, H; Schick, M

    2016-09-01

    The distribution of cholesterol between the two leaves of the plasma membrane in mammalian cells presents a conundrum; given cholesterol's known affinity for sphingomyelin, which resides predominantly in the exoplasmic leaf, why is it that experiment finds a majority of the cholesterol in the cytoplasmic leaf? This article reviews a recently proposed solution to this puzzle. PMID:26724709

  16. Alcohol consumption stimulates early steps in reverse cholesterol transport

    NARCIS (Netherlands)

    Gaag, M.S. van der; Tol, A. van; Vermunt, S.H.F.; Scheek, L.M.; Schaafsma, G.; Hendriks, H.F.J.

    2001-01-01

    Alcohol consumption is associated with increased HDL cholesterol levels, which may indicate stimulated reverse cholesterol transport. The mechanism is, however, not known. The aim of this study was to evaluate the effects of alcohol consumption on the first two steps of the reverse cholesterol pathw

  17. Effects of Cholesterol-altering Pharmaceuticals on Cholesterol Metabolism, Steroidogenesis, and Gene Expression in the Fathead Minnow (Pimephales promelas)

    Science.gov (United States)

    Pharmaceuticals that target cholesterol biosynthesis and uptake are among the most widely prescribed drugs and have been detected in the aquatic environment. Fibrates are a class of pharmaceuticals that indirectly modulate cholesterol biosynthesis through effects on peroxisome pr...

  18. Effect of testosterone deficiency on cholesterol metabolism in pigs fed a high-fat and high-cholesterol diet

    OpenAIRE

    Cai, Zhaowei; Xi, Haitao; Pan, Yongming; Jiang, Xiaoling; Chen, Liang; Cai, Yueqin; Zhu, Keyan; Chen, Cheng; XU, XIAOPING; Chen, Minli

    2015-01-01

    Background Testosterone deficiency is associated with increased serum cholesterol levels. However, how testosterone deficiency precisely affects cholesterol metabolism remains unclear. Therefore, in the current study, we examined the effect of testosterone deficiency on cholesterol metabolism and liver gene expression in pigs fed a high-fat and high-cholesterol (HFC) diet. Methods Sexually mature male miniature pigs (6–7 months old) were randomly divided into 3 groups as follows: intact male ...

  19. Accessibility of Cholesterol in Endoplasmic Reticulum Membranes and Activation of SREBP-2 Switch Abruptly at a Common Cholesterol Threshold

    OpenAIRE

    Sokolov, Anna; Radhakrishnan, Arun

    2010-01-01

    Recent studies have shown that cooperative interactions in endoplasmic reticulum (ER) membranes between Scap, cholesterol, and Insig result in switch-like control over activation of SREBP-2 transcription factors. This allows cells to rapidly adjust rates of cholesterol synthesis and uptake in response to even slight deviations from physiological set-point levels, thereby ensuring cholesterol homeostasis. In the present study we directly probe for the accessibility of cholesterol in purified E...

  20. Acute Pancreatitis and Pregnancy

    Science.gov (United States)

    ... Acute Pancreatitis > Acute Pancreatitis and Pregnancy test Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is ... of acute pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for ...

  1. Understanding Cholesterol and Heart Health | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... cholesterol throughout the body: Low-density lipoproteins (LDL): LDL cholesterol sometimes is called "bad" cholesterol. A high LDL ... or even death. The higher the level of LDL cholesterol in your blood, the GREATER your chance is ...

  2. Effects of saturated and unsaturated fats given with and without dietary cholesterol on hepatic cholesterol synthesis and hepatic lipid metabolism.

    Science.gov (United States)

    Bochenek, W; Rodgers, J B

    1978-01-27

    Hepatic cholesterol synthesis was studied in rats after consuming diets of varying neutral lipid and cholesterol content. Cholesterol synthesis was evaluated by measuring 3-hydroxy-3-methylglutaryl-CoA reductase and by determining the rate of 3H-labeled sterol production from [3H]mevalonate. Results were correlated with sterol balance data and hepatic lipid content. Hepatic cholesterol synthesis was relatively great when cholesterol was excluded from the diet. The source of neutral dietary lipids, saturated vs. unsaturated, produced no change in hepatic sterol synthesis. Values for fecal sterol outputs and hepatic cholesterol levels were also similar in rats consuming either saturated or unsaturated fats. When 1% cholesterol was added to the diet, hepatic cholesterol synthesis was suppressed but the degree of suppression was greater in rats consuming unsaturated vs. saturated fats. This was associated with greater accumulation of cholesterol in livers from rats consuming unsaturates and a reduction in fecal neutral sterol output in this group as opposed to results from rats on saturated fats. Cholesterol consumption also altered the fatty acid composition of hepatic phospholipids producing decreases in the percentages of essential polyunsaturated fatty acids. It is concluded that dietary cholesterol alters cholesterol and fatty acid metabolism in the liver and that this effect is enhanced by dietary unsaturated fats.

  3. A cholesterol-free, high-fat diet suppresses gene expression of cholesterol transporters in murine small intestine

    NARCIS (Netherlands)

    Bosch, van den H.M.; Wit, de N.J.W.; Hooiveld, G.J.E.J.; Vermeulen, H.; Veen, van der J.N.; Houten, S.M.; Kuipers, F.; Müller, M.R.; Meer, van der R.

    2008-01-01

    Transporters present in the epithelium of the small intestine determine the efficiency by which dietary and biliary cholesterol are taken up into the body and thus control whole-body cholesterol balance. Niemann-Pick C1 Like Protein 1 (Npc1l1) transports cholesterol into the enterocyte, whereas ATP-

  4. Fibroblast cholesterol efflux to plasma from metabolic syndrome subjects is not defective despite low high-density lipoprotein cholesterol

    NARCIS (Netherlands)

    R.P.F. Dullaart (Robin); A. Groen (Albert); G.M. Dallinga-Thie (Geesje); R. de Vries (Rindert); W. Sluiter (Wim); A. van Tol (Arie)

    2008-01-01

    textabstractObjective: We tested whether in metabolic syndrome (MetS) subjects the ability of plasma to stimulate cellular cholesterol efflux, an early step in the anti-atherogenic reverse cholesterol transport pathway, is maintained despite low high-density lipoprotein (HDL) cholesterol. Design: In

  5. Cholesterol efflux capacity: An introduction for clinicians.

    Science.gov (United States)

    Anastasius, Malcolm; Kockx, Maaike; Jessup, Wendy; Sullivan, David; Rye, Kerry-Anne; Kritharides, Leonard

    2016-10-01

    Epidemiologic studies have shown an inverse correlation between high-density lipoprotein (HDL) cholesterol (HDL-C) levels and cardiovascular disease outcomes. However, the hypothesis of a causal relationship between HDL-C and cardiovascular disease has been challenged by genetic and clinical studies. Serum cholesterol efflux capacity (CEC) is an important measure of HDL function in humans. Recent large clinical studies have shown a correlation between in vitro CEC and cardiovascular disease prevalence and incidence, which appears to be independent of HDL-C concentration. The present review summarizes recent large clinical studies and introduces important methodological considerations. Further studies are required to standardize and establish the reproducibility of this measure of HDL function and clarify whether modulating CEC will emerge as a useful therapeutic target. PMID:27659883

  6. Cholesterol in serum lipoprotein fractions after spaceflight

    Science.gov (United States)

    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.

  7. Structure of cholesterol/ceramide monolayer mixtures

    DEFF Research Database (Denmark)

    Scheffer, L.; Solomonov, I.; Weygand, M.J.;

    2005-01-01

    The structure of monolayers of cholesterol/ ceramide mixtures was investigated using grazing incidence x-ray diffraction, immunofluorescence, and atomic force microscopy techniques. Grazing incidence x-ray diffraction measurements showed the existence of a crystalline mixed phase of the two....... As ceramide incorporates the lipid backbone common to all sphingolipids, this arrangement may be relevant to the understanding of the molecular organization of lipid rafts....

  8. Potent and selective mediators of cholesterol efflux

    Energy Technology Data Exchange (ETDEWEB)

    Bielicki, John K; Johansson, Jan

    2015-03-24

    The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABAC1 that parallels that of full-length apolipoproteins. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.

  9. Common Force Field Thermodynamics of Cholesterol

    OpenAIRE

    Francesco Giangreco; Eiji Yamamoto; Yoshinori Hirano; Milan Hodoscek; Volker Knecht; Matteo di Giosia; Matteo Calvaresi; Francesco Zerbetto; Kenji Yasuoka; Tetsu Narumi; Masato Yasui; Siegfried Höfinger

    2013-01-01

    Four different force fields are examined for dynamic characteristics using cholesterol as a case study. The extent to which various types of internal degrees of freedom become thermodynamically relevant is evaluated by means of principal component analysis. More complex degrees of freedom (angle bending, dihedral rotations) show a trend towards force field independence. Moreover, charge assignments for membrane-embedded compounds are revealed to be critical with s...

  10. [HDL cholesterol as a sensitive diagnostic parameter in malaria].

    Science.gov (United States)

    Kittl, E M; Diridl, G; Lenhart, V; Neuwald, C; Tomasits, J; Pichler, H; Bauer, K

    1992-01-01

    In patients with malaria the lipid parameters triglycerides, cholesterol, and HDL-cholesterol were determined routinely. At the time of admission hypertriglyceridemia, hypocholesterolemia, and an extreme decrease in HDL-cholesterol were found. This dyslipoproteinemia was present in cases of falciparum malaria, as well as in cases of benign tertian malaria. The extent of HDL-cholesterol decrease showed no correlation to the severity of the clinical course of disease. HDL-cholesterol has proven to be an independent diagnostic laboratory finding in cases of suspected malarial infection. This parameter displays high diagnostic sensitivity, but no specificity for malaria. PMID:1546481

  11. Amyloid-β (1-40) restores adhesion properties of pulmonary surfactant, counteracting the effect of cholesterol.

    Science.gov (United States)

    Hane, F T; Drolle, E; Leonenko, Z

    2014-08-01

    A pulmonary surfactant (PS) is a thin lipid-protein film covering the surface of the lung alveoli at the air/liquid interface. The primary purpose of a PS is to control the surface tension of the air/liquid interface and to reduce the work of breathing. High levels of cholesterol in a PS are associated with life-threatening acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). Finding therapeutics to counteract the effect of cholesterol in a PS is a matter of contemporary research. In our earlier work, we showed that the addition of amyloid-β (1-40) (Aβ40), the protein implicated in Alzheimer's disease, can reverse the detrimental effects of cholesterol in surfactants by improving multilayer formation and restoring PS surface active properties. We hypothesized that this phenomenon was due to Aβ40 improving adhesion properties of a surfactant. In this work we used atomic force spectroscopy to demonstrate that Aβ40 counteracts the adhesive properties of a PS compromised by high levels of cholesterol in a PS and helps to restore the functionality of a PS. PMID:24947303

  12. Bronchitis - acute

    Science.gov (United States)

    ... sharing features on this page, please enable JavaScript. Acute bronchitis is swelling and inflammation in the main passages ... present only for a short time. Causes When acute bronchitis occurs, it almost always comes after having a ...

  13. Astragalus polysaccharides lowers plasma cholesterol through mechanisms distinct from statins.

    Directory of Open Access Journals (Sweden)

    Yunjiu Cheng

    Full Text Available To determine the efficacy and underlying mechanism of Astragalus polysaccharides (APS on plasma lipids in hypercholesterolemia hamsters. The effect of APS (0.25 g/kg/d on plasma and liver lipids, fecal bile acids and neutral sterol, cholesterol absorption and synthesis, HMG-CoA reductase activity, and gene and protein expressions in the liver and small intestine was investigated in twenty-four hypercholesterolemia hamsters. Treatment periods lasted for three months. APS significantly lowered plasma total cholesterol by 45.8%, triglycerides by 30%, and low-density lipoprotein-cholesterol by 47.4%, comparable to simvastatin. Further examinations revealed that APS reduced total cholesterol and triglycerides in the liver, increased fecal bile acid and neutral sterol excretion, inhibited cholesterol absorption, and by contrast, increased hepatic cholesterol synthesis and HMG-CoA reductase activity. Plasma total cholesterol or low-density lipoprotein-cholesterol levels were significantly correlated with cholesterol absorption rates. APS up-regulated cholesterol-7α-hydroxylase and LDL-receptor gene expressions. These new findings identify APS as a potential natural cholesterol lowering agent, working through mechanisms distinct from statins.

  14. Acute pancreatitis

    OpenAIRE

    Bo-Guang Fan; Åke Andrén-Sandberg

    2010-01-01

    Background : Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims : The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods : We reviewed the English-language literature (Medline) addressing pancreatitis. Results : Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingest...

  15. Acute pancreatitis

    OpenAIRE

    Bo-Guang Fan; Åke Andrén-Sandberg

    2010-01-01

    Background: Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims: The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods: We reviewed the English-language literature (Medline) addressing pancreatitis. Results: Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion....

  16. Preterm delivery and low maternal serum cholesterol level: Any correlation?

    Directory of Open Access Journals (Sweden)

    Ayodeji A Oluwole

    2014-01-01

    Full Text Available Background: The study assessed whether low maternal serum cholesterol during early pregnancy is associated with preterm delivery. Patients and Methods: It was a prospective observational cohort study involving pregnant women at gestational age of 14-20 weeks over a period of 12 months. Blood samples were obtained to measure total serum cholesterol concentrations and the sera were then analysed enzymatically by the cholesterol oxidase: p-aminophenazone (CHOD PAP method. Results: The study showed an incidence of 5.0% for preterm delivery in the low risk study patients. Preterm birth was 4.83-times more common with low total maternal cholesterol than with midrange total cholesterol (11.8% versus 2.2%, P = 0.024. Conclusion: Low maternal serum cholesterol (hypocholesterolaemia is associated with preterm delivery. Optimal maternal serum cholesterol during pregnancy may have merit, therefore pregnant women should be encouraged to follow a healthy, balanced diet.

  17. Preparation of cholesterol oxidase nanoparticles and their application in amperometric determination of cholesterol

    Energy Technology Data Exchange (ETDEWEB)

    Chawla, Sheetal; Rawal, Rachna; Sonia; Ramrati; Pundir, C. S., E-mail: pundircs@rediffmail.com [M. D. University, Department of Biochemistry (India)

    2013-09-15

    The nanoparticle (NP) aggregates of commercial cholesterol oxidase (ChOx) were prepared by desolvation method. The formation and characterization of ChOxNP aggregates were studied by transmission electron microscopy and scanning electron microscopy. NP aggregates were more stable, active and had a higher shelf life than that of free enzyme. An amperometric cholesterol biosensor was constructed by immobilizing ChOxNPs onto Au electrode. The biosensor showed optimum response within 8 s at pH 6.0 and 35 Degree-Sign C, when polarized at +0.27 V versus Ag/AgCl. The biosensor possesses high sensitivity and measures cholesterol concentrations as low as 1.56 mg/dl. The working linear range was 12.5-700 mg/dl for cholesterol. The biosensor was evaluated and employed for measurement of total cholesterol in human serum. The enzyme electrode lost 50 % of its initial activity during its regular use for 180 times over a period of 90 days when stored in 0.1 M sodium phosphate buffer, pH 7.0 at 4 Degree-Sign C.

  18. Iron load

    Directory of Open Access Journals (Sweden)

    Filippo Cassarà

    2013-03-01

    Full Text Available Recent research addressed the main role of hepcidin in the regulation of iron metabolism. However, while this mechanism could be relevant in causing iron load in Thalassemia Intermedia and Sickle-Cell Anemia, its role in Thalassemia Major (TM is marginal. This is mainly due to the high impact of transfusional requirement into the severe increase of body iron. Moreover, the damage of iron load may be worsened by infections, as HCV hepatitis, or liver and endocrinological damage. One of the most relevant associations was found between splenectomy and increase of risk for mortality due,probably, to more severe iron load. These issues suggest as morbidity and mortality of this group of patients they do not depend only by our ability in controlling heart damage but even in preventing or treating particular infections and complications. This finding is supported by the impairment of survival curves in patients with complications different from heart damage. However, because, during recent years different direct and indirect methods to detect iron overload in patients affected by secondary hemochromatosis have been implemented, our ability to maintain under control iron load is significantly improved. Anyway, the future in iron load management remains to be able to have an iron load map of our body for targeting chelation and other medical treatment according to the single organ damage.

  19. When cholesterol is not cholesterol: a note on the enzymatic determination of its concentration in model systems containing vegetable extracts

    Directory of Open Access Journals (Sweden)

    Pamplona Reinald

    2010-06-01

    Full Text Available Abstract Background Experimental evidences demonstrate that vegetable derived extracts inhibit cholesterol absorption in the gastrointestinal tract. To further explore the mechanisms behind, we modeled duodenal contents with several vegetable extracts. Results By employing a widely used cholesterol quantification method based on a cholesterol oxidase-peroxidase coupled reaction we analyzed the effects on cholesterol partition. Evidenced interferences were analyzed by studying specific and unspecific inhibitors of cholesterol oxidase-peroxidase coupled reaction. Cholesterol was also quantified by LC/MS. We found a significant interference of diverse (cocoa and tea-derived extracts over this method. The interference was strongly dependent on model matrix: while as in phosphate buffered saline, the development of unspecific fluorescence was inhibitable by catalase (but not by heat denaturation, suggesting vegetable extract derived H2O2 production, in bile-containing model systems, this interference also comprised cholesterol-oxidase inhibition. Several strategies, such as cholesterol standard addition and use of suitable blanks containing vegetable extracts were tested. When those failed, the use of a mass-spectrometry based chromatographic assay allowed quantification of cholesterol in models of duodenal contents in the presence of vegetable extracts. Conclusions We propose that the use of cholesterol-oxidase and/or peroxidase based systems for cholesterol analyses in foodstuffs should be accurately monitored, as important interferences in all the components of the enzymatic chain were evident. The use of adequate controls, standard addition and finally, chromatographic analyses solve these issues.

  20. Efficient detection of total cholesterol using (ChEt–ChOx/ZnO/Pt/Si) bioelectrode based on ZnO matrix

    Energy Technology Data Exchange (ETDEWEB)

    Batra, Neha; Sharma, Anjali [Department of Physics and Astrophysics, University of Delhi, Delhi 110007 (India); Tomar, Monika [Department of Physics, Miranda House, University of Delhi, Delhi 110007 (India); Gupta, Vinay, E-mail: drguptavinay@gmail.com [Department of Physics and Astrophysics, University of Delhi, Delhi 110007 (India)

    2014-07-01

    Present study highlights the importance of ZnO matrix prepared by vapour phase transport technique on platinum coated Si platform (ZnO/Pt/Si) as a potential matrix for the realization of highly sensitive and selective bioelectrode for detection of total cholesterol. Bienzymes cholesterol esterase (ChEt) and cholesterol oxidase (ChOx) have been immobilized onto the surface of ZnO thin film matrix by physical adsorption technique. The prepared bioelectrode (ChEt–ChOx/ZnO/Pt/Si) is utilized for detection of total cholesterol using the cyclic voltammetry technique. The bioelectrode (ChEt–ChOx/ZnO/Pt/Si) is found to exhibit efficient sensing response characteristics with high sensitivity of 190 μA mM{sup −1} cm{sup −2}; good linearity in the range of 0.5–12 mM total cholesterol concentration, and a very low Michaelis–Menten constant of 0.68 mM which indicates high affinity of bienzymes immobilized on ZnO towards the analyte (total cholesterol). The enhanced response is attributed to the development of ZnO thin film based matrix having good electron transport property and nanoporous morphology for effective loading of enzymes with favourable orientation. - Highlights: • Fabrication of a ZnO nanostructured thin film based efficient matrix • Utilizing prepared matrix for detection of total cholesterol (free + esterified) • Cholesterol oxidase and cholesterol esterase are the corresponding selective enzymes. • Vapour phase transport technique, for the fabrication of nanostructured ZnO matrix • The bioelectrode exhibits enhanced response characteristics towards total cholesterol detection.

  1. Data related to inflammation and cholesterol deposition triggered by macrophages exposition to modified LDL

    Directory of Open Access Journals (Sweden)

    Juan Toledo

    2016-09-01

    Full Text Available This article supports experimental evidence on the time-dependent effect on gene expression related to inflammation and cholesterol deposition in lipid-loaded cells. The cells employed were human monocytes THP1 line transformed into macrophages by treatment with phorbol esters. Macrophages were treated at different times with oxidized low density lipoprotein (Ox-LDL and then gene expression was measured. We also include data about the different types of oxidized lipoprotein obtained (low, media or high oxidation for differential exposure with Cu ions. These data include characterization to lipid and protein peroxidative damage and also quantification of cell viability by exposure to native and modified LDL. The present article complements data published in “Decreased OxLDL uptake and cholesterol efflux in THP1 cells elicited by cortisol and by cortisone through 11β-hydroxysteroid dehydrogenase type 1” Ledda et al. (in press [1].

  2. Data related to inflammation and cholesterol deposition triggered by macrophages exposition to modified LDL.

    Science.gov (United States)

    Toledo, Juan; Esteve, Montserrat; Grasa, Mar; Ledda, Angelo; Garda, Horacio; Gulfo, José; Ludovico, Ivo Díaz; Ramella, Nahuel; Gonzalez, Marina

    2016-09-01

    This article supports experimental evidence on the time-dependent effect on gene expression related to inflammation and cholesterol deposition in lipid-loaded cells. The cells employed were human monocytes THP1 line transformed into macrophages by treatment with phorbol esters. Macrophages were treated at different times with oxidized low density lipoprotein (Ox-LDL) and then gene expression was measured. We also include data about the different types of oxidized lipoprotein obtained (low, media or high oxidation) for differential exposure with Cu ions. These data include characterization to lipid and protein peroxidative damage and also quantification of cell viability by exposure to native and modified LDL. The present article complements data published in "Decreased OxLDL uptake and cholesterol efflux in THP1 cells elicited by cortisol and by cortisone through 11β-hydroxysteroid dehydrogenase type 1" Ledda et al. (in press) [1]. PMID:27331097

  3. Acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Bo-Guang Fan

    2010-01-01

    Full Text Available Background : Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims : The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods : We reviewed the English-language literature (Medline addressing pancreatitis. Results : Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion. There are a number of important issues regarding clinical highlights in the classification, treatment and prognosis of acute pancreatitis, and treatment options for complications of acute pancreatitis including pancreatic pseudocysts. Conclusions : Multidisciplinary approach should be used for the management of the patient with acute pancreatitis.

  4. Acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Bo-Guang Fan

    2010-05-01

    Full Text Available Background: Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims: The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods: We reviewed the English-language literature (Medline addressing pancreatitis. Results: Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion. There are a number of important issues regarding clinical highlights in the classification, treatment and prognosis of acute pancreatitis, and treatment options for complications of acute pancreatitis including pancreatic pseudocysts. Conclusions: Multidisciplinary approach should be used for the management of the patient with acute pancreatitis.

  5. Control of Angiogenesis by AIBP-mediated Cholesterol Efflux

    Science.gov (United States)

    Fang, Longhou; Choi, Soo-Ho; Baek, Ji Sun; Liu, Chao; Almazan, Felicidad; Ulrich, Florian; Wiesner, Philipp; Taleb, Adam; Deer, Elena; Pattison, Jennifer; Torres-Vázquez, Jesús; Li, Andrew C.; Miller, Yury I.

    2013-01-01

    Cholesterol is a structural component of the cell, indispensable for normal cellular function, but its excess often leads to abnormal proliferation, migration, inflammatory responses and/or cell death. To prevent cholesterol overload, ATP-binding cassette (ABC) transporters mediate cholesterol efflux from the cells to apolipoprotein A-I (ApoA-I) and to the ApoA-I-containing high-density lipoprotein (HDL)1-3. Maintaining efficient cholesterol efflux is essential for normal cellular function4-6. However, the role of cholesterol efflux in angiogenesis and the identity of its local regulators are poorly understood. Here we show that ApoA-I binding protein (AIBP) accelerates cholesterol efflux from endothelial cells (EC) to HDL and thereby regulates angiogenesis. AIBP/HDL-mediated cholesterol depletion reduces lipid rafts, interferes with VEGFR2 dimerization and signaling, and inhibits VEGF-induced angiogenesis in vitro and mouse aortic neovascularization ex vivo. Remarkably, Aibp regulates the membrane lipid order in embryonic zebrafish vasculature and functions as a non-cell autonomous regulator of zebrafish angiogenesis. Aibp knockdown results in dysregulated sprouting/branching angiogenesis, while forced Aibp expression inhibits angiogenesis. Dysregulated angiogenesis is phenocopied in Abca1/Abcg1-deficient embryos, and cholesterol levels are increased in Aibp-deficient and Abca1/Abcg1-deficient embryos. Our findings demonstrate that secreted AIBP positively regulates cholesterol efflux from EC and that effective cholesterol efflux is critical for proper angiogenesis. PMID:23719382

  6. Cholesterol: Its Regulation and Role in Central Nervous System Disorders

    Directory of Open Access Journals (Sweden)

    Matthias Orth

    2012-01-01

    Full Text Available Cholesterol is a major constituent of the human brain, and the brain is the most cholesterol-rich organ. Numerous lipoprotein receptors and apolipoproteins are expressed in the brain. Cholesterol is tightly regulated between the major brain cells and is essential for normal brain development. The metabolism of brain cholesterol differs markedly from that of other tissues. Brain cholesterol is primarily derived by de novo synthesis and the blood brain barrier prevents the uptake of lipoprotein cholesterol from the circulation. Defects in cholesterol metabolism lead to structural and functional central nervous system diseases such as Smith-Lemli-Opitz syndrome, Niemann-Pick type C disease, and Alzheimer’s disease. These diseases affect different metabolic pathways (cholesterol biosynthesis, lipid transport and lipoprotein assembly, apolipoproteins, lipoprotein receptors, and signaling molecules. We review the metabolic pathways of cholesterol in the CNS and its cell-specific and microdomain-specific interaction with other pathways such as the amyloid precursor protein and discuss potential treatment strategies as well as the effects of the widespread use of LDL cholesterol-lowering drugs on brain functions.

  7. Phytosterol ester constituents affect micellar cholesterol solubility in model bile.

    Science.gov (United States)

    Brown, Andrew W; Hang, Jiliang; Dussault, Patrick H; Carr, Timothy P

    2010-09-01

    Plant sterols and stanols (phytosterols) and their esters are nutraceuticals that lower LDL cholesterol, but the mechanisms of action are not fully understood. We hypothesized that intact esters and simulated hydrolysis products of esters (phytosterols and fatty acids in equal ratios) would differentially affect the solubility of cholesterol in model bile mixed micelles in vitro. Sodium salts of glycine- and taurine-conjugated bile acids were sonicated with phosphatidylcholine and either sterol esters or combinations of sterols and fatty acids to determine the amount of cholesterol solubilized into micelles. Intact sterol esters did not solubilize into micelles, nor did they alter cholesterol solubility. However, free sterols and fatty acids altered cholesterol solubility independently (no interaction effect). Equal contents of cholesterol and either campesterol, stigmasterol, sitosterol, or stigmastanol (sitostanol) decreased cholesterol solubility in micelles by approximately 50% compared to no phytosterol present, with stigmasterol performing slightly better than sitosterol. Phytosterols competed with cholesterol in a dose-dependent manner, demonstrating a 1:1 M substitution of phytosterol for cholesterol in micelle preparations. Unsaturated fatty acids increased the micelle solubility of sterols as compared with saturated or no fatty acids. No differences were detected in the size of the model micelles. Together, these data indicate that stigmasterol combined with saturated fatty acids may be more effective at lowering cholesterol micelle solubility in vivo.

  8. Cholesterol Metabolism and Prostate Cancer Lethality.

    Science.gov (United States)

    Stopsack, Konrad H; Gerke, Travis A; Sinnott, Jennifer A; Penney, Kathryn L; Tyekucheva, Svitlana; Sesso, Howard D; Andersson, Swen-Olof; Andrén, Ove; Cerhan, James R; Giovannucci, Edward L; Mucci, Lorelei A; Rider, Jennifer R

    2016-08-15

    Cholesterol metabolism has been implicated in prostate cancer pathogenesis. Here, we assessed the association of intratumoral mRNA expression of cholesterol synthesis enzymes, transporters, and regulators in tumor specimen at diagnosis and lethal prostate cancer, defined as mortality or metastases from prostate cancer in contrast to nonlethal disease without evidence of metastases after at least 8 years of follow-up. We analyzed the prospective prostate cancer cohorts within the Health Professionals Follow-up Study (n = 249) and the Physicians' Health Study (n = 153) as well as expectantly managed patients in the Swedish Watchful Waiting Study (n = 338). The expression of squalene monooxygenase (SQLE) was associated with lethal cancer in all three cohorts. Men with high SQLE expression (>1 standard deviation above the mean) were 8.3 times (95% confidence interval, 3.5 to 19.7) more likely to have lethal cancer despite therapy compared with men with the mean level of SQLE expression. Absolute SQLE expression was associated with lethal cancer independently from Gleason grade and stage, as was a SQLE expression ratio in tumor versus surrounding benign prostate tissue. Higher SQLE expression was tightly associated with increased histologic markers of angiogenesis. Collectively, this study establishes the prognostic value of intratumoral cholesterol synthesis as measured via SQLE, its second rate-limiting enzyme. SQLE expression at cancer diagnosis is prognostic for lethal prostate cancer both after curative-intent prostatectomy and in a watchful waiting setting, possibly by facilitating micrometastatic disease. Cancer Res; 76(16); 4785-90. ©2016 AACR.

  9. Beam loading

    CERN Document Server

    Gamp, Alexander

    2013-01-01

    We begin by giving a description of the radio-frequency generator-cavity-beam coupled system in terms of basic quantities. Taking beam loading and cavity detuning into account, expressions for the cavity impedance as seen by the generator and as seen by the beam are derived. Subsequently methods of beam-loading compensation by cavity detuning, radio-frequency feedback and feedforward are described. Examples of digital radio-frequency phase and amplitude control for the special case of superconducting cavities are also given. Finally, a dedicated phase loop for damping synchrotron oscillations is discussed.

  10. The Epigenetic Drug 5-Azacytidine Interferes with Cholesterol and Lipid Metabolism*

    Science.gov (United States)

    Poirier, Steve; Samami, Samaneh; Mamarbachi, Maya; Demers, Annie; Chang, Ta Yuan; Vance, Dennis E.; Hatch, Grant M.; Mayer, Gaétan

    2014-01-01

    DNA methylation and histone acetylation inhibitors are widely used to study the role of epigenetic marks in the regulation of gene expression. In addition, several of these molecules are being tested in clinical trials or already in use in the clinic. Antimetabolites, such as the DNA-hypomethylating agent 5-azacytidine (5-AzaC), have been shown to lower malignant progression to acute myeloid leukemia and to prolong survival in patients with myelodysplastic syndromes. Here we examined the effects of DNA methylation inhibitors on the expression of lipid biosynthetic and uptake genes. Our data demonstrate that, independently of DNA methylation, 5-AzaC selectively and very potently reduces expression of key genes involved in cholesterol and lipid metabolism (e.g. PCSK9, HMGCR, and FASN) in all tested cell lines and in vivo in mouse liver. Treatment with 5-AzaC disturbed subcellular cholesterol homeostasis, thereby impeding activation of sterol regulatory element-binding proteins (key regulators of lipid metabolism). Through inhibition of UMP synthase, 5-AzaC also strongly induced expression of 1-acylglycerol-3-phosphate O-acyltransferase 9 (AGPAT9) and promoted triacylglycerol synthesis and cytosolic lipid droplet formation. Remarkably, complete reversal was obtained by the co-addition of either UMP or cytidine. Therefore, this study provides the first evidence that inhibition of the de novo pyrimidine synthesis by 5-AzaC disturbs cholesterol and lipid homeostasis, probably through the glycerolipid biosynthesis pathway, which may contribute mechanistically to its beneficial cytostatic properties. PMID:24855646

  11. The epigenetic drug 5-azacytidine interferes with cholesterol and lipid metabolism.

    Science.gov (United States)

    Poirier, Steve; Samami, Samaneh; Mamarbachi, Maya; Demers, Annie; Chang, Ta Yuan; Vance, Dennis E; Hatch, Grant M; Mayer, Gaétan

    2014-07-01

    DNA methylation and histone acetylation inhibitors are widely used to study the role of epigenetic marks in the regulation of gene expression. In addition, several of these molecules are being tested in clinical trials or already in use in the clinic. Antimetabolites, such as the DNA-hypomethylating agent 5-azacytidine (5-AzaC), have been shown to lower malignant progression to acute myeloid leukemia and to prolong survival in patients with myelodysplastic syndromes. Here we examined the effects of DNA methylation inhibitors on the expression of lipid biosynthetic and uptake genes. Our data demonstrate that, independently of DNA methylation, 5-AzaC selectively and very potently reduces expression of key genes involved in cholesterol and lipid metabolism (e.g. PCSK9, HMGCR, and FASN) in all tested cell lines and in vivo in mouse liver. Treatment with 5-AzaC disturbed subcellular cholesterol homeostasis, thereby impeding activation of sterol regulatory element-binding proteins (key regulators of lipid metabolism). Through inhibition of UMP synthase, 5-AzaC also strongly induced expression of 1-acylglycerol-3-phosphate O-acyltransferase 9 (AGPAT9) and promoted triacylglycerol synthesis and cytosolic lipid droplet formation. Remarkably, complete reversal was obtained by the co-addition of either UMP or cytidine. Therefore, this study provides the first evidence that inhibition of the de novo pyrimidine synthesis by 5-AzaC disturbs cholesterol and lipid homeostasis, probably through the glycerolipid biosynthesis pathway, which may contribute mechanistically to its beneficial cytostatic properties. PMID:24855646

  12. Effects of cholesterol on plasma membrane lipid order in MCF-7 cells by two-photon microscopy

    Science.gov (United States)

    Zeng, Yixiu; Chen, Jianling; Yang, Hongqin; Wang, Yuhua; Li, Hui; Xie, Shusen

    2014-09-01

    Lipid rafts are cholesterol- and glycosphingolipids- enriched microdomains on plasma membrane surface of mammal cells, involved in a variety of cellular processes. Depleting cholesterol from the plasma membrane by drugs influences the trafficking of lipid raft markers. Optical imaging techniques are powerful tools to study lipid rafts in live cells due to its noninvasive feature. In this study, breast cancer cells MCF-7 were treated with different concentrations of MβCD to deplete cholesterol and an environmentally sensitive fluorescence probe, Laurdan was loaded to image lipid order by two-photon microscopy. The generalized polarization (GP) values were calculated to distinguish the lipid order and disorder phase. GP images and GP distributions of native and cholesterol-depleted MCF-7 cells were obtained. Our results suggest that even at low concentration (0.5 mM) of MβCD, the morphology of the MCF-7 cells changes. Small high GP areas (lipid order phase) decrease more rapidly than low GP areas (lipid disorder phase), indicating that lipid raft structure was altered more severely than nonraft domains. The data demonstrates that cholesterol dramatically affect raft coverage and plasma membrane fluidity in living cells.

  13. Potassium-doped carbon nanotubes toward the direct electrochemistry of cholesterol oxidase and its application in highly sensitive cholesterol biosensor

    Energy Technology Data Exchange (ETDEWEB)

    Li Xiaorong [State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China); Xu Jingjuan, E-mail: xujj@nju.edu.cn [State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China); Chen Hongyuan [State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China)

    2011-10-30

    We demonstrate herein a newly developed serum total cholesterol biosensor by using the direct electron transfer of cholesterol oxidase (ChOx), which is based on the immobilization of cholesterol oxidase and cholesterol esterase (ChEt) on potassium-doped multi-walled carbon nanotubes (KMWNTs) modified electrodes. The KMWNTs accelerate the electron transfer from electrode surface to the immobilized ChOx, achieving the direct electrochemistry of ChOx and maintaining its bioactivity. As a new platform in cholesterol analysis, the resulting electrode (ChOx/KMWNTs/GCE) exhibits a sensitive response to free cholesterol, with a linear range of 0.050-16.0 {mu}mol L{sup -1} and a detection limit of 5.0 nmol L{sup -1} (S/N = 3). Coimmobilization of ChEt and ChOx (ChEt/ChOx/KMWNTs/GCE) allows the determination of both free cholesterol and esterified cholesterol. The resulting biosensor shows the same linear range of 0.050-16.0 {mu}mol L{sup -1} for free cholesterol and cholesteryl oleate, with the detection limit of 10.0 and 12.0 nmol L{sup -1} (S/N = 3), respectively. The concentrations of total (free and esterified) cholesterol in human serum samples, determined by using the techniques developed in the present study, are in good agreement with those determined by the well-established techniques using the spectrophotometry.

  14. Influence of infant and juvenile diets on serum cholesterol, lipoprotein cholesterol, and apolipoprotein concentrations in juvenile baboons (Papio sp.).

    Science.gov (United States)

    Mott, G E; McMahan, C A; Kelley, J L; Farley, C M; McGill, H C

    1982-11-01

    The long-term effects of infant diet (breast milk or formula containing 2, 30, or 60 mg/dl cholesterol) and subsequent dietary cholesterol (1 mg/kcal) and fat (saturated or unsaturated) on serum lipid and apolipoprotein concentrations were estimated using 82 juvenile baboons 4-6 years of age. A significant interaction of infant diet (breast vs formula) with type of fat (saturated vs unsaturated) at 4-6 years of age was observed on HDL cholesterol and apolipoprotein A-I (apoA-I) concentrations. That is, animals breast-fed as infants had higher HDL cholesterol and apoA-I concentrations when fed unsaturated fat from weaning to 4-6 years of age than those fed saturated fat (77 vs 68 mg/dl). In contrast, animals fed formulas in infancy followed by a diet containing unsaturated fat had lower HDL cholesterol and apoA-I concentrations at 4-6 years of age than did those fed saturated fat (67 vs 78 mg/dl). However, breast feeding or feeding formulas containing various levels of cholesterol for 3 months during infancy did not result in statistically significant differences in total serum cholesterol, VLDL + LDL cholesterol and apolipoprotein B (apoB) concentrations. Dietary cholesterol after infancy significantly increased serum total cholesterol, VLDL + LDL and HDL cholesterol, apoA-I and apoB concentrations. All of these response variables also were higher in animals fed saturated fat compared to those fed unsaturated fat on the same level of cholesterol. At 4-6 years of age, regardless of diet, females had significantly higher serum VLDL + LDL cholesterol (57 vs 43 mg/dl) and apoB concentrations (39 vs 30 mg/dl) than did males.

  15. Preparation of intravenous cholesterol tracer using current good manufacturing practices.

    Science.gov (United States)

    Lin, Xiaobo; Ma, Lina; Racette, Susan B; Swaney, William P; Ostlund, Richard E

    2015-12-01

    Studies of human reverse cholesterol transport require intravenous infusion of cholesterol tracers. Because insoluble lipids may pose risk and because it is desirable to have consistent doses of defined composition available over many months, we investigated the manufacture of cholesterol tracer under current good manufacturing practice (CGMP) conditions appropriate for phase 1 investigation. Cholesterol tracer was prepared by sterile admixture of unlabeled cholesterol or cholesterol-d7 in ethanol with 20% Intralipid(®). The resulting material was filtered through a 1.2 micron particulate filter, stored at 4°C, and tested at time 0, 1.5, 3, 6, and 9 months for sterility, pyrogenicity, autoxidation, and particle size and aggregation. The limiting factor for stability was a rise in thiobarbituric acid-reacting substances of 9.6-fold over 9 months (P manufacturing methods can be achieved in the academic setting and need to be considered for critical components of future metabolic studies.

  16. Preparation of intravenous cholesterol tracer using current good manufacturing practices.

    Science.gov (United States)

    Lin, Xiaobo; Ma, Lina; Racette, Susan B; Swaney, William P; Ostlund, Richard E

    2015-12-01

    Studies of human reverse cholesterol transport require intravenous infusion of cholesterol tracers. Because insoluble lipids may pose risk and because it is desirable to have consistent doses of defined composition available over many months, we investigated the manufacture of cholesterol tracer under current good manufacturing practice (CGMP) conditions appropriate for phase 1 investigation. Cholesterol tracer was prepared by sterile admixture of unlabeled cholesterol or cholesterol-d7 in ethanol with 20% Intralipid(®). The resulting material was filtered through a 1.2 micron particulate filter, stored at 4°C, and tested at time 0, 1.5, 3, 6, and 9 months for sterility, pyrogenicity, autoxidation, and particle size and aggregation. The limiting factor for stability was a rise in thiobarbituric acid-reacting substances of 9.6-fold over 9 months (P manufacturing methods can be achieved in the academic setting and need to be considered for critical components of future metabolic studies. PMID:26416797

  17. Cholesterol monohydrate nucleation in ultrathin films on water

    DEFF Research Database (Denmark)

    Rapaport, H.; Kuzmenko, I.; Lafont, S.;

    2001-01-01

    The growth of a cholesterol crystalline phase, three molecular layers thick at the air-water interface, was monitored by grazing incidence x-ray diffraction and x-ray reflectivity. Upon compression, a cholesterol film transforms from a monolayer of trigonal symmetry and low crystallinity to a...... trilayer, composed of a highly crystalline bilayer in a rectangular lattice and a disordered top cholesterol layer. This system undergoes a phase transition into a crystalline trilayer incorporating ordered water between the hydroxyl groups of the top and middle sterol layers in an arrangement akin to the...... triclinic 3-D crystal structure of cholesterol . H(2)O. By comparison, the cholesterol derivative stigmasterol transforms, upon compression, directly into a crystalline trilayer in the rectangular lattice. These results may contribute to an understanding of the onset of cholesterol crystallization in...

  18. Apoprotein E genotype and the response of serum cholesterol to dietary fat, cholesterol and cafestol

    NARCIS (Netherlands)

    Weggemans, R.M.; Zock, P.L.; Ordovas, J.M.; Pedro-Botet, J.; Katan, M.B.

    2001-01-01

    Previous studies on the effect of apoprotein E (APOE) polymorphism on the response of serum lipids to diet showed inconsistent results. We therefore studied the effect of apoprotein E polymorphism on responses of serum cholesterol and lipoproteins to various dietary treatments. We combined data on r

  19. Percentage of Adults with High Cholesterol Whose LDL Cholesterol Levels Are Adequately Controlled

    Science.gov (United States)

    ... non-missing response to cholesterol questionnaire. Exclusion Criteria: Pregnant women. Estimates for 18-39 year olds were not ... for only one type of service, such as dental or vision care. Persons covered by ... and Prevention, National Center for Health Statistics from the National ...

  20. Load sensor

    NARCIS (Netherlands)

    Van den Ende, D.; Almeida, P.M.R.; Dingemans, T.J.; Van der Zwaag, S.

    2007-01-01

    The invention relates to a load sensor comprising a polymer matrix and a piezo-ceramic material such as PZT, em not bedded in the polymer matrix, which together form a compos not ite, wherein the polymer matrix is a liquid crystalline resin, and wherein the piezo-ceramic material is a PZT powder for

  1. Carbohydrate Loading.

    Science.gov (United States)

    Csernus, Marilyn

    Carbohydrate loading is a frequently used technique to improve performance by altering an athlete's diet. The objective is to increase glycogen stored in muscles for use in prolonged strenuous exercise. For two to three days, the athlete consumes a diet that is low in carbohydrates and high in fat and protein while continuing to exercise and…

  2. Metamaterial Loading

    Directory of Open Access Journals (Sweden)

    F. Paredes

    2012-01-01

    Full Text Available It is shown that printed antennas loaded with metamaterial resonators can be designed to exhibit multiband functionality. Two different antenna types and metamaterial loading are considered: (i printed dipoles or monopoles loaded with open complementary split ring resonators (OCSRRs and (ii meander line or folded dipole antennas loaded with split ring resonators (SRRs or spiral resonators (SRs. In the first case, multiband operation is achieved by series connecting one or more OCSRRs within the dipole/monopole. Such resonators force opens at their positions, and by locating them at a quarter wavelength (at the required operating frequencies from the feeding point, it is possible to achieve multiple radiation bands. In the second case, dual-band functionality is achieved through the perturbation of the antenna characteristics caused by the presence of the metamaterial resonators. This latter strategy is specially suited to achieve conjugate matching between the antenna and the chip in radiofrequency identification (RFID tags at two of the regulated UHF-RFID bands.

  3. Melittin-Lipid Bilayer Interactions and the Role of Cholesterol

    OpenAIRE

    Wessman, Per; Strömstedt, Adam A; Malmsten, Martin; Edwards, Katarina

    2008-01-01

    The membrane-destabilizing effect of the peptide melittin on phosphatidylcholine membranes is modulated by the presence of cholesterol. This investigation shows that inclusion of 40 mol % cholesterol in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine or 1,2-dioleoyl-sn-glycero-3-phosphocholine liposomes reduces melittin's affinity for the membrane. It is significant that the presence of cholesterol does not increase the amount of membrane-associated melittin needed to cause maximum leakage f...

  4. Interaction of Melittin with Membrane Cholesterol: A Fluorescence Approach

    OpenAIRE

    Raghuraman, H.; Chattopadhyay, Amitabha

    2004-01-01

    We have monitored the organization and dynamics of the hemolytic peptide melittin in membranes containing cholesterol by utilizing the intrinsic fluorescence properties of its functionally important sole tryptophan residue and circular dichroism spectroscopy. The significance of this study is based on the fact that the natural target for melittin is the erythrocyte membrane, which contains high amounts of cholesterol. Our results show that the presence of cholesterol inhibits melittin-induced...

  5. A review on lecithin:cholesterol acyltransferase deficiency.

    Science.gov (United States)

    Saeedi, Ramesh; Li, Min; Frohlich, Jiri

    2015-05-01

    Lecithin cholesterol acyl transferase (LCAT) is a plasma enzyme which esterifies cholesterol, and plays a key role in the metabolism of high-density lipoprotein cholesterol (HDL-C). Genetic disorders of LCAT are associated with lipoprotein abnormalities including low levels of HDL-C and presence of lipoprotein X, and clinical features mainly corneal opacities, changes in erythrocyte morphology and renal failure. Recombinant LCAT is being developed for the treatment of patients with LCAT deficiency. PMID:25172171

  6. Cholesterol esterification during differentiation of mouse erythroleukemia (Friend) cells

    Science.gov (United States)

    Mulas, Maria Franca; Mandas, Antonella; Abete, Claudia; Dessì, Sandra; Mocali, Alessandra; Paoletti, Francesco

    2011-01-01

    Cholesterol is an essential constituent of all mammalian cell membranes and its availability is therefore a prerequisite for cellular growth and other functions. Several lines of evidence are now indicating an association between alterations of cholesterol homeostasis and cell cycle progression. However, the role of cholesterol in cell differentiation is still largely unknown. To begin to address this issue, in this study we examined changes in cholesterol metabolism and in the mRNA levels of proteins involved in cholesterol import and esterification (multi-drug resistance, MDR-3) and acylCoA: cholesterol acyltransferase (ACAT) and cholesterol export (caveolin-1) in Friend virus-induced erythroleukemia cells (MELC), in the absence or in the presence of the chemical inducer of differentiation, hexamethylene bisacetamide (HMBA). FBS-stimulated growth of MELC was accompanied by an immediate elevation of cholesterol synthesis and cholesterol esterification, and by an increase in the levels of MDR-3 and ACAT mRNAs. A decrease in caveolin-1 expression was also observed. However, when MELC were treated with HMBA, the inhibition of DNA synthesis caused by HMBA treatment, was associated with a decrease in cholesterol esterification and in ACAT and MDR-3 mRNA levels and an increase in caveolin-1 mRNA. Detection of cytoplasmic neutral lipids by staining MELC with oil red O, a dye able to evidence CE but not FC, revealed that HMBA-treatment also reduced growth-stimulated accumulation of cholesterol ester to approximately the same extent as the ACAT inhibitor, SaH. Overall, these results indicate for the first time a role of cholesterol esterification and of some related genes in differentiation of erythroid cells. PMID:22184540

  7. Cholesterol esterification during differentiation of mouse erythroleukemia (Friend cells

    Directory of Open Access Journals (Sweden)

    Maria Franca Mulas

    2011-10-01

    Full Text Available Cholesterol is an essential constituent of all mammalian cell membranes, and its availability is therefore a prerequisite for cellular growth and other functions. Several lines of evidence are now indicating an association between alterations of cholesterol homeostasis and cell cycle progression. However, the role of cholesterol in cell differentiation is still largely unknown. To begin to address this issue, in this study we examined changes in cholesterol metabolism and in the mRNA levels of proteins involved in cholesterol import and esterification (multi-drug resistance, MDR-3 and acylCoA:cholesterol acyltransferase (ACAT and cholesterol export (caveolin-1 in Friend virus-induced erythroleukemia cells (MELC, in the absence or in the presence of the chemical inducer of differentiation, hexamethylene bisacetamide (HMBA. FBS-stimulated growth of MELC was accompanied by an immediate elevation of cholesterol synthesis and cholesterol esterification, and by an increase in the levels of MDR-3 and ACAT mRNAs. A decrease in caveolin-1 expression was also observed. However, when MELC were treated with HMBA, the inhibition of DNA synthesis caused by HMBA treatment, was associated with a decrease in cholesterol esterification and in ACAT and MDR-3 mRNA levels and an increase in caveolin-1 mRNA. Detection of cytoplasmic neutral lipids by staining MELC with oil red O, a dye able to evidence CE but not FC, revealed that HMBA-treatment also reduced growth-stimulated accumulation of cholesterol ester to approximately the same extent as the ACAT inhibitor, SaH. Overall, these results indicate for the first time a role of cholesterol esterification and of some related genes in differentiation of erythroid cells.

  8. Interaction of G protein coupled receptors and cholesterol.

    Science.gov (United States)

    Gimpl, Gerald

    2016-09-01

    G protein coupled receptors (GPCRs) form the largest receptor superfamily in eukaryotic cells. Owing to their seven transmembrane helices, large parts of these proteins are embedded in the cholesterol-rich plasma membrane bilayer. Thus, GPCRs are always in proximity to cholesterol. Some of them are functionally dependent on the specific presence of cholesterol. Over the last years, enormous progress on receptor structures has been achieved. While lipophilic ligands other than cholesterol have been shown to bind either inside the helix bundle or at the receptor-lipid interface, the binding site of cholesterol was either a single transmembrane helix or a groove between two or more transmembrane helices. A clear preference for one of the two membrane leaflets has not been observed. Not surprisingly, many hydrophobic residues (primarily leucine and isoleucine) were found to be involved in cholesterol binding. In most cases, the rough β-face of cholesterol contacted the transmembrane helix bundle rather than the surrounding lipid matrix. The polar hydroxy group of cholesterol was localized near the water-membrane interface with potential hydrogen bonding to residues in receptor loop regions. Although a canonical motif, designated as CCM site, was detected as a specific cholesterol binding site in case of the β2AR, this site was not found to be occupied by cholesterol in other GPCRs possessing the same motif. Cholesterol-receptor interactions can increase the compactness of the receptor structure and are able to enhance the conformational stability towards active or inactive receptor states. Overall, all current data suggest a high plasticity of cholesterol interaction sites in GPCRs. PMID:27108066

  9. CHOLESTEROL OXIDATION PRODUCTS IN MILK AND MILK PRODUCTS

    Directory of Open Access Journals (Sweden)

    A. Kemal SEÇKİN

    2004-02-01

    Full Text Available Cholesterol oxidation products (COPs are occurred by heat and light factors during processing, improper packaging and storage conditions. COPs are mutagenic, carcinogenity, cytotoxic, angiotoxic and damage to cell membrane and effect biosynthesis cholesterol in the metabolism . So, COPs have potential risk for public health. Also, in milk and milk products that have high cholesterol COPs can be also formed during processing and storage. Therefore it is necessary that measurements must be taken and standards must be in dairy about COPs.

  10. Cholesterol granuloma of the paratesticular tissue: A case report

    Science.gov (United States)

    Unal, Dursun; Kilic, Metin; Oner, Sedat; Erkinuresin, Taskın; Demirbas, Murat; Coban, Soner; Aydos, Mustafa Murat

    2015-01-01

    A 38-year-old man was admitted to our clinic with an enlarging right scrotal mass that had been present for 7 years. Right radical inguinal orchiectomy was performed and a histopathological diagnosis confirmed a very rare case of cholesterol granuloma of the paratesticular tissue. It can be very difficult to preoperatively distinguish testicular tumours from cholesterol granulomas of the testis or epididymis. Cholesterol granuloma should be kept in mind in patients with large and non-tender scrotal masses. PMID:26225185

  11. Alterations of serum cholesterol and serum lipoprotein in breast cancer of women

    OpenAIRE

    Hasija, Kiran; Bagga, Hardeep K.

    2005-01-01

    Fasting blood sample of 50 normal subjects (control) and 100 patients of breast cancer were investigated for serum total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, very low density lipoprotein, high density lipoprotein cholesterol:low density lipoprotein cholesterol ratio and total cholesterol:high density lipoprotein cholesterol ratio during breast cancer of women. Five cancer stages, types, age groups, parity and menopausal status were undertaken...

  12. Development of alimentary cholesterol in the plasma and the plasmatic lipoproteins in man, after ingestion of a meal containing octa-deuterated cholesterol; Devenir du cholesterol alimentaire dans le plasma et les lipoproteines plasmatiques chez l`homme, apres ingestion d`un repas contenant du cholesterol octa-deutere

    Energy Technology Data Exchange (ETDEWEB)

    Becue, T.; Ferezou, J.; Simon, G. [Paris-11 Univ., 91 - Orsay (France); Bernard, P.M.; Portugal, H. [Hopital Sainte-Marguerite, 13 - Marseille (France); Dubois, C.; Lairon, D.

    1994-12-31

    Cholesterol absorbed after a test-meal has two origins with man: the biliary cholesterol and the alimentary cholesterol. In order to understand the mechanism of the modification of cholesterol intestinal absorption by oat bran, the alimentary cholesterol has been labelled with octa-deuterated cholesterol, in test-diets. The kinetics of D-cholesterol in plasma and chylomicrons is described. 1 fig., 6 refs.

  13. Haptoglobin increases with age in rat hippocampus and modulates Apolipoprotein E mediated cholesterol trafficking in neuroblastoma cell lines

    Directory of Open Access Journals (Sweden)

    Maria Stefania eSpagnuolo

    2014-08-01

    Full Text Available Alteration in cholesterol metabolism has been implicated in the pathogenesis of several neurodegenerative disorders. Apolipoprotein E (ApoE is the major component of brain lipoproteins supporting cholesterol transport. We previously reported that the acute-phase protein Haptoglobin (Hpt binds ApoE, and influences its function in blood cholesterol homeostasis. Major aim of this study was to investigate whether Hpt influences the mechanisms by which cholesterol is shuttled from astrocytes to neurons. In detail it was studied Hpt effect on ApoE-dependent cholesterol efflux from astrocytes and ApoE-mediated cholesterol incorporation in neurons. We report here that Hpt impairs ApoE-mediated cholesterol uptake in human neuroblastoma cell line SH-SY5Y, and limits the toxicity of a massive concentration of cholesterol for these cells, while it does not affect cholesterol efflux from the human glioblastoma-astrocytoma cell line U-87 MG. As aging is the most important nongenetic risk factor for various neurodegenerative disorders, and our results suggest that Hpt modulates ApoE functions, we evaluated the Hpt and ApoE expression profiles in cerebral cortex and hippocampus of adolescent (2 months, adult (5 and 8 months, and middle-aged (16 months rats. Hpt mRNA level was higher in hippocampus of 8 and 16 month-old than in 2-month old rats (p<0.05, and Hpt concentration increased with the age from adolescence to middle-age (p<0.001. ApoE concentration, in hippocampus, was higher (p<0.001 in 5 month-old rats compared to 2 month but did not further change with aging. No age-related changes of Hpt (protein and mRNA were found in the cortex. Our results suggest that aging is associated with changes, particularly in the hippocampus, in the Hpt/ApoE ratio. Age-related changes in the concentration of Hpt were also found in human cerebrospinal fluids.The age-related changes might affect neuronal function and survival in brain, and have important implications in

  14. Crystallogeny fundamentals of the cholesterol gallstone

    Institute of Scientific and Technical Information of China (English)

    Wu Jie; Zhou Jianli; He Lijun; Qu Xingang; Gu Lin; Yang Haimin

    2007-01-01

    The nucleation mechanism and crystal growth process of the cholesterol gallstone are studied and a systematic theory expounded by crystallogeny is proposed. Normal feed and stone-forming feed were used to raise guinea pigs in the control and stone-causing groups respectively. The state and transformation of liquid crystal vesicles, the appearance of crystal nuclei, and the formation of microcrystal grains were observed under a polarizing microscope during the experimental period. It was found that the liquid crystal vesicles in the bile of the control group were small, scattered, and always existed as single forms, and no shaped gallstone crystals were formed.While in the stone-causing group, liquid crystal vesicles grew to larger ones, and then aggregated to form large liquid crystal cells. Solid crystal growth along the edge of these liquid crystal cells formed microcrystal grains. These demonstrated that bile liquid crystal vesicles form the basic nuclei of cholesterol gallstone. Heterogeneous nucleation is the common process in the formation of crystal nuclei and crystal growth.

  15. High-density lipoprotein cholesterol: How High

    Directory of Open Access Journals (Sweden)

    G Rajagopal

    2012-01-01

    Full Text Available The high-density lipoprotein cholesterol (HDL-C is considered anti-atherogenic good cholesterol. It is involved in reverse transport of lipids. Epidemiological studies have found inverse relationship of HDL-C and coronary heart disease (CHD risk. When grouped according to HDL-C, subjects having HDL-C more than 60 mg/dL had lesser risk of CHD than those having HDL-C of 40-60 mg/dL, who in turn had lesser risk than those who had HDL-C less than 40 mg/dL. No upper limit for beneficial effect of HDL-C on CHD risk has been identified. The goals of treating patients with low HDL-C have not been firmly established. Though many drugs are known to improve HDL-C concentration, statins are proven to improve CHD risk and mortality. Cholesteryl ester transfer protein (CETP is involved in metabolism of HDL-C and its inhibitors are actively being screened for clinical utility. However, final answer is still awaited on CETP-inhibitors.

  16. Specific Ion Effects in Cholesterol Monolayers

    Directory of Open Access Journals (Sweden)

    Teresa Del Castillo-Santaella

    2016-05-01

    Full Text Available The interaction of ions with interfaces and, in particular, the high specificity of these interactions to the particular ions considered, are central questions in the field of surface forces. Here we study the effect of different salts (NaI, NaCl, CaCl2 and MgCl2 on monolayers made of cholesterol molecules, both experimentally (surface area vs. lateral pressure isotherms measured by a Langmuir Film Balance and theoretically (molecular dynamics (MD all-atomic simulations. We found that surface isotherms depend, both quantitatively and qualitatively, on the nature of the ions by altering the shape and features of the isotherm. In line with the experiments, MD simulations show clear evidences of specific ionic effects and also provide molecular level details on ion specific interactions with cholesterol. More importantly, MD simulations show that the interaction of a particular ion with the surface depends strongly on its counterion, a feature ignored so far in most theories of specific ionic effects in surface forces.

  17. Cholesterol overload induces apoptosis in SH-SY5Y human neuroblastoma cells through the up regulation of flotillin-2 in the lipid raft and the activation of BDNF/Trkb signaling.

    Science.gov (United States)

    Huang, Yen-Ning; Lin, Ching-I; Liao, Hsiang; Liu, Chin-Yu; Chen, Yue-Hua; Chiu, Wan-Chun; Lin, Shyh-Hsiang

    2016-07-22

    Epidemiological investigations have shown that Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. It has been indicated that the cholesterol concentration in the brain of AD patients is higher than that in normal people. In this study, we investigated the effects of cholesterol concentrations, 0, as the control, 3.125, 12.5, and 25μM, on cholesterol metabolism, neuron survival, AD-related protein expressions, and cell morphology and apoptosis using SH-SY5Y human neuroblastoma cells. We observed that expressions of cholesterol hydroxylase (Cyp46), flotillin-2 (a marker of lipid raft content), and truncated tyrosine kinase B (TrkBtc) increased, while expressions of brain-derived neurotrophic factor (BDNF) and full-length TrkB (TrkBfl) decreased as the concentration of cholesterol loading increased. Down-regulation of the PI3K-Akt-glycogen synthase kinase (GSK)-3β cascade and cell apoptosis were also observed at higher concentrations of cholesterol, along with elevated levels of β-amyloid (Aβ), β-secretase (BACE), and reactive oxygen species (ROS). In conclusion, we found that cholesterol overload in neuronal cells imbalanced the cholesterol homeostasis and increased the protein expressions causing cell apoptosis, which illustrates the neurodegenerative pathology of abnormally elevated cholesterol concentrations found in AD patients.

  18. Cholesterol assimilation by Lactobacillus probiotic bacteria: an in vitro investigation.

    Science.gov (United States)

    Tomaro-Duchesneau, Catherine; Jones, Mitchell L; Shah, Divya; Jain, Poonam; Saha, Shyamali; Prakash, Satya

    2014-01-01

    Excess cholesterol is associated with cardiovascular diseases (CVD), an important cause of mortality worldwide. Current CVD therapeutic measures, lifestyle and dietary interventions, and pharmaceutical agents for regulating cholesterol levels are inadequate. Probiotic bacteria have demonstrated potential to lower cholesterol levels by different mechanisms, including bile salt hydrolase activity, production of compounds that inhibit enzymes such as 3-hydroxy-3-methylglutaryl coenzyme A, and cholesterol assimilation. This work investigates 11 Lactobacillus strains for cholesterol assimilation. Probiotic strains for investigation were selected from the literature: Lactobacillus reuteri NCIMB 11951, L. reuteri NCIMB 701359, L. reuteri NCIMB 702655, L. reuteri NCIMB 701089, L. reuteri NCIMB 702656, Lactobacillus fermentum NCIMB 5221, L. fermentum NCIMB 8829, L. fermentum NCIMB 2797, Lactobacillus rhamnosus ATCC 53103 GG, Lactobacillus acidophilus ATCC 314, and Lactobacillus plantarum ATCC 14917. Cholesterol assimilation was investigated in culture media and under simulated intestinal conditions. The best cholesterol assimilator was L. plantarum ATCC 14917 (15.18±0.55 mg/10(10) cfu) in MRS broth. L. reuteri NCIMB 701089 assimilated over 67% (2254.70±63.33 mg/10(10) cfu) of cholesterol, the most of all the strains, under intestinal conditions. This work demonstrates that probiotic bacteria can assimilate cholesterol under intestinal conditions, with L. reuteri NCIMB 701089 showing great potential as a CVD therapeutic. PMID:25295259

  19. Cholesterol Assimilation by Lactobacillus Probiotic Bacteria: An In Vitro Investigation

    Directory of Open Access Journals (Sweden)

    Catherine Tomaro-Duchesneau

    2014-01-01

    Full Text Available Excess cholesterol is associated with cardiovascular diseases (CVD, an important cause of mortality worldwide. Current CVD therapeutic measures, lifestyle and dietary interventions, and pharmaceutical agents for regulating cholesterol levels are inadequate. Probiotic bacteria have demonstrated potential to lower cholesterol levels by different mechanisms, including bile salt hydrolase activity, production of compounds that inhibit enzymes such as 3-hydroxy-3-methylglutaryl coenzyme A, and cholesterol assimilation. This work investigates 11 Lactobacillus strains for cholesterol assimilation. Probiotic strains for investigation were selected from the literature: Lactobacillus reuteri NCIMB 11951, L. reuteri NCIMB 701359, L. reuteri NCIMB 702655, L. reuteri NCIMB 701089, L. reuteri NCIMB 702656, Lactobacillus fermentum NCIMB 5221, L. fermentum NCIMB 8829, L. fermentum NCIMB 2797, Lactobacillus rhamnosus ATCC 53103 GG, Lactobacillus acidophilus ATCC 314, and Lactobacillus plantarum ATCC 14917. Cholesterol assimilation was investigated in culture media and under simulated intestinal conditions. The best cholesterol assimilator was L. plantarum ATCC 14917 (15.18 ± 0.55 mg/1010 cfu in MRS broth. L. reuteri NCIMB 701089 assimilated over 67% (2254.70 ± 63.33 mg/1010 cfu of cholesterol, the most of all the strains, under intestinal conditions. This work demonstrates that probiotic bacteria can assimilate cholesterol under intestinal conditions, with L. reuteri NCIMB 701089 showing great potential as a CVD therapeutic.

  20. Aspirin inhibits formation of cholesterol rafts in fluid lipid membranes.

    Science.gov (United States)

    Alsop, Richard J; Toppozini, Laura; Marquardt, Drew; Kučerka, Norbert; Harroun, Thad A; Rheinstädter, Maikel C

    2015-03-01

    Aspirin and other non-steroidal anti-inflammatory drugs have a high affinity for phospholipid membranes, altering their structure and biophysical properties. Aspirin has been shown to partition into the lipid head groups, thereby increasing membrane fluidity. Cholesterol is another well known mediator of membrane fluidity, in turn increasing membrane stiffness. As well, cholesterol is believed to distribute unevenly within lipid membranes leading to the formation of lipid rafts or plaques. In many studies, aspirin has increased positive outcomes for patients with high cholesterol. We are interested if these effects may be, at least partially, the result of a non-specific interaction between aspirin and cholesterol in lipid membranes. We have studied the effect of aspirin on the organization of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) membranes containing cholesterol. Through Langmuir-Blodgett experiments we show that aspirin increases the area per lipid and decreases compressibility at 32.5 mol% cholesterol, leading to a significant increase of fluidity of the membranes. Differential scanning calorimetry provides evidence for the formation of meta-stable structures in the presence of aspirin. The molecular organization of lipids, cholesterol and aspirin was studied using neutron diffraction. While the formation of rafts has been reported in binary DPPC/cholesterol membranes, aspirin was found to locally disrupt membrane organization and lead to the frustration of raft formation. Our results suggest that aspirin is able to directly oppose the formation of cholesterol structures through non-specific interactions with lipid membranes.

  1. Transfer of cholesterol from macrophages to lymphocytes in culture.

    Science.gov (United States)

    de Bittencourt Júnior, P I; Curi, R

    1998-02-01

    A major feature of macrophage metabolism is its capacity to produce and export cholesterol. Several reports have shown that the manipulation of lymphocyte cholesterol content elicits important changes in lymphocyte proliferation. These findings lead to an inquiry as to whether macrophage-derived cholesterol released into the lymphocyte surroundings may be transferred to the latter thus affecting lymphocyte function. In this study, cholesterol transfer from macrophages to lymphocytes was examined in vitro using rat cells in culture. The findings indicate that there may be a significant transfer of cholesterol from [4-14C]cholesterol labeled resident peritoneal macrophages to mesenteric lymph node resting lymphocytes (up to 173.9 +/- 2.7 pmol/10(7) lymphocytes/10(7) macrophages when co-cultivated for 48 h), in a lipoprotein-dependent manner. This represents the mass transfer of ca. 17 nmoles of cholesterol molecules per 10(7) lymphocytes from 10(7) macrophages (calculated on the basis of specific radioactivity incorporated into macrophages after the pre-labelling period), which suggests that macrophages are capable of replacing the whole lymphocyte cholesterol pool every 21 h. Moreover, an 111%-increase in the total cholesterol content of lymphocytes was found after co-cultivation with macrophages for 48 h. When compared to peritoneal cells, monocytes/macrophages obtained from circulating blood leukocytes presented a much higher cholesterol transfer capacity to lymphocytes (3.06 +/- 0.10 nmol/10(7) lymphocytes/10(7) macrophages co-cultivated for 24 h). Interestingly, inflammatory macrophages dramatically reduced their cholesterol transfer ability (by up to 91%, as compared to resident macrophages). Cholesterol transfer may involve a humoral influence, since it is not only observed when cells are co-cultivated in a single-well chamber system (cells in direct contact), but also in a two-compartment system (where cells can communicate but not by direct contact). Co

  2. Determination of cholesterol in human biliary calculus by TLC scanning

    Institute of Scientific and Technical Information of China (English)

    Yin Kang Yang; Kai Xiong Qiu; Yu Zhu Zhan; Er Yi Zhan; Hai Ming Yang; Ping Zheng

    2000-01-01

    AIM To study the physico-chemical properties of biliary calculus and the relationship between the calculusformation and the phase change of liquid crystal, providing the best evidence for the biliary calculusprevention and treatment.METHODS The cholesterol contents in thirty one cases of biliary calculus in Kunming were determined bydouble-wave-length TLC scanning with high efficiency silica gel films.RESULTS Under magnifiers, the granular biliary calculus from 31 patients were classified according totheir section structures and colours, as cholesterol cholelith, 25 cases; bilirubin cholelith, 4 cases andcompound cholelith, 2 cases. By TLC scanning, it was found that the content of cholesterol in human biliarycalculus was 71%- 100%, about 80% cholesterol bilestones whose cholesterol content was more than 90%being pure cholesterol bilestones.CONCLUSION Cholesterol bilestone is the main human biliary calculus in Kunming, which was inaccordance with X-ray analysis. Compared with the related reports, it is proved that the proportion ofcholesterol bilestones to biliary calculus is increasing because of the improved life standard and the decreaseof bilirubin bilestones resulted from bile duct ascariasis or bacteria infection in China since 90s, and that theincrease of cholesterol in-take leads to the increase of cholesterol metabolism disorder

  3. Cholesterol granuloma of the petrous apex: CT diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Lo, W.W.M.; Solti-Bohman, L.G.; Brackmann, D.E.; Gruskin, P.

    1984-12-01

    Cholesterol granuloma of the petrous apex is a readily recognizable and treatable entity that is more common than previously realized. Cholesterol granuloma grows slowly in the petrous apex as a mass lesion until it produces hearing loss, tinnitus, vertigo, and facial twitching. Twelve cases of cholesterol granuloma of the petrous apex are illustrated; ten of these analyzed in detail, especially with respect to CT findings. A sharply and smoothly marginated expansile lesion in the petrous apex, isodense with plain and nonenhancing on CT, is in all probability a cholesterol granuloma. Preoperative recognition by CT is important for planning proper treatment.

  4. Cholesterol and Copper Affect Learning and Memory in the Rabbit

    Directory of Open Access Journals (Sweden)

    Bernard G. Schreurs

    2013-01-01

    Full Text Available A rabbit model of Alzheimer’s disease based on feeding a cholesterol diet for eight weeks shows sixteen hallmarks of the disease including beta amyloid accumulation and learning and memory changes. Although we have shown that feeding 2% cholesterol and adding copper to the drinking water can retard learning, other studies have shown that feeding dietary cholesterol before learning can improve acquisition and feeding cholesterol after learning can degrade long-term memory. We explore the development of this model, the issues surrounding the role of copper, and the particular contributions of the late D. Larry Sparks.

  5. New horizons for cholesterol ester transfer protein inhibitors.

    Science.gov (United States)

    Schwartz, Gregory G

    2012-02-01

    High-density lipoprotein (HDL) cholesterol levels bear an inverse relationship to cardiovascular risk. To date, however, no intervention specifically targeting HDL has been demonstrated to reduce cardiovascular risk. Cholesterol ester transfer protein (CETP) mediates transfer of cholesterol ester from HDL to apolipoprotein B-containing particles. Most, but not all observational cohort studies indicate that genetic polymorphisms of CETP associated with reduced activity and higher HDL cholesterol levels are also associated with reduced cardiovascular risk. Some, but not all studies indicate that CETP inhibition in rabbits retards atherosclerosis, whereas transgenic CETP expression in mice promotes atherosclerosis. Torcetrapib, the first CETP inhibitor to reach phase III clinical development, was abandoned due to excess mortality associated with increases in aldosterone and blood pressure. Two other CETP inhibitors have entered phase III clinical development. Anacetrapib is a potent inhibitor of CETP that produces very large increases in HDL cholesterol and large reductions in low-density lipoprotein (LDL) cholesterol, beyond those achieved with statins. Dalcetrapib is a less potent CETP inhibitor that produces smaller increases in HDL cholesterol with minimal effect on LDL cholesterol. Both agents appear to allow efflux of cholesterol from macrophages to HDL in vitro, and neither agent affects blood pressure or aldosterone in vivo. Two large cardiovascular outcomes trials, one with anacetrapib and one with dalcetrapib, should provide a conclusive test of the hypothesis that inhibition of CETP decreases cardiovascular risk. PMID:22083134

  6. Retracted: Advances in the physiological and pathological implications of cholesterol.

    Science.gov (United States)

    Cortes, Victor A; Busso, Dolores; Mardones, Pablo; Maiz, Alberto; Arteaga, Antonio; Nervi, Flavio; Rigotti, Attilio

    2013-11-01

    Cholesterol has evolved to fulfill sophisticated biophysical, cell signalling, and endocrine functions in animal systems. At the cellular level, cholesterol is found in membranes where it increases both bilayer stiffness and impermeability to water and ions. Furthermore, cholesterol is integrated into specialized lipid-protein membrane microdomains with critical topographical and signalling functions. At the organismal level, cholesterol is the precursor of all steroid hormones, including gluco- and mineralo-corticoids, sex hormones, and vitamin D, which regulate carbohydrate, sodium, reproductive, and bone homeostasis, respectively. This sterol is also the immediate precursor of bile acids, which are important for intestinal absorption of dietary lipids as well as energy homeostasis and glucose regulation. Complex mechanisms maintain cholesterol within physiological ranges and the dysregulation of these mechanisms results in embryonic or adult diseases, caused by either excessive or reduced tissue cholesterol levels. The causative role of cholesterol in these conditions has been demonstrated by genetic and pharmacological manipulations in animal models of human disease that are discussed herein. Importantly, the understanding of basic aspects of cholesterol biology has led to the development of high-impact pharmaceutical therapies during the past century. The continuing effort to offer successful treatments for prevalent cholesterol-related diseases, such as atherosclerosis and neurodegenerative disorders, warrants further interdisciplinary research in the coming decades. PMID:23445165

  7. Reconstitution of Cholesterol-Dependent Vaginolysin into Tethered Phospholipid Bilayers

    DEFF Research Database (Denmark)

    Budvytyte, Rima; Pleckaityte, M.; Zvirbliene, A.;

    2013-01-01

    Functional reconstitution of the cholesterol-dependent cytolysin vaginolysin (VLY) from Gardnerella vaginalis into artificial tethered bilayer membranes (tBLMs) has been accomplished. The reconstitution of VLY was followed in real-time by electrochemical impedance spectroscopy (EIS). Changes of the...... EIS parameters of the tBLMs upon exposure to VLY solutions were consistent with the formation of water-filled pores in the membranes. It was found that reconstitution of VLY is a strictly cholesterol-dependent, irreversible process. At a constant cholesterol concentration reconstitution of VLY...... platform for the detection of the activity of VLY and possibly other cholesterol-dependent cytolysins....

  8. Effect of doxazosin on cholesterol synthesis in cell culture

    Energy Technology Data Exchange (ETDEWEB)

    D' Eletto, R.D.; Javitt, N.B.

    1989-01-01

    The effect of doxazosin on cholesterol synthesis was determined by measuring the content of deuterium-enriched cholesterol in rabbit fibroblasts with and without receptors for low-density lipoproteins (LDL) and in hepatoma (Hep G2 cells). Doxazosin, at concentrations of 5-20 mumol/L, increased LDL binding to hepatic cells in a dose-related manner. Also, in these hepatic cells, doxazosin produced dose-related decreases in both newly synthesized cholesterol and cholesterol ester. In rabbit fibroblasts that were LDL receptor negative, de novo cholesterol synthesis was markedly reduced by increasing concentrations of doxazosin. Taken together, these results suggest that doxazosin may have a direct inhibitory effect on cholesterol synthesis independent of the LDL receptor. The inhibition of cholesterol synthesis by doxazosin may cause cells to compensate by upregulating the LDL receptor, thereby increasing the importation of lipoprotein cholesterol and reducing LDL cholesterol in the medium. This hypothesis supports findings in the clinical setting whereby doxazosin has a beneficial effect on the lipid profile, and suggests a useful additional property for this antihypertensive agent.

  9. Apoprotein E phenotype determines serum cholesterol in infants during both high-cholesterol breast feeding and low-cholesterol formula feeding.

    Science.gov (United States)

    Kallio, M J; Salmenperä, L; Siimes, M A; Perheentupa, J; Gylling, H; Miettinen, T A

    1997-04-01

    Our objective was to establish the role of the apoprotein (apo) E phenotype in determining serum cholesterol levels in infants fed exclusively on high-fat, high-cholesterol human milk and in those fed a low-cholesterol, high-unsaturated fat formula. The total and lipoprotein cholesterol, apoB, and triglyceride concentrations in serum were quantified and related to the apoE phenotype in 151 infants at birth and at 2, 6, 9, and 12 months of age. Forty-four had the E3/4 or 4/4 phenotype (E4 group), 94 had the E3/3 phenotype (E3 group), and 13 had the E2/3 or 2/4 phenotype (E2 group). In cord blood, cholesterol concentrations tended to be higher in the E4 than in the E2 group. With exclusive breast-feeding, the concentrations rose significantly faster and higher in the E4 group than in the E3 group or, especially, the E2 group. The values (mmol/L, mean +/- SEM) were 1.6 +/- 0.15, 1.5 +/- 0.05, 1.4 +/- 0.1 (P = n.s.) at birth; 4.2 +/- 0.1, 3.8 +/- 0.08, 3.4 +/- 0.2 (P HDL, HDL2, and HDL3 cholesterol concentrations did not depend on the apoE phenotype. Among infants fed high-fat, high-cholesterol human milk, the total and LDL-cholesterol concentrations and the LDL apoB concentration of those with the apoE phenotype 4/4 or 3/4 rose faster and to higher levels than in other infants. Among formula-fed infants, receiving a low-cholesterol, high-unsaturated fat diet, the differences between the apoE groups were smaller.

  10. Cholesterol-Enhanced Polylactide-Based Stereocomplex Micelle for Effective Delivery of Doxorubicin

    OpenAIRE

    Jixue Wang; Weiguo Xu; Jianxun Ding; Shengfan Lu; Xiaoqing Wang; Chunxi Wang; Xuesi Chen

    2015-01-01

    Nanoscale micelles as an effective drug delivery system have attracted increasing interest in malignancy therapy. The present study reported the construction of the cholesterol-enhanced doxorubicin (DOX)-loaded poly(D-lactide)-based micelle (CDM/DOX), poly(L-lactide)-based micelle (CLM/DOX), and stereocomplex micelle (CSCM/DOX) from the equimolar enantiomeric 4-armed poly(ethylene glycol)–polylactide copolymers in aqueous condition. Compared with CDM/DOX and CLM/DOX, CSCM/DOX showed the small...

  11. Saturated fatty acid (SFA) status and SFA intake exhibit different relations with serum total cholesterol and lipoprotein cholesterol : a mechanistic explanation centered around lifestyle-induced low-grade inflammation

    NARCIS (Netherlands)

    Ruiz Nunez, Begona; Kuipers, Remko S.; Luxwolda, Martine F.; De Graaf, Deti J.; Breeuwsma, Benjamin B.; Dijck-Brouwer, Janneke; Muskiet, Frits A. J.

    2014-01-01

    We investigated the relations between fatty acid status and serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol and total cholesterol/HDL cholesterol ratio in five Tanzanian ethnic groups and one Dutch group. Total cholesterol/HDL cholesterol rati

  12. Load sensor

    OpenAIRE

    van den Ende, D.; Almeida, P.M.R.; Dingemans, T.J.; Van der Zwaag, S.

    2007-01-01

    The invention relates to a load sensor comprising a polymer matrix and a piezo-ceramic material such as PZT, em not bedded in the polymer matrix, which together form a compos not ite, wherein the polymer matrix is a liquid crystalline resin, and wherein the piezo-ceramic material is a PZT powder forming 30-60% by volume of the composite, and wherein the PZT powder forms 40-50% by volume of the composite.

  13. Cholesterol efflux via ATP-binding cassette transporter A1 (ABCA1) and cholesterol uptake via the LDL receptor influences cholesterol-induced impairment of beta cell function in mice

    NARCIS (Netherlands)

    Kruit, J. K.; Kremer, P. H. C.; Dai, L.; Tang, R.; Ruddle, P.; de Haan, W.; Brunham, L. R.; Verchere, C. B.; Hayden, M. R.

    2010-01-01

    Cellular cholesterol accumulation is an emerging mechanism for beta cell dysfunction in type 2 diabetes. Absence of the cholesterol transporter ATP-binding cassette transporter A1 (ABCA1) results in increased islet cholesterol and impaired insulin secretion, indicating that impaired cholesterol effl

  14. Assessment of modes of action and efficacy of plasma cholesterol-lowering drugs : measurement of cholesterol absorption, cholesterol synthesis and bile acid synthesis and turnover using novel stable isotope techniques

    NARCIS (Netherlands)

    Stellaard, Frans; Kuipers, Folkert

    2005-01-01

    Several processes are involved in control of plasma cholesterol levels, e.g., intestinal cholesterol absorption, endogenous cholesterol synthesis and transport and bile acid synthesis. Adaptation of either of these processes allows the body to adapt to changes in dietary cholesterol intake. Disturba

  15. Rationale and design of the dal-OUTCOMES trial: efficacy and safety of dalcetrapib in patients with recent acute coronary syndrome

    DEFF Research Database (Denmark)

    Schwartz, Gregory G; Olsson, Anders G; Ballantyne, Christie M;

    2009-01-01

    BACKGROUND: Despite contemporary therapies for acute coronary syndrome (ACS), morbidity and mortality remain high. Low levels of high-density lipoprotein (HDL) cholesterol are common among patients with ACS and may contribute to ongoing risk. Strategies that raise levels of HDL cholesterol, such ...

  16. LDL Cholesterol, Statins And PCSK 9 Inhibitors

    Science.gov (United States)

    Gupta, Sanjiv

    2015-01-01

    Reduction of low density lipoprotein cholesterol (LDLc) is of vital importance for the prevention of atherosclerotic cardiovascular disease (ASCVD). Statin is the most effective therapy today to lower LDLc by inhibiting HMG-CoA-reductase. However despite intensive statin therapy, there remains a residual risk of recurrent myocardial infarction in about 20–30% cases. Moreover a few patients develop statin intolerance. For severe hypercholesterolemia, statins alone or in combination of ezetimibe, niacin and fenofibrate have been advocated. For homozygous familial hypercholesterolemia (HOFH), a microsomal triglyceride transfer protein MTP inhibitor (Lopitamide) and antisense oligonucleotide (ASO) (Mipomersen) have recently been approved by FDA, USA through ‘Risk evaluation and Mitigation Strategy (REMS)’. Possible future therapies include PCSK-9 inhibitors which have excellent lipid lowering properties. Three monoclonal antibodies (PCSK 9 Inhibitors) alirocumab, evolocumab and Bococizumab are under advanced clinical stage IV trials and awaiting approval by FDA and European Medicines Agency. PMID:26432726

  17. Cholesterol interactions with ceramide and sphingomyelin.

    Science.gov (United States)

    García-Arribas, Aritz B; Alonso, Alicia; Goñi, Felix M

    2016-09-01

    Sphingolipids contain in their polar heads chemical groups allowing them to establish a complex network of H-bonds (through different OH and NHgroups) with other lipids in the bilayer. In the recent years the specific interaction of sphingomyelin (SM) with cholesterol (Chol) has been examined, largely in the context of the "lipid raft" hypothesis. Formation of SM-Ceramide (Cer) complexes, proposed to exist in cell membranes in response to stress, has also been described. More recently, a delicate balance of phase formation and transformation in ternary mixtures of SM, Chol and Cer, with mutual displacement of Chol and Cer from their interaction with SM is considered to exist. In addition, data demonstrating direct Chol-Cer interaction are becoming available. PMID:27132117

  18. Acute modification in plasma lipid levels in ultramarathon runners.

    Science.gov (United States)

    Emed, Luiz Gustavo Marin; Passaglia, Daniela Gunther; Guerios, Surya T; João, Paula G D; Moser, André I S; Abdalla, Dulcinéia S P; Guarita-Souza, Luis Cesar; Mikilita, Emanuella Stella; Baena, Cristina Pellegrino; da Costa, Ana Beatriz Brenner Affonso; Faria-Neto, José Rocha

    2016-09-01

    We aimed to evaluate the effects of a 24-h ultramarathon, an aerobic test of high physical load, on lipid profile and apolipoproteins B (ApoB) and A1 (ApoA1) levels, minimally modified low-density lipoprotein (LDL), and oxidised LDL. Prospective evaluation of 16 male athletes who participated in an ultramarathon run, where the objective was to run the greatest distance possible in 24 h. Fourteen participants completed the run. The mean distance achieved was 133.1 km (maximum of 169.6 km). There was a trend in reduction of triglycerides and total cholesterol (P = 0.06 and 0.05, respectively), without significant modifications in high-density lipoprotein, LDL and ApoA1 levels (P = 0.16; 0.55 and 0.67). There was a marked reduction in ApoB levels (P < 0.001), correlated directly to the distance covered (Pearson R = 0.68). Accordingly, an increase in the LDL/ApoB ratio was observed. The stress of this physical activity was not associated to an increase in minimally modified LDL or oxidised LDL. Lipid profile levels were not acutely altered by prolonged physical activity. Similarly, there was no evidence of greater oxidation of LDL over a 24-h period of physical activity. The reduction in ApoB was directly proportional to the distance covered, suggesting an acute positive change in phenotype of LDL molecules. PMID:26710938

  19. Acute modification in plasma lipid levels in ultramarathon runners.

    Science.gov (United States)

    Emed, Luiz Gustavo Marin; Passaglia, Daniela Gunther; Guerios, Surya T; João, Paula G D; Moser, André I S; Abdalla, Dulcinéia S P; Guarita-Souza, Luis Cesar; Mikilita, Emanuella Stella; Baena, Cristina Pellegrino; da Costa, Ana Beatriz Brenner Affonso; Faria-Neto, José Rocha

    2016-09-01

    We aimed to evaluate the effects of a 24-h ultramarathon, an aerobic test of high physical load, on lipid profile and apolipoproteins B (ApoB) and A1 (ApoA1) levels, minimally modified low-density lipoprotein (LDL), and oxidised LDL. Prospective evaluation of 16 male athletes who participated in an ultramarathon run, where the objective was to run the greatest distance possible in 24 h. Fourteen participants completed the run. The mean distance achieved was 133.1 km (maximum of 169.6 km). There was a trend in reduction of triglycerides and total cholesterol (P = 0.06 and 0.05, respectively), without significant modifications in high-density lipoprotein, LDL and ApoA1 levels (P = 0.16; 0.55 and 0.67). There was a marked reduction in ApoB levels (P < 0.001), correlated directly to the distance covered (Pearson R = 0.68). Accordingly, an increase in the LDL/ApoB ratio was observed. The stress of this physical activity was not associated to an increase in minimally modified LDL or oxidised LDL. Lipid profile levels were not acutely altered by prolonged physical activity. Similarly, there was no evidence of greater oxidation of LDL over a 24-h period of physical activity. The reduction in ApoB was directly proportional to the distance covered, suggesting an acute positive change in phenotype of LDL molecules.

  20. Exposure to polymers reverses inhibition of pulmonary surfactant by serum, meconium, or cholesterol in the captive bubble surfactometer.

    Science.gov (United States)

    López-Rodríguez, Elena; Ospina, Olga Lucía; Echaide, Mercedes; Taeusch, H William; Pérez-Gil, Jesús

    2012-10-01

    Dysfunction of pulmonary surfactant in the lungs is associated with respiratory pathologies such as acute respiratory distress syndrome or meconium aspiration syndrome. Serum, cholesterol, and meconium have been described as inhibitory agents of surfactant's interfacial activity once these substances appear in alveolar spaces during lung injury and inflammation. The deleterious action of these agents has been only partly evaluated under physiologically relevant conditions. We have optimized a protocol to assess surfactant inhibition by serum, cholesterol, or meconium in the captive bubble surfactometer. Specific measures of surface activity before and after native surfactant was exposed to inhibitors included i), film formation, ii), readsorption of material from surface-associated reservoirs, and iii), interfacial film dynamics during compression-expansion cycling. Results show that serum creates a steric barrier that impedes surfactant reaching the interface. A mechanical perturbation of this barrier allows native surfactant to compete efficiently with serum to form a highly surface-active film. Exposure of native surfactant to cholesterol or meconium, on the other hand, modifies the compressibility of surfactant films though optimal compressibility properties recover on repetitive compression-expansion cycling. Addition of polymers like dextran or hyaluronic acid to surfactant fully reverses inhibition by serum. These polymers also prevent surfactant inhibition by cholesterol or meconium, suggesting that the protective action of polymers goes beyond the mere enhancement of interfacial adsorption as described by depletion force theories. PMID:23062337

  1. Serum cholesterol decline and depression in the postpartum period

    NARCIS (Netherlands)

    Dam, van R.M.; Schuit, A.J.; Schouten, E.G.; Vader, H.L.; Pop, V.J.M.

    1999-01-01

    We examined the relation between total serum cholesterol decline and depression in the postpartum period in a prospective study of 266 Dutch women, who were followed until 34 weeks after delivery. The decline in serum cholesterol between week 32 of pregnancy and week 10 postpartum was similar for wo

  2. The ins and outs of reverse cholesterol transport

    NARCIS (Netherlands)

    Groen, AK; Elferink, RPJO; Verkade, HJ; Kuipers, F

    2004-01-01

    It is generally assumed that HDL is the obligate transport vehicle for 'reverse cholesterol transport'. the pathway for removal of excess cholesterol from peripheral tissues via the liver into bile and subsequent excretion via the feces. During the last few years, intensive research has generated ex

  3. CDC Vital Signs: High Blood Pressure and Cholesterol

    Science.gov (United States)

    ... 1.36 MB] Read the MMWR Science Clips High Blood Pressure and Cholesterol Out of Control Recommend on Facebook ... by County http://apps.nccd.cdc.gov/GISCVH2/ High Blood Pressure and High Cholesterol Among US Adults SOURCES: National ...

  4. Low serum cholesterol, serotonin metabolism, and violent death

    NARCIS (Netherlands)

    P.H.A. Steegmans

    1995-01-01

    textabstractA high serum cholesterol level is a well documented risk factor for atherosclerotic cardiovascular disease. Consequently, a low serum cholesterol has in general been viewed as beneficial. However, since the early 70s, results from several cohort studies and randomized trials have suggest

  5. Cholesterol Check (A Cup of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    2015-09-10

    High blood cholesterol is a risk factor for cardiovascular disease. This podcast discusses the importance of a healthy diet and regular cholesterol screening.  Created: 9/10/2015 by MMWR.   Date Released: 9/10/2015.

  6. Composition of and cholesterol in Araucana and commercial eggs.

    Science.gov (United States)

    Peterson, D W; Lilyblade, A; Clifford, C K; Ernst, R; Clifford, A J; Dunn, P

    1978-01-01

    Araucana eggs from six sources and commercial-type white eggs of two major supermarket brands and from the University of California flock were collected and analyzed for cholesterol content of the yolk. The yolks of Araucana eggs were significantly higher in cholesterol than those of commercial white eggs. PMID:563887

  7. Transport of cholesterol autoxidation products in rabbit lipoproteins

    International Nuclear Information System (INIS)

    Radiolabeled pure [4-14C] cholesterol was kept at 600C under air to autoxidize for 5 weeks, after which approximately 12% cholesterol oxidation products were formed. The mixture, suspended in gelatin, was given to rabbits by gastric gavage. Rabbits were killed 4, 24 and 48 h after treatment. Cholesterol and its autoxidation products were separated by thin-layer chromatography into 5 fractions and radioactivities of each fraction were measured. Percentages of each fraction of cholesterol oxidation products and cholesterol in the original mixture before administration and in the rabbit sera after administration were similar, suggesting that the rates of absorption of cholesterol oxidation products are not significantly different from that of cholesterol. Lipoproteins were fractioned by ultracentrifugation into VLDL, LDL and HDL. Radioactivities of each fraction in lipoproteins separated by thin layer chromatography showed that fractions containing cholestane-3β, 5α, 6β-triol, 7α- and 7β-hydroxycholesterol and 7-ketocholesterol were more selectively transported in VLDL, whereas most of the 25-hydroxycholesterol was present in LDL. HDL contained only minute amounts of cholesterol oxidation products. 22 refs

  8. LDL cholesterol still a problem in old age?

    DEFF Research Database (Denmark)

    Postmus, Iris; Deelen, Joris; Sedaghat, Sanaz;

    2015-01-01

    BACKGROUND: Observational studies in older subjects have shown no or inverse associations between cholesterol levels and mortality. However, in old age plasma low-density lipoprotein cholesterol (LDL-C) may not reflect the lifetime level due to reverse causality, and hence the risk may be underes...

  9. Cholesterol and Sphingomyelin-Containing Model Condensed Lipid Monolayers: Heterogeneities Involving Ordered Microdomains Assessed by Two Cholesterol Derivatives.

    Science.gov (United States)

    Lecompte, Marie-France; Gaibelet, Gérald; Lebrun, Chantal; Tercé, François; Collet, Xavier; Orlowski, Stéphane

    2015-11-01

    Lipid monolayers are often considered as model membranes, but they are also the physiologic lipid part of the peripheral envelope of lipoproteins and cytosolic lipid bodies. However, their structural organization is still rather elusive, in particular when both cholesterol and sphingomyelin are present. To investigate such structural organization of hemimembranes, we measured, using alternative current voltammetry, the differential capacitance of condensed phosphatidylcholine-based monolayers as a function of applied potential, which is sensitive to their lipid composition and molecular arrangement. Especially, monolayers containing both sphingomyelin and cholesterol, at 15% w/w, presented specific characteristics of the differential capacitance versus potential curves recorded, which was indicative of specific interactions between these two lipid components. We then compared the behavior of two cholesterol derivatives (at 15% w/w), 21-methylpyrenyl-cholesterol (Pyr-met-Chol) and 22-nitrobenzoxadiazole-cholesterol (NBD-Chol), with that of cholesterol when present in model monolayers. Indeed, these two probes were chosen because of previous findings reporting opposite behaviors within bilayer membranes regarding their interaction with ordered lipids, with only Pyr-met-Chol mimicking cholesterol well. Remarkably, in monolayers containing sphingomyelin or not, Pyr-met-Chol and NBD-Chol presented contrasting behaviors, and Pyr-met-Chol mimicked cholesterol only in the presence of sphingomyelin. These two observations (i.e., optimal amounts of sphingomyelin and cholesterol, and the ability to discriminate between Pyr-met-Chol and NBD-Chol) can be interpreted by the existence of heterogeneities including ordered patches in sphingomyelin- and cholesterol-containing monolayers. Since such monolayer lipid arrangement shares some properties with the raft-type lipid microdomains well-described in sphingomyelin- and cholesterol-containing bilayer membranes, our data thus

  10. Loads and loads and loads: the influence of prospective load, retrospective load, and ongoing task load in prospective memory

    OpenAIRE

    Beat eMeier; Zimmermann, Thomas D.

    2015-01-01

    In prospective memory tasks different kinds of load can occur. Adding a prospective memory task can impose a load on ongoing task performance. Adding ongoing task load can affect prospective memory performance. The existence of multiple target events increases prospective load and adding complexity to the to-be-remembered action increases retrospective load. In two experiments, we systematically examined the effects of these different types of load on prospective memory performance. Results s...

  11. Apolipoprotein A-I Helsinki promotes intracellular acyl-CoA cholesterol acyltransferase (ACAT) protein accumulation.

    Science.gov (United States)

    Toledo, Juan D; Garda, Horacio A; Cabaleiro, Laura V; Cuellar, Angela; Pellon-Maison, Magali; Gonzalez-Baro, Maria R; Gonzalez, Marina C

    2013-05-01

    Reverse cholesterol transport is a process of high antiatherogenic relevance in which apolipoprotein AI (apoA-I) plays an important role. The interaction of apoA-I with peripheral cells produces through mechanisms that are still poorly understood the mobilization of intracellular cholesterol depots toward plasma membrane. In macrophages, these mechanisms seem to be related to the modulation of the activity of acyl-CoA cholesterol acyltransferase (ACAT), the enzyme responsible for the intracellular cholesterol ester biosynthesis that is stored in lipid droplets. The activation of ACAT and the accumulation of lipid droplets play a key role in the transformation of macrophages into foam cells, leading to the formation of atheroma or atherosclerotic plaque. ApoA-I Helsinki (or ∆K107) is a natural apoA-I variant with a lysine deletion in the central protein region, carriers of which have increased atherosclerosis risk. We herein show that treatment of cultured RAW macrophages or CHOK1 cells with ∆K107, but not with wild-type apoA-I or a variant containing a similar deletion at the C-terminal region (∆K226), lead to a marked increase (more than 10 times) in the intracellular ACAT1 protein level as detected by western blot analysis. However, we could only detect a slight increase in cholesteryl ester produced by ∆K107 mainly when Chol loading was supplied by low-density lipoprotein (LDL). Although a similar choline-phospholipid efflux is evoked by these apoA-I variants, the change in phosphatidylcholine/sphyngomyelin distribution produced by wild-type apoA-I is not observed with either ∆K107 or ∆K226. PMID:23456478

  12. Ursodeoxycholic Acid for the Treatment of Cholesterol Gallstones

    International Nuclear Information System (INIS)

    Cholesterol is the principal constituent of more than three quarters of gallstones. Pure cholesterol crystals are quite soft, and protein contributes importantly to the strength of cholesterol stones. The risk of gallstones does not correlate with total serum cholesterol levels, but it does correlate with decreased high-density lipoprotein cholesterol and increased triglyceride levels. At least 10 percent of adults have gallstones where female: male ratio of about 2:1 in the younger age groups with increasing prevalence with age. Nine patients with gallstones (6 females and 3 males) were included in the study. Patients were treated with ursodeoxycholic acids tablets in two oral doses, one after breakfast, and the other after dinner for 9 months. Ultrasound examination was repeated every 3 months. Re-examination by abdominal ultrasonography revealed that gallstone 1 cm or less in diameter disappeared within 6 months, and the largest stone 3.06 cm in diameter disappeared within 9 months.

  13. Enzymatic-fluorometric quantification of cholesterol in bovine milk

    DEFF Research Database (Denmark)

    Larsen, Torben

    2012-01-01

    The present paper describes an enzymatic–fluorometric method for the determination of cholesterol in milk and other opaque matrices. The initial step of the method is to liberate chemically and physically bound cholesterol from the milk fat globule membrane by enzymatic action. The method is able...... to discriminate between esterified and free cholesterol in milk. The analysis is cost effective and is developed to work directly on whole, fresh milk thereby eliminating time consuming and tedious pre-treatment procedures of the sample. More than 1000 milk samples were analysed on the day of sampling. The total...... concentration of milk cholesterol ranged from 80 to 756 μM (n = 1068; mean 351 μM). Milk cholesterol was significantly correlated to milk fat concentration as analysed by mid-infra red spectrometry (r = 0.630; n = 853) and by an enzymatic–fluorometric method (triacylglycerol) (r = 0.611; n = 842)....

  14. Bad cholesterol and good mood: exploring the link

    Directory of Open Access Journals (Sweden)

    Yashaswi Gupta

    2016-01-01

    Full Text Available It is a well-known fact that high cholesterol increases the risks of heart disease. Hence, physicians actively encourage cholesterol-lowering interventions using medications and lifestyle modifications. However, there is considerable evidence that aggressive lowering of cholesterol is associated with depression, bipolar disorders, violent behaviour, and suicidal ideation. It has been hypothesised that low cholesterol leads to low levels of serotonin, a chemical that is responsible for maintaining mood balance. South Korea and India have highest number of suicides in Asia. It is a significant challenge for physicians to search an alternative that will not only maintain healthy level of cholesterol, but also contribute to psychological well-being of the patient. Generally, the role of diet and physical activity is considered secondary to medications. However, dietary supplements like coenzyme Q10 (CoQ10, omega-3 fatty acids, niacin, and physical activity like Yoga are extremely beneficial for improving lipid profile and symptoms of depression.

  15. SND1 overexpression deregulates cholesterol homeostasis in hepatocellular carcinoma.

    Science.gov (United States)

    Navarro-Imaz, Hiart; Rueda, Yuri; Fresnedo, Olatz

    2016-09-01

    SND1 is a multifunctional protein participating, among others, in gene transcription and mRNA metabolism. SND1 is overexpressed in cancer cells and promotes viability and tumourigenicity of hepatocellular carcinoma cells. This study shows that cholesterol synthesis is increased in SND1-overexpressing hepatoma cells. Neither newly synthesised nor extracellularly supplied cholesterol are able to suppress this increase; however, inhibition of cholesterol esterification reverted the activated state of sterol-regulatory element-binding protein 2 (SREBP2) and cholesterogenesis. These results highlight SND1 as a potential regulator of cellular cholesterol distribution and homeostasis in hepatoma cells, and support the rationale for the therapeutic use of molecules that influence cholesterol management when SND1 is overexpressed. PMID:27238764

  16. Interleukin-10 increases reverse cholesterol transport in macrophages through its bidirectional interaction with liver X receptor α

    Energy Technology Data Exchange (ETDEWEB)

    Halvorsen, Bente, E-mail: Bente.Halvorsen@rr-research.no [Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo (Norway); Institute of Clinical Medicine, University of Oslo, Oslo (Norway); K.G. Jebsen Inflammation Research Center, University of Oslo, Oslo (Norway); Holm, Sverre [Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo (Norway); Yndestad, Arne [Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo (Norway); Institute of Clinical Medicine, University of Oslo, Oslo (Norway); K.G. Jebsen Inflammation Research Center, University of Oslo, Oslo (Norway); Scholz, Hanne [Section for Transplantation, Institute for Surgical Research, Oslo University Hospital Rikshospitalet, Oslo (Norway); Sagen, Ellen Lund [Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo (Norway); Nebb, Hilde [Department of Nutrition, Institute for Basic Medical Sciences, University of Oslo, Oslo (Norway); Institute of Clinical Medicine, University of Oslo, Oslo (Norway); Holven, Kirsten B. [Department of Nutrition, Institute for Basic Medical Sciences, University of Oslo, Oslo (Norway); Dahl, Tuva B. [Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo (Norway); Institute of Clinical Medicine, University of Oslo, Oslo (Norway); Aukrust, Pål [Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo (Norway); Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo (Norway); Institute of Clinical Medicine, University of Oslo, Oslo (Norway); K.G. Jebsen Inflammation Research Center, University of Oslo, Oslo (Norway)

    2014-08-08

    Highlights: • IL-10 promotes reverse cholesterol efflux from lipid loaded macrophages. • IL-10 increases the expression of ABCA-1 and ABCG-1. • IL-10 exhibits cross-talk with the nuclear receptor LXRα. - Abstract: Interleukin (IL)-10 is a prototypical anti-inflammatory cytokine that has been shown to attenuate atherosclerosis development. In addition to its anti-inflammatory properties, the anti-atherogenic effect of IL-10 has recently also been suggested to reflect a complex effect of IL-10 on lipid metabolism in macrophages. In the present study we examined the effects of IL-10 on cholesterol efflux mechanism in lipid-loaded THP-1 macrophages. Our main findings were: (i) IL-10 significantly enhanced cholesterol efflux induced by fetal-calf serum, high-density lipoprotein (HDL){sub 2} and apolipoprotein A-1. (ii) The IL-10-mediated effects on cholesterol efflux were accompanied by an increased IL-10-mediated expression of the ATP-binding cassette transporters ABCA1 and ABCG1, that was further enhanced when the cells were co-activated with the liver X receptor (LXR)α agonist (22R)-hydroxycholesterol. (iii) The effect of LXRα activation on the IL-10-mediated effects on the ATP-binding cassette transporters seems to include enhancing effects on the IL-10 receptor 1 (IL10R1) expression and interaction with STAT-3 signaling. (iv) These enhancing effects on ABCA1 and ABCG1 was not seen when the cells were stimulated with the IL-10 family members IL-22 and IL-24. This study suggests that the anti-atherogenic properties of IL-10 may include enhancing effects on cholesterol efflux mechanism that involves cross-talk with LXRα activation.

  17. Helicobacter pylori's cholesterol uptake impacts resistance to docosahexaenoic acid.

    Science.gov (United States)

    Correia, Marta; Casal, Susana; Vinagre, João; Seruca, Raquel; Figueiredo, Ceu; Touati, Eliette; Machado, José C

    2014-05-01

    Helicobacter pylori colonizes half of the world population and is associated with gastric cancer. We have previously demonstrated that docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid known for its anti-inflammatory and antitumor effects, directly inhibits H. pylori growth in vitro and in mice. Nevertheless, the concentration of DHA shown to reduce H. pylori mice gastric colonization was ineffective in vitro. Related to the auxotrophy of H. pylori for cholesterol, we hypothesize that other mechanisms, in addition to DHA direct antibacterial effect, must be responsible for the reduction of the infection burden. In the present study we investigated if DHA affects also H. pylori growth, by reducing the availability of membrane cholesterol in the epithelial cell for H. pylori uptake. Levels of cholesterol in gastric epithelial cells and of cholesteryl glucosides in H. pylori were determined by thin layer chromatography and gas chromatography. The consequences of epithelial cells' cholesterol depletion on H. pylori growth were assessed in liquid cultures. We show that H. pylori uptakes cholesterol from epithelial cells. In addition, DHA lowers cholesterol levels in epithelial cells, decreases its de novo synthesis, leading to a lower synthesis of cholesteryl glucosides by H. pylori. A previous exposition of H. pylori to cholesterol influences the bacterium response to the direct inhibitory effect of DHA. Overall, our results suggest that a direct effect of DHA on H. pylori survival is modulated by its access to epithelial cell cholesterol, supporting the notion that cholesterol enhances the resistance of H. pylori. The cholesterol-dependent resistance of H. pylori to antimicrobial compounds raises new important aspects for the development of new anti-bacterial strategies. PMID:24447914

  18. Bacterial colonization of host cells in the absence of cholesterol.

    Directory of Open Access Journals (Sweden)

    Stacey D Gilk

    2013-01-01

    Full Text Available Reports implicating important roles for cholesterol and cholesterol-rich lipid rafts in host-pathogen interactions have largely employed sterol sequestering agents and biosynthesis inhibitors. Because the pleiotropic effects of these compounds can complicate experimental interpretation, we developed a new model system to investigate cholesterol requirements in pathogen infection utilizing DHCR24(-/- mouse embryonic fibroblasts (MEFs. DHCR24(-/- MEFs lack the Δ24 sterol reductase required for the final enzymatic step in cholesterol biosynthesis, and consequently accumulate desmosterol into cellular membranes. Defective lipid raft function by DHCR24(-/- MEFs adapted to growth in cholesterol-free medium was confirmed by showing deficient uptake of cholera-toxin B and impaired signaling by epidermal growth factor. Infection in the absence of cholesterol was then investigated for three intracellular bacterial pathogens: Coxiella burnetii, Salmonella enterica serovar Typhimurium, and Chlamydia trachomatis. Invasion by S. Typhimurium and C. trachomatis was unaltered in DHCR24(-/- MEFs. In contrast, C. burnetii entry was significantly decreased in -cholesterol MEFs, and also in +cholesterol MEFs when lipid raft-associated α(Vβ(3 integrin was blocked, suggesting a role for lipid rafts in C. burnetii uptake. Once internalized, all three pathogens established their respective vacuolar niches and replicated normally. However, the C. burnetii-occupied vacuole within DHCR24(-/- MEFs lacked the CD63-positive material and multilamellar membranes typical of vacuoles formed in wild type cells, indicating cholesterol functions in trafficking of multivesicular bodies to the pathogen vacuole. These data demonstrate that cholesterol is not essential for invasion and intracellular replication by S. Typhimurium and C. trachomatis, but plays a role in C. burnetii-host cell interactions.

  19. The Contribution of Serine 194 Phosphorylation to Steroidogenic Acute Regulatory Protein Function

    OpenAIRE

    Sasaki, Goro; Zubair, Mohamad; Ishii, Tomohiro; Mitsui, Toshikatsu; Hasegawa, Tomonobu; Auchus, Richard J

    2014-01-01

    The steroidogenic acute regulatory protein (StAR) facilitates the delivery of cholesterol to the inner mitochondrial membrane, where the cholesterol side-chain cleavage enzyme catalyzes the initial step of steroid hormone biosynthesis. StAR was initially identified in adrenocortical cells as a phosphoprotein, the expression and phosphorylation of which were stimulated by corticotropin. A number of in vitro studies have implicated cAMP-dependent phosphorylation at serine 194 (S194, S195 in hum...

  20. Acute effects of vinegar intake on some biochemical risk factors of atherosclerosis in hypercholesterolemic rabbits

    Directory of Open Access Journals (Sweden)

    rohani Ali

    2010-01-01

    Full Text Available Abstract Background Exaggerated postprandial spikes in blood glucose and lipids induce proportional increases in oxidative stress, which acutely trigger impairment endothelial, inflammation and increased risk of future cardiovascular events. In this research, we have investigated acute effects of vinegar intake on some of the biochemical atherosclerosis risk factors in high cholesterol fed rabbits to see if we can find a probable protective value for it. Methods The rabbits were randomly divided into four groups: normal diet, high cholesterol diet (%1cholesterol, %1 cholesterol with 5 ml vinegar (low dose, %1 cholesterol with 10 ml vinegar (high dose. After fasting for 12-15 hours, blood samples were taken to determine baseline values. Three hours after feeding, blood samples were collected again to investigate acute effects of vinegar intake on the measured factors. Results Using high-dose vinegar with cholesterolemic diet caused significant reduce in LDL-cholesterol (LDL-C, oxidized-LDL (ox-LDL, malondialdehyde (MDA, total cholesterol (TC and apolipoprotein B (ApoB in comparison with hypercholesterolemic diet. Consumption low-dose vinegar with cholesterolemic diet induced a significant decrease in fibrinogen and glucose compared to hypercholesterolemic diet. Level of serum nitrite, nitrate, triacylglycerol (TAG, HDL-cholesterol (HDL-C, apolipoprotein A (ApoA, serum glutamic pyruvic transaminase (SGPT, serum glutamic oxaloacetate transaminase (SGOT and C-reactive protein (CRP were not significantly difference in low and high doses vinegar with cholesterolemic diet compared to hypercholesterolemic diet. A significant difference was observed for LDL-C, ApoB100 and TC between low and high doses vinegar. Conclusion This study suggest that vinegar, might have some acute effects on biochemical risk factors of atherosclerosis and a probable protective value can be considered for its postprandial use.

  1. Atorvastatin increases HDL cholesterol by reducing CETP expression in cholesterol-fed APOE*3-Leiden.CETP mice

    NARCIS (Netherlands)

    Haan, W. de; Hoogt, C.C. van der; Westerterp, M.; Hoekstra, M.; Dallinga-Thie, G.M.; Princen, H.M.G.; Romijn, J.A.; Jukema, J.W.; Havekes, L.M.; Rensen, P.C.N.

    2008-01-01

    Objective: In addition to lowering low-density lipoprotein (LDL)-cholesterol, statins modestly increase high-density lipoprotein (HDL)-cholesterol in humans and decrease cholesteryl ester transfer protein (CETP) mass and activity. Our aim was to determine whether the increase in HDL depends on CETP

  2. Function of MRP1/ABCC1 is not dependent on cholesterol or cholesterol-stabilized lipid rafts

    NARCIS (Netherlands)

    Meszaros, Peter; Klappe, Karin; Hummel, Ina; Hoekstra, Dick; Kok, Jan Willem

    2011-01-01

    MRP1 (multidrug-resistance-related protein 1)/ABCC1 (ATP-binding cassette transporter C1) has been localized in cholesterol-enriched lipid rafts, which suggests a role for these lipid rafts and/or cholesterol in MRP1 function. In the present study, we have shown for the first time that nearly comple

  3. A cholesterol-free, high-fat diet suppresses gene expression of cholesterol transporters in murine small intestine

    NARCIS (Netherlands)

    den Bosch, Heleen M. de Vogel-van; de Wit, Nicole J. W.; Hooiveld, Guido J. E. J.; Vermeulen, Hanneke; van der Veen, Jelske N.; Houten, Sander M.; Kuipers, Folkert; Mueller, Michael; van der Meer, Roelof

    2008-01-01

    A cholesterol-free, high-fat diet suppresses gene expression of cholesterol transporters in murine small intestine. Am J Physiol Gastrointest Liver Physiol 294: G1171-G1180, 2008. First published March 20, 2008; doi:10.1152/ajpgi.00360.2007.-Transporters present in the epithelium of the small intest

  4. How cholesterol interacts with membrane proteins: an exploration of cholesterol-binding sites including CRAC, CARC and tilted domains

    Directory of Open Access Journals (Sweden)

    Jacques eFantini

    2013-02-01

    Full Text Available The plasma membrane of eukaryotic cells contains several types of lipids displaying high biochemical variability in both their apolar moiety (e.g. the acyl chain of glycerolipids and their polar head (e.g. the sugar structure of glycosphingolipids. Among these lipids, cholesterol is unique because its biochemical variability is almost exclusively restricted to the oxidation of its polar -OH group. Although generally considered the most rigid membrane lipid, cholesterol can adopt a broad range of conformations due to the flexibility of its isooctyl chain linked to the polycyclic sterane backbone. Moreover, cholesterol is an asymmetric molecule displaying a planar face and a rough  face. Overall, these structural features open up a number of possible interactions between cholesterol and membrane lipids and proteins, consistent with the prominent regulatory functions that this unique lipid exerts on membrane components. The aim of this review is to describe how cholesterol interacts with membrane lipids and proteins at the molecular/atomic scale, with special emphasis on transmembrane domains of proteins containing either the consensus cholesterol-binding motifs CRAC and CARC or a tilted peptide. Despite their broad structural diversity, all these domains bind cholesterol through common molecular mechanisms, leading to the identification of a subset of amino acid residues that are overrepresented in both linear and three-dimensional membrane cholesterol-binding sites.

  5. The influence of cholesterol and biomass concentration on the uptake of cholesterol by Lactobacillus from MRS broth

    Directory of Open Access Journals (Sweden)

    Małgorzata Ziarno

    2007-06-01

    Full Text Available The aim of this study was the determination of some factors influence (i.e. the vitality of bacteria cells and the cholesterol concentration on the ability of selected Lactobacillus sp. to cholesterol uptake during culture in MRS broth. Three Lactobacillus strains (Lb. delbrueckii subsp. bulgaricus, Lb. acidophilus, Lb. casei isolated from commercial single species lyophilized dairy starter cultures and three Lactobacillus strains (Lb. plantarum, Lb. delbrueckii subsp. bulgaricus, Lb. acidophilus originated from commercial pharmaceuticals were used in this study. The uptake of cholesterol from MRS broth during the growth of Lactobacillus sp., expressed as the difference between the final and the initial concentrations of cholesterol, ranged from 0.053 to 0.153 g/dm³, apart from the initial cholesterol content and the origin of Lactobacillus sp. The results confirmed that biomass concentration have a statistically significant effect on uptake of cholesterol. The ten-fold increase of the amount of intact cells biomass caused about 1.5-2-fold increase of the amount of cholesterol removed. The influence of the concentration of biomass of alive cells on the removal of cholesterol was bigger than in case of the heat-sterilized cells.

  6. Regulation of reverse cholesterol transport - a comprehensive appraisal of available animal studies

    NARCIS (Netherlands)

    Annema, Wijtske; Tietge, Uwe J. F.

    2012-01-01

    Plasma levels of high density lipoprotein (HDL) cholesterol are strongly inversely correlated to the risk of atherosclerotic cardiovascular disease. A major recognized functional property of HDL particles is to elicit cholesterol efflux and consequently mediate reverse cholesterol transport (RCT). T

  7. Dose effects of dietary phytosterols on cholesterol metabolism: a controlled feeding study123

    OpenAIRE

    Racette, Susan B.; Lin, Xiaobo; Lefevre, Michael; Spearie, Catherine Anderson; MOST, MARLENE M.; Ma, Lina; Ostlund, Richard E

    2009-01-01

    Background: Phytosterol supplementation of 2 g/d is recommended by the National Cholesterol Education Program to reduce LDL cholesterol. However, the effects of different intakes of phytosterol on cholesterol metabolism are uncertain.

  8. High Blood Cholesterol Q&A Dr. Michael Lauer | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... this page please turn Javascript on. Feature: High Cholesterol High Blood Cholesterol Q&A with Dr. Michael Lauer Past Issues / ... heavier and older, what does recent research on cholesterol and heart health tell us that Americans need ...

  9. LCAT, HDL Cholesterol and Ischemic Cardiovascular Disease: A Mendelian Randomization Study of HDL Cholesterol in 54,500 Individuals

    DEFF Research Database (Denmark)

    Haase, Christiane L; Tybjærg-Hansen, Anne; Ali Qayyum, Abbas;

    2012-01-01

    Background:Epidemiologically, high-density lipoprotein (HDL) cholesterol levels associate inversely with risk of ischemic cardiovascular disease. Whether this is a causal relation is unclear.Methods:We studied 10,281 participants in the Copenhagen City Heart Study (CCHS) and 50,523 participants...... in the Copenhagen General Population Study (CGPS), of which 991 and 1,693 participants, respectively, had developed myocardial infarction (MI) by August 2010. Participants in the CCHS were genotyped for all six variants identified by resequencing lecithin-cholesterol acyltransferase in 380 individuals. One variant......, S208T (rs4986970, allele frequency 4%), associated with HDL cholesterol levels in both the CCHS and the CGPS was used to study causality of HDL cholesterol using instrumental variable analysis.Results:Epidemiologically, in the CCHS, a 13% (0.21 mmol/liter) decrease in plasma HDL cholesterol levels...

  10. Self-assembled nanoparticles of cholesterol-conjugated carboxymethyl curdlan as a novel carrier of epirubicin

    Science.gov (United States)

    Li, Lei; Gao, Fu-ping; Tang, Hong-bo; Bai, Yong-gang; Li, Rui-feng; Li, Xue-min; Liu, Ling-rong; Wang, Yin-song; Zhang, Qi-qing

    2010-07-01

    The purpose of this study was to develop nanoparticles made of cholesterol-conjugated carboxymethyl curdlan (CCMC) entrapping epirubicin (EPB) and establish their in vitro and in vivo potential. CCMC was synthesized and characterized by Fourier transform infrared spectra (FT-IR) and proton nuclear magnetic resonance spectra (1H NMR). The degrees of substitution (DS) of the cholesterol moiety were 2.3, 3.5 and 6.4, respectively. EPB-loaded CCMC-3.5 nanoparticles were prepared by the remote loading method. The physicochemical characteristics, drug loading efficiency and drug release kinetics of EPB-loaded CCMC-3.5 nanoparticles were characterized. The in vitro release profiles revealed that EPB release was sensitive to the pH as well as the drug loading contents. The cellular cytotoxicity and cellular uptake were accessed by using human cervical carcinoma (HeLa) cells. The EPB-loaded CCMC-3.5 nanoparticles were found to be more cytotoxic and have a broader distribution within the cells than the free EPB. The in vivo pharmacokinetics and biodistribution were investigated after intravenous injection in rats. Promisingly, a 4.0-fold increase in the mean residence time (MRT), a 4.31-fold increase in the half-life time and a 6.69-fold increase in the area under the curve (\\mathrm {AUC}_{0 \\to \\infty }) of EPB were achieved for the EPB-loaded CCMC-3.5 self-assembled nanoparticles compared with the free EPB. The drug level was significantly increased in liver at 24 and 72 h however, it decreased in heart at 8 and 24 h compared with the free EPB. The in vivo anti-tumor study indicated that the EPB-loaded CCMC-3.5 self-assembled nanoparticles showed greater anti-tumor efficacy than the free EPB. Taken together, the novel CCMC self-assembled nanoparticles might have potential application as anti-cancer drug carriers in a drug delivery system due to good results in vitro and in vivo.

  11. Serum albumin acts as a shuttle to enhance cholesterol efflux from cells[S

    OpenAIRE

    Sankaranarayanan, Sandhya; de la Llera-Moya, Margarita; Drazul-Schrader, Denise; Phillips, Michael C.; Kellner-Weibel, Ginny; Rothblat, George H.

    2013-01-01

    An important mechanism contributing to cell cholesterol efflux is aqueous transfer in which cholesterol diffuses from cells into the aqueous phase and becomes incorporated into an acceptor particle. Some compounds can enhance diffusion by acting as shuttles transferring cholesterol to cholesterol acceptors, which act as cholesterol sinks. We have examined whether particles in serum can enhance cholesterol efflux by acting as shuttles. This task was accomplished by incubating radiolabeled J774...

  12. Cholesterol organization in membranes at low concentrations: effects of curvature stress and membrane thickness.

    OpenAIRE

    Rukmini, R; Rawat, S S; Biswas, S. C.; Chattopadhyay, A

    2001-01-01

    Cholesterol is often found distributed nonrandomly in domains in biological and model membranes and has been reported to be distributed heterogeneously among various intracellular membranes. Although a large body of literature exists on the organization of cholesterol in plasma membranes or membranes with high cholesterol content, very little is known about organization of cholesterol in membranes containing low amounts of cholesterol. Using a fluorescent cholesterol analog (25-[N-[(7-nitrobe...

  13. Acute dyspnea

    International Nuclear Information System (INIS)

    Radiodiagnosis is applied to determine the causes of acute dyspnea. Acute dyspnea is shown to aggravate the course of pulmonary diseases (bronchial asthma, obstructive bronchitis, pulmonary edema, throboembolism of pulmonary arteries etc) and cardiovascular diseases (desiseas of myocardium). The main tasks of radiodiagnosis are to determine volume and state of the lungs, localization and type of pulmonary injuries, to verify heart disease and to reveal concomitant complications

  14. Resveratrol Protects Rabbits Against Cholesterol Diet-Induced Hyperlipidaemia.

    Science.gov (United States)

    Tanko, Y; Jimoh, A; Ahmed, A; Mohammed, A; Ayo, J O

    2016-01-01

    The excessive consumption of high cholesterol diet has been associated with an increased incidence oflipidaemia. Lipidaemia is enhanced by formation of oxidative stress, lipid peroxidation and hyperglycaemia. The aim ofthese experiments was to investigate the protective effect of resveratrol co-administered with cholesterol diet inducedhyperlipidaemia in rabbits. Thirty rabbits divided into six groups of five animal (group= 5) each: group 1 = normal control,group 2 = cholesterol diet/high fat diet group only (HFD), group 3 = resveratrol 200 mg/kg (R200), group 4 = resveratrol400 mg/kg (R400), group 5 = HFD + R200 and group 6 = HFD + R400. The normal group was fed with standard animalfeeds only; while the HFD groups were fed with standard animal feeds + cholesterol diet (10% Groundnut oil, 20%Groundnut mill and 2% cholesterol). Resveratrol-treated rabbits received resveratrol suspended in 10 g/Lcarboxymethylcellulose (CMC) and the control group received the vehicle only, CMC. The preparations were administeredfor 8 weeks of experimental protocol. At the end of the study period, the animals were sacrificed. Blood and plasma sampleswere collected. Serum evaluation of lipid profile such as total cholesterol (TC), triacylglycerol (Tg), low density lipoproteincholesterol (LDP-c) and high density lipoprotein cholesterol (HDL-c) were also assessed. The results obtained showsignificant (P resveratrol treated groups compared to HFD group only.In conclusion, the findings indicated that Resveratrol may contain polar products able to lower plasma lipid concentrationsand might be beneficial in treatment of hyperlipidemia and atherosclerosis. PMID:27574767

  15. CHOLESTEROL LEVELS AND SUICIDAL BEHAVIOR: A CASE CONTROL STUDY

    Directory of Open Access Journals (Sweden)

    Nikhil

    2014-06-01

    Full Text Available BACKGROUND: In modern psychiatry, there is a movement to understand mental health, not solely based on behaviors and subjective report, but also based on objective markers of illness. Several studies have focused on a relationship between serum cholesterol levels and aggressive behaviors including suicide. AIM: To identify a potential link between cholesterol and suicidal behavior. MATERIAL AND METHODS: 150 patients with psychiatry diagnosis were divided into three equal groups (50 each: those who had a recent suicidal attempt, those who had suicidal ideations but no attempts and those with psychiatry diagnosis but no suicidal ideations and attempts. Blood sample for total cholesterol level was on IPD or OPD basis. The study was started after taking approval from institute ethical committee. Analysis was done using Chi square test. OBSERVATIONS AND RESULTS: It was found that maximum patients who attempted suicide belonged to major depression and schizophrenia followed by substance dependence and bipolar affective disorder (BPAD with major depression and there was statistical difference in cholesterol levels of patients with suicide attempt, with suicidal ideations and control group. 42% and 44% of major depression and schizophrenia cases respectively had low total serum cholesterol levels (below 160 mg%. CONCLUSION: There is a potential link between serum total cholesterol levels and suicidal behavior. Taking the literature as a whole there is substantial evidence that low cholesterol levels are found in suicidal behaviors of various psychiatric illnesses especially major depressive disorder, schizophrenia, substance dependence and bipolar depressive disorder

  16. Cholesterol induces fetal rat enterocyte death in culture

    Directory of Open Access Journals (Sweden)

    Gazzola J.

    2004-01-01

    Full Text Available The effect of cholesterol on fetal rat enterocytes and IEC-6 cells (line originated from normal rat small intestine was examined. Both cells were cultured in the presence of 20 to 80 µM cholesterol for up to 72 h. Apoptosis was determined by flow cytometric analysis and fluorescence microscopy. The expression of HMG-CoA reductase and peroxisome proliferator-activated receptor gamma (PPARgamma was measured by RT-PCR. The addition of 20 µM cholesterol reduced enterocyte proliferation as early as 6 h of culture. Reduction of enterocyte proliferation by 28 and 41% was observed after 24 h of culture in the presence and absence of 10% fetal calf serum, respectively, with the effect lasting up to 72 h. Treatment of IEC-6 cells with cholesterol for 24 h raised the proportion of cells with fragmented DNA by 9.7% at 40 µM and by 20.8% at 80 µM. When the culture period was extended to 48 h, the effect of cholesterol was still more pronounced, with the percent of cells with fragmented DNA reaching 53.5% for 40 µM and 84.3% for 80 µM. Chromatin condensation of IEC-6 cells was observed after treatment with cholesterol even at 20 µM. Cholesterol did not affect HMG-CoA reductase expression. A dose-dependent increase in PPARgamma expression in fetal rat enterocytes was observed. The expression of PPAR-gamma was raised by 7- and 40-fold, in the presence and absence of fetal calf serum, respectively, with cholesterol at 80 mM. The apoptotic effect of cholesterol on enterocytes was possibly due to an increase in PPARgamma expression.

  17. Low HDL cholesterol, aggression and altered central serotonergic activity.

    Science.gov (United States)

    Buydens-Branchey, L; Branchey, M; Hudson, J; Fergeson, P

    2000-03-01

    Many studies support a significant relation between low cholesterol levels and poor impulse, aggression and mood control. Evidence exists also for a causal link between low brain serotonin (5-HT) activity and these behaviors. Mechanisms linking cholesterol and hostile or self-destructive behavior are unknown, but it has been suggested that low cholesterol influences 5-HT function. This study was designed to explore the relationship between plasma cholesterol, measures of impulsivity and aggression, and indices of 5-HT function in personality disordered cocaine addicts. Thirty-eight hospitalized male patients (age 36.8+/-7.1) were assessed with the DSM-III-R, the Buss-Durkee Hostility Inventory (BDHI), the Barratt Impulsiveness Scale (BIS) and the Brown-Goodwin Assessment for Life History of Aggression. Fasting basal cholesterol (total, LDL and HDL) was determined 2 weeks after cocaine discontinuation. On the same day 5-HT function was assessed by neuroendocrine (cortisol and prolactin) and psychological (NIMH and 'high' self-rating scales) responses following meta-chlorophenylpiperazine (m-CPP) challenges. Reduced neuroendocrine responses, 'high' feelings and increased 'activation-euphoria' following m-CPP have been interpreted as indicating 5-HT alterations in a variety of psychiatric conditions. Significantly lower levels of HDL cholesterol were found in patients who had a history of aggression (P=0.005). Lower levels of HDL cholesterol were also found to be significantly associated with more intense 'high' and 'activation-euphoria' responses as well as with blunted cortisol responses to m-CPP (P=0.033, P=0.025 and P=0.018, respectively). This study gives further support to existing evidence indicating that in some individuals, the probability of exhibiting impulsive and violent behaviors may be increased when cholesterol is low. It also suggests that low cholesterol and alterations in 5-HT activity may be causally related.

  18. Antiatherogenic activity of extracts of Argania spinosa L. pericarp: beneficial effects on lipid peroxidation and cholesterol homeostasis.

    Science.gov (United States)

    Berrougui, Hicham; Cherki, Mounia; Koumbadinga, Geremy Abdull; Isabelle, Maxim; Douville, Jasmin; Spino, Claude; Khalil, Abdelouahed

    2007-09-01

    Prevention of lipoprotein oxidation by natural compounds may prevent atherosclerosis via reducing early atherogenesis. In this study, we investigated for the first time the beneficial properties of methanolic extract of argania pericarp (MEAP) towards atherogenesis by protecting human low-density lipoprotein (LDL) against oxidation while promoting high-density lipoprotein (HDL)-mediated cholesterol efflux. By measuring the formation of malondialdehyde (MDA) and conjugated diene as well as the lag phase and the progression rate of lipid peroxidation, the MEAP was found to possess an inhibitory effect. In addition, MEAP reduced the rate of disappearance of alpha-tocopherol as well as the apoB electrophoretic mobility in a dose-dependent manner. These effects are related to the free radical scavenging and copper-chelating effects of MEAP. In terms of cell viability, MEAP has shown a cytotoxic effect (0-40 microg/mL). Incubation of 3H-cholesterol-loaded J774 macrophages with HDL in the presence of increasing concentrations of MEAP enhanced HDL-mediated cholesterol efflux independently of ABCA1 receptor pathways. Our findings suggest that argania seed pericarp provides a source of natural antioxidants that inhibit LDL oxidation and enhance cholesterol efflux and thus can prevent development of cardiovascular diseases. PMID:18066138

  19. Statins: Cholesterol guidelines and Indian perspective

    Directory of Open Access Journals (Sweden)

    Anil S Menon

    2015-01-01

    Full Text Available Statins have become an important drug in preventing the occurrence of atherosclerotic cardiovascular disease (ASCVD. The effectiveness of statins in reducing ASCVD has been established in large-scale clinical trials. The lipid management guidelines have been periodically modified due to accumulating evidence about the proportionate benefit achieved with a progressive reduction in cholesterol levels with higher doses of statins and even in those at low risk of development of ASCVD. The current American College of Cardiology/American Heart Association guidelines have based its recommendations from data gathered exclusively from randomized controlled trials. It has simplified the use of statins, but also raised questions regarding the validity of its cardiovascular event risk prediction tool. Epidemiology of cardiovascular disease in India differs from the western population; there is an increased the prevalence of metabolic syndrome and atherogenic dyslipidemia phenotype a group not addressed in the current guidelines. The guidelines are based on trials, which do not have a representative South Asian population. This article reviews the relevant literature, and examines the issues involved in adopting the guidelines to the Indian population.

  20. Does fat in milk, butter and and cholesterol differently?

    DEFF Research Database (Denmark)

    Tholstrup, T,; Høy, Carl-Erik; Andersen, L.N.;

    2004-01-01

    and 8 hours following intake of the meals. Results: Fasting LDL cholesterol concentration was significantly higher after butter than cheese diet (p 0.037), with a borderline significant difference in total cholesterol (p = 0.054) after the experimental periods of three weeks. Postprandial glucose showed...... a higher response after cheese diet than after milk diet (p = 0.010, diet X time interaction). Conclusions: A different effect of fat in milk and butter could not be confirmed in this study. The moderately lower LDL cholesterol after cheese diet compared to butter diet should be investigated further....

  1. Reverse cholesterol transport: From classical view to new insights

    Institute of Scientific and Technical Information of China (English)

    Astrid; E; van; der; Velde

    2010-01-01

    Cholesterol is of vital importance for the human body. It is a constituent for most biological membranes, it is needed for the formation of bile salts, and it is the pre- cursor for steroid hormones and vitamin D. However, the presence of excess cholesterol in cells, and in particular in macrophages in the arterial vessel wall, might be harmful. The accumulation of cholesterol in arteries can lead to atherosclerosis, and in turn, to other cardiovascular diseases. The route that is primarily thought to be re...

  2. 三磷酸腺苷结合盒转运体A1在巨噬细胞胆固醇流出中的作用%Effects of ATP binding cassette transporter A1 on cholesterol efflux in macrophages

    Institute of Scientific and Technical Information of China (English)

    唐朝克; 严鹏科; 杨永宗

    2003-01-01

    Tangier disease is caused by mutations in ATP binding cassette transporter AI( ABCA1).ABCA1 interacts with lipid-free apolipoproteins, promoting phospholipid and cholesterol ettlux fzom cells and giving rise to HDL particles. ABCA1 may act as a phospholipid translocase facilitating phospholipid binding to apoA-Ⅰ. ABCA1 gene expression is upregulated in cholesterol-loaded cells as a result of activation of IXR/RXR- mediated gene transcription. LXR and RXR coordinately induce a battery of genes mediating cellular cholesterol efllux, centripetal cholesterol tramport, and cholesterol excretion in bile. Small- molecule activators of LXR/RXR or other stimulators of macrophage or intestinal cholesterol efl]ux hold great promise as future treat-ments for atherosclerosis.

  3. Assessing Cholesterol Storage in Live Cells and C. elegans by Stimulated Raman Scattering Imaging of Phenyl-Diyne Cholesterol

    Science.gov (United States)

    Lee, Hyeon Jeong; Zhang, Wandi; Zhang, Delong; Yang, Yang; Liu, Bin; Barker, Eric L.; Buhman, Kimberly K.; Slipchenko, Lyudmila V.; Dai, Mingji; Cheng, Ji-Xin

    2015-01-01

    We report a cholesterol imaging method using rationally synthesized phenyl-diyne cholesterol (PhDY-Chol) and stimulated Raman scattering (SRS) microscope. The phenyl-diyne group is biologically inert and provides a Raman scattering cross section that is 88 times larger than the endogenous C = O stretching mode. SRS microscopy offers an imaging speed that is faster than spontaneous Raman microscopy by three orders of magnitude, and a detection sensitivity of 31 μM PhDY-Chol (~1,800 molecules in the excitation volume). Inside living CHO cells, PhDY-Chol mimics the behavior of cholesterol, including membrane incorporation and esterification. In a cellular model of Niemann-Pick type C disease, PhDY-Chol reflects the lysosomal accumulation of cholesterol, and shows relocation to lipid droplets after HPβCD treatment. In live C. elegans, PhDY-Chol mimics cholesterol uptake by intestinal cells and reflects cholesterol storage. Together, our work demonstrates an enabling platform for study of cholesterol storage and trafficking in living cells and vital organisms.

  4. Comparison of biosensors based on entrapment of cholesterol oxidase and cholesterol esterase in electropolymerized films of polypyrrole and diaminonaphthalene derivatives for amperometric determination of cholesterol.

    Science.gov (United States)

    Vidal, J C; Garcia-Ruiz, E; Espuelas, J; Aramendia, T; Castillo, J R

    2003-09-01

    Cholesterol amperometric biosensors constructed with enzymes entrapped in electropolymerized layers of polypyrrole and poly-naphthalene derivative polymers are compared. The biosensors are based on entrapment of cholesterol oxidase and/or cholesterol esterase in monolayer or multilayer films electrochemically synthesised from pyrrole, 1,8-diaminonaphthalene (1,8-DAN), and 1,5-diaminonaphthalene (1,5-DAN) monomers. Seven configurations were assayed and compared, and different analytical properties were obtained depending on the kind of polymer and the arrangement of the layers. The selectivity properties were evaluated for the different monolayer and bilayer configurations proposed as a function of the film permeation factor. All the steps involved in the preparation of the biosensors and determination of cholesterol were carried out in a flow system. Sensitivity and selectivity depend greatly on hydrophobicity, permeability, compactness, thickness, and the kind of the polymer used. In some cases a protective outer layer of non-conducting poly( o-phenylenediamine) polymer improves the analytical characteristics of the biosensor. A comparative study was made of the analytical performance of each of the configurations developed. The biosensors were also applied to the flow-injection determination of cholesterol in a synthetic serum. PMID:12923606

  5. Acute myelogenous leukemia (AML) - children

    Science.gov (United States)

    Acute myelogenous leukemia - children; AML; Acute myeloid leukemia - children; Acute granulocytic leukemia - children; Acute myeloblastic leukemia - children; Acute non-lymphocytic leukemia (ANLL) - children

  6. Three cases of cholesterol granuloma in the mandible

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Min Jung; Huh, Kyung Hoe; Yi, Won Jin; Moon, Je Woon; Choi, Soon Chul [Seoul National Univ. School of Dentitry, Seoul (Korea, Republic of); Shin, Jae Myung [Inje Univ. College of Medicine, Kimhae (Korea, Republic of)

    2007-12-15

    Cholesterol granuloma is an unusual clinical entity described as an inflammatory granulation in response to the deposit of cholesterol crystals. It can develop in any portion of air cells within the temporal bone as a result of a lack of aeration and inadequate drainage, especially in the middle ear cavity. Here, we report very unusual three cases of cholesterol granuloma developed in mandible. In the first case a 68-year-old male with a large mass arising from the mandible was observed. Panoramic radiograph and computed tomography scans revealed a huge expanding lesion in the mandible. In the second case a 47-years-old female with a cystic lesion in the mandible was observed. And in the third case a 19-year-old male complaining atypical facial pain had a large lesion in the mandibular ramous. The histopathologic examinations of the cases showed numerous cholesterol crystal surrounded by multinucleated foreign body giant cells.

  7. Preterm delivery and low maternal serum cholesterol level: any correlation?

    Directory of Open Access Journals (Sweden)

    Ayodeji A. Oluwole

    2014-04-01

    Results: The study showed an incidence of 5.0% for preterm delivery in the low risk study patients. Preterm birth was 4.83-times more common with low total maternal cholesterol than with midrange total cholesterol (11.8% versus 2.2%, P = 0.024. Conclusions: We can infer from the study that the low maternal serum cholesterol (hypocholesterolaemia is associated with preterm delivery. We can therefore recommend on this basis that the concept of an optimal range for maternal serum cholesterol during pregnancy may have merit and pregnant women should be encouraged to follow a healthy, balanced diet and ensure regular antenatal visit to their healthcare provider. [Int J Reprod Contracept Obstet Gynecol 2014; 3(2.000: 442-446

  8. Interaction between cholesterol and chitosan in Langmuir monolayers

    Directory of Open Access Journals (Sweden)

    Felippe J. Pavinatto

    2005-06-01

    Full Text Available Chitosan incorporated in the aqueous subphase is found to affect the Langmuir monolayers of cholesterol, causing the surface pressure and the surface potential isotherms to become more expanded. The mean molecular area per cholesterol molecule in the condensed monolayer increases from 53 Ų in the absence of chitosan to 61 Ų for a concentration of 0.100 mg/mL of chitosan in the subphase. If additional chitosan is incorporated in the subphase, no change is noted, which points to saturation in the effects from chitosan. The interaction between chitosan and cholesterol probably occurs via hydrogen bonding. The monolayer expansion is also manifested in the monolayer morphology, as indicated by Brewster angle microscopy measurements, where larger cholesterol domains are visualized when chitosan is present in the subphase.

  9. Alternative to decrease cholesterol in sheep milk cheeses.

    Science.gov (United States)

    Gómez-Cortés, P; Viturro, E; Juárez, M; de la Fuente, M A

    2015-12-01

    The presence of cholesterol in foods is of nutritional interest because high levels of this molecule in human plasma are associated with an increasing risk of cardiovascular disease and nowadays consumers are demanding healthier products. The goal of this experiment was to diminish the cholesterol content of Manchego, the most popular Spanish cheese manufactured from ewes milk. For this purpose three bulk milks coming from dairy ewe fed with 0 (Control), 3 and 6% of linseed supplement on their diet were used. Nine cheeses (3 per bulk milk) were manufactured and ripened for 3 months. Cholesterol of ewes milk cheese from 6% to 12% linseed supplemented diets decreased by 9.6% and 16.1% respectively, therefore supplying a healthier profile. In a second experiment, different sources of unsaturated fatty acids (rich in oleic, linoleic and α-linolenic acids) were supplemented to dairy ewes and no significant differences were found on cheese cholesterol levels. PMID:26041199

  10. Cellular Cholesterol Directly Activates Smoothened in Hedgehog Signaling.

    Science.gov (United States)

    Huang, Pengxiang; Nedelcu, Daniel; Watanabe, Miyako; Jao, Cindy; Kim, Youngchang; Liu, Jing; Salic, Adrian

    2016-08-25

    In vertebrates, sterols are necessary for Hedgehog signaling, a pathway critical in embryogenesis and cancer. Sterols activate the membrane protein Smoothened by binding its extracellular, cysteine-rich domain (CRD). Major unanswered questions concern the nature of the endogenous, activating sterol and the mechanism by which it regulates Smoothened. We report crystal structures of CRD complexed with sterols and alone, revealing that sterols induce a dramatic conformational change of the binding site, which is sufficient for Smoothened activation and is unique among CRD-containing receptors. We demonstrate that Hedgehog signaling requires sterol binding to Smoothened and define key residues for sterol recognition and activity. We also show that cholesterol itself binds and activates Smoothened. Furthermore, the effect of oxysterols is abolished in Smoothened mutants that retain activation by cholesterol and Hedgehog. We propose that the endogenous Smoothened activator is cholesterol, not oxysterols, and that vertebrate Hedgehog signaling controls Smoothened by regulating its access to cholesterol. PMID:27545348

  11. Cholesterol granuloma of the orbit: An atypical presentation

    Directory of Open Access Journals (Sweden)

    Syed A R Rizvi

    2014-01-01

    Full Text Available Cholesterol granuloma is a rare, well-defined lesion of the orbit. In the orbit, diploe of the frontal bone is involved almost exclusively. We report an atypical case of cholesterol granuloma involving superomedial quadrant of orbit. A 42-year-old male presented with progressive, painless, proptosis with infero-temporal displacement of left eye. A large mass was felt beneath the bony orbital margin in the superomedial quadrant of the left orbit. Computerized tomography (CT scan revealed an extraconal superomedial, heterogeneous enhancing mass which was isodense with brain and pushing the globe inferolaterally and anteriorly. Excision biopsy of the tumor revealed the typical features of a cholesterol granuloma without any epithelial elements. Cholesterol granuloma of the orbit is a rare entity, but it can be diagnosed and differentiated from other lesions of the superior orbit by its characteristic clinical, radiological and histopathological features. An appropriate intervention in time carries a good prognosis with almost no recurrence.

  12. Cholesterol-Lowering Probiotics as Potential Biotherapeutics for Metabolic Diseases

    Directory of Open Access Journals (Sweden)

    Manoj Kumar

    2012-01-01

    Full Text Available Cardiovascular diseases are one of the major causes of deaths in adults in the western world. Elevated levels of certain blood lipids have been reported to be the principal cause of cardiovascular disease and other disabilities in developed countries. Several animal and clinical trials have shown a positive association between cholesterol levels and the risks of coronary heart disease. Current dietary strategies for the prevention of cardiovascular disease advocate adherence to low-fat/low-saturated-fat diets. Although there is no doubt that, in experimental conditions, low-fat diets offer an effective means of reducing blood cholesterol concentrations on a population basis, these appear to be less effective, largely due to poor compliance, attributed to low palatability and acceptability of these diets to the consumers. Due to the low consumer compliance, attempts have been made to identify other dietary components that can reduce blood cholesterol levels. Supplementation of diet with fermented dairy products or lactic acid bacteria containing dairy products has shown the potential to reduce serum cholesterol levels. Various approaches have been used to alleviate this issue, including the use of probiotics, especially Bifidobacterium spp. and Lactobacillus spp.. Probiotics, the living microorganisms that confer health benefits on the host when administered in adequate amounts, have received much attention on their proclaimed health benefits which include improvement in lactose intolerance, increase in natural resistance to infectious disease in gastrointestinal tract, suppression of cancer, antidiabetic, reduction in serum cholesterol level, and improved digestion. In addition, there are numerous reports on cholesterol removal ability of probiotics and their hypocholesterolemic effects. Several possible mechanisms for cholesterol removal by probiotics are assimilation of cholesterol by growing cells, binding of cholesterol to cellular surface

  13. Emerging Roles for Cholesterol and Lipoproteins in Lung Disease

    OpenAIRE

    Gowdy, Kymberly M; Fessler, Michael B.

    2012-01-01

    Dyslipidemia, the condition of elevated serum triglycerides, elevated low-density lipoprotein cholesterol, and/or low high-density lipoprotein cholesterol, is a public health problem of growing concern. Dyslipidemia clusters with other disorders of the metabolic syndrome that together influence, and may derive from, chronic inflammation. While best recognized as a risk factor for atherosclerotic cardiovascular disease, lipid dysregulation has recently been shown to influence a variety of dise...

  14. Cholesterol Check (A Minute of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    2015-09-10

    Heart disease and stroke are among the leading causes of death in the U.S. One of the main risk factors is high blood cholesterol. In this podcast, Dr. Carla Mercado discusses the importance of a healthy diet and regular screening to prevent high blood cholesterol.  Created: 9/10/2015 by MMWR.   Date Released: 9/10/2015.

  15. Preterm delivery and low maternal serum cholesterol level: any correlation?

    OpenAIRE

    Oluwole, Ayodeji A.; Maymunah A. Adegbesan-Omilabu; Kehinde S. Okunade

    2014-01-01

    Background: Preterm birth is a major challenge in perinatal health care with prematurity accounting for 40-60% of all perinatal deaths in Nigeria. The physiologic hypercholesterolaemia of later pregnancy suggests an adaptive function for pregnancy maintenance or fetal growth. Decreased levels of maternal total cholesterol and low-density lipoprotein cholesterol have been reported in association with preterm delivery. Methods: This was a prospective observational cohort study designed to a...

  16. Tissue cholesterol content alterations in streptozotocin-induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Xin-ting WANG; Jia LI; Li LIU; Nan HU; Shi JIN; Can LIU; Dan MEI; Xiao-dong LIU

    2012-01-01

    Aim:Diabetes is associated with elevated serum total cholesterol level and disrupted lipoprotein subfractions.The aim of this study was to examine alterations in the tissue cholesterol contents closely related to diabetic complications.Methods:Intraperitoneal injection of streptozotocin was used to induce type 1 diabetes in adult male Sprague-Dawley rats.On d 35 after the injection,liver,heart,intestine,kidney,pancreas,cerebral cortex and hippocampus were isolated from the rats.The content of total and free cholesterol in the tissues was determined using HPLC.The ATP-binding cassette protein A1 (ABCA1) protein and ApoE mRNA were measured using Western blot and QT-PCR analyses,respectively.Results:In diabetic rats,the level of free cholesterol was significantly decreased in the peripheral tissues,but significantly elevated in hippocampus,as compared with those in the control rats.Diabetic rats showed a trend of decreasing the total cholesterol level in the peripheral tissues,but significant change was only found in kidney and liver.In diabetic rats,the level of the ABCA1 protein was significantly increased in the peripheral tissues and cerebral cortex; the expression of ApoE mRNA was slightly decreased in hippocampus and cerebral cortex,but the change had no statistical significance.Conclusion:Type 1 diabetes decreases the free cholesterol content in the peripheral tissues and increases the free cholesterol content in hippocampus.The decreased free cholesterol level in the peripheral tissues may be partly due to the increased expression of the ABCA1 protein.

  17. Optimizing Conditions to Cholesterol Adsorbed with Carboxymethyl Chitosan

    OpenAIRE

    Mardiyah Kurniasih; Dwi Kartika; Riyanti Riyanti

    2016-01-01

    A research on optimizing conditions to cholesterol adsorbed have been performed. Optimization was performed by varying: contact time, adsorbent weight and temperature of the system's. A full factorial experimental design was used in this study. Characterization performed on the synthesized chitosan and carboxymethyl chitosan including FTIR, water content, ash content, solubility, porosity, and swelling effect. The results showed that carboxymethyl chitosan able to adsorb cholesterol under con...

  18. HIV-Cholesterol Connection Suggests a New Antiretroviral Strategy

    OpenAIRE

    Zahedi Mujawar; Honor Rose; Morrow, Matthew P.; Tatiana Pushkarsky; Larisa Dubrovsky; Nigora Mukhamedova; Ying Fu; Anthony Dart; Orenstein, Jan M.; Bobryshev, Yuri V.; Michael Bukrinsky; Dmitri Sviridov

    2006-01-01

    Several steps of HIV-1 replication critically depend on cholesterol. HIV infection is associated with profound changes in lipid and lipoprotein metabolism and an increased risk of coronary artery disease. Whereas numerous studies have investigated the role of anti-HIV drugs in lipodystrophy and dyslipidemia, the effects of HIV infection on cellular cholesterol metabolism remain uncharacterized. Here, we demonstrate that HIV-1 impairs ATP-binding cassette transporter A1 (ABCA1)-dependent chole...

  19. Cholesterol depletion disorganizes oocyte membrane rafts altering mouse fertilization.

    Directory of Open Access Journals (Sweden)

    Jorgelina Buschiazzo

    Full Text Available Drastic membrane reorganization occurs when mammalian sperm binds to and fuses with the oocyte membrane. Two oocyte protein families are essential for fertilization, tetraspanins and glycosylphosphatidylinositol-anchored proteins. The firsts are associated to tetraspanin-enriched microdomains and the seconds to lipid rafts. Here we report membrane raft involvement in mouse fertilization assessed by cholesterol modulation using methyl-β-cyclodextrin. Cholesterol removal induced: (1 a decrease of the fertilization rate and index; and (2 a delay in the extrusion of the second polar body. Cholesterol repletion recovered the fertilization ability of cholesterol-depleted oocytes, indicating reversibility of these effects. In vivo time-lapse analyses using fluorescent cholesterol permitted to identify the time-point at which the probe is mainly located at the plasma membrane enabling the estimation of the extent of the cholesterol depletion. We confirmed that the mouse oocyte is rich in rafts according to the presence of the raft marker lipid, ganglioside GM1 on the membrane of living oocytes and we identified the coexistence of two types of microdomains, planar rafts and caveolae-like structures, by terms of two differential rafts markers, flotillin-2 and caveolin-1, respectively. Moreover, this is the first report that shows characteristic caveolae-like invaginations in the mouse oocyte identified by electron microscopy. Raft disruption by cholesterol depletion disturbed the subcellular localization of the signal molecule c-Src and the inhibition of Src kinase proteins prevented second polar body extrusion, consistent with a role of Src-related kinases in fertilization via signaling complexes. Our data highlight the functional importance of intact membrane rafts for mouse fertilization and its dependence on cholesterol.

  20. Apolipoprotein M promotes mobilization of cellular cholesterol in vivo

    DEFF Research Database (Denmark)

    Elsøe, Sara; Christoffersen, Christina; Luchoomun, Jayraz;

    2013-01-01

    The HDL associated apolipoprotein M (apoM) protects against experimental atherosclerosis but the mechanism is unknown. ApoM increases prebeta-HDL formation. We explored whether plasma apoM affects mobilization of cholesterol from peripheral cells in mice.......The HDL associated apolipoprotein M (apoM) protects against experimental atherosclerosis but the mechanism is unknown. ApoM increases prebeta-HDL formation. We explored whether plasma apoM affects mobilization of cholesterol from peripheral cells in mice....

  1. Elastic deformation and failure of lipid bilayer membranes containing cholesterol.

    OpenAIRE

    Needham, D; Nunn, R. S.

    1990-01-01

    Giant bilayer vesicles were reconstituted from several lipids and lipid/cholesterol (CHOL) mixtures: stearolyloleoylphosphatidylcholine (SOPC), bovine sphingomyelin (BSM), diarachidonylphosphatidylcholine (DAPC), SOPC/CHOL, BSM/CHOL, DAPC/CHOL, and extracted red blood cell (RBC) lipids with native cholesterol. Single-walled vesicles were manipulated by micropipette suction and several membrane material properties were determined. The properties measured were the elastic area compressibility m...

  2. Cholesterol-Enhanced Polylactide-Based Stereocomplex Micelle for Effective Delivery of Doxorubicin

    Directory of Open Access Journals (Sweden)

    Jixue Wang

    2015-01-01

    Full Text Available Nanoscale micelles as an effective drug delivery system have attracted increasing interest in malignancy therapy. The present study reported the construction of the cholesterol-enhanced doxorubicin (DOX-loaded poly(D-lactide-based micelle (CDM/DOX, poly(L-lactide-based micelle (CLM/DOX, and stereocomplex micelle (CSCM/DOX from the equimolar enantiomeric 4-armed poly(ethylene glycol–polylactide copolymers in aqueous condition. Compared with CDM/DOX and CLM/DOX, CSCM/DOX showed the smallest hydrodynamic size of 96 ± 4.8 nm and the slowest DOX release. The DOX-loaded micelles exhibited a weaker DOX fluorescence inside mouse renal carcinoma cells (i.e., RenCa cells compared to free DOX·HCl, probably because of a slower DOX release. More importantly, all the DOX-loaded micelles, especially CSCM/DOX, exhibited the excellent antiproliferative efficacy that was equal to or even better than free DOX·HCl toward RenCa cells attributed to their successful internalization. Furthermore, all of the DOX-loaded micelles exhibited the satisfactory hemocompatibility compared to free DOX·HCl, indicating the great potential for systemic chemotherapy through intravenous injection.

  3. Cholesterol-dependent hemolytic activity of Passiflora quadrangularis leaves

    Directory of Open Access Journals (Sweden)

    L.N. Yuldasheva

    2005-07-01

    Full Text Available Plants used in traditional medicine are rich sources of hemolysins and cytolysins, which are potential bactericidal and anticancer drugs. The present study demonstrates for the first time the presence of a hemolysin in the leaves of Passiflora quadrangularis L. This hemolysin is heat stable, resistant to trypsin treatment, has the capacity to froth, and acts very rapidly. The hemolysin activity is dose-dependent, with a slope greater than 1 in a double-logarithmic plot. Polyethylene glycols of high molecular weight were able to reduce the rate of hemolysis, while liposomes containing cholesterol completely inhibited it. In contrast, liposomes containing phosphatidylcholine were ineffective. The Passiflora hemolysin markedly increased the conductance of planar lipid bilayers containing cholesterol but was ineffective in cholesterol-free bilayers. Successive extraction of the crude hemolysin with n-hexane, chloroform, ethyl acetate, and n-butanol resulted in a 10-fold purification, with the hemolytic activity being recovered in the n-butanol fraction. The data suggest that membrane cholesterol is the primary target for this hemolysin and that several hemolysin molecules form a large transmembrane water pore. The properties of the Passiflora hemolysin, such as its frothing ability, positive color reaction with vanillin, selective extraction with n-butanol, HPLC profile, cholesterol-dependent membrane susceptibility, formation of a stable complex with cholesterol, and rapid erythrocyte lysis kinetics indicate that it is probably a saponin.

  4. Europium tetracycline biosensor for the determination of cholesterol

    Science.gov (United States)

    Courrol, Lilia Coronato; Silva, Flávia Rodrigues de Oliveira; Samad, Ricardo Elgul; Mansano, Ronaldo Domingues; Vieira, Nilson Dias, Jr.

    2007-02-01

    Development of cholesterol biosensors is of great importance in clinical analysis because the concentration of cholesterol in blood is a fundamental parameter for the prevention and diagnosis of a number of clinical disorders such as heart disease, hypertension and arteriosclerosis. In general, determination of cholesterol is based on spectrophotometry; but this method involves complicated procedures and the cost is high because expensive enzyme must be used in each assay. We report here the observation, for the first time, of the enhancement of Europium-Tetracycline complex emission in cholesterol solutions. This enhancement was initially observed with the addition of the enzyme cholesterol oxidase, which produces H IIO II, the agent driver of the Europium tetracycline complex, to the solution. However, it was found that the enzyme is not needed to enhance the luminescence. A calibration curve was determined, resulting in an easy-handling immobilization method with a cheap stable material. This method shows that the complex can be used as a sensor to determine cholesterol in biological systems with good selectivity, fast response, miniature size, and reproducible results.

  5. The Role of Cholesterol in Driving IAPP-Membrane Interactions.

    Science.gov (United States)

    Sciacca, Michele F M; Lolicato, Fabio; Di Mauro, Giacomo; Milardi, Danilo; D'Urso, Luisa; Satriano, Cristina; Ramamoorthy, Ayyalusamy; La Rosa, Carmelo

    2016-07-12

    Our knowledge of the molecular events underlying type 2 diabetes mellitus-a protein conformational disease characterized by the aggregation of islet amyloid polypeptide (IAPP) in pancreatic β cells-is limited. However, amyloid-mediated membrane damage is known to play a key role in IAPP cytotoxicity, and therefore the effects of lipid composition on modulating IAPP-membrane interactions have been the focus of intense research. In particular, membrane cholesterol content varies with aging and consequently with adverse environmental factors such as diet and lifestyle, but its role in the development of the disease is controversial. In this study, we employ a combination of experimental techniques and in silico molecular simulations to shed light on the role of cholesterol in IAPP aggregation and the related membrane disruption. We show that if anionic POPC/POPS vesicles are used as model membranes, cholesterol has a negligible effect on the kinetics of IAPP fibril growth on the surface of the bilayer. In addition, cholesterol inhibits membrane damage by amyloid-induced poration on membranes, but enhances leakage through fiber growth on the membrane surface. Conversely, if 1:2 DOPC/DPPC raft-like model membranes are used, cholesterol accelerates fiber growth. Next, it enhances pore formation and suppresses fiber growth on the membrane surface, leading to leakage. Our results highlight a twofold effect of cholesterol on the amyloidogenicity of IAPP and help explain its debated role in type 2 diabetes mellitus. PMID:27410742

  6. Cholesterol-dependent Conformational Plasticity in GPCR Dimers.

    Science.gov (United States)

    Prasanna, Xavier; Sengupta, Durba; Chattopadhyay, Amitabha

    2016-01-01

    The organization and function of the serotonin1A receptor, an important member of the GPCR family, have been shown to be cholesterol-dependent, although the molecular mechanism is not clear. We performed a comprehensive structural and dynamic analysis of dimerization of the serotonin1A receptor by coarse-grain molecular dynamics simulations totaling 3.6 ms to explore the molecular details of its cholesterol-dependent association. A major finding is that the plasticity and flexibility of the receptor dimers increase with increased cholesterol concentration. In particular, a dimer interface formed by transmembrane helices I-I was found to be sensitive to cholesterol. The modulation of dimer interface appears to arise from a combination of direct cholesterol occupancy and indirect membrane effects. Interestingly, the presence of cholesterol at the dimer interface is correlated with increased dimer plasticity and flexibility. These results represent an important step in characterizing the molecular interactions in GPCR organization with potential relevance to therapeutic interventions. PMID:27535203

  7. Loads and loads and loads: The influence of prospective load, retrospective load, and ongoing task load in prospective memory

    Directory of Open Access Journals (Sweden)

    Beat eMeier

    2015-06-01

    Full Text Available In prospective memory tasks different kinds of load can occur. Adding a prospective memory task can impose a load on ongoing task performance. Adding ongoing task load can affect prospective memory performance. The existence of multiple target events increases prospective load and adding complexity to the to-be-remembered action increases retrospective load. In two experiments, we systematically examined the effects of these different types of load on prospective memory performance. Results showed an effect of prospective load on costs in the ongoing task for categorical targets (Experiment 2, but not for specific targets (Experiment 1. Retrospective load and ongoing task load both affected remembering the retrospective component of the prospective memory task. We suggest that prospective load can enhance costs in the ongoing task due to additional monitoring requirements. Retrospective load and ongoing task load seem to impact the division of resources between the ongoing task and retrieval of the retrospective component, which may affect disengagement from the ongoing task. In general, the results demonstrate that the different types of load affect prospective memory differentially.

  8. Self-assembled nanoparticles of cholesterol-modified O-carboxymethyl chitosan as a novel carrier for paclitaxel

    Energy Technology Data Exchange (ETDEWEB)

    Wang Yinsong; Li Rongshan; Wang Yumei; Zhao Jing [College of Pharmacy, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070 (China); Jiang Qian; Liu Linglong; Zhang Qiqing [Institute of Biomedical Engineering, Chinese Academy of Medical Science, Peking Union Medical College, PO Box 25(204), Tianjin 300192 (China)], E-mail: wangyinsong@tijmu.edu.cn, E-mail: zhangqiq@xmu.edu.cn

    2008-04-09

    Self-assembled nanoparticles of cholesterol-modified O-carboxymethyl chitosan (CCMC) were prepared to be used as a novel carrier for paclitaxel (PTX) in this study. CCMC-6.9 was synthesized by the covalent conjugation of cholesterol to O-carboxymethyl chitosan with the succinyl linkage and the degree of substitution (DS) of the cholesterol moiety was 6.9%. CCMC-6.9 formed self-assembled nanoparticles with a size of 209.5 nm in aqueous media. Paclitaxel-loaded CCMC-6.9 self-assembled nanoparticles were prepared using a dialysis method and their characteristics were analyzed by dynamic laser light scattering (LLS), transmission electron microscopy (TEM) and ultraviolet spectroscopy (UV). PTX-loaded CCMC-6.9 self-assembled nanoparticles were almost spherical in shape and their size increased from 245.6 to 355.3 nm with PTX-loading content increasing from 18.7% to 34.9%. In vitro release of PTX from CCMC-6.9 self-assembled nanoparticles was carried out by the dynamic dialysis method. PTX continuously released in phosphate buffered saline (PBS) solutions for 84 h at 37 deg. C and its release was sensitive to the pH of the release media. The biodistribution of PTX-loaded CCMC-6.9 self-assembled nanoparticles was studied in female Balb/c mice. Compared with PTX in the solution of Cremophor EL (polyethoxylated castor oil)/ethanol (PTX-Cre), CCMC-6.9 self-assembled nanoparticles significantly increased the uptake of PTX in plasma, liver and spleen, but decreased the uptake in heart and kidney. These results suggest that CCMC-6.9 self-assembled nanoparticles can effectively solubilize PTX and modify its tissue biodistribution, which may be advantageous in enhancing the therapeutic index and reducing the toxicity of PTX.

  9. Remnant Cholesterol, Low-Density Lipoprotein Cholesterol, and Blood Pressure as Mediators From Obesity to Ischemic Heart Disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Smith, George Davey;

    2015-01-01

    RATIONALE: 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. OBJECTIVE: To test the hypothesis that the increased IHD risk because of obesity is mediated through...... 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...... 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. CONCLUSIONS: The increased IHD risk because...

  10. Dietary saturated fat/cholesterol, but not unsaturated fat or starch, induces C-reactive protein associated early atherosclerosis and ectopic fat deposition in diabetic pigs

    Directory of Open Access Journals (Sweden)

    Serlie Mireille J

    2011-07-01

    Full Text Available Abstract Background Diabetes is thought to accelerate cardiovascular disease depending on the type of diet. This study in diabetic subjects was performed to investigate the metabolic, inflammatory and cardiovascular effects of nutritional components typically present in a Western, Mediterranean or high glycaemic diet. Methods Streptozotocin-diabetic pigs (~45 kg were fed for 10 weeks supplemental (40% of dietary energy saturated fat/cholesterol (SFC, unsaturated fat (UF or starch (S in an eucaloric dietary intervention study. Results Fasting plasma total, LDL and HDL cholesterol concentrations were 3-5 fold higher (p 2 = 0.95. Retroperitoneal fat depot weight (g was intermediate in SFC (260 ± 72, lowest in S (135 ± 51 and highest (p Conclusion Dietary saturated fat/cholesterol induces inflammation, atherosclerosis and ectopic fat deposition whereas an equally high dietary unsaturated fat load does not induce these abnormalities and shows beneficial effects on postprandial glycaemia in diabetic pigs.

  11. Effect of Moderate Alcohol Consumption on Parameters of Reverse Cholesterol Transport in Postmenopausal Women

    NARCIS (Netherlands)

    Sierksma, A.; Vermunt, S.H.F.; Lankhuizen, I.M.; Gaag, M.S. van der; Scheek, L.M.; Grobbee, D.E.; Tol, A. van; Hendriks, H.F.J.

    2004-01-01

    Background: Alcohol consumption is associated with increased high-density lipoprotein (HDL) cholesterol levels. One of the main antiatherogenic functions of HDL is reverse cholesterol transport. Three early steps of reverse cholesterol transport are (1) cellular cholesterol efflux, (2) plasma choles

  12. Plasma plant sterols serve as poor markers of cholesterol absorption in man

    NARCIS (Netherlands)

    Jakulj, Lily; Mohammed, Hussein; van Dijk, Theo H.; Boer, Theo; Turner, Scott; Groen, Albert K.; Vissers, Maud N.; Stroes, Erik S. G.

    2013-01-01

    The validation of the use of plasma plant sterols as a marker of cholesterol absorption is frail. Nevertheless, plant sterol concentrations are routinely used to describe treatment-induced changes in cholesterol absorption. Their use has also been advocated as a clinical tool to tailor cholesterol-l

  13. Trans-intestinal cholesterol effl ux is not mediated through high density lipoprotein

    NARCIS (Netherlands)

    Vrins, C.L.; Ottenhoff, R.; Oever, K. van den; Waart, D.R. de; Kruyt, J.K.; Zhao, Y.; Berkel, T.J. van; Havekes, L.M.; Aerts, J.M.; Eck, M. van; Rensen, P.C.; Groen, A.K.

    2012-01-01

    Transintestinal cholesterol efflux (TICE) provides an attractive target to increase body cholesterol excretion. At present, the cholesterol donor responsible for direct delivery of plasma cholesterol to the intestine is unknown. In this study, we investigated the role of HDL in TICE. ATP-binding cas

  14. Atorvastatin treatment lowers fasting remnant-like particle cholesterol and LDL subfraction cholesterol without affecting LDL size in type 2 diabetes mellitus : Relevance for non-HDL cholesterol and apolipoprotein B guideline targets

    NARCIS (Netherlands)

    Kappelle, Paul J. W. H.; Dallinga-Thie, Geesje M.; Dullaart, Robin P. F.

    2010-01-01

    The extent to which atorvastatin treatment affects LDL size, LDL subfraction levels and remnant-like particle cholesterol (RLP-C) was determined in type 2 diabetes. We also compared LDL size and RLP-C in relation to guideline cut-off values for LDL cholesterol, non-HDL cholesterol and apolipoprotein

  15. Atorvastatin treatment lowers fasting remnant-like particle cholesterol and LDL subfraction cholesterol without affecting LDL size in type 2 diabetes mellitus: Relevance for non-HDL cholesterol and apolipoprotein B guideline targets

    NARCIS (Netherlands)

    P.J.W.H. Kappelle; G.M. Dallinga-Thie; R.P.F. Dullaart

    2010-01-01

    The extent to which atorvastatin treatment affects LDL size, LDL subfraction levels and remnant-like particle cholesterol (RLP-C) was determined in type 2 diabetes. We also compared LDL size and RLP-C in relation to guideline cut-off values for LDL cholesterol, non-HDL cholesterol and apolipoprotein

  16. Hydrophobic ionic liquid immoblizing cholesterol oxidase on the electrodeposited Prussian blue on glassy carbon electrode for detection of cholesterol

    International Nuclear Information System (INIS)

    A novel cholesterol biosensor was fabricated on hydrophobic ionic liquid (IL)/aqueous solution interface. The hydrophobic IL thin film played a signal amplification role because it not only enriched the cholesterol from the aqueous solution, but also immobilized matrix for cholesterol oxidase (ChOx). Prussian blue (PB) as advanced sensing materials was used as effective low-potential electron transfer mediation toward hydrogen peroxide (H2O2). The fabricated IL-ChOx/PB/Glassy carbon electrode (GCE) was characterized by electrochemical impedance spectroscopy (EIS) and cyclic voltammogram (CV), respectively. And it exhibited a linear response to cholesterol in the range of 0.01–0.40 mM with a detection limit of 4.4 μM. In addition, the kinetics behavior of cholesterol at IL-Chox/PB/GCE electrode was examined, and the electrocatalytic mechanism was proposed as shown in first scheme. ChOx immobilized in hydrophobic IL thin film was used as the first electrocatalyst for the cholesterol into H2O2, and the PB film onto the GCE was used as the second electrocatalyst for the 2e− reduction of the produced H2O2 into H2O

  17. Curcumin inhibits cellular cholesterol accumulation by regulating SREBP-1/caveolin-1 signaling pathway in vascular smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    Hao-yu YUAN; Shuang-yu KUANG; Xing ZHENG; Hong-yan LING; Yun-bo YANG; Peng-ke YAN; Kai LI; Duan-fang LIAO

    2008-01-01

    Aim: To investigate the protective effect and the possible mechanism of curcumin on anti-atherosclerosis. Methods: Morphological changes of atherosclerotic le-sions taken from apoE knockout (apoE-/-) mice were determined by hematoxylin-eosin staining. Intracellular lipid droplets and lipid levels were assayed by oil red O staining and HPLC. The protein expression of caveolin-1 was quantified by West-ern blotting. Translocation and the expression of sterol response element-bind-ing protein-1 (SREBP-1) were indirectly detected by an immunofluorescence analysis. Results: The administration of 20 mg.kg-1.d-1 curcumin to apoE-/1 mice for 4 months induced a 50% reduction of atherosclerotic lesions and yielded a 5-fold increase in the caveolin-1 expression level as compared to the model group. Rat vascular smooth muscle cells (VSMC) pretreated with 50 mg.L-1 ox-lipid den-sity lipoprotein(ox-LDL) for 48 h increased cellular lipid contents, and stimulated SREBP-1 translocation, but decreased the caveolin-1 expression level. Lipid-loaded cells exposed to curcumin at various concentrations (12.5, 25, and 50 μmol.L-1) for different durations (0, 6, 12, 24, and 48 h) significantly diminished the number and area of cellular lipid droplets, total cholesterol, cholesterol ester, and free choles-terol accompanying the elevation of the caveolin-1 expression level (approximately 3-fold); the translocation of SREBP-1 from the cytoplasm to the nucleus was inhibited compared with the models. Lipid-loaded VSMC exposed to N-acetyl-Leu-Leu-norleucinal, a SREBP-1 protease inhibitor, showed increased nuclear trans-location of SREBP-1, reduced caveolin-1 expression level, and upregulated cellu-lar lipid levels. Conclusion: Curcumin inhibits ox-LDL-induced cholesterol accu-mulation in cultured VSMC through increasing the caveolin-1 expression via the inhibition of nuclear translocation of SREBP-1.

  18. The origin of cholesterol in chyle demonstrated by nuclear indicator methods

    International Nuclear Information System (INIS)

    In order to obtain information about the mechanism of the intestinal absorption of cholesterol, rats having a lymphatic abdominal fistula are used. The animals receive either 4-14C- cholesterol subcutaneously or orally, or the 1-14C acetate. The study of the specific radio-activities of the cholesterol in chyle, in serum, in the lining, and in the intestinal contents makes it possible to define the roles played by the transfer cholesterol from the serum, by the cholesterol synthesised intestinally, and by the absorption cholesterol, in the formations of the lymph and of the chylomicrons. A new theory is proposed for the mechanism of cholesterol absorption. (author)

  19. Effects of lovastatin and dietary cholesterol on sterol homeostasis in healthy human subjects.

    OpenAIRE

    Duane, W C

    1993-01-01

    We measured biliary and fecal sterol outputs in 12 human subjects on a metabolic ward in four randomly allocated, 6-7 wk periods: (a) lovastatin (40 mg b.i.d.) + low cholesterol diet (mean 246 mg/d), (b) lovastatin + high cholesterol diet (mean 1,071 mg/d), (c) low cholesterol diet alone, (d) high cholesterol diet alone. In addition to lowering serum LDL cholesterol, lovastatin significantly lowered biliary secretion of cholesterol, fecal output of endogenous neutral sterols, cholesterol bala...

  20. Patterns of cholesterol metabolism: pathophysiological and therapeutic implications for dyslipidemias and the metabolic syndrome.

    Science.gov (United States)

    Lupattelli, G; De Vuono, S; Mannarino, E

    2011-09-01

    Investigating cholesterol metabolism, which derives from balancing cholesterol synthesis and absorption, opens new perspectives in the pathogenesis of dyslipidemias and the metabolic syndrome (MS). Cholesterol metabolism is studied by measuring plasma levels of campesterol, sitosterol and cholestanol, that is, plant sterols which are recognised as surrogate cholesterol-absorption markers and lathosterol or squalene, that is, cholesterol precursors, which are considered surrogate cholesterol-synthesis markers. This article presents current knowledge on cholesterol synthesis and absorption, as evaluated by means of cholesterol precursors and plant sterols, and discusses patterns of cholesterol balance in the main forms of primary hyperlipidaemia and MS. Understanding the mechanism(s) underlying these patterns of cholesterol synthesis and absorption will help to predict the response to hypolipidemic treatment, which can then be tailored to ensure the maximum clinical benefit for patients.

  1. Extreme nonfasting remnant cholesterol vs extreme LDL cholesterol as contributors to cardiovascular disease and all-cause mortality in 90000 individuals from the general population

    DEFF Research Database (Denmark)

    Varbo, Anette; Freiberg, Jacob J; Nordestgaard, Børge G

    2015-01-01

    BACKGROUND: Increased nonfasting remnant cholesterol, like increased LDL cholesterol, is causally associated with increased risk for ischemic heart disease (IHD). We tested the hypothesis that extreme concentrations of nonfasting remnant and LDL cholesterol are equal contributors to the risk of IHD......, myocardial infarction (MI), and all-cause mortality. METHODS: We compared stepwise increasing concentrations of nonfasting remnant and LDL cholesterol for association with risk of IHD, MI, and all-cause mortality in approximately 90 000 individuals from the Danish general population. During up to 22 years.......4 (1.9-2.9) for remnant cholesterol of ≥1.5 mmol/L (58 mg/dL) (P for trend LDL cholesterol LDL cholesterol of 3-3.99 mmol/L (115.8-154 mg/dL) to 2.3 (1.9-2.8) for LDL cholesterol...

  2. Electrical load detection aparatus

    DEFF Research Database (Denmark)

    2010-01-01

    A load detection technique for a load comprising multiple frequency-dependant sub-loads comprises measuring a representation of the impedance characteristic of the load; providing stored representations of a multiplicity of impedance characteristics of the load; each one of the stored representat...

  3. Comparative Study of the Condensing Effects of Ergosterol and Cholesterol.

    Science.gov (United States)

    Hung, Wei-Chin; Lee, Ming-Tao; Chung, Hsien; Sun, Yi-Ting; Chen, Hsiung; Charron, Nicholas E; Huang, Huey W

    2016-05-10

    Cholesterol, due to its condensing effect, is considered an important regulator of membrane thickness. Other sterols, due to their structural similarities to cholesterol, are often assumed to have a universal effect on membrane properties similar to the condensing effect of cholesterol, albeit possibly to different degrees. We used x-ray diffraction to investigate this assumption. By the combination of lamellar diffraction and grazing-angle scattering, we measured the membrane thickness and the tilt-angle distribution of the lipid's hydrocarbon chains. This method is sensitive to phase separation, which is important for examining the miscibility of sterols and phospholipids. Mixtures of ergosterol or cholesterol with dimyristoylphosphatidylcholine, palmitoyloleoylphosphatidylcholine, and dioleoylphosphatidylcholine were systematically studied. We found that mixing ergosterol with phospholipids into a single phase became increasingly difficult with higher sterol concentrations and also with higher concentrations of unsaturated lipid chains. The only condensing effect of ergosterol was found in dimyristoylphosphatidylcholine, although the effect was less than one-third of the effect of cholesterol. Unlike cholesterol, ergosterol could not maintain a fixed electron density profile of the surrounding lipids independent of hydration. In dioleoylphosphatidylcholine and palmitoyloleoylphosphatidylcholine, ergosterol made the membranes thinner, opposite to the effect of cholesterol. In all cases, the tilt-angle variation of the chain diffraction was consistent with the membrane thickness changes measured by lamellar diffraction, i.e., a thickening was always associated with a reduction of chain tilt angles. Our findings do not support the notion that different sterols have a universal behavior that differs only in degree. PMID:27166810

  4. Measurement of rates of cholesterol synthesis using tritiated water

    International Nuclear Information System (INIS)

    Rates of sterol synthesis in various tissues commonly are assessed by assaying levels of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase on isolated microsomes or by measuring the rates of incorporation of various 14C-labeled substrates or [3H]water into cholesterol by whole cell preparations in vitro or by the tissues of the whole animal in vivo. While measurement of activities of HMG-CoA reductase or rates of incorporation of 14C-labeled substrates into cholesterol give useful relative rates of sterol production, neither method yields absolute rates of cholesterol synthesis. The use of [3H]water circumvents the problem of variable and unknown dilution of the specific activity of the precursor pool encountered when 14C-labeled substrates are used and does yield absolute rates of cholesterol synthesis provided that the 3H/C incorporation ratio is known for a particular tissue. In 12 different experimental situations it has been found that from 21 to 27 micrograms atoms of 3H are incorporated into cholesterol from [3H]water in different tissues of several animal species, so that the 3H/C incorporation ratio is similar under nearly all experimental conditions and varies from 0.78 to 1.00. When administered in vivo, [3H]water rapidly equilibrates with intracellular water and is incorporated into sterols within the various organs at rates that are linear with respect to time. From such data it is possible to obtain absolute rates of cholesterol synthesis in the whole animal and in the various organs of the animal. Current data suggest, therefore, that use of [3H]water yields the most accurate rates of cholesterol synthesis both in vitro and in vivo

  5. Ionic channels and nerve membrane lipids. Cholesterol-tetrodotoxin interaction.

    Science.gov (United States)

    Villegas, R; Barnola, F V; Camejo, G

    1970-04-01

    Experiments were carried out to investigate possible interactions of tetrodotoxin (TTX) with lipid molecules isolated from nerve fiber plasma membranes of the squid Dosidicus gigas. TTX has a highly selective ability to block the channel normally used by Na(+) to cross the axolemma during nervous impulse conduction. In order to investigate the interaction each lipid sample was spread on 5 x 10(-7)M TTX and TTX-free 0.15 M NaCl solutions adjusted to pH 7.4 with 7 x 10(-3)M phosphate buffer. The surface pressure-area diagrams of the lipid monolayers revealed that TTX interacts only with cholesterol. The expansion of the cholesterol monolayers at 5 x 10(-7)M TTX was 2 A(2)/molecule at zero pressure for the experiments at 20 degrees C and 2.5 A(2)/molecule for those at 25 degrees C. Similar results were obtained in KCl subphases. The apparent dissociation constant of the cholesterol-TTX complex calculated from dose-response experiments is 2.6 x 10(-7)M. Experiments at pH 10.1 revealed that the zwitter ionic form of TTX is less active. Experiments with cholesterol derivatives (cholesteryl acetate, cholesterol methyl ether, cholestanol, and cholestanyl acetate) indicate that for the interaction with TTX a partial negatively charged group at C-3 and a double bond between C-5 and C-6 on the steroid nucleus are required. Tetrodonic acid, a biologically inactive derivative of TTX, does not interact with cholesterol. The results lead us to propose that cholesterol is part of the Na(+) channel. PMID:5435784

  6. The influence of cholesterol on phospholipid membrane curvature and bending elasticity.

    OpenAIRE

    Chen, Z.; Rand, R P

    1997-01-01

    The behavior of dioleoylphosphatidylethanolamine (DOPE)/cholesterol/tetradecane and dioleoylphosphatidylcholine (DOPC)/cholesterol/tetradecane were examined using x-ray diffraction and the osmotic stress method. DOPE/tetradecane, with or without cholesterol, forms inverted hexagonal (HII) phases in excess water. DOPC/tetradecane forms lamellar phases without cholesterol at lower temperatures. With tetradecane, as little as 5 mol% cholesterol in DOPC induced the formation of HII phases of very...

  7. Selective delipidation of plasma HDL enhances reverse cholesterol transport in vivo

    OpenAIRE

    Sacks, Frank M.; Rudel, Lawrence L.; Conner, Adam; Akeefe, Hassibullah; Kostner, Gerhard; Baki, Talal; Rothblat, George; de la Llera-Moya, Margarita; Asztalos, Bela; Perlman, Timothy; Zheng, Chunyu; Alaupovic, Petar; Maltais, Jo-Ann B.; Brewer, H. Bryan

    2009-01-01

    Uptake of cholesterol from peripheral cells by nascent small HDL circulating in plasma is necessary to prevent atherosclerosis. This process, termed reverse cholesterol transport, produces larger cholesterol-rich HDL that transfers its cholesterol to the liver facilitating excretion. Most HDL in plasma is cholesterol-rich. We demonstrate that treating plasma with a novel selective delipidation procedure converts large to small HDL [HDL-selectively delipidated (HDL-sdl)]. HDL-sdl contains seve...

  8. Prenatal Ethanol Exposure Up-Regulates the Cholesterol Transporters ATP-Binding Cassette A1 and G1 and Reduces Cholesterol Levels in the Developing Rat Brain

    OpenAIRE

    Zhou, Chunyan; Chen, Jing; Zhang, Xiaolu; Costa, Lucio G.; Guizzetti, Marina

    2014-01-01

    Aims: Cholesterol plays a pivotal role in many aspects of brain development; reduced cholesterol levels during brain development, as a consequence of genetic defects in cholesterol biosynthesis, leads to severe brain damage, including microcephaly and mental retardation, both of which are also hallmarks of the fetal alcohol syndrome. We had previously shown that ethanol up-regulates the levels of two cholesterol transporters, ABCA1 (ATP binding cassette-A1) and ABCG1, leading to increased cho...

  9. Cholesterol metabolism changes under long-term dietary restrictions while the cholesterol homeostasis remains unaffected in the cortex and hippocampus of aging rats

    OpenAIRE

    Smiljanic, Kosara; Vanmierlo, Tim; Djordjevic, Aleksandra Mladenovic; Perovic, Milka; Ivkovic, Sanja; Luetjohann, Dieter; Kanazir, Selma

    2014-01-01

    Maintaining cholesterol homeostasis in the brain is vital for its proper functioning. While it is well documented that dietary restriction modulates the metabolism of cholesterol peripherally, little is known as to how it can affect cholesterol metabolism in the brain. The present study was designed to elucidate the impact of long-term dietary restriction on brain cholesterol metabolism. Three-month-old male Wistar rats were exposed to long-term dietary restriction until 12 and 24 months of a...

  10. Dietary Cholesterol Affects Plasma Lipid Levels, the Intravascular Processing of Lipoproteins and Reverse Cholesterol Transport without Increasing the Risk for Heart Disease

    OpenAIRE

    Jacqueline Barona; Maria Luz Fernandez

    2012-01-01

    The associations between dietary cholesterol and heart disease are highly controversial. While epidemiological studies and clinical interventions have shown the lack of correlation between cholesterol intake and cardiovascular disease (CVD) risk, there is still concern among health practitioners and the general population regarding dietary cholesterol. In this review, several clinical studies utilizing cholesterol challenges are analyzed in terms of changes that occur in lipoprotein metabolis...

  11. The mechanism of dietary cholesterol effects on lipids metabolism in rats

    Directory of Open Access Journals (Sweden)

    Wang Jing-Feng

    2010-01-01

    Full Text Available Abstract Background Cholesterol administration has been reported to influence hepatic lipid metabolism in rats. In the present study, the effect of dietary cholesterol on hepatic activity and mRNA expression of the enzymes involved in lipid metabolism were investigated. Fourteen male Wistar rats were randomly divided into 2 groups and fed 1% cholesterol or cholesterol free AIN76 diets for 4 weeks. Results The serum triglyceride and high density lipoprotein cholesterol levels were significantly decreased but the total cholesterol and non high density lipoprotein cholesterol levels were significantly increased in the cholesterol-fed rats compared with the control rats. And the concentrations of the hepatic total cholesterol and triglyceride increased about 4-fold and 20-fold separately by dietary cholesterol. The activities of hepatic malic enzyme, glucose-6-phosphate dehydrogenase, fatty acid synthase, phosphatidate phophatase and carnitine palmitoyl transferase were depressed by the cholesterol feeding (40%, 70%, 50%, 15% and 25% respectively. The results of mRNA expression showed that fatty acid synthase, carnitine palmitoyl transferase 1, carnitine palmitoyl transferase 2, and HMG-CoA reductase were down-regulated (35%, 30%, 50% and 25% respectively and acyl-CoA: cholesterol acyltransferase and cholesterol 7α-hydroxylase were up regulated (1.6 and 6.5 folds in liver by the cholesterol administration. Conclusions The dietary cholesterol increased the triglyceride accumulation in liver, but did not stimulate the activity and the gene expression of hepatic enzymes related to triglyceride and fatty acid biosynthesis.

  12. PCSK9 LNA antisense oligonucleotides induce sustained reduction of LDL cholesterol in nonhuman primates.

    Science.gov (United States)

    Lindholm, Marie W; Elmén, Joacim; Fisker, Niels; Hansen, Henrik F; Persson, Robert; Møller, Marianne R; Rosenbohm, Christoph; Ørum, Henrik; Straarup, Ellen M; Koch, Troels

    2012-02-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a therapeutic target for the reduction of low-density lipoprotein cholesterol (LDL-C). PCSK9 increases the degradation of the LDL receptor, resulting in high LDL-C in individuals with high PCSK9 activity. Here, we show that two locked nucleic acid (LNA) antisense oligonucleotides targeting PCSK9 produce sustained reduction of LDL-C in nonhuman primates after a loading dose (20 mg/kg) and four weekly maintenance doses (5 mg/kg). PCSK9 messenger RNA (mRNA) and serum PCSK9 protein were reduced by 85% which resulted in a 50% reduction in circulating LDL-C. Serum total cholesterol (TC) levels were reduced to the same extent as LDL-C with no reduction in high-density lipoprotein levels, demonstrating a specific pharmacological effect on LDL-C. The reduction in hepatic PCSK9 mRNA correlated with liver LNA oligonucleotide content. This verified that anti-PCSK9 LNA oligonucleotides regulated LDL-C through an antisense mechanism. The compounds were well tolerated with no observed effects on toxicological parameters (liver and kidney histology, alanine aminotransferase, aspartate aminotransferase, urea, and creatinine). The pharmacologic evidence and initial safety profile of the compounds used in this study indicate that LNA antisense oligonucleotides targeting PCSK9 provide a viable therapeutic strategy and are potential complements to statins in managing high LDL-C.

  13. Human immunodeficiency virus impairs reverse cholesterol transport from macrophages.

    Directory of Open Access Journals (Sweden)

    Zahedi Mujawar

    2006-10-01

    Full Text Available Several steps of HIV-1 replication critically depend on cholesterol. HIV infection is associated with profound changes in lipid and lipoprotein metabolism and an increased risk of coronary artery disease. Whereas numerous studies have investigated the role of anti-HIV drugs in lipodystrophy and dyslipidemia, the effects of HIV infection on cellular cholesterol metabolism remain uncharacterized. Here, we demonstrate that HIV-1 impairs ATP-binding cassette transporter A1 (ABCA1-dependent cholesterol efflux from human macrophages, a condition previously shown to be highly atherogenic. In HIV-1-infected cells, this effect was mediated by Nef. Transfection of murine macrophages with Nef impaired cholesterol efflux from these cells. At least two mechanisms were found to be responsible for this phenomenon: first, HIV infection and transfection with Nef induced post-transcriptional down-regulation of ABCA1; and second, Nef caused redistribution of ABCA1 to the plasma membrane and inhibited internalization of apolipoprotein A-I. Binding of Nef to ABCA1 was required for down-regulation and redistribution of ABCA1. HIV-infected and Nef-transfected macrophages accumulated substantial amounts of lipids, thus resembling foam cells. The contribution of HIV-infected macrophages to the pathogenesis of atherosclerosis was supported by the presence of HIV-positive foam cells in atherosclerotic plaques of HIV-infected patients. Stimulation of cholesterol efflux from macrophages significantly reduced infectivity of the virions produced by these cells, and this effect correlated with a decreased amount of virion-associated cholesterol, suggesting that impairment of cholesterol efflux is essential to ensure proper cholesterol content in nascent HIV particles. These results reveal a previously unrecognized dysregulation of intracellular lipid metabolism in HIV-infected macrophages and identify Nef and ABCA1 as the key players responsible for this effect. Our findings

  14. Treatment of young rats with cholestyramine or a hypercholesterolemic diet does not influence the response of serum cholesterol to dietary cholesterol in later life

    NARCIS (Netherlands)

    Beynen, A.C.; Bruijne, J.J. de; Katan, M.B.

    1985-01-01

    Groups of 10 female Wistar rats (aged 4 weeks) were fed for 29 days either a low-cholesterol commercial diet, a commercial diet containing 2% (w/w) cholesterol, 0.5% cholate and 5% olive oil or a diet containing 2% cholestyramine. The rats were then fed the low-cholesterol commercial diet for the ne

  15. Plasma lipoprotein profiles and arylesterase activities in two inbred strains of rabbits with high or low response of plasma cholesterol to dietary cholesterol

    NARCIS (Netherlands)

    Beynen, A.C.; Katan, M.B.; Zutphen, van L.F.M.

    1984-01-01

    1. 1. Cholesterol feeding for 4 weeks of female and male rabbits of two inbred strains increased plasma cholesterol concentrations by about 11 and 48 mmole/I in the hypo- and hyperresponsive strain, respectively. 2. 2. On the low-cholesterol pre-experimental diet, the hyporesponsive animals had sign

  16. Cholesterol metabolism and esterases in four strains of rats with differential cholesterolemic responses to a high-cholesterol, high-cholate diet.

    NARCIS (Netherlands)

    Beynen, A.C.; Lemmens, A.G.; Katan, M.B.; Bruijne, de J.J.; Zutphen, van L.F.M.

    1987-01-01

    1. 1. The increase in serum cholesterol after feeding a diet containing 2% (w/w) of cholesterol and 0.5% of cholate for 13 days was 200 and 800% in two hypo- and two hyper-responsive inbred strains of rats, respectively. 2. 2. While remaining on the high-cholesterol, high-cholate diet for longer per

  17. Insoluble fraction of buckwheat (Fagopyrum esculentum Moench) protein possessing cholesterol-binding properties that reduce micelle cholesterol solubility and uptake by Caco-2 cells.

    Science.gov (United States)

    Metzger, Brandon T; Barnes, David M; Reed, Jess D

    2007-07-25

    Buckwheat (Fagopyrum esculentum Moench) protein (BWP) exhibits hypocholesterolemic activity in several animal models by increasing fecal excretion of neutral and acidic sterols. In the current study, the ability of BWP to disrupt micelle cholesterol solubility by sequestration of cholesterol was investigated. When BWP (0.2%) was incubated with cholesterol and micelle lipid components prior to micelle formation, cholesterol solubility was reduced 40%. In contrast, cholesterol solubility was not decreased when BWP (0.2%) was incubated after micelle formation and incorporation of soluble cholesterol. Buckwheat flour, from which BWP was derived, had no significant effect on cholesterol solubility. Cholesterol uptake in Caco-2 cells from micelles made in the presence of BWP (0.2%) was reduced by 47, 36, 35, and 33% when compared with buckwheat flour, bovine serum albumin, casein, and gelatin, respectively. Reduction in cholesterol uptake in Caco-2 cells was dose-dependent, with maximum reductions at 0.1-0.4% BWP. In cholesterol-binding experiments, 83% of the cholesterol was associated with an insoluble BWP fraction, indicating strong cholesterol-binding capacity that disrupts solubility and uptake by Caco-2 cells.

  18. Distribution load estimation (DLE)

    Energy Technology Data Exchange (ETDEWEB)

    Seppaelae, A.; Lehtonen, M. [VTT Energy, Espoo (Finland)

    1998-08-01

    The load research has produced customer class load models to convert the customers` annual energy consumption to hourly load values. The reliability of load models applied from a nation-wide sample is limited in any specific network because many local circumstances are different from utility to utility and time to time. Therefore there is a need to find improvements to the load models or, in general, improvements to the load estimates. In Distribution Load Estimation (DLE) the measurements from the network are utilized to improve the customer class load models. The results of DLE will be new load models that better correspond to the loading of the distribution network but are still close to the original load models obtained by load research. The principal data flow of DLE is presented

  19. Acute pollution of recipients in urban areas

    DEFF Research Database (Denmark)

    Rauch, W.; Harremoës, P.

    1997-01-01

    Oxygen and ammonia concentration are key parameters of acute water pollution in urban rivers. These two abiotic parameters are statistically assessed for a historical rain series by means of a simplified deterministic model of the integrated drainage system. Continuous simulation of the system...... performance indicates that acute water pollution is caused by intermittent discharges from both sewer system and wastewater treatment plant. Neglecting one of them in the evaluation of the environmental impact gives a wrong impression of total system behavior. Detention basins and alternative operational...... modes in the treatment plant under wet weather loading have a limited positive effect for minimizing acute water pollution. (C) 1997 IAWQ. Published by Elsevier Science Ltd....

  20. Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents.

    Science.gov (United States)

    Martin, Mauricio G; Ahmed, Tariq; Korovaichuk, Alejandra; Venero, Cesar; Menchón, Silvia A; Salas, Isabel; Munck, Sebastian; Herreras, Oscar; Balschun, Detlef; Dotti, Carlos G

    2014-05-30

    Cognitive decline is one of the many characteristics of aging. Reduced long-term potentiation (LTP) and long-term depression (LTD) are thought to be responsible for this decline, although the precise mechanisms underlying LTP and LTD dampening in the old remain unclear. We previously showed that aging is accompanied by the loss of cholesterol from the hippocampus, which leads to PI3K/Akt phosphorylation. Given that Akt de-phosphorylation is required for glutamate receptor internalization and LTD, we hypothesized that the decrease in cholesterol in neuronal membranes may contribute to the deficits in LTD typical of aging. Here, we show that cholesterol loss triggers p-Akt accumulation, which in turn perturbs the normal cellular and molecular responses induced by LTD, such as impaired AMPA receptor internalization and its reduced lateral diffusion. Electrophysiology recordings in brain slices of old mice and in anesthetized elderly rats demonstrate that the reduced hippocampal LTD associated with age can be rescued by cholesterol perfusion. Accordingly, cholesterol replenishment in aging animals improves hippocampal-dependent learning and memory in the water maze test.

  1. Optimizing Conditions to Cholesterol Adsorbed with Carboxymethyl Chitosan

    Directory of Open Access Journals (Sweden)

    Mardiyah Kurniasih

    2016-05-01

    Full Text Available A research on optimizing conditions to cholesterol adsorbed have been performed. Optimization was performed by varying: contact time, adsorbent weight and temperature of the system's. A full factorial experimental design was used in this study. Characterization performed on the synthesized chitosan and carboxymethyl chitosan including FTIR, water content, ash content, solubility, porosity, and swelling effect. The results showed that carboxymethyl chitosan able to adsorb cholesterol under conditions optimal adsorbent with cholesterol ratio (1:200 with a contact time of 90 minutes at temperature of 40 °C. Meanwhile, at a temperature of 55 °C carboxymethyl chitosan capable of adsorb cholesterol under conditions optimal adsorbent with cholesterol ratio (1:300 with a contact time of 30 minutes. Chitosan and carboxymethyl chitosan synthesized has a water content of 7.4 and 10.2%, ash content of 0.14 and 2.29%, solubility in distilled water at 1.10-5and 1.98.10-3%, solubility in acetic acid 0.02 and 0.04%, porosity at 88.3% and 88.8%, and swelling at 163.13 and 182.98%.

  2. The micromethod for determination of cholesterol, cholesteryl esters and phospholipids

    Directory of Open Access Journals (Sweden)

    Okabe,Akinobu

    1974-12-01

    Full Text Available We examined the method for determining microquantities of lipids, including cholesterol, cholesteryl esters and phospholipids. A standard colorimetric procedure of cholesteryl esters was modified to accommodate a quantitative thin-layer chromatography. This method involved the following steps. (1 Separation of lipids by a thin-layer chromatography: Lipids were applied to Silica gel G plates. Plates were developed with petroleum ether-diethyl etheracetic acid (82: 18: 2, vIvIv. (2 Elution of cholesterol and its esters from scraped silica gel: After scraping the silica gel with adhered cholesterol and its esters, they were eluted with chloroform-methanol (4: 1, v,tv. In the case of phspholipids, the silica gel was calcified. (3 Colorimetric determination of the lipids: Cholesterol and its esters eluted from the silica gel were determined by the method of ZAK with ROSENTHAL'S color reagent directly and after saponification, respectively. Phospholipids were calculated from the phosphorous content determined by the method of KATES. On the basis of examination of recovery and analyses of lipids extracted from tissue, it was concluded that this method permitted a reliable estimation of microquantities of cholesterol, its esters and phospholipids from small amounts of biological materials.

  3. 3 Benzyl-6-chloropyrone: a suicide inhibitor of cholesterol esterase

    International Nuclear Information System (INIS)

    Cholesterol, absorbed from the intestine, appears in lymph as the ester. Cholesterol esterase is essential for this process, since depletion of the enzyme blocks and repletion restores, absorption. Selective inhibitors of cholesterol esterase may thus prove useful in reducing cholesterol uptake. A series of potential suicide substrates were synthesized which, following cleavage by the enzyme, would attack the putative nucleophile in the active site. One of these, 3-benzyl-6-chloropyrone (3BCP), inhibited both synthesis and hydrolysis of 14C-cholesteryl oleate with an I50 of approximately 150 μM. The inactivation was time-dependent and characteristic of a suicide mechanism. The α pyrone structure (lactone analog) is cleaved by a serine-hydroxyl in the active site. This generates an enoyl chloride which inactivates the imidazole believed to play a part in the catalytic function of the enzyme. Inhibition by 3BCP is selective for cholesterol esterase. The activity of pancreatic lipase as not affected by concentrations up to 1 mM

  4. [An operative case of cholesterol granuloma of the petrous apex].

    Science.gov (United States)

    Saino, M; Kayama, T; Kuroki, A; Siraisi, Y; Sato, K; Nakai, O

    1996-11-01

    A 59-year-old man presented with a rare cholesterol granuloma of the petrous apex manifesting as headache, left facial dysesthesia, diplopia, left hearing impairment, and left tinnitus. Neurological examination revealed dysesthesia of territory in all divisions of the left trigeminal nerve, left incomplete abducens nerve palsy, left mixed hearing impairment, and left tinnitus. Plain CT scan showed a smoothly marginated mass involving the left petrous apex. The mass was isodense with the brain parenchyma and not enhanced by contrast medium. The mass appeared heterogeneously slightly hyperintense on the T1-weighted MR image and homogeneously hyperintense on the T2-weighted MR image except for the peripheral portion. The mass was not enhanced after intravenous gadolinium DTPA administration. Surgery via a petrosal approach totally removed the mass in the intracranial, extradural space. Histological examination showed typical features of cholesterol granuloma, with cholesterin clefts, hemosiderin deposits, and erythrocytes in non-specific granulation tissue. Cholesterol granuloma most commonly occurs in the middle ear cavity, and rarely in the petrous apex. The characteristic hyperintense appearance of cholesterol granuloma on T1- and T2-weighted MR images is very useful for differentiation from other lesions of the petrous apex and the cerebellopontine angle such as cholesteatoma, mucocele, chordoma, and meningioma. Solid cholesterol granuloma of the petrous apex should be treated by total removal via craniotomy, not by drainage which is commonly performed by otorhinologists. PMID:8934474

  5. Effect of cellular cholesterol depletion on rabies virus infection.

    Science.gov (United States)

    Hotta, Kozue; Bazartseren, Boldbarrtar; Kaku, Yoshihiro; Noguchi, Akira; Okutani, Akiko; Inoue, Satoshi; Yamada, Akio

    2009-01-01

    Although there are several reports on candidates for rabies virus (RABV) receptor, possible roles played by these receptor candidates in determination of highly neurotropic nature of RABV have not been well understood. Since these candidate receptors for RABV were reported to be frequently associated with cholesterol-rich microdomains characterized by lipid rafts and caveolae structures, we attempted to determine whether the disturbance of microdomains caused by the cholesterol depletion showed any effects on RABV infection. When the cellular cholesterol was depleted by methyl-beta-cyclodextrin (MBCD) treatment, increase in RABV adsorption and infection, but not multiplication rather than suppression was observed in both BHK-21 and HEp-2 cells. These effects exerted by MBCD treatment on RABV infection could be reversed by cholesterol reconstitution. These results suggest that RABV enters BHK-21 or HEp-2 cells through ports of entry other than those located on cholesterol-rich microdomains and raise the possibility that RABV uses different mechanisms to enter the non-neuronal cells. PMID:19010362

  6. Acute abdomen

    Directory of Open Access Journals (Sweden)

    Wig J

    1978-01-01

    Full Text Available 550 cases of acute abdomen have been analysed in detail includ-ing their clinical presentation and operative findings. Males are more frequently affected than females in a ratio of 3: 1. More than 45% of patients presented after 48 hours of onset of symptoms. Intestinal obstruction was the commonest cause of acute abdomen (47.6%. External hernia was responsible for 26% of cases of intestinal obstruction. Perforated peptic ulcer was the commonest cause of peritonitis in the present series (31.7% while incidence of biliary peritonitis was only 2.4%.. The clinical accuracy rate was 87%. The mortality in operated cases was high (10% while the over-all mortality rate was 7.5%.

  7. Plasma PCSK9 concentrations during an oral fat load and after short term high-fat, high-fat high-protein and high-fructose diets

    Directory of Open Access Journals (Sweden)

    Cariou Bertrand

    2013-01-01

    Full Text Available Abstract Background PCSK9 (Proprotein Convertase Subtilisin Kexin type 9 is a circulating protein that promotes hypercholesterolemia by decreasing hepatic LDL receptor protein. Under non interventional conditions, its expression is driven by sterol response element binding protein 2 (SREBP2 and follows a diurnal rhythm synchronous with cholesterol synthesis. Plasma PCSK9 is associated to LDL-C and to a lesser extent plasma triglycerides and insulin resistance. We aimed to verify the effect on plasma PCSK9 concentrations of dietary interventions that affect these parameters. Methods We performed nutritional interventions in young healthy male volunteers and offspring of type 2 diabetic (OffT2D patients that are more prone to develop insulin resistance, including: i acute post-prandial hyperlipidemic challenge (n=10, ii 4 days of high-fat (HF or high-fat/high-protein (HFHP (n=10, iii 7 (HFruc1, n=16 or 6 (HFruc2, n=9 days of hypercaloric high-fructose diets. An acute oral fat load was also performed in two patients bearing the R104C-V114A loss-of-function (LOF PCSK9 mutation. Plasma PCSK9 concentrations were measured by ELISA. For the HFruc1 study, intrahepatocellular (IHCL and intramyocellular lipids were measured by 1H magnetic resonance spectroscopy. Hepatic and whole-body insulin sensitivity was assessed with a two-step hyperinsulinemic-euglycemic clamp (0.3 and 1.0 mU.kg-1.min-1. Findings HF and HFHP short-term diets, as well as an acute hyperlipidemic oral load, did not significantly change PCSK9 concentrations. In addition, post-prandial plasma triglyceride excursion was not altered in two carriers of PCSK9 LOF mutation compared with non carriers. In contrast, hypercaloric 7-day HFruc1 diet increased plasma PCSK9 concentrations by 28% (p=0.05 in healthy volunteers and by 34% (p=0.001 in OffT2D patients. In another independent study, 6-day HFruc2 diet increased plasma PCSK9 levels by 93% (p Conclusions Plasma PCSK9 concentrations vary

  8. 电磁辐射后大鼠睾丸类固醇激素合成急性调节蛋白和细胞色素P450胆固醇侧链裂解酶mRNA的变化%Change of steroidogenic acute regulatory protein and cytochrome P450 cholesterol side-chain cleavage mRNA in testis of rats after electromagnetic irradiation

    Institute of Scientific and Technical Information of China (English)

    周文; 杨进清; 王虚步; 刘勇; 张广斌

    2005-01-01

    electromagnetic irradiation.But under the condition of electromagnetic exposure,the change of testosterone and its mechanism remain unknown. OBJECTIVE:To study the effect of electromagnetic irradiation on steroidogenic acute regulatory protein(StAR) and cytochrome P450 cholesterol side-chain cleavage(P450scc) in the tissues of the testis of the adult rats,and to preliminarily reveal the molecular mechanism of electromagnetic radiation that affects the synthesis of testosterone. DESIGN:A randomized controlled study. SETTING:Department of Nuclear Medicine and Staff Room of Labour Hygiene, Institute of Field Surgery,Daping Hospital of the Third Military Medical University of Chinese PLA. PARTICIPANTS:The study was completed in the Department of Nuclear Medicine and Staff Room of Labour Hygiene, Institute of Field Surgery,Daping Hospital of the Third Military Medical University of Chinese PLA from June 2003 to May 2004.A total of 75 male Wistar rats of clean degree II,weighing 180 to 220 g,were randomly divided into 5 groups:control group,and groups of 3,6,24,72 hours after electromagnetic irradiation with 15 rats in each group. INTERVENTIONS:The rats were exposed to microwave with the peak power of 90 W/cm2 for 15 minutes successively,and all the rats survived the irradiation.The serum contents of testosterone of rats in the groups of 3,6,24,72 hours after electromagnetic irradiation and control group were measured by using radioimmunoassay(RIA) respectively;meanwhile the levels of the StAR and P450scc mRNA in testis tissue were also determined with RT-PCR. MAIN OUTCOME MEASURES:Serum contents of testosterone in the groups of 3,6,24,72 hours after electromagnetic irradiation and control group;the expression levels of the StAR and P450scc mRNA in testis tissues. RESULTS:The serum contents of testosterone,the StAR and P450scc mRNA levels at the point of 3 hours after electromagnetic irradiation were significantly lower than those in the control group,and they were decreased by 83

  9. Risk Factors for Senile Corneal Arcus in Patients with Acute Myocardial Infarction

    OpenAIRE

    Mirnaghi Moosavi; Ahmad Sareshtedar; Siamak Zarei-Ghanavati; Mehran Zarei-Ghanavati; Nazanin Ramezanfar

    2010-01-01

    Purpose: To investigate the association between senile corneal arcus and atherosclerosis risk factors in patients with recent acute myocardial infarction. Methods: In this cross sectional study, atherosclerosis risk factors including fasting blood sugar, total cholesterol and triglyceride levels were measured in 165 patients with recent (less than three months′ duration) acute myocardial infarction. Slitlamp examination was performed to detect corneal arcus. Associations between senile co...

  10. Risk Factors for Senile Corneal Arcus in Patients with Acute Myocardial Infarction

    OpenAIRE

    Moosavi, Mirnaghi; Sareshtedar, Ahmad; Zarei-Ghanavati, Siamak; Zarei-Ghanavati, Mehran; Ramezanfar, Nazanin

    2010-01-01

    Purpose To investigate the association between senile corneal arcus and atherosclerosis risk factors in patients with recent acute myocardial infarction. Methods In this cross sectional study, atherosclerosis risk factors including fasting blood sugar, total cholesterol and triglyceride levels were measured in 165 patients with recent (less than three months’ duration) acute myocardial infarction. Slitlamp examination was performed to detect corneal arcus. Associations between senile corneal ...

  11. Distribution load estimation - DLE

    Energy Technology Data Exchange (ETDEWEB)

    Seppaelae, A. [VTT Energy, Espoo (Finland)

    1996-12-31

    The load research project has produced statistical information in the form of load models to convert the figures of annual energy consumption to hourly load values. The reliability of load models is limited to a certain network because many local circumstances are different from utility to utility and time to time. Therefore there is a need to make improvements in the load models. Distribution load estimation (DLE) is the method developed here to improve load estimates from the load models. The method is also quite cheap to apply as it utilises information that is already available in SCADA systems

  12. Wind Loads on Structures

    DEFF Research Database (Denmark)

    Dyrbye, Claes; Hansen, Svend Ole

    pressure to structural response) and design criteria. Starting with an introduction of the wind load chain, the book moves on to meteorological considerations, atmospheric boundary layer, static wind load, dynamic wind load and scaling laws used in wind-tunnel tests. The dynamic wind load covers vibrations......Wind loads have to be taken into account when designing civil engineering structures. The wind load on structures can be systematised by means of the wind load chain: wind climate (global), terrain (wind at low height), aerodynamic response (wind load to pressure), mechanical response (wind...

  13. The Observation of Highly Ordered Domains in Membranes with Cholesterol

    Energy Technology Data Exchange (ETDEWEB)

    Armstrong, Clare L [McMaster University; Marquardt, Drew [Brock University, St. Catharines, ON, Canada; Dies, Hannah [McMaster University; Kucerka, Norbert [Canadian Neutron Beam Centre and Comelius University (Slovakia); Yamani, Zahra [Canadian Neutron Beam Centre, National Research Council, Chalk River Laboratorie; Harroun, Thad [Brock University, St. Catharines, ON, Canada; Katsaras, John [ORNL; Shi, A-C [McMaster University; Rheinstadter, Maikel C [McMaster University

    2013-01-01

    Rafts, or functional domains, are transient nano- or mesoscopic structures in the exoplasmic leaflet of the plasma membrane, and are thought to be essential for many cellular processes. Using neutron diffraction and computer modelling, we present evidence for the existence of highly ordered lipid domains in the cholesterol-rich (32.5 mol%) liquid-ordered (lo) phase of dipalmitoylphosphatidylcholine membranes. The liquid ordered phase in one-component lipid membranes has previously been thought to be a homogeneous phase. The presence of highly ordered lipid domains embedded in a disordered lipid matrix implies non-uniform distribution of cholesterol between the two phases. The experimental results are in excellent agreement with recent computer simulations of DPPC/cholesterol complexes [Meinhardt, Vink and Schmid (2013). Proc Natl Acad Sci USA 110(12): 4476 4481], which reported the existence of nanometer size lo domains in a liquid disordered lipid environment.

  14. High levels of confusion for cholesterol awareness campaigns.

    Science.gov (United States)

    Hall, Danika V

    2008-09-15

    Earlier this year, two industry-sponsored advertising campaigns for cholesterol awareness that target the general public were launched in Australia. These campaigns aimed to alert the public to the risks associated with having high cholesterol and encouraged cholesterol testing for wider groups than those specified by the National Heart Foundation. General practitioners should be aware of the potential for the two campaigns to confuse the general public as to who should be tested, and where. The campaign sponsors (Unilever Australasia and Pfizer) each have the potential to benefit by increased market share for their products, and increased profits. These disease awareness campaigns are examples of what is increasingly being termed "condition branding" by pharmaceutical marketing experts. PMID:18803537

  15. Catabolism and biotechnological applications of cholesterol degrading bacteria.

    Science.gov (United States)

    García, J L; Uhía, I; Galán, B

    2012-11-01

    Cholesterol is a steroid commonly found in nature with a great relevance in biology, medicine and chemistry, playing an essential role as a structural component of animal cell membranes. The ubiquity of cholesterol in the environment has made it a reference biomarker for environmental pollution analysis and a common carbon source for different microorganisms, some of them being important pathogens such as Mycobacterium tuberculosis. This work revises the accumulated biochemical and genetic knowledge on the bacterial pathways that degrade or transform this molecule, given that the characterization of cholesterol metabolism would contribute not only to understand its role in tuberculosis but also to develop new biotechnological processes that use this and other related molecules as starting or target materials.

  16. Effects of Lowering LDL Cholesterol on Progression of Kidney Disease

    DEFF Research Database (Denmark)

    Haynes, Richard; Lewis, David; Emberson, Jonathan;

    2014-01-01

    Lowering LDL cholesterol reduces the risk of developing atherosclerotic events in CKD, but the effects of such treatment on progression of kidney disease remain uncertain. Here, 6245 participants with CKD (not on dialysis) were randomly assigned to simvastatin (20 mg) plus ezetimibe (10 mg) daily...... or matching placebo. The main prespecified renal outcome was ESRD (defined as the initiation of maintenance dialysis or kidney transplantation). During 4.8 years of follow-up, allocation to simvastatin plus ezetimibe resulted in an average LDL cholesterol difference (SEM) of 0.96 (0.02) mmol/L compared...... with placebo; rate ratio, 0.93; 95% CI, 0.86 to 1.01; P=0.09). Exploratory analyses also showed no significant effect on the rate of change in eGFR. Lowering LDL cholesterol by 1 mmol/L did not slow kidney disease progression within 5 years in a wide range of patients with CKD....

  17. Spectral study of some fatty acid-cholesterol mixtures

    Science.gov (United States)

    Honciuc, Maria; Carbunescu, Eugenia G.; Popa, Carmen; Slavnicu, Elena; Badragan, Iulian

    2000-02-01

    This paper analyses the behavior of fatty acid-cholesterol mixtures, components of biological membranes, under the influence of the electromagnetic filed. The mixtures acid lauric-cholesterol, prepared in this layers of 24 micrometers , have a liquid crystal behavior at room temperature. Spectra obtained in the range (330 divided by 800) nm put into evidence some regions of resonance between the oscillatory system characterizing the textures and the electromagnetic field. The result are discussed in terms of Maxwell's formalism. A good agreement between experiment and theory was obtained for the lauric acid. The impurification with cholesterol leads to a greater disorder in the system and the agreement with the theory is no more satisfactory.

  18. Preparation of a Polypyrrole-Polyvinylsulphonate Composite Film Biosensor for Determination of Cholesterol Based on Entrapment of Cholesterol Oxidase

    Directory of Open Access Journals (Sweden)

    Ahmet Yaşar

    2009-08-01

    Full Text Available In this paper, a novel amperometric cholesterol biosensor with immobilization of cholesterol oxidase on electrochemically polymerized polypyrrole–polyvinylsulphonate (PPy–PVS films has been accomplished via the entrapment technique on the surface of a platinum electrode. Electropolymerization of pyrrole and polyvinylsulphonate on the Pt surface was carried out by cyclic voltammetry between -1.0 and +2.0 V (vs. Ag/AgCl at a scan rate of 100 mV upon the Pt electrode with an electrochemical cell containing pyrrole and polyvinylsulphonate. The amperometric determination is based on the electrochemical detection of H2O2 generated in the enzymatic reaction of cholesterol. Determination of cholesterol was carried out by the oxidation of enzymatically produced H2O2 at 0.4 V vs. Ag/AgCl. The effects of pH and temperature were investigated and optimum parameters were found to be 7.25 and 35 °C, respectively. The storage stability and operational stability of the enzyme electrode were also studied. The results show that 32% of the response current was retained after 19 activity assays. The prepared cholesterol biosensor retained 43% of initial activity after 45 days when stored in 0.1 M phosphate buffer solution at 4 °C.

  19. Intracellular cholesterol transport proteins enhance hydrolysis of HDL-CEs and facilitate elimination of cholesterol into bile.

    Science.gov (United States)

    Wang, Jing; Bie, Jinghua; Ghosh, Shobha

    2016-09-01

    While HDL-associated unesterified or free cholesterol (FC) is thought to be rapidly secreted into the bile, the fate of HDL-associated cholesteryl esters (HDL-CEs) that represent >80% of HDL-cholesterol, is only beginning to be understood. In the present study, we examined the hypothesis that intracellular cholesterol transport proteins [sterol carrier protein 2 (SCP2) and fatty acid binding protein-1 (FABP1)] not only facilitate CE hydrolase-mediated hydrolysis of HDL-CEs, but also enhance elimination of cholesterol into bile. Adenovirus-mediated overexpression of FABP1 or SCP2 in primary hepatocytes significantly increased hydrolysis of HDL-[(3)H]CE, reduced resecretion of HDL-CE-derived FC as nascent HDL, and increased its secretion as bile acids. Consistently, the flux of [(3)H]cholesterol from HDL-[(3)H]CE to biliary bile acids was increased by overexpression of SCP2 or FABP1 in vivo and reduced in SCP2(-/-) mice. Increased flux of HDL-[(3)H]CE to biliary FC was noted with FABP1 overexpression and in SCP2(-/-) mice that have increased FABP1 expression. Lack of a significant decrease in the flux of HDL-[(3)H]CE to biliary FC or bile acids in FABP1(-/-) mice indicates the likely compensation of its function by an as yet unidentified mechanism. Taken together, these studies demonstrate that FABP1 and SCP2 facilitate the preferential movement of HDL-CEs to bile for final elimination. PMID:27381048

  20. Urotensin II promotes atherosclerosis in cholesterol-fed rabbits.

    Directory of Open Access Journals (Sweden)

    Yafeng Li

    Full Text Available Urotensin II (UII is a vasoactive peptide composed of 11 amino acids that has been implicated to contribute to the development of cardiovascular disease. The purpose of this study was to investigate whether UII affects the development of atherosclerosis in cholesterol-fed rabbits. UII was infused for 16 weeks through an osmotic mini-pump into male Japanese White rabbits fed on a high-cholesterol diet. Plasma lipids and body weight were measured every 4 weeks. Aortic atherosclerotic lesions along with cellular components, collagen fibers, matrix metalloproteinase-1 and -9 were examined. Moreover, vulnerability index of atherosclerotic plaques was evaluated. UII infusion significantly increased atherosclerotic lesions within the entire aorta by 21% over the control (P = 0.013. Atherosclerotic lesions were increased by 24% in the aortic arch (P = 0.005, 11% in the thoracic aorta (P = 0.054 and 18% in the abdominal aorta (P = 0.035. These increases occurred without changes in plasma levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides or body weight. Immunohistochemical staining revealed that macrophages and matrix metalloproteinase-9 were significantly enhanced by 2.2-fold and 1.6-fold in UII group. In vitro studies demonstrated that UII up-regulated the expression of vascular cell adhesion protein-1 and intercellular adhesion molecule-1 in human umbilical vein endothelial cells, which was inhibited by the UII receptor antagonist urantide. In conclusion, our results showed that UII promotes the development of atherosclerotic lesions and destabilizes atherosclerotic plaques in cholesterol-fed rabbits.