Discovery of a potent and selective free fatty acid receptor 1 agonist with low lipophilicity and high oral bioavailability

DEFF Research Database (Denmark)

Christiansen, Elisabeth; Due-Hansen, Maria E; Urban, Christian

2013-01-01

The free fatty acid receptor 1 (FFA1, also known as GPR40) mediates enhancement of glucose-stimulated insulin secretion and is emerging as a new target for the treatment of type 2 diabetes. Several FFA1 agonists are known, but the majority of these suffer from high lipophilicity. We have previously...... reported the FFA1 agonist 3 (TUG-424). We here describe the continued structure-activity exploration and optimization of this compound series, leading to the discovery of the more potent agonist 40, a compound with low lipophilicity, excellent in vitro metabolic stability and permeability, complete oral...

Lipophilic drug transfer between liposomal and biological membranes

DEFF Research Database (Denmark)

Fahr, Alfred; van Hoogevest, Peter; Kuntsche, Judith

2006-01-01

This review presents the current knowledge on the interaction of lipophilic, poorly water soluble drugs with liposomal and biological membranes. The center of attention will be on drugs having the potential to dissolve in a lipid membrane without perturbing them too much. The degree of interaction...... is described as solubility of a drug in phospholipid membranes and the kinetics of transfer of a lipophilic drug between membranes. Finally, the consequences of these two factors on the design of lipid-based carriers for oral, as well as parenteral use, for lipophilic drugs and lead selection of oral...... lipophilic drugs is described. Since liposomes serve as model-membranes for natural membranes, the assessment of lipid solubility and transfer kinetics of lipophilic drug using liposome formulations may additionally have predictive value for bioavailability and biodistribution and the pharmacokinetics...

Lipophilic extracts from banana fruit residues: a source of valuable phytosterols.

Science.gov (United States)

Oliveira, Lúcia; Freire, Carmen S R; Silvestre, Armando J D; Cordeiro, Nereida

2008-10-22

The chemical composition of the lipophilic extracts of unripe pulp and peel of banana fruit 'Dwarf Cavendish' was studied by gas chromatography-mass spectrometry. Fatty acids, sterols, and steryl esters are the major families of lipophilic components present in banana tissues, followed by diacylglycerols, steryl glucosides, long chain fatty alcohols, and aromatic compounds. Fatty acids are more abundant in the banana pulp (29-90% of the total amount of lipophilic extract), with linoleic, linolenic, and oleic acids as the major compounds of this family. In banana peel, sterols represent about 49-71% of the lipophilic extract with two triterpenic ketones (31-norcyclolaudenone and cycloeucalenone) as the major components. The detection of high amounts of steryl esters (469-24405 mg/kg) and diacylglycerols (119-878 mg/kg), mainly present in the banana peel extract, explains the increase in the abundance of fatty acids and sterols after alkaline hydrolysis. Several steryl glucosides were also found in significative amounts (273-888 mg/kg), particularly in banana pulp (888 mg/kg). The high content of sterols (and their derivatives) in the 'Dwarf Cavendish' fruit can open new strategies for the valorization of the banana residues as a potential source of high-value phytochemicals with nutraceutical and functional food additive applications.

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.

Adsorptive stripping voltammetry in lipophilic vitamins determination

Directory of Open Access Journals (Sweden)

Milan Sýs

2016-06-01

Full Text Available The aim of this contribution was to check if adsorptive stripping differential pulse voltammetry (AdSDPV is suitable tool for sensitive simultenous electrochemical detection of lipophilic vitamins. Retinol (vitamin A1, cholecalciferol (vitamin D3, α-tocopherol (vitamin E and phylloquinone (vitamin K1 were selected as representatives. All electrochemical measurements were performed in two separate steps due to the lipophilic character of the analytes. In the first step, an accumulation of lipophilic vitamin on the surface of glassy carbon electrode (GCE was done by immersing working electrode into the aqueous‑acetonitrile solutions (50%, v/v of each vitamin (50.0 µmol.L-1 at 400 rpm for 5 min. In the second one, differential pulse voltammetry of accumulated vitamins was performed in 0.01 mol.L-1 acetate (pH 4.5 buffer at potential step (Estep 5 mV, potential of amplitude (Eampl 25 mV, interval time (t 0.1 s and scan rate (ν 50 mV.s-1. It was observed that electrochemical behaviour of lipophilic vitamins adsorbed on surface of solid GCE in the aqueous electrolyte was very similar to those performed in organic/aqueous electrolyte in literature. Due to reversible electrochemical behaviour of vitamin K1 (phylloquinone/phyllohydroquinone redox couple, it was possible to detect all lipophilic vitamins only in one analysis. Observed values of peak potentials (Ep were sufficiently different for their recognition which was confirmed by the analysis of real sample. The results obtained in this study showed that simultaneous determination of some lipophilic vitamins is possible requiring further optimization study. For this reason, it is necessary to understand this work as an initial step in simultaneous determination of lipophilic vitamins without application of any chromatographic technique.

Acrolein impairs the cholesterol transport functions of high density lipoproteins.

Science.gov (United States)

Chadwick, Alexandra C; Holme, Rebecca L; Chen, Yiliang; Thomas, Michael J; Sorci-Thomas, Mary G; Silverstein, Roy L; Pritchard, Kirkwood A; Sahoo, Daisy

2015-01-01

High density lipoproteins (HDL) are considered athero-protective, primarily due to their role in reverse cholesterol transport, where they transport cholesterol from peripheral tissues to the liver for excretion. The current study was designed to determine the impact of HDL modification by acrolein, a highly reactive aldehyde found in high abundance in cigarette smoke, on the cholesterol transport functions of HDL. HDL was chemically-modified with acrolein and immunoblot and mass spectrometry analyses confirmed apolipoprotein crosslinking, as well as acrolein adducts on apolipoproteins A-I and A-II. The ability of acrolein-modified HDL (acro-HDL) to serve as an acceptor of free cholesterol (FC) from COS-7 cells transiently expressing SR-BI was significantly decreased. Further, in contrast to native HDL, acro-HDL promotes higher neutral lipid accumulation in murine macrophages as judged by Oil Red O staining. The ability of acro-HDL to mediate efficient selective uptake of HDL-cholesteryl esters (CE) into SR-BI-expressing cells was reduced compared to native HDL. Together, the findings from our studies suggest that acrolein modification of HDL produces a dysfunctional particle that may ultimately promote atherogenesis by impairing functions that are critical in the reverse cholesterol transport pathway.

High Cholesterol/Low Cholesterol: Effects in Biological Membranes: A Review.

Science.gov (United States)

Subczynski, Witold K; Pasenkiewicz-Gierula, Marta; Widomska, Justyna; Mainali, Laxman; Raguz, Marija

2017-12-01

Lipid composition determines membrane properties, and cholesterol plays a major role in this determination as it regulates membrane fluidity and permeability, as well as induces the formation of coexisting phases and domains in the membrane. Biological membranes display a very diverse lipid composition, the lateral organization of which plays a crucial role in regulating a variety of membrane functions. We hypothesize that, during biological evolution, membranes with a particular cholesterol content were selected to perform certain functions in the cells of eukaryotic organisms. In this review, we discuss the major membrane properties induced by cholesterol, and their relationship to certain membrane functions.

Does lipophilicity per se induce adjuvant effects?

DEFF Research Database (Denmark)

Hansen, Jitka Stilund; Larsen, Søren Thor; Poulsen, Lars K.

2007-01-01

Anthopogenically introduced substances and pollutants are suspected to promote sensitization and development of allergic airway diseases, that is, acting as adjuvants. Lipophilicity may serve as an immunological warning signal, promoting adjuvant effects. Whether the lipophilicity of an inhaled...... respiratory patterns were significantly affected in the MP groups. The OVA + Al(OH)3 group had a significantly higher IgG1 and IgE production, as well as higher eosinophil infiltration in the BAL fluid. These studies showed that effects of adjuvants not are necessarily due to their lipophilicity; that is...

Cholesterol Facts and Statistics

Science.gov (United States)

... Managing High Cholesterol Cholesterol-lowering Medicine High Cholesterol Statistics and Maps High Cholesterol Facts High Cholesterol Maps ... Deo R, et al. Heart disease and stroke statistics—2017 update: a report from the American Heart ...

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.

The Human Skin Barrier Is Organized as Stacked Bilayers of Fully Extended Ceramides with Cholesterol Molecules Associated with the Ceramide Sphingoid Moiety

DEFF Research Database (Denmark)

Iwai, Ichiro; Han, Hongmei; Hollander, Lianne den

2012-01-01

not previously described in a biological system-stacked bilayers of fully extended ceramides (CERs) with cholesterol molecules associated with the CER sphingoid moiety. This arrangement rationalizes the skin's low permeability toward water and toward hydrophilic and lipophilic substances, as well as the skin...

Rethinking reverse cholesterol transport and dysfunctional high-density lipoproteins.

Science.gov (United States)

Gillard, Baiba K; Rosales, Corina; Xu, Bingqing; Gotto, Antonio M; Pownall, Henry J

2018-04-12

Human plasma high-density lipoprotein cholesterol concentrations are a negative risk factor for atherosclerosis-linked cardiovascular disease. Pharmacological attempts to reduce atherosclerotic cardiovascular disease by increasing plasma high-density lipoprotein cholesterol have been disappointing so that recent research has shifted from HDL quantity to HDL quality, that is, functional vs dysfunctional HDL. HDL has varying degrees of dysfunction reflected in impaired reverse cholesterol transport (RCT). In the context of atheroprotection, RCT occurs by 2 mechanisms: one is the well-known trans-hepatic pathway comprising macrophage free cholesterol (FC) efflux, which produces early forms of FC-rich nascent HDL (nHDL). Lecithin:cholesterol acyltransferase converts HDL-FC to HDL-cholesteryl ester while converting nHDL from a disc to a mature spherical HDL, which transfers its cholesteryl ester to the hepatic HDL receptor, scavenger receptor B1 for uptake, conversion to bile salts, or transfer to the intestine for excretion. Although widely cited, current evidence suggests that this is a minor pathway and that most HDL-FC and nHDL-FC rapidly transfer directly to the liver independent of lecithin:cholesterol acyltransferase activity. A small fraction of plasma HDL-FC enters the trans-intestinal efflux pathway comprising direct FC transfer to the intestine. SR-B1 -/- mice, which have impaired trans-hepatic FC transport, are characterized by high plasma levels of a dysfunctional FC-rich HDL that increases plasma FC bioavailability in a way that produces whole-body hypercholesterolemia and multiple pathologies. The design of future therapeutic strategies to improve RCT will have to be formulated in the context of these dual RCT mechanisms and the role of FC bioavailability. Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Pectin penta-oligogalacturonide reduces cholesterol accumulation by promoting bile acid biosynthesis and excretion in high-cholesterol-fed mice.

Science.gov (United States)

Zhu, Ru-Gang; Sun, Yan-Di; Hou, Yu-Ting; Fan, Jun-Gang; Chen, Gang; Li, Tuo-Ping

2017-06-25

Haw pectin penta-oligogalacturonide (HPPS) has important role in improving cholesterol metabolism and promoting the conversion of cholesterol to bile acids (BA) in mice fed high-cholesterol diet (HCD). However, the mechanism is not clear. This study aims to investigate the effects of HPPS on cholesterol accumulation and the regulation of hepatic BA synthesis and transport in HCD-fed mice. Results showed that HPPS significantly decreased plasma and hepatic TC levels but increased plasma high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) levels, compared to HCD. BA analysis showed that HPPS markedly decreased hepatic and small intestine BA levels but increased the gallbladder BA levels, and finally decreased the total BA pool size, compared to HCD. Studies of molecular mechanism revealed that HPPS promoted hepatic ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor BI (SR-BI) expression but did not affect ATB binding cassette transporter G5/G8 (ABCG5/8) expression. HPPS inactivated hepatic farnesoid X receptor (FXR) and target genes expression, which resulted in significant increase of cholesterol 7α-hydroxylase 1 (CYP7A1) and sterol 12α-hydroxylase (CYP8B1) expression, with up-regulations of 204.2% and 33.5% for mRNA levels, respectively, compared with HCD. In addition, HPPS markedly enhanced bile salt export pump (BSEP) expression but didn't affect the sodium/taurocholate co-transporting polypeptide (NTCP) expression. In conclusion, the study revealed that HPPS reduced cholesterol accumulation by promoting BA synthesis in the liver and excretion in the feces, and might promote macrophage-to-liver reverse cholesterol transport (RCT) but did not liver-to-fecal RCT. Copyright © 2017 Elsevier B.V. All rights reserved.

Hypolipidemic and Antioxidative Effects of Aqueous Enzymatic Extract from Rice Bran in Rats Fed a High-Fat and -Cholesterol Diet

Science.gov (United States)

Wang, Yu-Xin; Li, Yang; Sun, An-Min; Wang, Feng-Jiao; Yu, Guo-Ping

2014-01-01

Purpose: The aqueous enzymatic extract from rice bran (AEERB) was rich in protein, γ-oryzanol and tocols. The aim of this study was to investigate the effects of AEERB on the regulation of lipid metabolism and the inhibition of oxidative damage. Methods: The antioxidant activity of AEERB in vitro was measured in terms of radical scavenging capacity, ferric reducing ability power (FRAP) and linoleic acid emulsion system-ferric thiocyanate method (FTC). Male Wistar rats were fed with a normal diet and a high-fat and high-cholesterol diet with or without AEERB. After treatment, biochemical assays of serum, liver and feces lipid levels, the antioxidant enzyme activity, malondialdehyde (MDA) and protein carbonyl were determined. Result: AEERB is completely soluble in water and rich in hydrophilic and lipophilic functional ingredients. AEERB scavenged DPPH• and ABTS•+ and exhibited antioxidant activity slightly lower than that of ascorbic acid in the linoleic acid system. The administration of AEERB reduced serum lipid levels and the atherogenic index compared with those of the hyperlipidemic diet group (HD). The administration of AEERB significantly lowered liver lipid levels, inhibited hepatic 3-hydroxyl-3-methylglutaryl CoA reductase activity, and efficiently promoted the fecal excretion of total lipids and total cholesterol (TC) (p < 0.05). Dietary AEERB enhanced antioxidant status in the serum, liver and brain by increasing the antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and decreasing the content of MDA and protein carbonyl. Conclusions: The results indicated that AEERB might act as a potent hypolipidemic and antioxidant functional food. PMID:25230211

Hypolipidemic and Antioxidative Effects of Aqueous Enzymatic Extract from Rice Bran in Rats Fed a High-Fat and -Cholesterol Diet

Directory of Open Access Journals (Sweden)

Yu-Xin Wang

2014-09-01

Full Text Available Purpose: The aqueous enzymatic extract from rice bran (AEERB was rich in protein, γ-oryzanol and tocols. The aim of this study was to investigate the effects of AEERB on the regulation of lipid metabolism and the inhibition of oxidative damage. Methods: The antioxidant activity of AEERB in vitro was measured in terms of radical scavenging capacity, ferric reducing ability power (FRAP and linoleic acid emulsion system-ferric thiocyanate method (FTC. Male Wistar rats were fed with a normal diet and a high-fat and high-cholesterol diet with or without AEERB. After treatment, biochemical assays of serum, liver and feces lipid levels, the antioxidant enzyme activity, malondialdehyde (MDA and protein carbonyl were determined. Result: AEERB is completely soluble in water and rich in hydrophilic and lipophilic functional ingredients. AEERB scavenged DPPH• and ABTS•+ and exhibited antioxidant activity slightly lower than that of ascorbic acid in the linoleic acid system. The administration of AEERB reduced serum lipid levels and the atherogenic index compared with those of the hyperlipidemic diet group (HD. The administration of AEERB significantly lowered liver lipid levels, inhibited hepatic 3-hydroxyl-3-methylglutaryl CoA reductase activity, and efficiently promoted the fecal excretion of total lipids and total cholesterol (TC (p < 0.05. Dietary AEERB enhanced antioxidant status in the serum, liver and brain by increasing the antioxidant enzyme activity of superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GSH-Px and decreasing the content of MDA and protein carbonyl. Conclusions: The results indicated that AEERB might act as a potent hypolipidemic and antioxidant functional food.

Hypolipidemic and antioxidative effects of aqueous enzymatic extract from rice bran in rats fed a high-fat and -cholesterol diet.

Science.gov (United States)

Wang, Yu-Xin; Li, Yang; Sun, An-Min; Wang, Feng-Jiao; Yu, Guo-Ping

2014-09-16

The aqueous enzymatic extract from rice bran (AEERB) was rich in protein, γ-oryzanol and tocols. The aim of this study was to investigate the effects of AEERB on the regulation of lipid metabolism and the inhibition of oxidative damage. The antioxidant activity of AEERB in vitro was measured in terms of radical scavenging capacity, ferric reducing ability power (FRAP) and linoleic acid emulsion system-ferric thiocyanate method (FTC). Male Wistar rats were fed with a normal diet and a high-fat and high-cholesterol diet with or without AEERB. After treatment, biochemical assays of serum, liver and feces lipid levels, the antioxidant enzyme activity, malondialdehyde (MDA) and protein carbonyl were determined. AEERB is completely soluble in water and rich in hydrophilic and lipophilic functional ingredients. AEERB scavenged DPPH• and ABTS•+ and exhibited antioxidant activity slightly lower than that of ascorbic acid in the linoleic acid system. The administration of AEERB reduced serum lipid levels and the atherogenic index compared with those of the hyperlipidemic diet group (HD). The administration of AEERB significantly lowered liver lipid levels, inhibited hepatic 3-hydroxyl-3-methylglutaryl CoA reductase activity, and efficiently promoted the fecal excretion of total lipids and total cholesterol (TC) (p < 0.05). Dietary AEERB enhanced antioxidant status in the serum, liver and brain by increasing the antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and decreasing the content of MDA and protein carbonyl. The results indicated that AEERB might act as a potent hypolipidemic and antioxidant functional food.

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

Directory of Open Access Journals (Sweden)

Mohamed Ramadan El Sayed Aly

2015-10-01

Full Text Available 3β-Azidocholest-5-ene (3 and (3β-3-(prop-2-yn-1-yloxycholest-5-ene (10 were prepared as substrates to synthesize a variety of three-motif pharmacophoric conjugates through CuAAC. Basically, these conjugates included cholesterol and 1,2,3-triazole moieties, while the third, the pharmacophore, was either a chalcone, a lipophilic residue or a carbohydrate tag. These compounds were successfully prepared in good yields and characterized by NMR, MS and IR spectroscopic techniques. Chalcone conjugate 6c showed the best antimicrobial activity, while the lactoside conjugate 27 showed the best cytotoxic effect in vitro.

Effects of NS lactobacillus strains on lipid metabolism of rats fed a high-cholesterol diet

Science.gov (United States)

2013-01-01

Background Elevated serum cholesterol level is generally considered to be a risk factor for the development of cardiovascular diseases which seriously threaten human health. The cholesterol-lowering effects of lactic acid bacteria have recently become an area of great interest and controversy for many researchers. In this study, we investigated the effects of two NS lactobacillus strains, Lactobacillus plantarum NS5 and Lactobacillus delbrueckii subsp. bulgaricus NS12, on lipid metabolism of rats fed a high cholesterol diet. Methods Thirty-two SD rats were assigned to four groups and fed either a normal or a high-cholesterol diet. The NS lactobacillus treated groups received the high-cholesterol diet supplemented with Lactobacillus plantarum NS5 or Lactobacillus delbrueckii subsp. bulgaricus NS12 in drinking water. The rats were sacrificed after a 6-week feeding period. Body weights, visceral organ and fat weights, serum and liver cholesterol and lipid levels, intestinal microbiota and liver mRNA expression levels related to cholesterol metabolism were analyzed. Liver lipid deposition and adipocyte size were evaluated histologically. Results Compared with rats fed a high cholesterol diet, serum total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B and free fatty acids levels were decreased and apolipoprotein A-I level was increased in NS5 or NS12 strain treated rats, and with no significant change in high-density lipoprotein cholesterol level. Liver cholesterol and triglyceride levels were also significantly decreased in NS lactobacillus strains treated groups. Meanwhile, the NS lactobacillus strains obviously alleviated hepatic injuries, decreased liver lipid deposition and reduced adipocyte size of high cholesterol diet fed rats. NS lactobacillus strains restored the changes in intestinal microbiota compositions, such as the increase in Bacteroides and the decrease in Clostridium. NS lactobacillus strains also regulated the mRNA expression

Effects of Yogurt Containing Fermented Pepper Juice on the Body Fat and Cholesterol Level in High Fat and High Cholesterol Diet Fed Rat.

Science.gov (United States)

Yeon, Su-Jung; Hong, Go-Eun; Kim, Chang-Kyu; Park, Woo Joon; Kim, Soo-Ki; Lee, Chi-Ho

2015-01-01

This experiment investigated whether yogurt containing fermented pepper juice (FPJY) affects cholesterol level in high fat and high cholesterol diet (HFCD) fed rat. Twenty five Sprague-Dawley male rats of 7 wk were divided into 5 groups, and fed following diets for 9 wk; CON (control diet), HFCD (HFCD), PY (HFCD supplemented with 2% of plain yogurt), LFY (HFCD supplemented with 2% of FPJY), and HFY (HFCD supplemented with 5% of FPJY). In the LFY group, hepatic total lipid level decreased significantly compared to the HFCD group (p0.05). In HFY group, body weight and hepatic total lipid level significantly decreased over the HFCD group (p0.05). Liver weight decreased as FPJY content was increased. Results suggested FPJY would inhibit organ hypertrophy and accumulation of body fat, hepatic lipid, and cholesterol in HFCD fed rat.

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.

Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol.

Science.gov (United States)

Ray, Kausik K; Landmesser, Ulf; Leiter, Lawrence A; Kallend, David; Dufour, Robert; Karakas, Mahir; Hall, Tim; Troquay, Roland P T; Turner, Traci; Visseren, Frank L J; Wijngaard, Peter; Wright, R Scott; Kastelein, John J P

2017-04-13

In a previous study, a single injection of inclisiran, a chemically synthesized small interfering RNA designed to target PCSK9 messenger RNA, was found to produce sustained reductions in low-density lipoprotein (LDL) cholesterol levels over the course of 84 days in healthy volunteers. We conducted a phase 2, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial of inclisiran administered as a subcutaneous injection in patients at high risk for cardiovascular disease who had elevated LDL cholesterol levels. Patients were randomly assigned to receive a single dose of placebo or 200, 300, or 500 mg of inclisiran or two doses (at days 1 and 90) of placebo or 100, 200, or 300 mg of inclisiran. The primary end point was the change from baseline in LDL cholesterol level at 180 days. Safety data were available through day 210, and data on LDL cholesterol and proprotein convertase subtilisin-kexin type 9 (PCSK9) levels were available through day 240. A total of 501 patients underwent randomization. Patients who received inclisiran had dose-dependent reductions in PCSK9 and LDL cholesterol levels. At day 180, the least-squares mean reductions in LDL cholesterol levels were 27.9 to 41.9% after a single dose of inclisiran and 35.5 to 52.6% after two doses (PLDL cholesterol levels: 48% of the patients who received the regimen had an LDL cholesterol level below 50 mg per deciliter (1.3 mmol per liter) at day 180. At day 240, PCSK9 and LDL cholesterol levels remained significantly lower than at baseline in association with all inclisiran regimens. Serious adverse events occurred in 11% of the patients who received inclisiran and in 8% of the patients who received placebo. Injection-site reactions occurred in 5% of the patients who received injections of inclisiran. In our trial, inclisiran was found to lower PCSK9 and LDL cholesterol levels among patients at high cardiovascular risk who had elevated LDL cholesterol levels. (Funded by the Medicines Company

Phenolics and Lipophilized Phenolics as Antioxidants in Fish Oil Enriched Emulsions,

DEFF Research Database (Denmark)

Sørensen, Ann-Dorit Moltke; Nielsen, Nina Skall; Jacobsen, Charlotte

work better as antioxidants in bulk oil, whereas lipophilic compounds are better antioxidants in emulsions. This presentation is an overview of our previous work in the area of fish oil enriched emulsions with antioxidants. Our studies have shown that the lipophilicity of the compounds is not the only...... with increased lipophilicity. Instead a cut-off effect was observed in relation to the alkyl chain length lipophilized to the phenolic compound. Furthermore, the efficacy of lipophilic antioxidants is influenced by the type of food system. Thus, our results show that the antioxidant behavior may not be as simple...

Dynamic root uptake model for neutral lipophilic organics

DEFF Research Database (Denmark)

Trapp, Stefan

2002-01-01

and output to stem with the transpiration stream plus first-order metabolism and dilution by exponential growth. For chemicals with low or intermediate lipophilicity (log Kow , 2), there was no relevant difference between dynamic model and equilibrium approach. For lipophilic compounds, the dynamic model...

The recent advances on carrier materials for microencapsulating lipophilic cores

Directory of Open Access Journals (Sweden)

JIN Minfeng

2014-12-01

Full Text Available Lipophilic ingredients,such as polyunsaturated fatty acids,play an important role in industrialized foods to fortify the nutrients.However,these materials are normally sensitive to oxygen,light or heat to be oxidized,and hard to flow and mix within the bulk food due to the hydrophobic nature.Microencapsulation of lipophilic materials could effectively extend their shelf lives,mask unsatisfied flavors,change their physicochemical properties,and enhance the mixing capacities.This work reviewed the different carrier materials applied in microencapsulating the lipophilic ingredients,and discussed their characteristics and effects on encapsulation efficiencies and release profiles of lipophilic cores.

Chemical research of lipophilic fractions of sickle alfalfa herbs

Directory of Open Access Journals (Sweden)

S. V. Kovalev

2013-06-01

Full Text Available Lipophilic fraction (LF of known medicinal plants are still less studied, despite the fact that they have a unique group of biological active compounds (BAC. The main active substances of LF are chlorophylls, carotenoids, tocopherols, sterols, unsaturated fatty acids, phospholipids, and other bioactive substances that exhibit a wide spectrum of pharmacological action. In this regard, a comprehensive study of advanced plant of flora of Ukraine to increase the assortments of herbal remedies is an urgent problem. The aim of this work was to obtain and chemical research of lipophilic fractions of sickle alfalfa herbs. The alfalfa herb harvested throughout the growing season in Kharkov and Poltava regions in 2011-2012. Lipophilic fraction was obtained by extraction with chloroform in a Soxhlet apparatus. Detection of carotenoids and chlorophylls by thin layer chromatography (TLC on plates of "Silufol" in one-dimensional and two-dimensional variants, the solvent system were: hexane: acetone (6:2 - I way, hexane-acetone (6:4 - II way. Assay of the lipophilic fraction by three-dimensional fluorescence spectroscopy (3DF-spectroscopy was used for the analysis of mixtures containing fluorescent components. 3DF-spectres, that have the appearance of the surface, are characterized by a functions I = f (λexc, λem, recorded in the ultraviolet and visible ranges. Assay of the carotenoids and chlorophylls carried out by spectrophotometry. The reference solution was chloroform. Assay of fatty acids was performed by gas-liquid chromatography (GLC of methyl esters of fatty acids via chromatograph with flame ionization detector "Shimadzu GC-14B". 20.0 g crushed sickle alfalfa herbs were exhaustively extracted with chloroform in a Soxhlet apparatus for produce a lipophilic fractions. The chloroform extract was evaporated in order to remove the extractant. The percentage of lipophilic fraction in the herbs was 7.5%. Quantity of the carotenoids and chlorophylls

Plasma 27-hydroxycholesterol/cholesterol ratio is increased in low high density lipoprotein-cholesterol healthy subjects.

Science.gov (United States)

Nunes, Valéria S; Leança, Camila C; Panzoldo, Natália B; Parra, Eliane; Zago, Vanessa; Cazita, Patrícia M; Nakandakare, Edna R; de Faria, Eliana C; Quintão, Eder C R

2013-10-01

Sterol 27-hydroxylase converts cholesterol to 27-hydroxycholesterol (27-OHC) which is widely distributed among tissues and is expressed at high levels in the vascular endothelium and macrophages. There is a continuous flow of this oxysterol from the tissues into the liver, where it is converted to bile acids. Measure plasma concentrations of 27-OHC in subjects that differ according to their plasma HDL-C concentration. Healthy men presenting low HDL-C (1.55 mmol/L), n=18, BMIm² were recruited after excluding secondary causes that might interfere with their plasma lipid concentrations such as smoking, heavy drinking and diabetes. Blood samples were drawn after a 12h fasting period for the measurement of 27-OHC by the combined GC/MS analysis utilizing deuterium-label internal standards. The plasma ratio 27-OHC/total cholesterol (median and range nmoL/mmoL) was 50.41 (27.47-116.00) in the High HDL-C subjects and 63.34 (36.46-91.18) in the Low HDL-C subjects (p=0.0258). Our data indicate that the production of 27-OHC by extrahepatic tissues and its transport to the liver may represent an alternative pathway for a deficient reverse cholesterol transport system when plasma HDL-C is low. © 2013.

determination of lipophilic extractives in ionic liquid extracts

African Journals Online (AJOL)

dell

Chem. 9: 63-69. Freire CSR, Pinto PCR, Santiago AS,. Silvestre AJD, Evtuquin DV and Neto. CP 2006a Comparative study of lipophilic extractives of hardwoods and corresponding ECF bleached kraft pulps. BioResources. 1: 3-17. Freire CSR, Silvestre AJD and Neto CP. 2005. Lipophilic extractives in. Eucalyptus globulus.

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

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

Highly selective Ba2+ separations with acyclic, lipophilic di-[N-(X)sulfonyl carbamoyl] polyethers.

Science.gov (United States)

Elshani, Sadik; Chun, Sangki; Amiri-Eliasi, Bijan; Bartsch, Richard A

2005-01-14

New lipophilic acyclic polyethers with two N-(X)sulfonyl carbamoyl groups of "tunable" acidity exhibit remarkable selectivity for Ba2+ over other alkaline earth metal ions in competitive solvent extraction and transport across polymer inclusion membranes.

Metabolic and cardiac changes in high cholesterol-fructose-fed rats

DEFF Research Database (Denmark)

Axelsen, Lene N; Pedersen, Henrik D; Petersen, Jørgen S

2010-01-01

Introduction: High cholesterol-fructose (HCF) fed rats have previously been described as an animal model of impaired cardiac insulin signaling and decreased contractile performance. In this study, we evaluated the metabolic and cardiac effects of a HCF diet in rats. Methods: Male Sprague-Dawley r......Introduction: High cholesterol-fructose (HCF) fed rats have previously been described as an animal model of impaired cardiac insulin signaling and decreased contractile performance. In this study, we evaluated the metabolic and cardiac effects of a HCF diet in rats. Methods: Male Sprague...

Associations of Drug Lipophilicity and Extent of Metabolism with Drug-Induced Liver Injury.

Science.gov (United States)

McEuen, Kristin; Borlak, Jürgen; Tong, Weida; Chen, Minjun

2017-06-22

Drug-induced liver injury (DILI), although rare, is a frequent cause of adverse drug reactions resulting in warnings and withdrawals of numerous medications. Despite the research community's best efforts, current testing strategies aimed at identifying hepatotoxic drugs prior to human trials are not sufficiently powered to predict the complex mechanisms leading to DILI. In our previous studies, we demonstrated lipophilicity and dose to be associated with increased DILI risk and, and in our latest work, we factored reactive metabolites into the algorithm to predict DILI. Given the inconsistency in determining the potential for drugs to cause DILI, the present study comprehensively assesses the relationship between DILI risk and lipophilicity and the extent of metabolism using a large published dataset of 1036 Food and Drug Administration (FDA)-approved drugs by considering five independent DILI annotations. We found that lipophilicity and the extent of metabolism alone were associated with increased risk for DILI. Moreover, when analyzed in combination with high daily dose (≥100 mg), lipophilicity was statistically significantly associated with the risk of DILI across all datasets ( p < 0.05). Similarly, the combination of extensive hepatic metabolism (≥50%) and high daily dose (≥100 mg) was also strongly associated with an increased risk of DILI among all datasets analyzed ( p < 0.05). Our results suggest that both lipophilicity and the extent of hepatic metabolism can be considered important risk factors for DILI in humans, and that this relationship to DILI risk is much stronger when considered in combination with dose. The proposed paradigm allows the convergence of different published annotations to a more uniform assessment.

High cholesterol level is essential for myelin membrane growth.

Science.gov (United States)

Saher, Gesine; Brügger, Britta; Lappe-Siefke, Corinna; Möbius, Wiebke; Tozawa, Ryu-ichi; Wehr, Michael C; Wieland, Felix; Ishibashi, Shun; Nave, Klaus-Armin

2005-04-01

Cholesterol in the mammalian brain is a risk factor for certain neurodegenerative diseases, raising the question of its normal function. In the mature brain, the highest cholesterol content is found in myelin. We therefore created mice that lack the ability to synthesize cholesterol in myelin-forming oligodendrocytes. Mutant oligodendrocytes survived, but CNS myelination was severely perturbed, and mutant mice showed ataxia and tremor. CNS myelination continued at a reduced rate for many months, and during this period, the cholesterol-deficient oligodendrocytes actively enriched cholesterol and assembled myelin with >70% of the cholesterol content of wild-type myelin. This shows that cholesterol is an indispensable component of myelin membranes and that cholesterol availability in oligodendrocytes is a rate-limiting factor for brain maturation.

Common Misconceptions about Cholesterol

Science.gov (United States)

... Venous Thromboembolism Aortic Aneurysm More Common Misconceptions about Cholesterol Updated:Jan 29,2018 How much do you ... are some common misconceptions — and the truth. High cholesterol isn’t a concern for children. High cholesterol ...

Assessment of the chromatographic lipophilicity of eight cephalosporins on different stationary phases.

Science.gov (United States)

Dąbrowska, Monika; Starek, Małgorzata; Komsta, Łukasz; Szafrański, Przemysław; Stasiewicz-Urban, Anna; Opoka, Włodzimierz

2017-04-01

The retention behaviors were investigated for a series of eight cephalosporins in thin-layer chromatography (TLC) using stationary phases of RP-2, RP-8, RP-18, NH 2 , DIOL, and CN chemically bonded silica gel. Additionally, various binary mobile phases (water/methanol and water/acetone) were used in different volume proportions. The retention behavior of the analyzed molecules was defined by R M0 constant. In addition, reversed phase high performance liquid chromatography (RP-HPLC) was performed in lipophilicity studies by using immobilized artificial membrane (IAM) stationary phase. Obtained chromatographic data (R M0 and logk' IAM ) were correlated with the lipophilicity, expressed as values of the log calculated (logP calc ) and experimental (logP exp(shake-flask) ) partition coefficient. Principal component analysis (PCA) was applied in order to obtain an overview of similarity or dissimilarity among the analyzed compounds. Hierarchical cluster analysis (HCA) was performed to compare the separation characteristics of the applied stationary phases. This study was undertaken to identify the best chromatographic system and chromatographic data processing method to enable the prediction of logP values. A comprehensive chromatographic investigation into the retention of the analyzed cephalosporins revealed a similar behavior on RP-18, RP-8 and CN stationary phases. The weak correlations obtained between experimental and certain computed lipophilicity indices revealed that R M0 and PC1/RM are relevant lipophilicity parameters and the RP-8, CN and RP-18 plates are appropriate stationary phases for lipophilicity investigation, whereas computational approaches still cannot fully replace experimentation. Copyright © 2017 Elsevier B.V. All rights reserved.

Cholesterol IQ Quiz

Science.gov (United States)

... Artery Disease Venous Thromboembolism Aortic Aneurysm More Cholesterol IQ Quiz Updated:Jul 5,2017 Begin the quiz ... What Your Cholesterol Levels Mean Common Misconceptions Cholesterol IQ Quiz • HDL, LDL, and Triglycerides • Causes of High ...

LDL: The "Bad" Cholesterol

Science.gov (United States)

... There are two main types of cholesterol: LDL (bad) cholesterol and HDL (good) cholesterol: LDL stands for low-density lipoproteins. It is called the "bad" cholesterol because a high LDL level leads to ...

High-cocoa polyphenol-rich chocolate improves HDL cholesterol in Type 2 diabetes patients.

Science.gov (United States)

Mellor, D D; Sathyapalan, T; Kilpatrick, E S; Beckett, S; Atkin, S L

2010-11-01

To examine the effects of chocolate on lipid profiles, weight and glycaemic control in individuals with Type 2 diabetes. Twelve individuals with Type 2 diabetes on stable medication were enrolled in a randomized, placebo-controlled double-blind crossover study. Subjects were randomized to 45 g chocolate with or without a high polyphenol content for 8 weeks and then crossed over after a 4-week washout period. Changes in weight, glycaemic control, lipid profile and high-sensitivity C-reactive protein were measured at the beginning and at the end of each intervention. HDL cholesterol increased significantly with high polyphenol chocolate (1.16 ± 0.08 vs. 1.26 ± 0.08 mmol/l, P = 0.05) with a decrease in the total cholesterol: HDL ratio (4.4 ± 0.4 vs. 4.1 ± 0.4 mmol/l, P = 0.04). No changes were seen with the low polyphenol chocolate in any parameters. Over the course of 16 weeks of daily chocolate consumption neither weight nor glycaemic control altered from baseline. High polyphenol chocolate is effective in improving the atherosclerotic cholesterol profile in patients with diabetes by increasing HDL cholesterol and improving the cholesterol:HDL ratio without affecting weight, inflammatory markers, insulin resistance or glycaemic control.

Neutrophil–lymphocyte ratio is associated with low high-density lipoprotein cholesterol in healthy young men

Directory of Open Access Journals (Sweden)

Duran Tok

2014-04-01

Full Text Available Objective: It has been reported that the neutrophil–lymphocyte ratio is significantly elevated in patients with low high-density lipoprotein cholesterol (<35 mg/dL. But in this study, some patients had hypertension that may have affected the neutrophil–lymphocyte ratio. This study consisted of 1274 asymptomatic healthy young men. In contrast with the previous study, we investigated the neutrophil–lymphocyte ratio in healthy young men with low high-density lipoprotein cholesterol compared with controls. Methods: We studied 1274 asymptomatic young males (military personnel screening who underwent routine health check-up. Of them, 102 subjects had low high-density lipoprotein cholesterol. Results: The neutrophil–lymphocyte ratio was significantly higher among the men with low high-density lipoprotein cholesterol than that of the control group (P < 0.001. Conclusion: We conclude that the neutrophil–lymphocyte ratio is significantly elevated in asymptomatic healthy young men with low high-density lipoprotein cholesterol compared with control participants.

Plasma cholesterol and endogenous cholesterol synthesis during refeeding in anorexia nervosa.

Science.gov (United States)

Feillet, F; Feillet-Coudray, C; Bard, J M; Parra, H J; Favre, E; Kabuth, B; Fruchart, J C; Vidailhet, M

2000-04-01

Normal or high levels of cholesterol have been measured in patients with anorexia nervosa (AN). Given that cholesterol intake in AN is usually very low, the reasons for this anomaly are not clearly understood. We studied lipid and lipoprotein profiles and endogenous cholesterol synthesis, estimated by serum lathosterol, in a population of 14 girls with AN, before and during a period of 30 days refeeding. The initial body mass index (BMI) of the patients was 13.41+/-1.62 kg/m(2). No changes were observed during refeeding in endocrine parameters (ACTH, cortisol and estradiol). At Day 0 the lipids data measured here showed normal levels of triglycerides, and total cholesterol at the upper limits of the normal range (5.44+/-1 mmol/l). At this time, total and LDL cholesterol were negatively correlated with transthyretin and BMI. Serum lathosterol (a precursor in cholesterol synthesis pathway) increased significantly (5.99+/-1.75 (Day 0) vs. 8.39+/-2.96 (Day 30); P=0.02) while there was a significant decrease in apo B (0.79+/-0.33 (Day 0) vs. 0. 60+/-0.17 g/l (Day 30), P=0.02) with refeeding. Thus, patients with initial high cholesterol levels have the worst nutritional status and high cholesterol levels are not related to a de novo synthesis. This profile returns to normal with refeeding. An increase of cellular cholesterol uptake may be responsible for this apparently paradoxical evolution with increase of cholesterol synthesis and decrease of apo B during renutrition.

Highly sensitive and selective cholesterol biosensor based on direct electron transfer of hemoglobin.

Science.gov (United States)

Zhao, Changzhi; Wan, Li; Jiang, Li; Wang, Qin; Jiao, Kui

2008-12-01

A cholesterol biosensor based on direct electron transfer of a hemoglobin-encapsulated chitosan-modified glassy carbon electrode has been developed for highly sensitive and selective analysis of serum samples. Modified by films containing hemoglobin and cholesterol oxidase, the electrode was prepared by encapsulation of enzyme in chitosan matrix. The hydrogen peroxide produced by the catalytic oxidation of cholesterol by cholesterol oxidase was reduced electrocatalytically by immobilized hemoglobin and used to obtain a sensitive amperometric response to cholesterol. The linear response of cholesterol concentrations ranged from 1.00 x 10(-5) to 6.00 x 10(-4) mol/L, with a correlation coefficient of 0.9969 and estimated detection limit of cholesterol of 9.5 micromol/L at a signal/noise ratio of 3. The cholesterol biosensor can efficiently exclude interference by the commonly coexisting ascorbic acid, uric acid, dopamine, and epinephrine. The sensitivity to the change in the concentration of cholesterol as the slope of the calibration curve was 0.596 A/M. The relative standard deviation was under 4.0% (n=5) for the determination of real samples. The biosensor is satisfactory in the determination of human serum samples.

The Drosophila DHR96 nuclear receptor binds cholesterol and regulates cholesterol homeostasis

OpenAIRE

Horner, Michael A.; Pardee, Keith; Liu, Suya; King-Jones, Kirst; Lajoie, Gilles; Edwards, Aled; Krause, Henry M.; Thummel, Carl S.

2009-01-01

Cholesterol homeostasis is required to maintain normal cellular function and avoid the deleterious effects of hypercholesterolemia. Here we show that the Drosophila DHR96 nuclear receptor binds cholesterol and is required for the coordinate transcriptional response of genes that are regulated by cholesterol and involved in cholesterol uptake, trafficking, and storage. DHR96 mutants die when grown on low levels of cholesterol and accumulate excess cholesterol when maintained on a high-choleste...

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.

Heuristic lipophilicity potential for computer-aided rational drug design

Science.gov (United States)

Du, Qishi; Arteca, Gustavo A.; Mezey, Paul G.

1997-09-01

In this contribution we suggest a heuristic molecular lipophilicitypotential (HMLP), which is a structure-based technique requiring noempirical indices of atomic lipophilicity. The input data used in thisapproach are molecular geometries and molecular surfaces. The HMLP is amodified electrostatic potential, combined with the averaged influences fromthe molecular environment. Quantum mechanics is used to calculate theelectron density function ρ(r) and the electrostatic potential V(r), andfrom this information a lipophilicity potential L(r) is generated. The HMLPis a unified lipophilicity and hydrophilicity potential. The interactions ofdipole and multipole moments, hydrogen bonds, and charged atoms in amolecule are included in the hydrophilic interactions in this model. TheHMLP is used to study hydrogen bonds and water-octanol partitioncoefficients in several examples. The calculated results show that the HMLPgives qualitatively and quantitatively correct, as well as chemicallyreasonable, results in cases where comparisons are available. Thesecomparisons indicate that the HMLP has advantages over the empiricallipophilicity potential in many aspects. The HMLP is a three-dimensional andeasily visualizable representation of molecular lipophilicity, suggested asa potential tool in computer-aided three-dimensional drug design.

Kefiran reduces atherosclerosis in rabbits fed a high cholesterol diet.

Science.gov (United States)

Uchida, Masashi; Ishii, Itsuko; Inoue, Chika; Akisato, Yoshie; Watanabe, Kenta; Hosoyama, Saori; Toida, Toshihiko; Ariyoshi, Noritaka; Kitada, Mitsukazu

2010-09-30

Kefiran is an exopolysaccharide produced by Lactobacillus kefiranofaciens, and has been proposed to have many health-promoting properties. We investigated the antiatherogenic effect of kefiran on rabbits fed a high-cholesterol diet. Male New Zealand White rabbits were fed a 0.5% cholesterol diet without (control group, n = 7) or with kefiran (kefiran group, n = 8) for eight weeks. The aorta was analyzed by histochemistry and atherosclerotic lesions were quantified. Lipids and sugars in serum were measured. Foam cell formation of RAW264.7 by βVLDL derived from both groups of rabbits was also investigated. Cholesterol, triglyceride and phospholipids levels of serum and lipoprotein fractions were not significantly different between these groups. Atherosclerotic lesions of the aorta in the kefiran group were statistically lower than those of the control group, with marked differences in the abdominal aorta. T-lymphocytes were not detectable in the aorta of the kefiran group. Cholesterol contents in stools were almost identical in both groups. Cholesterol content in the liver of the kefiran group was statistically lower than in the control group. Galactose content of βVLDL derived from the kefiran group was higher, and the lipid peroxidation level was much lower than in the control group. RAW264.7 macrophages treated with βVLDL from the kefiran group showed a more spherical shape and accumulated statistically lower cholesterol than macrophages treated with βVLDL from the control group. Orally derived kefiran is absorbed in the blood. Kefiran prevents the onset and development of atherosclerosis in hypercholesterolemic rabbits by anti-inflammatory and anti-oxidant actions.

Chromatographic lipophilicity determination using large volume injections of the solvents non-miscible with the mobile phase.

Science.gov (United States)

Sârbu, Costel; Naşcu-Briciu, Rodica Domnica; Casoni, Dorina; Kot-Wasik, Agata; Wasik, Andrzej; Namieśnik, Jacek

2012-11-30

A new perspective in the lipophilicity evaluation through RP-HPLC is permitted by analysis of the retention factor (k) obtained by injecting large volumes of test samples prepared in solvents immiscible with mobile phase. The experiment is carried out on representative groups of compounds with increased toxicity (mycotoxins and alkaloids) and amines with important biological activity (naturally occurring monoamine compounds and related drugs), which are covering a large interval of lipophilicity. The stock solution of each compound was prepared in hexane and the used mobile phases were mixtures of methanol or acetonitrile and water, in suited volume ratio. The injected volume was between 10 and 100 μL, while the used stationary phases were RP-18 and RP-8. On both reverse stationary phases the retention factors were linearly decreasing while the injection volume was increasing. In all cases, the linear models were highly statistically significant. On the basis of the obtained results new lipophilicity indices were purposed and discussed. The developed lipophilicity indices and the computationally expressed ones are correlated at a high level of statistical significance. Copyright © 2012 Elsevier B.V. All rights reserved.

Should we change our lipid management strategies to focus on non-high-density lipoprotein cholesterol?

NARCIS (Netherlands)

Rana, Jamal S.; Boekholdt, S. Matthijs

2010-01-01

Purpose of review Despite aggressive low-density lipoprotein cholesterol lowering, patients continue to be at significant risk of cardiovascular events. Assessment of non-high-density lipoprotein cholesterol (non-HDL-C) provides a measure of cholesterol contained in all atherogenic particles. In the

RP TLC-based lipophilicity assessment of some natural and synthetic coumarins

Energy Technology Data Exchange (ETDEWEB)

Rabtti, El Hadi M.A.; Natic, Maja M.; Milojkovic-Opsenica, Dusanka M.; Trifkovic, Jelena D.; Vuckovic, Ivan M.; Tesic, Zivoslav Lj., E-mail: ztesic@chem.bg.ac.rs [Faculty of Chemistry, University of Belgrade, Belgrade (Serbia); Vajs, Vlatka E. [Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Belgrade (Serbia)

2012-03-15

The lipophilic character of twelve coumarins was investigated by reversed-phase thin-layer chromatography (RP TLC) on RP-18 silica. The three different binary solvent systems composed of water and organic modifier (methanol, tetrahydrofuran or acetonitrile) were used in order to determine retention parameter (R{sub M}{sup 0}) and octanol-water partition coefficient (log P{sub OW})as a measure of the lipophilicity of the tested compounds. Lipophilicity parameter (log P{sub OW}) was experimentally determined using eight standard solutes with known log P{sub OW} values which were analyzed under the same chromatographic conditions as the target substances. Lipophilicity parameters together with 2D molecular descriptors were subjected to the multivariate statistical analysis (principal component analysis (PCA) and partial least square (PLS) regression) in order to reveal the most influential factors governing the retention, i.e., lipophilicity of the investigated compounds. The quantitative structure-retention relationship models reveal the importance of descriptors which describe the size and the shape of the molecule as well as their polar properties. (author)

Age-dependent effect of high cholesterol diets on anxiety-like behavior in elevated plus maze test in rats.

Science.gov (United States)

Hu, Xu; Wang, Tao; Luo, Jia; Liang, Shan; Li, Wei; Wu, Xiaoli; Jin, Feng; Wang, Li

2014-09-01

Cholesterol is an essential component of brain and nerve cells and is essential for maintaining the function of the nervous system. Epidemiological studies showed that patients suffering from anxiety disorders have higher serum cholesterol levels. In this study, we investigated the influence of high cholesterol diet on anxiety-like behavior in elevated plus maze in animal model and explored the relationship between cholesterol and anxiety-like behavior from the aspect of central neurochemical changes. Young (3 weeks old) and adult (20 weeks old) rats were given a high cholesterol diet for 8 weeks. The anxiety-like behavior in elevated plus maze test and changes of central neurochemical implicated in anxiety were measured. In young rats, high cholesterol diet induced anxiolytic-like behavior, decreased serum corticosterone (CORT), increased hippocampal brain-derived neurotrophic factor (BDNF), increased hippocampal mineralocorticoid receptor (MR) and decreased glucocorticoid receptor (GR). In adult rats, high cholesterol diet induced anxiety-like behavior and increase of serum CORT and decrease of hippocampal BDNF comparing with their respective control group that fed the regular diet. High cholesterol diet induced age-dependent effects on anxiety-like behavior and central neurochemical changes. High cholesterol diet might affect the central nervous system (CNS) function differently, and resulting in different behavior performance of anxiety in different age period.

Radiosensitization of hypoxic bacterial cells by nitroimidazoles of low lipophilicity: steady-state and rapid-mix studies

International Nuclear Information System (INIS)

Anderson, R.F.; Patel, K.B.; Sehmi, D.S.

1981-01-01

Radiosensitization of hypoxic bacterial cells by five 2-nitroimidazoles, with similar reduction potentials to misonidazole but having lower lipophilicites, has been measured in Escherichia coli AB 1157 and Streptococcus lactis 712. Sensitization efficiency progressively decreased with decreasing lepophilicity in E. coli but not in S. lactis. This difference is discussed in terms of the differing membrane properties of the two bacteria; E. coli resembled a multicompartment model, as would also be expected with mammalian cells. Rapid-mix experiments are described which show that the radiosensitization observed after experiments are described which show that the radiosensitization observed after preirradiation contact times between ca. 3 and 30 msec is dependent on the lipophilicity of the sensitizer, higher lipophilicity resulting in a lower contact time being required for radiosensitization. This result and the observation that a highly lipophilic compound affects only half the full oxygen enhancement level after short contact times suggest that part of the sensitization process occurs in a lipophilic compartment of the cell

Phospholipase A2-treated human high-density lipoprotein and cholesterol movements: exchange processes and lecithin: cholesterol acyltransferase reactivity.

Science.gov (United States)

Chollet, F; Perret, B P; Chap, H; Douste-Blazy, L

1986-02-12

Human HDL3 (d 1.125-1.21 g/ml) were treated by an exogenous phospholipase A2 from Crotalus adamenteus in the presence of albumin. Phosphatidylcholine hydrolysis ranged between 30 and 90% and the reisolated particle was essentially devoid of lipolysis products. (1) An exchange of free cholesterol was recorded between radiolabelled erythrocytes at 5-10% haematocrit and HDL3 (0.6 mM total cholesterol) from 0 to 12-15 h. Isotopic equilibration was reached. Kinetic analysis of the data indicated a constant rate of free cholesterol exchange of 13.0 microM/h with a half-time of equilibration around 3 h. Very similar values of cholesterol exchange, specific radioactivities and kinetic parameters were measured when phospholipase-treated HDL replaced control HDL. (2) The lecithin: cholesterol acyltransferase reactivity of HDL3, containing different amounts of phosphatidylcholine, as achieved by various degrees of phospholipase A2 treatment, was measured using a crude preparation of lecithin: cholesterol acyltransferase (the d 1.21-1.25 g/ml plasma fraction). The rate of esterification was determined between 0 and 12 h. Following a 15-30% lipolysis, the lecithin: cholesterol acyltransferase reactivity of HDL3 was reduced about 30-40%, and then continued to decrease, though more slowly, as the phospholipid content was further lowered in the particle. (3) The addition of the lecithin: cholesterol acyltransferase preparation into an incubation medium made of labelled erythrocytes and HDL3 promoted a movement of radioactive cholesterol out of cells, above the values of exchange, and an accumulation of cholesteryl esters in HDL. This reflected a mass consumption of free cholesterol, from both the cellular and the lipoprotein compartments upon the lecithin: cholesterol acyltransferase action. As a consequence of a decreased reactivity, phospholipase-treated HDL (with 2/3 of phosphatidylcholine hydrolyzed) proved much less effective in the lecithin: cholesterol acyltransferase

Association between high-density lipoprotein cholesterol level and pulmonary function in healthy Korean adolescents: the JS high school study.

Science.gov (United States)

Park, Ji Hye; Mun, Seyeon; Choi, Dong Phil; Lee, Joo Young; Kim, Hyeon Chang

2017-12-11

Accumulating evidence suggests that high-density lipoprotein (HDL) cholesterol is associated with pulmonary function and pulmonary disorders. The aim of this study was to evaluate the association between HDL cholesterol and pulmonary function in healthy adolescents. This cross-sectional study was based on data collected for the JS High School study. The analysis included 644 adolescents (318 male and 326 female) aged 15-16 years old and free from asthma or chronic obstructive pulmonary disease. Fasting blood samples were collected for hematologic and biochemical assessment. Forced vital capacity volume (FVC) and forced expiratory volume in the 1 s (FEV1) were measured using dry-rolling-seal spirometry. The associations between HDL cholesterol and pulmonary function were analyzed using multiple linear regression models. Among male adolescents, an increase of 1.0 mg/dL in HDL cholesterol was associated with 10 mL decrease in FVC (p = 0.013) and FEV1 (p = 0.013) after adjusting for age, height, weight, alcohol drinking, smoking, physical activity, systolic blood pressure, total cholesterol, triglyceride, and monthly household income. Percent predicted values of FVC (p = 0.036) and FEV1 (p = 0.017) were also inversely associated with HDL cholesterol. However, among female adolescents, HDL cholesterol level was not significantly associated with absolute or percent predictive value of FVC and FEV1. Higher HDL cholesterol level may be associated with decreased pulmonary function among healthy male adolescents. The sex differences observed in the association between HDL cholesterol and pulmonary function need further investigation.

Lack of Abcg1 results in decreased plasma HDL cholesterol levels and increased biliary cholesterol secretion in mice fed a high cholesterol diet

NARCIS (Netherlands)

Wiersma, Harmen; Nijstad, Niels; de Boer, Jan Freark; Out, Ruud; Hogewerf, Wytse; Van Berkel, Theo J.; Kuipers, Folkert; Tietge, Uwe J. F.

Objective: The ATP Binding Cassette transporter G1 (ABCG1) has been implicated in cholesterol efflux towards HDL and reverse cholesterol transport (RCT). Biliary cholesterol secretion is considered as an important step in RCT. The aim of the present study was to determine the consequences of Abcg1

Age-dependent effect of high cholesterol diets on anxiety-like behavior in elevated plus maze test in rats

Science.gov (United States)

2014-01-01

Background Cholesterol is an essential component of brain and nerve cells and is essential for maintaining the function of the nervous system. Epidemiological studies showed that patients suffering from anxiety disorders have higher serum cholesterol levels. In this study, we investigated the influence of high cholesterol diet on anxiety-like behavior in elevated plus maze in animal model and explored the relationship between cholesterol and anxiety-like behavior from the aspect of central neurochemical changes. Methods Young (3 weeks old) and adult (20 weeks old) rats were given a high cholesterol diet for 8 weeks. The anxiety-like behavior in elevated plus maze test and changes of central neurochemical implicated in anxiety were measured. Results In young rats, high cholesterol diet induced anxiolytic-like behavior, decreased serum corticosterone (CORT), increased hippocampal brain-derived neurotrophic factor (BDNF), increased hippocampal mineralocorticoid receptor (MR) and decreased glucocorticoid receptor (GR). In adult rats, high cholesterol diet induced anxiety-like behavior and increase of serum CORT and decrease of hippocampal BDNF comparing with their respective control group that fed the regular diet. Discussion High cholesterol diet induced age-dependent effects on anxiety-like behavior and central neurochemical changes. High cholesterol diet might affect the central nervous system (CNS) function differently, and resulting in different behavior performance of anxiety in different age period. PMID:25179125

Isoflavone and Protein Constituents of Lactic Acid-Fermented Soy Milk Combine to Prevent Dyslipidemia in Rats Fed a High Cholesterol Diet

OpenAIRE

Kobayashi, Maki; Egusa, Shintaro; Fukuda, Mitsuru

2014-01-01

A high cholesterol diet induces dyslipidemia. This study investigated whether isoflavone aglycones in lactic acid-fermented soy milk (LFS) improve lipid metabolism in rats fed a high cholesterol diet. Male Sprague-Dawley rats aged seven weeks were fed an AIN-93G diet, a 1% cholesterol diet (a high cholesterol diet), a high-cholesterol diet containing 4% isoflavone extract of LFS (LFS extract diet), a high-cholesterol diet containing 19.4% ethanol-washed LFS (ethanol-washed LFS diet, isoflavon...

Lipophilic Chemicals from Diesel Exhaust Particles Trigger Calcium Response in Human Endothelial Cells via Aryl Hydrocarbon Receptor Non-Genomic Signalling

Directory of Open Access Journals (Sweden)

Bendik C. Brinchmann

2018-05-01

Full Text Available Exposure to diesel exhaust particles (DEPs affects endothelial function and may contribute to the development of atherosclerosis and vasomotor dysfunction. As intracellular calcium concentration [Ca2+]i is considered important in myoendothelial signalling, we explored the effects of extractable organic matter from DEPs (DEP-EOM on [Ca2+]i and membrane microstructure in endothelial cells. DEP-EOM of increasing polarity was obtained by pressurized sequential extraction of DEPs with n-hexane (n-Hex-EOM, dichloromethane (DCM-EOM, methanol, and water. Chemical analysis revealed that the majority of organic matter was extracted by the n-Hex- and DCM-EOM, with polycyclic aromatic hydrocarbons primarily occurring in n-Hex-EOM. The concentration of calcium was measured in human microvascular endothelial cells (HMEC-1 using micro-spectrofluorometry. The lipophilic n-Hex-EOM and DCM-EOM, but not the more polar methanol- and water-soluble extracts, induced rapid [Ca2+]i increases in HMEC-1. n-Hex-EOM triggered [Ca2+]i increase from intracellular stores, followed by extracellular calcium influx consistent with store operated calcium entry (SOCE. By contrast, the less lipophilic DCM-EOM triggered [Ca2+]i increase via extracellular influx alone, resembling receptor operated calcium entry (ROCE. Both extracts increased [Ca2+]i via aryl hydrocarbon receptor (AhR non-genomic signalling, verified by pharmacological inhibition and RNA-interference. Moreover, DCM-EOM appeared to induce an AhR-dependent reduction in the global plasma membrane order, as visualized by confocal fluorescence microscopy. DCM-EOM-triggered [Ca2+]i increase and membrane alterations were attenuated by the membrane stabilizing lipid cholesterol. In conclusion, lipophilic constituents of DEPs extracted by n-hexane and DCM seem to induce rapid AhR-dependent [Ca2+]i increase in HMEC-1 endothelial cells, possibly involving both ROCE and SOCE-mediated mechanisms. The semi-lipophilic fraction

Synthetic lipophilic antioxidant BO-653 suppresses HCV replication.

Science.gov (United States)

Yasui, Fumihiko; Sudoh, Masayuki; Arai, Masaaki; Kohara, Michinori

2013-02-01

The influence of the intracellular redox state on the hepatitis C virus (HCV) life cycle is poorly understood. This study demonstrated the anti-HCV activity of 2,3-dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran (BO-653), a synthetic lipophilic antioxidant, and examined whether BO-653's antioxidant activity is integral to its anti-HCV activity. The anti-HCV activity of BO-653 was investigated in HuH-7 cells bearing an HCV subgenomic replicon (FLR3-1 cells) and in HuH-7 cells infected persistently with HCV (RMT-tri cells). BO-653 inhibition of HCV replication was also compared with that of several hydrophilic and lipophilic antioxidants. BO-653 suppressed HCV replication in FLR3-1 and RMT-tri cells in a concentration-dependent manner. The lipophilic antioxidants had stronger anti-HCV activities than the hydrophilic antioxidants, and BO-653 displayed the strongest anti-HCV activity of all the antioxidants examined. Therefore, the anti-HCV activity of BO-653 was examined in chimeric mice harboring human hepatocytes infected with HCV. The combination treatment of BO-653 and polyethylene glycol-conjugated interferon-α (PEG-IFN) decreased serum HCV RNA titer more than that seen with PEG-IFN alone. These findings suggest that both the lipophilic property and the antioxidant activity of BO-653 play an important role in the inhibition of HCV replication. Copyright © 2012 Wiley Periodicals, Inc.

Lipophilization and MS characterization of the main anthocyanins purified from hibiscus flowers.

Science.gov (United States)

Grajeda-Iglesias, Claudia; Salas, Erika; Barouh, Nathalie; Baréa, Bruno; Figueroa-Espinoza, Maria Cruz

2017-09-01

Hibiscus sabdariffa flowers represent an interesting source of anthocyanins, one of the most important plant pigments, which are responsible of the intense red color of the calyces, and have potential as natural colorants for food applications. Nevertheless, anthocyanins are highly hydrosoluble and unstable compounds. On this basis, the aim of this work was to increase the lipophilicity of the hibiscus anthocyanins by lipophilization, in order to obtain amphiphilic colorants, which could be easily incorporated in lipid-rich food matrices. Octanoyl derivatives of delphinidin-3-O-sambubioside and cyanidin-3-O-sambubioside were chemically obtained for the first time, and characterized by means of HPLC-ESI-MS data. Copyright © 2017. Published by Elsevier Ltd.

Prevalence of Low High-density Lipoprotein Cholesterol Among Adults, by Physical Activity: United States, 2011-2014.

Science.gov (United States)

Zwald, Marissa L; Akinbami, Lara J; Fakhouri, Tala H I; Fryar, Chryl D

2017-03-01

Data from the National Health and Nutrition Examination Survey •The prevalence of low high-density lipoprotein (HDL) cholesterol was significantly higher among adults who did not meet recommended physical activity guidelines (21.0%) than adults who met the guidelines (17.7%). •Low HDL cholesterol prevalence differed significantly for both men and women by adherence to physical activity guidelines. •Prevalence of low HDL cholesterol declined as age increased for both those who did and did not meet the physical activity guidelines. •Non-Hispanic white and non-Hispanic black adults who did not meet the physical activity guidelines had a higher prevalence than those who met the guidelines. •Low HDL cholesterol prevalence declined with increasing education level regardless of adherence to physical activity guidelines. Regular physical activity can improve cholesterol levels among adults, including increasing high-density lipoprotein (HDL) cholesterol (1). HDL cholesterol is known as "good" cholesterol because high levels can reduce cardiovascular disease risk (2). The 2008 Physical Activity Guidelines for Americans recommend that adults engage in 150 minutes or more of moderate-intensity aerobic activity per week, 75 minutes of vigorous-intensity aerobic activity per week, or an equivalent combination (3). Adherence to these guidelines is expected to decrease the prevalence of low HDL cholesterol levels (4-8). This report presents national data for 2011-2014 on low HDL cholesterol prevalence among U.S. adults aged 20 and over, by whether they met these guidelines. All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.

Effect of lipophilization of dihydrocaffeic acid on its antioxidative properties in fish oil enriched emulsion

DEFF Research Database (Denmark)

Sørensen, Ann-Dorit Moltke; de Diego, Sara; Petersen, Lone Kristine

oxidation than PUFAs from vegetable oils due to their highly polyunsaturated nature, it is necessary to develop methods to protect these PUFAs. Many food systems are emulsions. Due to the so-called polar paradox phenomenon, hydrophilic antioxidants may in many cases be better antioxidants in bulk oil than...... lipophilic compounds, whereas lipophilic antioxidants are more efficient than hydrophilic antioxidants in emulsions. This phenomenon has been explained by the affinity of the compounds towards the different phases in bulk oil and emulsions. The hydrophilic character of many naturally occurring antioxidants...... that generally, lipophilized dihydrocaffeic acid and rutin increased the oxidative stability of o/w emulsions and fish oil enriched milk compared with their parent compound. The results supported a cut-off effect in relation to the acyl chain length esterified to the phenolic compound. Octyl dihydrocaffeate (C8...

Alternative measures of lipophilicity: from octanol-water partitioning to IAM retention.

Science.gov (United States)

Giaginis, Costas; Tsantili-Kakoulidou, Anna

2008-08-01

This review describes lipophilicity parameters currently used in drug design and QSAR studies. After a short historical overview, the complex nature of lipophilicity as the outcome of polar/nonpolar inter- and intramolecular interactions is analysed and considered as the background for the discussion of the different lipophilicity descriptors. The first part focuses on octanol-water partitioning of neutral and ionisable compounds, evaluates the efficiency of predictions and provides a short description of the experimental methods for the determination of distribution coefficients. A next part is dedicated to reversed-phase chromatographic techniques, HPLC and TLC in lipophilicity assessment. The two methods are evaluated for their efficiency to simulate octanol-water and the progress achieved in the refinement of suitable chromatographic conditions, in particular in the field of HPLC, is outlined. Liposomes as direct models of biological membranes are examined and phospolipophilicity is compared to the traditional lipophilicity concept. Difficulties associated with liposome-water partitioning are discussed. The last part focuses on Immobilised Artificial Membrane (IAM) chromatography as an alternative which combines membrane simulation with rapid measurements. IAM chromatographic retention is compared to octanol-water and liposome-water partitioning as well as to reversed-phase retention and its potential to predict biopartitioning and biological activities is discussed.

Lipophilic Toxins in WA - Clear and present danger: monitoring and management of lipophilic shellfish toxins in Washington State

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Lipophilic shellfish toxins comprise an extensive suite of compounds including those associated with the human syndromes known as diarrhetic shellfish poisoning...

Are You Taking the Right Treatment for Your High Cholesterol?

Science.gov (United States)

... open('/content/cro/en/health/prescription-drugs/best-buy-drugs/evaluating-statin-drugs-to-treat--high-cholesterol-and- ... talking with your doctor How to share Best Buy Drug reports About us Less common issues: Diabetes, memory ...

High Cholesterol and Complementary Health Practices: What the Science Says

Science.gov (United States)

... professionals High Cholesterol and Complementary Health Practices: What the Science Says Share: February 2013 Dietary Supplements Red Yeast ... to exploring complementary health products and practices in the context of rigorous ... health researchers, and disseminating authoritative information ...

Assessing the lipophilicity of fragments and early hits

Science.gov (United States)

Mortenson, Paul N.; Murray, Christopher W.

2011-07-01

A key challenge in many drug discovery programs is to accurately assess the potential value of screening hits. This is particularly true in fragment-based drug design (FBDD), where the hits often bind relatively weakly, but are correspondingly small. Ligand efficiency (LE) considers both the potency and the size of the molecule, and enables us to estimate whether or not an initial hit is likely to be optimisable to a potent, druglike lead. While size is a key property that needs to be controlled in a small molecule drug, there are a number of additional properties that should also be considered. Lipophilicity is amongst the most important of these additional properties, and here we present a new efficiency index (LLEAT) that combines lipophilicity, size and potency. The index is intuitively defined, and has been designed to have the same target value and dynamic range as LE, making it easily interpretable by medicinal chemists. Monitoring both LE and LLEAT should help both in the selection of more promising fragment hits, and controlling molecular weight and lipophilicity during optimisation.

Isoflavone and Protein Constituents of Lactic Acid-Fermented Soy Milk Combine to Prevent Dyslipidemia in Rats Fed a High Cholesterol Diet

Science.gov (United States)

Kobayashi, Maki; Egusa, Shintaro; Fukuda, Mitsuru

2014-01-01

A high cholesterol diet induces dyslipidemia. This study investigated whether isoflavone aglycones in lactic acid-fermented soy milk (LFS) improve lipid metabolism in rats fed a high cholesterol diet. Male Sprague-Dawley rats aged seven weeks were fed an AIN-93G diet, a 1% cholesterol diet (a high cholesterol diet), a high-cholesterol diet containing 4% isoflavone extract of LFS (LFS extract diet), a high-cholesterol diet containing 19.4% ethanol-washed LFS (ethanol-washed LFS diet, isoflavone-poor diet), or a high cholesterol diet containing 23.2% intact LFS (intact LFS diet) for five weeks. The plasma total cholesterol (TC) level was increased in the rats fed the LFS extract diet compared with those fed the high cholesterol diet. The TC level was decreased by the intact LFS and ethanol-washed LFS diets. The cholesterol-lowering effect was stronger in the rats fed the intact LFS diet than those fed the ethanol-washed LFS diet. The plasma triglyceride (TG) level was unchanged in the rats fed the LFS extract diet, but it decreased in rats fed the intact LFS and ethanol-washed LFS diets. Although, compared with the high cholesterol diet, the LFS extract and ethanol-washed LFS diets did not reduce hepatic cholesterol and TG, both levels were remarkably lowered by the intact LFS diet. These results suggest that the improvement in lipid metabolism of rats fed a high-cholesterol diet containing LFS isoflavone aglycones is not due to an independent effect but due to a cooperative effect with soy protein. PMID:25514389

Isoflavone and Protein Constituents of Lactic Acid-Fermented Soy Milk Combine to Prevent Dyslipidemia in Rats Fed a High Cholesterol Diet

Directory of Open Access Journals (Sweden)

Maki Kobayashi

2014-12-01

Full Text Available A high cholesterol diet induces dyslipidemia. This study investigated whether isoflavone aglycones in lactic acid-fermented soy milk (LFS improve lipid metabolism in rats fed a high cholesterol diet. Male Sprague-Dawley rats aged seven weeks were fed an AIN-93G diet, a 1% cholesterol diet (a high cholesterol diet, a high-cholesterol diet containing 4% isoflavone extract of LFS (LFS extract diet, a high-cholesterol diet containing 19.4% ethanol-washed LFS (ethanol-washed LFS diet, isoflavone-poor diet, or a high cholesterol diet containing 23.2% intact LFS (intact LFS diet for five weeks. The plasma total cholesterol (TC level was increased in the rats fed the LFS extract diet compared with those fed the high cholesterol diet. The TC level was decreased by the intact LFS and ethanol-washed LFS diets. The cholesterol-lowering effect was stronger in the rats fed the intact LFS diet than those fed the ethanol-washed LFS diet. The plasma triglyceride (TG level was unchanged in the rats fed the LFS extract diet, but it decreased in rats fed the intact LFS and ethanol-washed LFS diets. Although, compared with the high cholesterol diet, the LFS extract and ethanol-washed LFS diets did not reduce hepatic cholesterol and TG, both levels were remarkably lowered by the intact LFS diet. These results suggest that the improvement in lipid metabolism of rats fed a high-cholesterol diet containing LFS isoflavone aglycones is not due to an independent effect but due to a cooperative effect with soy protein.

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.

Preparation and performance of lipophilic α-zirconium phosphate with high thermal stability and its application in thermal-plastic polymers

Directory of Open Access Journals (Sweden)

Ya Du

2015-10-01

Full Text Available To prepare lipophilic α-zirconium phosphate with high grafting ratio and thermal stability (OZrP-HT and explore its potential application in thermal-plastic polymers, a novel method was developed by surface lipophilicity enhancement strategy. The commercial α-zirconium phosphate (α-ZrP was pre-intercalated by n-propylamine (PA and grafted by silane coupling agents. Then the pre-intercalated PA was removed by heat-treatment, and the obtained OZrP-HT was utilized to fabricate the phosphorous-containing polyester (P-co-PET/OZrP-HT nanocomposites by melt-blending method. The prepared OZrP-HT and P-co-PET/OZrP-HT nanocomposites were characterized by Wide Angle X-ray Diffraction (WAXD, Fourier Transform Infrared Spectroscopy (FTIR, Thermogravimetric Analysis (TGA, Transmission Electron Microscope (TEM, etc. The results show that OZrP-HT with high grafting ratio (13.78 wt% and thermal stability (Tonset=368 °C was successfully prepared via this novel method and was uniformly intercalated by P-co-PET molecular chains. OZrP-HT had no significant effect on the fiber processability of P-co-PET polymer, and flame retardant properties of (P-co-PET/OZrP-HT nanocomposites were improved. This method may be suitable for organic modification of general inorganic layered compounds and could extend the potential applications in thermo-plastic polymers.

Synthesis and study of lipophilic crown ethers and thia-ligands. Application to nuclear fuel reprocessing

International Nuclear Information System (INIS)

Guyon, Vincent

1992-01-01

In the field of metal extraction from the solutions of nuclear fuel reprocessing, new specific complexing agents that are more efficient than tributyl phosphate must possess a high lipophilic character. The use of lipophilic crown ethers and thia-ligands has eliminated the problem related to their loss in the aqueous media. Moreover, it has made their complexes more soluble in organic solvents. The increase of lipophilic character of monocyclic polyethers has been realized with the addition of an alkyl chain and the development of a new process has made possible the separation of cis-syn-cis and cis-anti-cis isomers of dicyclohexano 18 crown 6 on an industrial scale. The creation of a rapid NMR method of analysis has permitted to study the extracting capacity of those crown ethers in relation to monovalent and divalent cations in nitric acid media and also to demonstrate the influence brought by different substituents. Some new lipophilic thia-ligands (macrocycles and podands) have also been prepared and the study of palladium extraction in nitric acid media by these compounds has led to a better understanding of the relation between the structure and the extracting capacity. Of easy access, some podands have an extracting selectivity and an extracting kinetic for this metal which are highly superior than those of dialkyl sulphides actually employed in the industry. This makes their use possible in the nuclear area. (author) [fr

Self-Reported High-Cholesterol Prevalence in the Brazilian Population: Analysis of the 2013 National Health Survey

Directory of Open Access Journals (Sweden)

Paulo A. Lotufo

Full Text Available Abstract Background: Data on the prevalence of dyslipidemia in Brazil are scarce, with surveys available only for some towns. Objective: To evaluate the prevalence of the self-reported medical diagnosis of high cholesterol in the Brazilian adult population by use of the 2013 National Health Survey data. Methods: Descriptive study assessing the 2013 National Health Survey data, a household-based epidemiological survey with a nationally representative sample and self-reported information. The sample consisted of 60,202 individuals who reported a medical diagnosis of dyslipidemia. The point prevalence and 95% confidence interval (95%CI for the medical diagnosis of high cholesterol/triglyceride by gender, age, race/ethnicity, geographic region and educational level were calculated. Adjusted odds ratio was calculated. Results: Of the 60,202 participants, 14.3% (95%CI=13.7-14.8 never had their cholesterol or triglyceride levels tested, but a higher frequency of women, white individuals, elderly and those with higher educational level had their cholesterol levels tested within the last year. The prevalence of the medical diagnosis of high cholesterol was 12.5% (9.7% in men and 15.1% in women, and women had 60% higher probability of a diagnosis of high cholesterol than men. The frequency of the medical diagnosis of high cholesterol increased up to the age of 59 years, being higher in white individuals or those of Asian heritage, in those with higher educational level and in residents of the Southern and Southeastern regions. Conclusion: The importance of dyslipidemia awareness in the present Brazilian epidemiological context must be emphasized to guide actions to control and prevent coronary heart disease, the leading cause of death in Brazil and worldwide.

Lipophilic Polycation Vehicles Display High Plasmid DNA Delivery to Multiple Cell Types.

Science.gov (United States)

Wu, Yaoying; Smith, Adam E; Reineke, Theresa M

2017-08-16

A class of cationic poly(alkylamidoamine)s (PAAAs) containing lipophilic methylene linkers were designed and examined as in vitro plasmid DNA (pDNA) delivery agents. The PAAAs were synthesized via step-growth polymerization between a diamine monomer and each of four different diacid chloride monomers with varying methylene linker lengths, including glutaryl chloride, adipoyl chloride, pimeloyl chloride, and suberoyl chloride, which served to systematically increase the lipophilicity of the polymers. The synthesized polymers successfully complexed with pDNA in reduced serum medium at N/P ratios of 5 and greater, resulting in polyplexes with hydrodynamic diameters of approximately 1 μm. These polyplexes were tested for in vitro transgene expression and cytotoxicity using HDFa (human dermal fibroblast), HeLa (human cervical carcinoma), HMEC (human mammary epithelial), and HUVEC (human umbilical vein endothelial) cells. Interestingly, select PAAA polyplex formulations were found to be more effective than Lipofectamine 2000 at promoting transgene expression (GFP) while maintaining comparable or higher cell viability. Transgene expression was highest in HeLa cells (∼90% for most formulations) and lowest in HDFa cells (up to ∼20%) as measured by GFP fluorescence. In addition, the cytotoxicity of PAAA polyplex formulations was significantly increased as the molecular weight, N/P ratio, and methylene linker length were increased. The PAAA vehicles developed herein provide a new delivery vehicle design strategy of displaying attributes of both polycations and lipids, which show promise as a tunable scaffold for refining the structure-activity-toxicity profiles for future genome editing studies.

Modified Folin-Ciocalteu antioxidant capacity assay for measuring lipophilic antioxidants.

Science.gov (United States)

Berker, Kadriye Isil; Ozdemir Olgun, F Ayca; Ozyurt, Dilek; Demirata, Birsen; Apak, Resat

2013-05-22

The Folin-Ciocalteu (FC) method of performing a total phenolics assay, originally developed for protein determination, has recently evolved as a total antioxidant capacity assay but was found to be incapable of measuring lipophilic antioxidants due to the high affinity of the FC chromophore, that is, multivalent-charged phospho-tungsto-molybdate(V), toward water. Thus, the FC method was modified and standardized so as to enable simultaneous measurement of lipophilic and hydrophilic antioxidants in NaOH-added isobutanol-water medium. Optimal conditions were as follows: dilution ratio of aqueous FC reagent with iso-BuOH (1:2, v/v), final NaOH concentration of 3.5 × 10(-2) M, reaction time of 20 min, and maximum absorption wavelength of 665 nm. The modified procedure was successfully applied to the total antioxidant capacity assay of trolox, quercetin, ascorbic acid, gallic acid, catechin, caffeic acid, ferulic acid, rosmarinic acid, glutathione, and cysteine, as well as of lipophilic antioxidants such as α-tocopherol (vitamin E), butylated hydroxyanisole, butylated hydroxytoluene, tertiary butylhydroquinone, lauryl gallate, and β-carotene. The modified FC method reliably quantified ascorbic acid, whereas the conventional method could not. The modified method was reproducible and additive in terms of total antioxidant capacity values of constituents of complex mixtures such as olive oil extract and herbal tea infusion. The trolox equivalent antioxidant capacities of the tested antioxidant compounds correlated well with those found by the Cupric Reducing Antioxidant Capacity reference method.

Lipophilic phytochemicals from banana fruits of several Musa species.

Science.gov (United States)

Vilela, Carla; Santos, Sónia A O; Villaverde, Juan J; Oliveira, Lúcia; Nunes, Alberto; Cordeiro, Nereida; Freire, Carmen S R; Silvestre, Armando J D

2014-11-01

The chemical composition of the lipophilic extract of ripe pulp of banana fruit from several banana cultivars belonging to the Musa acuminata and Musa balbisiana species (namely 'Chinese Cavendish', 'Giant Cavendish', 'Dwarf Red', 'Grand Nain', 'Eilon', 'Gruesa', 'Silver', 'Ricasa', 'Williams' and 'Zelig') was studied by gas chromatography-mass spectrometry for the first time. The banana cultivars showed similar amounts of lipophilic extractives (ca. 0.4% of dry material weight) as well as qualitative chemical compositions. The major groups of compounds identified in these fractions were fatty acids and sterols making up 68.6-84.3% and 11.1-28.0%, respectively, of the total amount of lipophilic components. Smaller amounts of long chain aliphatic alcohols and α-tocopherol were also identified. These results are a relevant contribution for the valorisation of these banana cultivars as sources of valuable phytochemicals (ω-3 and ω-6 fatty acids, and sterols) with well-established beneficial nutritional and health effects. Copyright © 2014 Elsevier Ltd. All rights reserved.

Isotope dilution/mass spectrometry of serum cholesterol with [3,4-13C]cholesterol: proposed definitive method

International Nuclear Information System (INIS)

Pelletier, O.; Wright, L.A.; Breckenridge, W.C.

1987-01-01

We describe a new gas-chromatographic/mass-spectrometric (GC/MS) isotope-dilution method for determination of serum cholesterol. The method has been fully optimized and documented to provide the high accuracy and precision expected for a Definitive Method. In the presence of [3,4- 13 C]cholesterol, cholesteryl esters in serum are hydrolyzed under optimum conditions and the entire cholesterol pool is extracted and derivatized to silyl ethers. The cholesterol derivatives are resolved from other sterols by gas-liquid chromatography on a fused silica column, and selected ions characteristic of cholesterol and the [3,4- 13 C]cholesterol are monitored with a GC/MS quandrupole system. We estimated the cholesterol content of samples by bracketing each sample with standards of comparable cholesterol concentration that also contained the [3,4- 13 C]cholesterol. The procedure was highly reproducible (CV less than 0.5%), better accuracy and precision being obtained with [3,4- 13 C]cholesterol than with heptadeuterated cholesterol. Mean values per gram of dry serum for one serum pool assayed by this method and that of the National Bureau of Standards differed by 0.5%. We conclude that the method satisfies the criteria for a Definitive Method

Role of Hepatic Lipase and Endothelial Lipase in High-Density Lipoprotein-Mediated Reverse Cholesterol Transport

NARCIS (Netherlands)

Annema, Wijtske; Tietge, Uwe J. F.

Reverse cholesterol transport (RCT) constitutes a key part of the atheroprotective properties of high-density lipoproteins (HDL). Hepatic lipase (HL) and endothelial lipase (EL) are negative regulators of plasma HDL cholesterol levels. Although overexpression of EL decreases overall

Characterising the extent of misreporting of high blood pressure, high cholesterol, and diabetes using the Australian Health Survey.

Science.gov (United States)

Peterson, Karen Louise; Jacobs, Jane Philippa; Allender, Steven; Alston, Laura Veronica; Nichols, Melanie

2016-08-02

Measuring and monitoring the true prevalence of risk factors for chronic conditions is essential for evidence-based policy and health service planning. Understanding the prevalence of risk factors for cardiovascular disease (CVD) in Australia relies heavily on self-report measures from surveys, such as the triennial National Health Survey. However, international evidence suggests that self-reported data may substantially underestimate actual risk factor prevalence. This study sought to characterise the extent of misreporting in a large, nationally-representative health survey that included objective measures of clinical risk factors for CVD. This study employed a cross-sectional analysis of 7269 adults aged 18 years and over who provided fasting blood samples as part of the 2011-12 Australian Health Survey. Self-reported prevalence of high blood pressure, high cholesterol and diabetes was compared to measured prevalence, and univariate and multivariate logistic regression analyses identified socio-demographic characteristics associated with underreporting for each risk factor. Approximately 16 % of the total sample underreported high blood pressure (measured to be at high risk but didn't report a diagnosis), 33 % underreported high cholesterol, and 1.3 % underreported diabetes. Among those measured to be at high risk, 68 % did not report a diagnosis for high blood pressure, nor did 89 % of people with high cholesterol and 29 % of people with high fasting plasma glucose. Younger age was associated with underreporting high blood pressure and high cholesterol, while lower area-level disadvantage and higher income were associated with underreporting diabetes. Underreporting has important implications for CVD risk factor surveillance, policy planning and decisions, and clinical best-practice guidelines. This analysis highlights concerns about the reach of primary prevention efforts in certain groups and implications for patients who may be unaware of their

Characterising the extent of misreporting of high blood pressure, high cholesterol, and diabetes using the Australian Health Survey

Directory of Open Access Journals (Sweden)

Karen Louise Peterson

2016-08-01

Full Text Available Abstract Background Measuring and monitoring the true prevalence of risk factors for chronic conditions is essential for evidence-based policy and health service planning. Understanding the prevalence of risk factors for cardiovascular disease (CVD in Australia relies heavily on self-report measures from surveys, such as the triennial National Health Survey. However, international evidence suggests that self-reported data may substantially underestimate actual risk factor prevalence. This study sought to characterise the extent of misreporting in a large, nationally-representative health survey that included objective measures of clinical risk factors for CVD. Methods This study employed a cross-sectional analysis of 7269 adults aged 18 years and over who provided fasting blood samples as part of the 2011–12 Australian Health Survey. Self-reported prevalence of high blood pressure, high cholesterol and diabetes was compared to measured prevalence, and univariate and multivariate logistic regression analyses identified socio-demographic characteristics associated with underreporting for each risk factor. Results Approximately 16 % of the total sample underreported high blood pressure (measured to be at high risk but didn’t report a diagnosis, 33 % underreported high cholesterol, and 1.3 % underreported diabetes. Among those measured to be at high risk, 68 % did not report a diagnosis for high blood pressure, nor did 89 % of people with high cholesterol and 29 % of people with high fasting plasma glucose. Younger age was associated with underreporting high blood pressure and high cholesterol, while lower area-level disadvantage and higher income were associated with underreporting diabetes. Conclusions Underreporting has important implications for CVD risk factor surveillance, policy planning and decisions, and clinical best-practice guidelines. This analysis highlights concerns about the reach of primary prevention efforts in certain

Trans-intestinal cholesterol efflux is not mediated through high density lipoprotein

NARCIS (Netherlands)

Vrins, Carlos L. J.; Ottenhoff, Roelof; van den Oever, Karin; de Waart, Dirk R.; Kruyt, J. Kar; Zhao, Ying; van Berkel, Theo J. C.; Havekes, Louis M.; Aerts, Johannes M.; van Eck, Miranda; Rensen, Patrick C. N.; Groen, Albert 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

Reduction of lipophilic extractives in mechanical pulps; Mekaanisen massan uuteainepitoisuuden alentaminen - EKT 07

Energy Technology Data Exchange (ETDEWEB)

Edelmann, K. [VTT Energy, Jyvaeskylae (Finland)

1998-12-31

Adsorption of lipophilic extractives released from wood to various filtrates and pressed fractions in the production of thermomechanical pulp on various inorganic substrates has been studied. Both commercial and experimental adsorbents were used. Equilibrium concentrations of lipophilic extractives were determined. Best adsorption results were achieved with talcum and cationized kaolin. Adsorption behaviour of Al2O3 granulate was varied with respect to surface charge and surface energy. In addition to adsorption, oxidation of lipophilic extractives through ozonation and cavitation was studied. In the oxidation studies also other compounds than lipophilic extractives should be followed in order to determine the chemical changes of the process water. The adsorption process is economically more feasible, if the concentration of lipophilic extractives were four to five times higher than the present value 50 mg/l. However more work has to be directed to the development of production methods of the adsorbent itself. Dynamics of the adsorption process should closely be studied. Combined adsorption and ozonation especially in the presence of an oxidation catalyst might be an interesting topic for further studies. (orig.)

Reduction of lipophilic extractives in mechanical pulps; Mekaanisen massan uuteainepitoisuuden alentaminen - EKT 07

Energy Technology Data Exchange (ETDEWEB)

Edelmann, K [VTT Energy, Jyvaeskylae (Finland)

1999-12-31

Adsorption of lipophilic extractives released from wood to various filtrates and pressed fractions in the production of thermomechanical pulp on various inorganic substrates has been studied. Both commercial and experimental adsorbents were used. Equilibrium concentrations of lipophilic extractives were determined. Best adsorption results were achieved with talcum and cationized kaolin. Adsorption behaviour of Al2O3 granulate was varied with respect to surface charge and surface energy. In addition to adsorption, oxidation of lipophilic extractives through ozonation and cavitation was studied. In the oxidation studies also other compounds than lipophilic extractives should be followed in order to determine the chemical changes of the process water. The adsorption process is economically more feasible, if the concentration of lipophilic extractives were four to five times higher than the present value 50 mg/l. However more work has to be directed to the development of production methods of the adsorbent itself. Dynamics of the adsorption process should closely be studied. Combined adsorption and ozonation especially in the presence of an oxidation catalyst might be an interesting topic for further studies. (orig.)

Agmatine ameliorates atherosclerosis progression and endothelial dysfunction in high cholesterol-fed rabbits.

Science.gov (United States)

El-Awady, Mohammed S; Suddek, Ghada M

2014-06-01

The aim of this work was to explore possible effects of agmatine, an endogenous inhibitor of inducible nitric oxide synthase (iNOS), against hypercholesterolemia-induced lipid profile changes and endothelial dysfunction. Hypercholesterolemia was induced by feeding rabbits with a high-cholesterol diet (HCD, 0.5%) for 8 weeks. Another HCD-fed group was orally administered agmatine (10 mg/kg/day) during weeks 5 through 8. Serum lipid profile, malondialdehyde (MDA), nitric oxide (NO) and lactate dehydrogenase (LDH) were determined. Aorta was isolated to analyse vascular reactivity, atherosclerotic lesions and intima/media (I/M) ratio. HCD induced a significant increase in serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides and high-density lipoprotein cholesterol (HDL-C). Agmatine administration significantly decreased HCD-induced elevations in serum TC and LDL-C, MDA, LDH and NO while significantly increased HDL-C levels. Additionally, agmatine significantly protected against HCD-induced attenuation of rabbit aortic endothelium-dependent relaxation to acetylcholine. HCD and agmatine did not significantly influence aortic endothelium-independent relaxation to sodium nitroprusside. Moreover, agmatine significantly reduced the elevation in aortic atherosclerotic lesion area and I/M ratio. This study is the first to reveal that agmatine has the ability to ameliorate hypercholesterolemia-induced lipemic-oxidative and endothelial function injuries possibly by its antioxidant potential and/or iNOS inhibition. © 2014 Royal Pharmaceutical Society.

HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events

NARCIS (Netherlands)

Barter, Philip; Gotto, Antonio M.; LaRosa, John C.; Maroni, Jaman; Szarek, Michael; Grundy, Scott M.; Kastelein, John J. P.; Bittner, Vera; Fruchart, Jean-Charles

2007-01-01

BACKGROUND: High-density lipoprotein (HDL) cholesterol levels are a strong inverse predictor of cardiovascular events. However, it is not clear whether this association is maintained at very low levels of low-density lipoprotein (LDL) cholesterol. METHODS: A post hoc analysis of the recently

[Cholesterol reducing food certainly is useful].

Science.gov (United States)

Stalenhoef, A F

1997-12-27

The effect of a low-cholesterol diet in open intervention studies depends in the long run on motivation, knowledge and dedication. The mean decrease of the serum cholesterol level is 10% (range: 0-20). Epidemiological and cohort studies clearly prove a connection between the intake of saturated fat, the serum cholesterol level and the risk of coronary heart disease and death. High-fat food slows down the clearance of the degradation products rich in cholesterol which appear in the blood after a meal and which are highly atherogenic (these products are not found at a fasting cholesterol assay). Cholesterol-reducing nutrition has additional useful effects, for instance on the blood pressure and the coagulation. The recommendations for healthy, low-cholesterol nutrition for the population as a whole apply particularly to patients with a high risk of coronary heart disease. Although advice given to individuals often has a disappointing effect, influencing the life pattern should be included in the strategy to reduce the risk of coronary heart disease.

Consequences of exchanging carbohydrates for proteins in the cholesterol metabolism of mice fed a high-fat diet.

Directory of Open Access Journals (Sweden)

Frédéric Raymond

Full Text Available Consumption of low-carbohydrate, high-protein, high-fat diets lead to rapid weight loss but the cardioprotective effects of these diets have been questioned. We examined the impact of high-protein and high-fat diets on cholesterol metabolism by comparing the plasma cholesterol and the expression of cholesterol biosynthesis genes in the liver of mice fed a high-fat (HF diet that has a high (H or a low (L protein-to-carbohydrate (P/C ratio. H-P/C-HF feeding, compared with L-P/C-HF feeding, decreased plasma total cholesterol and increased HDL cholesterol concentrations at 4-wk. Interestingly, the expression of genes involved in hepatic steroid biosynthesis responded to an increased dietary P/C ratio by first down-regulation (2-d followed by later up-regulation at 4-wk, and the temporal gene expression patterns were connected to the putative activity of SREBF1 and 2. In contrast, Cyp7a1, the gene responsible for the conversion of cholesterol to bile acids, was consistently up-regulated in the H-P/C-HF liver regardless of feeding duration. Over expression of Cyp7a1 after 2-d and 4-wk H-P/C-HF feeding was connected to two unique sets of transcription regulators. At both time points, up-regulation of the Cyp7a1 gene could be explained by enhanced activations and reduced suppressions of multiple transcription regulators. In conclusion, we demonstrated that the hypocholesterolemic effect of H-P/C-HF feeding coincided with orchestrated changes of gene expressions in lipid metabolic pathways in the liver of mice. Based on these results, we hypothesize that the cholesterol lowering effect of high-protein feeding is associated with enhanced bile acid production but clinical validation is warranted. (246 words.

Consequences of exchanging carbohydrates for proteins in the cholesterol metabolism of mice fed a high-fat diet.

Science.gov (United States)

Raymond, Frédéric; Wang, Long; Moser, Mireille; Metairon, Sylviane; Mansourian, Robert; Zwahlen, Marie-Camille; Kussmann, Martin; Fuerholz, Andreas; Macé, Katherine; Chou, Chieh Jason

2012-01-01

Consumption of low-carbohydrate, high-protein, high-fat diets lead to rapid weight loss but the cardioprotective effects of these diets have been questioned. We examined the impact of high-protein and high-fat diets on cholesterol metabolism by comparing the plasma cholesterol and the expression of cholesterol biosynthesis genes in the liver of mice fed a high-fat (HF) diet that has a high (H) or a low (L) protein-to-carbohydrate (P/C) ratio. H-P/C-HF feeding, compared with L-P/C-HF feeding, decreased plasma total cholesterol and increased HDL cholesterol concentrations at 4-wk. Interestingly, the expression of genes involved in hepatic steroid biosynthesis responded to an increased dietary P/C ratio by first down-regulation (2-d) followed by later up-regulation at 4-wk, and the temporal gene expression patterns were connected to the putative activity of SREBF1 and 2. In contrast, Cyp7a1, the gene responsible for the conversion of cholesterol to bile acids, was consistently up-regulated in the H-P/C-HF liver regardless of feeding duration. Over expression of Cyp7a1 after 2-d and 4-wk H-P/C-HF feeding was connected to two unique sets of transcription regulators. At both time points, up-regulation of the Cyp7a1 gene could be explained by enhanced activations and reduced suppressions of multiple transcription regulators. In conclusion, we demonstrated that the hypocholesterolemic effect of H-P/C-HF feeding coincided with orchestrated changes of gene expressions in lipid metabolic pathways in the liver of mice. Based on these results, we hypothesize that the cholesterol lowering effect of high-protein feeding is associated with enhanced bile acid production but clinical validation is warranted. (246 words).

Profiling of lipophilic and phenolic phytochemicals of four cultivars from cherimoya (Annona cherimola Mill.).

Science.gov (United States)

Santos, Sónia A O; Vilela, Carla; Camacho, João F; Cordeiro, Nereida; Gouveia, Manuela; Freire, Carmen S R; Silvestre, Armando J D

2016-11-15

The lipophilic and phenolic extractives of the ripe mesocarp of four cherimoya cultivars ('Perry Vidal', 'Mateus I', 'Mateus III' and 'Funchal') from Madeira Island, were studied for the first time. The predominant lipophilic compounds are kaurene diterpenes (42.2-59.6%), fatty acids (18.0-35.6%) and sterols (9.6-23.7%). Kaur-16-en-19-oic acid is the major lipophilic component of all cultivars accounting between 554 and 1350mgkg(-1) of dry material. The studied fruits also contain a high variety of flavan-3-ols, including galloylated and non-galloylated compounds. Five phenolic compounds were identified for the first time: catechin, (epi)catechin-(epi)gallocatechin, (epi)gallocatechin, (epi)afzelechin-(epi)catechin and procyanidin tetramer. 'Mateus I' and 'Mateus III' cultivars present the highest content of phenolic compounds (6299 and 9603mgkg(-1) of dry weight, respectively). These results support the use of this fruit as a rich source of health-promoting components, with the capacity to prevent or delay the progress of oxidative-stress related disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neuroprotective effects of phytosterol esters against high cholesterol-induced cognitive deficits in aged rat.

Science.gov (United States)

Rui, Xu; Wenfang, Li; Jing, Cheng; Meng, Chen; Chengcheng, Ding; Jiqu, Xu; Shuang, Rong

2017-03-22

Accumulating epidemiological and experimental studies have confirmed that a high-cholesterol diet is detrimental to cognitive performance in animal models. Phytosterols, a class of naturally occurring structural components in plant foods, have been demonstrated to possess cholesterol-lowering and antioxidant effects. Phytosterol esters (PSE) are esters of phytosterol. The aim of this study was to evaluate the neuroprotective effects of PSE on cognitive deficit induced by a cholesterol-enriched diet in aged rats, and to explore their underlying mechanisms for these effects. Based on their Morris water maze performance, the latencies differed by <1.5 standard deviations (SDs) on days 3-5 of testing, 60 rats were chosen from 12-month-old female Sprague Dawley aged rats and were randomized into three groups, which were fed either a control diet, a high cholesterol diet (HCD) or a high-cholesterol diet supplemented with 2% PSE (HCD + PSE) for 6 months. In our study, we found that PSE treatment maintained the body weight balance, reduced the serum lipid levels, and improved the cognitive performance of aged rats in the Morris water maze test, as evaluated by shortened escape latencies. Importantly, histological and immunohistochemical results in the brain showed that PSE supplementation may have a neuroprotective effect that alleviates neuroinflammation in aged rats. This neuroprotective effect significantly inhibited degeneration, resulting in a significant increase in the number of pyramidal cells and an apparent decrease in the number of astrocytes compared to rats that were fed only a HCD. Furthermore, PSE improved cholinergic activities by restoring the acetylcholine (ACh) content and decreasing acetylcholinesterase (AChE) activity in the cerebral cortex, as well as by elevating choline acetyl transferase (ChAT) activity in the hippocampus and the cerebral cortex. These results suggest that PSE can play a useful role in alleviating cognitive deficit induced by a

Effects of Persian leek (Allium ampeloprasum) on hepatic lipids and the expression of proinflammatory gene in hamsters fed a high-fat/ high-cholesterol diet.

Science.gov (United States)

Fatoorechi, Vahideh; Rismanchi, Marjan; Nasrollahzadeh, Javad

2016-01-01

Persian leek is one of the most widely used herbal foods among Iranians. In this study, effects of oral administration of Persian leek on plasma and liver lipids were examined in hamster. Male Syrian hamsters were randomly divided into three groups: control (standard diet), high fat control (high-fat/high-cholesterol diet), Persian leek (high-fat/high-cholesterol diet + 1% per weight of diet from dried powdered Persian leek) for 14 weeks. High fat diet increased plasma and liver lipids as compared to standard diet. Adding Persian leek to the high-fat/high-cholesterol diet resulted in no significant changes in the concentration of the plasma lipids or liver cholesterol. However, liver triglycerides (TG), plasma Alanine aminotransferase and gene expression of tumor necrosis factor- α were decreased in hamsters fed high-fat diet containing Persian leek as compared to high-fat diet only. Persian leek might be considered as a herbal food that can reduce liver TG accumulation induced by high fat diets.

Estimating the burden of disease attributable to high cholesterol in ...

African Journals Online (AJOL)

Objectives. To estimate the burden of disease attributable to high cholesterol in adults aged 30 years and older in South Africa in 2000. Design. World Health Organization comparative risk assessment (CRA) methodology was followed. Small community studies were used to derive the prevalence by population group.

Cholesterol Medicines: MedlinePlus Health Topic

Science.gov (United States)

... heart diseases . There are two main types of cholesterol. LDL is the "bad" cholesterol. A high LDL level leads to a buildup of cholesterol in ... 75 years old, you have diabetes, and your LDL cholesterol level is 70 mg/dL or higher You ...

The Efficiency of Irradiated Garlic Powder in Mitigation of Hypercholesterolemic Risk Factor in High cholesterol Fed Rats

International Nuclear Information System (INIS)

El-Neily, H.F.G.; El-Shennawy, H.M.

2011-01-01

The present study was conducted to explore the efficiency of radiation processed dried garlic powder at 10, 15 and 20 kGy on the average daily body gain, internal organ weights, certain hematological and biochemical parameters; including total plasma protein, albumin, globulin, total cholesterol, low and high density lipoprotein cholesterol (LDL-C and HDL-C), triglyceride levels, and aspartate aminotransferase (AST), alanine aminotransferase (ALT) activities in rats fed with a high-cholesterol diet. Experimental rats were fed a high cholesterol diet (10 g kg -1 ) with and without raw or radiation processed dried garlic powder at the above-mentioned doses for 6 weeks. Control rats were fed a casein diet (C). 20 g kg -1 dietary raw or irradiated dried garlic powder was used to supplemented cholesterol diet (Ch). It was observed that cholesterol-fed (Ch) animals had a significant increase in relative liver weight, plasma total cholesterol, LDL-C, triglyceride levels, LDL/HDL ratio, AST and ALT activities and a significant decrease in HDL-C level compared to the control group of rats fed on a Casein diet (C). However, when the rats were fed with a high cholesterol diet mixed with 20 g kg -1 raw (ChRG) or irradiated dried garlic powder at 10 (ChG10), 15 (ChG15), and 20 kGy (ChG20), there was a significant reduction in their relative liver weight, hemoglobin, haematocrit, plasma total cholesterol, LDL-C, triglyceride levels, LDL/HDL ratio, and increased HDL level and amended AST and ALT activities levels as compared with the group which was on a diet containing high cholesterol without garlic powder (Ch). No significant changes were observed in relative spleen, kidney, lung, heart and testes weights, as well as, the total plasma protein, albumin, globulin concentrations in all of treated groups. These results show that the dietary 20 g kg -1 irradiated dried garlic powder at 10, 15 and 20 kGy are beneficial in reducing plasma cholesterol, triglycerides, LDL-C levels, El

Corn silk extract improves cholesterol metabolism in C57BL/6J mouse fed high-fat diets.

Science.gov (United States)

Cha, Jae Hoon; Kim, Sun Rim; Kang, Hyun Joong; Kim, Myung Hwan; Ha, Ae Wha; Kim, Woo Kyoung

2016-10-01

Corn silk (CS) extract contains large amounts of maysin, which is a major flavonoid in CS. However, studies regarding the effect of CS extract on cholesterol metabolism is limited. Therefore, the purpose of this study was to determine the effect of CS extract on cholesterol metabolism in C57BL/6J mouse fed high-fat diets. Normal-fat group fed 7% fat diet, high-fat (HF) group fed 25% fat diet, and high-fat with corn silk (HFCS) group were orally administered CS extract (100 mg/kg body weight) daily. Serum and hepatic levels of total lipids, triglycerides, and total cholesterol as well as serum free fatty acid, glucose, and insulin levels were determined. The mRNA expression levels of acyl-CoA: cholesterol acyltransferase (ACAT), cholesterol 7-alpha hydroxylase (CYP7A1), farnesoid X receptor (FXR), lecithin cholesterol acyltransferase (LCAT), low-density lipoprotein receptor, 3-hyroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), adiponectin, leptin, and tumor necrosis factor α were determined. Oral administration of CS extract with HF improved serum glucose and insulin levels as well as attenuated HF-induced fatty liver. CS extracts significantly elevated mRNA expression levels of adipocytokines and reduced mRNA expression levels of HMG-CoA reductase, ACAT, and FXR. The mRNA expression levels of CYP7A1 and LCAT between the HF group and HFCS group were not statistically different. CS extract supplementation with a high-fat diet improves levels of adipocytokine secretion and glucose homeostasis. CS extract is also effective in decreasing the regulatory pool of hepatic cholesterol, in line with decreased blood and hepatic levels of cholesterol though modulation of mRNA expression levels of HMG-CoA reductase, ACAT, and FXR.

Direct-to-consumer television advertising exposure, diagnosis with high cholesterol, and statin use.

Science.gov (United States)

Niederdeppe, Jeff; Byrne, Sahara; Avery, Rosemary J; Cantor, Jonathan

2013-07-01

While statin drugs are recommended for secondary prevention of coronary heart disease (CHD), there is no medical consensus on whether or not a statin should be added to lifestyle change efforts for primary prevention of CHD. Previous research suggests that exposure to direct-to-consumer advertising (DTCA) increases drug demand among those at comparatively low risk. Research has yet to examine whether individual-level DTCA exposure may influence statin use among men and women at high, moderate, or low risk for future cardiac events. To determine the relationship between estimated exposure to DTCA for statin drugs and two clinical variables: diagnosis with high cholesterol and statin use. We used logistic regression to analyze repeated cross-sectional surveys of the United States population, merged with data on the frequency of DTCA appearances on national, cable, and local television, between 2001 and 2007. American adults (n=106,685) aged 18 and older. Levels of exposure to statin DTCA, based on ad appearances and TV viewing patterns; self-reports of whether or not a respondent has been diagnosed with high cholesterol, and whether or not a respondent took a statin in the past year. Adjusting for potential confounders, we estimate that exposure to statin ads increased the odds of being diagnosed with high cholesterol by 16 to 20 %, and increased statin use by 16 to 22 %, among both men and women (p<0.05). These associations were driven almost exclusively by men and women at low risk for future cardiac events. There was also evidence of a negative association between DTCA exposure and statin use among high-risk women (p<0.05) CONCLUSIONS: This study provides new evidence that DTCA may promote over-diagnosis of high cholesterol and over-treatment for populations where risks of statin use may outweigh potential benefits.

Hypolipidemic Effect of Tomato Juice in Hamsters in High Cholesterol Diet-Induced Hyperlipidemia.

Science.gov (United States)

Lee, Li-Chen; Wei, Li; Huang, Wen-Ching; Hsu, Yi-Ju; Chen, Yi-Ming; Huang, Chi-Chang

2015-12-17

Tomato is a globally famous food and contains several phytonutrients including lycopene, β-carotene, anthocyanin, and flavonoids. The increased temperature used to produce tomato juice, ketchup, tomato paste and canned tomato enhances the bioactive composition. We aimed to verify the beneficial effects of processed tomato juice from Kagome Ltd. (KOT) on hypolipidemic action in hamsters with hyperlipidemia induced by a 0.2% cholesterol and 10% lard diet (i.e., high-cholesterol diet (HCD)). Male Golden Syrian hamsters were randomly divided into two groups for treatment: normal (n = 8), standard diet (control); and experimental (n = 32), HCD. The 32 hamsters were further divided into four groups (n = 8 per group) to receive vehicle or KOT by oral gavage at 2787, 5573, or 13,934 mg/kg/day for six weeks, designated the HCD-1X, -2X and -5X groups, respectively. The efficacy and safety of KOT supplementation was evaluated by lipid profiles of serum, liver and feces and by clinical biochemistry and histopathology. HCD significantly increased serum levels of total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), LDL-C/HDL-C ratio, hepatic and fetal TC and TG levels, and degree of fatty liver as compared with controls. KOT supplementation dose-dependently decreased serum TC, TG, LDL-C levels, LDL-C/HDL-C ratio, hepatic TC and TG levels, and fecal TG level. Our study provides experiment-based evidence to support that KOT may be useful in treating or preventing the onset of hyperlipidemia.

Hypolipidemic Effect of Tomato Juice in Hamsters in High Cholesterol Diet-Induced Hyperlipidemia

Directory of Open Access Journals (Sweden)

Li-Chen Lee

2015-12-01

Full Text Available Tomato is a globally famous food and contains several phytonutrients including lycopene, β-carotene, anthocyanin, and flavonoids. The increased temperature used to produce tomato juice, ketchup, tomato paste and canned tomato enhances the bioactive composition. We aimed to verify the beneficial effects of processed tomato juice from Kagome Ltd. (KOT on hypolipidemic action in hamsters with hyperlipidemia induced by a 0.2% cholesterol and 10% lard diet (i.e., high-cholesterol diet (HCD. Male Golden Syrian hamsters were randomly divided into two groups for treatment: normal (n = 8, standard diet (control; and experimental (n = 32, HCD. The 32 hamsters were further divided into four groups (n = 8 per group to receive vehicle or KOT by oral gavage at 2787, 5573, or 13,934 mg/kg/day for six weeks, designated the HCD-1X, -2X and -5X groups, respectively. The efficacy and safety of KOT supplementation was evaluated by lipid profiles of serum, liver and feces and by clinical biochemistry and histopathology. HCD significantly increased serum levels of total cholesterol (TC, triacylglycerol (TG, high-density lipoprotein cholesterol (HDL-C, and low-density lipoprotein cholesterol (LDL-C, LDL-C/HDL-C ratio, hepatic and fetal TC and TG levels, and degree of fatty liver as compared with controls. KOT supplementation dose-dependently decreased serum TC, TG, LDL-C levels, LDL-C/HDL-C ratio, hepatic TC and TG levels, and fecal TG level. Our study provides experiment-based evidence to support that KOT may be useful in treating or preventing the onset of hyperlipidemia.

Impact of high cholesterol and endoplasmic reticulum stress on metabolic diseases: An updated mini-review

Directory of Open Access Journals (Sweden)

Erdi Sozen

2017-08-01

Full Text Available Endoplasmic reticulum (ER is the major site of protein folding and calcium storage. Beside the role of ER in protein homeostasis, it controls the cholesterol production and lipid-membrane biosynthesis as well as surviving and cell death signaling mechanisms in the cell. It is well-documented that elevated plasma cholesterol induces adverse effects in cardiovascular diseases (CVDs, liver disorders, such as non-alcoholic fatty liver disease (NAFLD, non-alcoholic steatosis hepatitis (NASH, and metabolic diseases which are associated with oxidative and ER stress. Recent animal model and human studies have showed high cholesterol and ER stress as an emerging factors involved in the development of many metabolic diseases. In this review, we will summarize the crucial effects of hypercholesterolemia and ER stress response in the pathogenesis of CVDs, NAFLD/NASH, diabetes and obesity which are major health problems in western countries. Keywords: Endoplasmic reticulum stress, High cholesterol, Cardiovascular diseases, Non-alcoholic fatty liver disease, Non-alcoholic steatosis hepatitis

Cholesterol and related sterols autoxidation.

Science.gov (United States)

Zerbinati, Chiara; Iuliano, Luigi

2017-10-01

Cholesterol is a unique lipid molecule providing the building block for membranes, hormones, vitamin D and bile acid synthesis. Metabolism of cholesterol involves several enzymes acting on the sterol nucleus or the isooctyl tail. In the recent years, research interest has been focused on oxysterols, cholesterol derivatives generated by the addition of oxygen to the cholesterol backbone. Oxysterols can be produced enzymatically or by autoxidation. Autoxidation of cholesterol proceeds through type I or type II mechanisms. Type I autoxidation is initiated by free radical species, such as those arising from the superoxide/hydrogen peroxide/hydroxyl radical system. Type II autoxidation occurs stoichiometrically by non-radical highly reactive oxygen species such as singlet oxygen, HOCl, and ozone. The vulnerability of cholesterol towards high reactive species has raised considerable interest for mechanistic studies and for the potential biological activity of oxysterols, as well as for the use of oxysterols as biomarkers for the non-invasive study of oxidative stress in vivo. Copyright © 2017. Published by Elsevier Inc.

Lipophilic manganese porphyrin crosses blood-brain barrier

International Nuclear Information System (INIS)

Nelson, J.A.; Cegnar, J.; Spence, A.M.; Richards, T.L.; Golden, R.N.; Muzi, M.

1987-01-01

Most reports on manganese porphyrins as MR imaging contrast agents have focused on a water-soluble compound, Mn-TPPS4. Phototherapy researchers have noted that lipophilic components of hematoporphyrin derivative sensitize normal brain tissue to light-stimulated photodestruction. This observation suggests that a lipophilic paramagnetic agent might be useful for brain contrast enhancement. The current experiments were designed to test the MR imaging effects of a lipid-soluble compound, Mn-mesoporphyrin. An intravenous injection of 0.05 μmoles/kg was administered to rats with a well-characterized astrocytic glioma implanted into the right cerebral hemisphere. MR imaging experiments performed at 2 T on a General Electric CSI-II system revealed T1 relaxation shortening in both normal brain and tumor. Delayed images at 24 hours revealed persistent selective contrast agent enhancement at the gross tumor site

Reduced and high molecular weight barley beta-glucans decrease plasma total and non-HDL-cholesterol in hypercholesterolemic Syrian golden hamsters.

Science.gov (United States)

Wilson, Thomas A; Nicolosi, Robert J; Delaney, Bryan; Chadwell, Kim; Moolchandani, Vikas; Kotyla, Timothy; Ponduru, Sridevi; Zheng, Guo-Hua; Hess, Richard; Knutson, Nathan; Curry, Leslie; Kolberg, Lore; Goulson, Melanie; Ostergren, Karen

2004-10-01

Consumption of concentrated barley beta-glucan lowers plasma cholesterol because of its soluble dietary fiber nature. The role of molecular weight (MW) in lowering serum cholesterol is not well established. Prior studies showed that enzymatic degradation of beta-glucan eliminates the cholesterol-lowering activity; however, these studies did not evaluate the MW of the beta-glucan. The current study was conducted to evaluate whether barley beta-glucan concentrates, partially hydrolyzed to reduce MW, possess cholesterol-lowering and antiatherogenic activities. The reduced MW fraction was compared with a high MW beta-glucan concentrate from the same barley flour. Concentrated beta-glucan preparations were evaluated in Syrian Golden F(1)B hamsters fed a hypercholesterolemic diet (HCD) with cholesterol, hydrogenated coconut oil, and cellulose. After 2 wk, hamsters were fed HCD or diets that contained high or reduced MW beta-glucan at a concentration of 8 g/100 g at the expense of cellulose. Decreases in plasma total cholesterol (TC) and non-HDL-cholesterol (non-HDL-C) concentrations occurred in the hamsters fed reduced MW and high MW beta-glucan diets. Plasma HDL-C concentrations did not differ. HCD-fed hamsters had higher plasma triglyceride concentrations. Liver TC, free cholesterol, and cholesterol ester concentrations did not differ. Aortic cholesterol ester concentrations were lower in the reduced MW beta-glucan-fed hamsters. Consumption of either high or reduced MW beta-glucan increased concentrations of fecal total neutral sterols and coprostanol, a cholesterol derivative. Fecal excretion of cholesterol was greater than in HCD-fed hamsters only in those fed the reduced MW beta-glucan. Study results demonstrate that the cholesterol-lowering activity of barley beta-glucan may occur at both lower and higher MW.

Genetically elevated apolipoprotein A-I, high-density lipoprotein cholesterol levels, and risk of ischemic heart disease

DEFF Research Database (Denmark)

Lundegaard, Christiane; Tybjærg-Hansen, Anne; Grande, Peer

2010-01-01

Epidemiologically, levels of high-density lipoprotein (HDL) cholesterol and its major protein constituent, apolipoprotein A-I (apoA-I), are inversely related to risk of ischemic heart disease (IHD).......Epidemiologically, levels of high-density lipoprotein (HDL) cholesterol and its major protein constituent, apolipoprotein A-I (apoA-I), are inversely related to risk of ischemic heart disease (IHD)....

Lipophilicity of basic drugs measured by hydrophilic interaction chromatography.

Science.gov (United States)

Bard, Bruno; Carrupt, Pierre-Alain; Martel, Sophie

2009-05-28

RPLC gains acceptance in pharmaceutical research for the rapid determination of lipophilicity but remains limited for the determination of partition coefficients of moderate to strong basic compounds under their neutral form because stationary phases are not compatible with high pH conditions. In this work, HILIC technique was used to accurately measure log P(oct) of the neutral form of basic drugs by measuring the difference between 2 isocratic log k values (Delta log k(0-95)) of their cationic form.

Design and optimization of self-nanoemulsifying formulations for lipophilic drugs

International Nuclear Information System (INIS)

Zhao, Tianjing; Maniglio, Devid; Motta, Antonella; Migliaresi, Claudio; Chen, Jie; Chen, Bin

2015-01-01

The purpose of the current study was to develop and optimize novel self-nanoemulsifying drug delivery systems (SNEDDS) with a high proportion of essential oil as carriers for lipophilic drugs. Solubility and droplet size as a function of the composition were investigated, and a ternary phase diagram was constructed in order to identify the self-emulsification regions. The optimized SNEDDS formulation consisted of lemon essential oil (oil), Cremophor RH40 (surfactant) and Transcutol HP (co-surfactant) in the ratio 50:30:20 (v/v). Ibuprofen was chosen as the model drug. The droplet size, ζ-potential and stability of the drug-loaded optimized formulations were determined. The stability of SNEDDS was proved after triple freezing/thawing cycles and storage at 4 °C and 25 °C for 3 months. In vitro drug release studies of optimized SNEDDS revealed a significant increase of the drug release and release rate in comparison to the Ibuprofen suspension (80% versus approximately 40% in 2 h). The results indicated that these SNEDDS formulations could be used to improve the bioavailability of lipophilic drugs. (paper)

Polygenic determinants in extremes of high-density lipoprotein cholesterol[S

Science.gov (United States)

Dron, Jacqueline S.; Wang, Jian; Low-Kam, Cécile; Khetarpal, Sumeet A.; Robinson, John F.; McIntyre, Adam D.; Ban, Matthew R.; Cao, Henian; Rhainds, David; Dubé, Marie-Pierre; Rader, Daniel J.; Lettre, Guillaume; Tardif, Jean-Claude

2017-01-01

HDL cholesterol (HDL-C) remains a superior biochemical predictor of CVD risk, but its genetic basis is incompletely defined. In patients with extreme HDL-C concentrations, we concurrently evaluated the contributions of multiple large- and small-effect genetic variants. In a discovery cohort of 255 unrelated lipid clinic patients with extreme HDL-C levels, we used a targeted next-generation sequencing panel to evaluate rare variants in known HDL metabolism genes, simultaneously with common variants bundled into a polygenic trait score. Two additional cohorts were used for validation and included 1,746 individuals from the Montréal Heart Institute Biobank and 1,048 individuals from the University of Pennsylvania. Findings were consistent between cohorts: we found rare heterozygous large-effect variants in 18.7% and 10.9% of low- and high-HDL-C patients, respectively. We also found common variant accumulation, indicated by extreme polygenic trait scores, in an additional 12.8% and 19.3% of overall cases of low- and high-HDL-C extremes, respectively. Thus, the genetic basis of extreme HDL-C concentrations encountered clinically is frequently polygenic, with contributions from both rare large-effect and common small-effect variants. Multiple types of genetic variants should be considered as contributing factors in patients with extreme dyslipidemia. PMID:28870971

Effect of apolipoprotein E-free high density lipoproteins on cholesterol metabolism in cultured pig hepatocytes

International Nuclear Information System (INIS)

Bachorik, P.S.; Virgil, D.G.; Kwiterovich, P.O. Jr.

1987-01-01

We studied cholesterol synthesis from [ 14 C]acetate, cholesterol esterification from [ 14 C]oleate, and cellular cholesterol and cholesteryl ester levels after incubating cells with apoE-free high density lipoproteins (HDL) or low density lipoproteins (LDL). LDL suppressed synthesis by up to 60%, stimulated esterification by up to 280%, and increased cell cholesteryl ester content about 4-fold. Esterification increased within 2 h, but synthesis was not suppressed until after 6 h. ApoE-free HDL suppressed esterification by about 50% within 2 h. Cholesterol synthesis was changed very little within 6 h, unless esterification was maximally suppressed; synthesis was then stimulated about 4-fold. HDL lowered cellular unesterified cholesterol by 13-20% within 2 h and promoted the removal of newly synthesized cholesterol and cholesteryl esters. These changes were transient; by 24 h, both esterification and cellular unesterified cholesterol returned to control levels, and cholesteryl esters increased 2-3-fold. HDL core lipid was taken up selectively from 125 I-labeled [ 3 H]cholesteryl ester- and ether-labeled HDL. LDL core lipid uptake was proportional to LDL apoprotein uptake. The findings suggest that 1) the cells respond initially to HDL or LDL with changes in esterification, and 2) HDL mediates both the removal of free cholesterol from the cell and the delivery of HDL cholesteryl esters to the cell

Silicon Alleviates Nonalcoholic Steatohepatitis by Reducing Apoptosis in Aged Wistar Rats Fed a High-Saturated Fat, High-Cholesterol Diet.

Science.gov (United States)

Garcimartín, Alba; López-Oliva, M Elvira; Sántos-López, Jorge A; García-Fernández, Rosa A; Macho-González, Adrián; Bastida, Sara; Benedí, Juana; Sánchez-Muniz, Francisco J

2017-06-01

Background: Lipoapoptosis has been identified as a key event in the progression of nonalcoholic fatty liver disease (NAFLD), and hence, antiapoptotic agents have been recommended as a possible effective treatment for nonalcoholic steatohepatitis (NASH). Silicon, included in meat as a functional ingredient, improves lipoprotein profiles and liver antioxidant defenses in aged rats fed a high-saturated fat, high-cholesterol diet (HSHCD). However, to our knowledge, the antiapoptotic effect of this potential functional meat on the liver has never been tested. Objective: This study was designed to evaluate the effect of silicon on NASH development and the potential antiapoptotic properties of silicon in aged rats. Methods: One-year-old male Wistar rats weighing ∼500 g were fed 3 experimental diets containing restructured pork (RP) for 8 wk: 1 ) a high-saturated fat diet, as an NAFLD control, with 16.9% total fat, 0.14 g cholesterol/kg diet, and 46.8 mg SiO 2 /kg (control); 2 ) the HSHCD as a model of NASH, with 16.6% total fat, 16.3 g cholesterol/kg diet, and 46.8 mg SiO 2 /kg [high-cholesterol diet (Chol-C)]; and 3 ) the HSHCD with silicon-supplemented RP with amounts of fat and cholesterol identical to those in the Chol-C diet, but with 750 mg SiO 2 /kg (Chol-Si). Detailed histopathological assessments were performed, and the NAFLD activity score (NAS) was calculated. Liver apoptosis and damage markers were evaluated by Western blotting and immunohistochemical staining. Results: Chol-C rats had a higher mean NAS (7.4) than did control rats (1.9; P silicon substantially affects NASH development in aged male Wistar rats fed an HSHCD by partially blocking apoptosis. These results suggest that silicon-enriched RP could be used as an effective nutritional strategy in preventing NASH. © 2017 American Society for Nutrition.

High serum total cholesterol is a long-term cause of osteoporotic fracture.

Science.gov (United States)

Trimpou, P; Odén, A; Simonsson, T; Wilhelmsen, L; Landin-Wilhelmsen, K

2011-05-01

Risk factors for osteoporotic fractures were evaluated in 1,396 men and women for a period of 20 years. Serum total cholesterol was found to be an independent osteoporotic fracture risk factor whose predictive power improves with time. The purpose of this study was to evaluate long-term risk factors for osteoporotic fracture. A population random sample of men and women aged 25-64 years (the Gothenburg WHO MONICA project, N = 1,396, 53% women) was studied prospectively. The 1985 baseline examination recorded physical activity at work and during leisure time, psychological stress, smoking habits, coffee consumption, BMI, waist/hip ratio, blood pressure, total, HDL and LDL cholesterol, triglycerides, and fibrinogen. Osteoporotic fractures over a period of 20 years were retrieved from the Gothenburg hospital registers. Poisson regression was used to analyze the predictive power for osteoporotic fracture of each risk factor. A total number of 258 osteoporotic fractures occurred in 143 participants (10.2%). As expected, we found that previous fracture, smoking, coffee consumption, and lower BMI each increase the risk for osteoporotic fracture independently of age and sex. More unexpectedly, we found that the gradient of risk of serum total cholesterol to predict osteoporotic fracture significantly increases over time (p = 0.0377). Serum total cholesterol is an independent osteoporotic fracture risk factor whose predictive power improves with time. High serum total cholesterol is a long-term cause of osteoporotic fracture.

Early incorporation of cell-derived cholesterol into pre-beta-migrating high-density lipoprotein

International Nuclear Information System (INIS)

Castro, G.R.; Fielding, C.J.

1988-01-01

Cultures of human skin fibroblasts were labeled to high cholesterol specific activity with [ 3 H]cholesterol and incubated briefly (1-3 min) with normal human plasma. The plasma was fractionated by two-dimensional agarose-polyacrylamide gel electrophoresis and the early appearance of cholesterol label among plasma lipoproteins determined. A major part of the label at 1-min incubation was in a pre-beta-migrating apo A-I lipoprotein fraction with a molecular weight of ca. 70,000. Label was enriched about 30-fold in this fraction relative to its content of apo A-I (1-2% of total apo A-I). The proportion of label in this lipoprotein was strongly correlated with its concentration in plasma. Further incubation (2 min) in the presence of unlabeled cells demonstrated transfer of label from this fraction to a higher molecular weight pre-beta apo A-I species, to low-density lipoprotein, and to the alpha-migrating apo A-I that made up the bulk (96%) of total apo A-I in plasma. The data suggest that a significant part of cell-derived cholesterol is transferred specifically to a pre-beta-migrating lipoprotein A-I species as part of a cholesterol transport transfer sequence in plasma

Estimating the burden of disease attributable to high cholesterol in

African Journals Online (AJOL)

High cholesterol is an important cardiovascular risk factor in all population groups in South Africa. S Afr Mea12007; 97: 708—715. The value of abnormal blood lipids and apo—lipoprotein levels to predict ischaemic heart disease (IHD) has been studied for decades, with the initial focus shifting from studying the relationship ...

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

to HDL-cholesterol functionality

Directory of Open Access Journals (Sweden)

Malara Marzena

2016-05-01

Full Text Available The purpose of this study was to analyse the scientific evidence concerning the effects of two enzymes – paraoxonase 1 and myeloperoxidase – on the functions of HDL-cholesterol. It is well documented that disturbed circulating lipoproteins (a high total and high LDL-cholesterol, and low HDL-cholesterol bring about atherosclerosis and an increased risk of cardiovascular disease (CVD which is recognised as the main cause of death all around the world. In consequence, numerous studies have focused on procedures which will improve the plasma lipoproteins profile by decreasing the total cholesterol and the LDL-cholesterol (LDL-C and increasing the HDL-cholesterol (HDL-C. However, the anti-atherogenic role of HDL-C has been challenged in studies showing that genetically elevated HDL-cholesterol does not offer protection against CVD. Moreover, it has been found that raising the circulating HDL-cholesterol fails to reduce atherosclerosis. The doubts concerning the protective role of HDL-C have been supported by in vitro studies which indicate that the HDL-C from patients with atherosclerosis does not have a protective action, but does stimulate inflammation and free radical synthesis. The above data suggests that HDL-C, commonly recognised as protective against atherosclerosis, in some circumstances becomes pro-atherogenic, and is thus dysfunctional. Our review focuses on two enzymes – paraoxonase 1 (PON1 and myeloperoxidase (MPO – which markedly affect the properties of HDL-C and contribute to its anti – or pro-atherogenic activity. Moreover, the effects of the diet and physical activity on PON1 and MPO are summarised with respect to the HDL-C functionality.

Efficacy of functional foods mixture in improving hypercholesterolemia, inflammatory and endothelial dysfunction biomarkers-induced by high cholesterol diet.

Science.gov (United States)

Al-Muzafar, Hessah Mohammed; Amin, Kamal Adel

2017-10-06

Hypercholesterolemia associated with cardiovascular diseases is a global health issue that could be alleviated by functional foods. This study aimed to explore the effects of a high-cholesterol diet on lipid profile, cardiac, inflammatory, and endothelial dysfunction biomarkers, and the possible improvement by functional foods mixture. Male albino rats weighing 100-150 g were randomly divided into four equal groups: 1st control, giving a normal diet; the 2nd received high-cholesterol diet for 8 weeks, the 3rd received the high-cholesterol diet + functional foods mixture, and the 4th administered high-cholesterol diet +atorvastatin (20 mg) orally. The results showed a significant increase in lipid profile and cardiac biomarkers levels (lactate dehydrogenase, creatine kinase and homocystein), also inflammatory markers, as, tumor necrotic factor alpha and chronic reactive proteins were elevated, moreover, vascular adhesion molecule-1 and nitric oxide synthase were disturbed in high-cholesterol diet compared with normal group. While administration of atorvastatin and functional foods mixture ameliorated these alterations. Administration of functional foods mixture and atorvastatin were effective in treating hypercholesterolemia, reduce the risk of inflammation and cardiovascular biomarkers with a high safety margin. These efficiencies may be due to its active ingredient that improve the imbalance in the measured biomarkers.

High ratio of triglycerides to hdl-cholesterol predicts extensive coronary disease

Directory of Open Access Journals (Sweden)

Protasio Lemos da Luz

2008-01-01

Full Text Available An abnormal ratio of triglycerides to HDL-cholesterol (TG/HDL-c indicates an atherogenic lipid profile and a risk for the development of coronary disease. OBJECTIVE: To investigate the association between lipid levels, specifically TG/HDL-c, and the extent of coronary disease. METHODS: High-risk patients (n = 374 submitted for coronary angiography had their lipid variables measured and coronary disease extent scored by the Friesinger index. RESULTS: The subjects consisted of 220 males and 154 females, age 57.2 ± 11.1 years, with total cholesterol of 210± 50.3 mg/dL, triglycerides of 173.8 ± 169.8 mg/dL, HDL-cholesterol (HDL-c of 40.1 ± 12.8 mg/dL, LDL-cholesterol (LDL-c of 137.3 ± 46.2 mg/dL, TG/HDL-c of 5.1 ± 5.3, and a Friesinger index of 6.6 ± 4.7. The relationship between the extent of coronary disease (dichotomized by a Friesenger index of 5 and lipid levels (normal vs. abnormal was statistically significant for the following: triglycerides, odds ratio of 2.02 (1.31-3.1; p = 0.0018; HDL-c, odds ratio of 2.21 (1.42-3.43; p = 0.0005; and TG/HDL-c, odds ratio of 2.01(1.30-3.09; p = 0.0018. However, the relationship was not significant between extent of coronary disease and total cholesterol [1.25 (0.82-1.91; p = 0.33] or LDL-c [1.47 (0.96-2.25; p = 0.0842]. The chi-square for linear trends for Friesinger > 4 and lipid quartiles was statistically significant for triglycerides (p = 0.0017, HDL-c (p = 0.0001, and TG/HDL-c (p = 0.0018, but not for total cholesterol (p = 0.393 or LDL-c (p = 0.0568. The multivariate analysis by logistic regression OR gave 1.3 ± 0.79 (p = .0001 for TG/HDL-c, 0.779 ± 0.074 (p = .0001 for HDL-c, and 1.234 ± 0.097 (p = 0.03 for LDL. Analysis of receiver operating characteristic curves showed that only TG/HDL-c and HDL-c were useful for detecting extensive coronary disease, with the former more strongly associated with disease. CONCLUSIONS: Although some lipid variables were associated with the extent of

Are lipophilic beta-blockers preferable for peri-operative ...

African Journals Online (AJOL)

Adele

management of hypertension and post myocardial infarction.4-6. Are lipophilic ... studies in hypertensive medical patients showed no difference in cardiovascular ... atenolol and bendroflumethiazide arm.7 In meta-analyses of beta-blocker ...

Gemfibrozil treatment of the high triglyceride-low high-density lipoprotein cholesterol trait in men with established atherosclerosis

NARCIS (Netherlands)

Knipscheer, H. C.; Nurmohamed, M. T.; van den Ende, A.; Plaat, B.; Pruijs, H. J.; Mulder, W. J.; Kastelein, J. J.

1994-01-01

To study the short-term efficacy, tolerability and safety of the treatment with gemfibrozil 600 mg twice daily or placebo in male patients with established atherosclerosis, with a lipid profile matching the 'high triglyceride-low high-density lipoprotein (HDL) cholesterol trait'. Double-blind

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

Science.gov (United States)

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

1984-01-17

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

Niacin to Boost Your HDL "Good" Cholesterol

Science.gov (United States)

Niacin can boost 'good' cholesterol Niacin is a B vitamin that may raise your HDL ("good") cholesterol. But side effects might outweigh benefits for most ... been used to increase high-density lipoprotein (HDL) cholesterol — the "good" cholesterol that helps remove low-density ...

Comparison of different statin therapy to change low-density lipoprotein cholesterol and high-density lipoprotein cholesterol level in Korean patients with and without diabetes.

Science.gov (United States)

Khang, Ah Reum; Song, Young Shin; Kim, Kyoung Min; Moon, Jae Hoon; Lim, Soo; Park, Kyong Soo; Jang, Hak Chul; Choi, Sung Hee

2016-01-01

It is difficult to apply the proper intensity of statin for new treatment guidelines in clinical settings because of few data about the statin efficacy in Asians. We conducted a retrospective, observational study to estimate the percentage changes in lipid parameters and glucose induced by different statins. We analyzed 3854 patients including those with nondiabetes and diabetes treated at the outpatient clinic between 2003 and 2013 who were statin-naïve and maintained fixed-dose of statin for at least 18 months. Moderate- and low-intensity statin therapy was effective in reducing low-density lipoprotein cholesterol (LDL-C) to statin group. The effects of statins in elevating high-density lipoprotein cholesterol were similar in each statin groups, except the ezetimibe-simvastatin group (4.5 ± 2.1%) and high-dose atorvastatin groups (9.7 ± 3.3% and 8.7 ± 2.4% for 40 mg and 80 mg of atorvastatin/day, respectively). High-density lipoprotein cholesterol increased less and LDL-C decreased more in diabetes than in nondiabetes. There were no significant changes of fasting glucose after statin use in nondiabetic patients. Moderate- or low-intensity statin was effective enough in reaching National Cholesterol Education Program Adult Treatment Panel III LDL-C target goals in Koreans. Low-intensity statin showed around 30% LDL-C reduction from the baseline level in Koreans, which is comparable to moderate-intensity statin in new guideline. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Innovative polymeric system (IPS) for solvent-free lipophilic drug transdermal delivery via dissolving microneedles.

Science.gov (United States)

Dangol, Manita; Yang, Huisuk; Li, Cheng Guo; Lahiji, Shayan Fakhraei; Kim, Suyong; Ma, Yonghao; Jung, Hyungil

2016-02-10

Lipophilic drugs are potential drug candidates during drug development. However, due to the need for hazardous organic solvents for their solubilization, these drugs often fail to reach the pharmaceutical market, and in doing so highlight the importance of solvent free systems. Although transdermal drug delivery systems (TDDSs) are considered prospective safe drug delivery routes, a system involving lipophilic drugs in solvent free or powder form has not yet been described. Here, we report, for the first time, a novel approach for the delivery of every kind of lipophilic drug in powder form based on an innovative polymeric system (IPS). The phase transition of powder form of lipophilic drugs due to interior chemical bonds between drugs and biodegradable polymers and formation of nano-sized colloidal structures allowed the fabrication of dissolving microneedles (DMNs) to generate a powerful TDDS. We showed that IPS based DMN with powder capsaicin enhances the therapeutic effect for treatment of the rheumatic arthritis in a DBA/1 mouse model compared to a solvent-based system, indicating the promising potential of this new solvent-free platform for lipophilic drug delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

HDL cholesterol: atherosclerosis and beyond

NARCIS (Netherlands)

Bochem, A.E.

2013-01-01

Cardiovascular disease (CVD) is the leading cause of death in the Western world. Myocardial infarction and stroke are the result of a compromised blood flow which may result from cholesterol accumulation in the vessel wall due to high plasma levels of LDL cholesterol. High plasma levels of HDL

Characteristics of human hypo- and hyperresponders to dietary cholesterol.

Science.gov (United States)

Katan, M B; Beynen, A C

1987-03-01

The characteristics of people whose serum cholesterol level is unusually susceptible to consumption of cholesterol were investigated. Thirty-two volunteers from the general population of Wageningen, the Netherlands, each participated in three controlled dietary trials in 1982. A low-cholesterol diet was fed during the first half and a high-cholesterol diet during the second half of each trial, and the change (response) of serum cholesterol was measured. The responses in the three trials were averaged to give each subject's mean responsiveness. Fecal excretion of cholesterol and its metabolites were measured in the second trial, and body cholesterol synthesis was calculated. Responsiveness showed a positive correlation with serum high density lipoprotein2 (HDL2) cholesterol (r = 0.41, p less than 0.05) and with serum total cholesterol level on a high-cholesterol diet (r = 0.31, p = 0.09). A negative relation was found with habitual cholesterol consumption (r = -0.62, p less than 0.01), with body mass index (r = -0.50, p less than 0.01), and with the rate of endogenous cholesterol synthesis (r = -0.40, p less than 0.05), but not with the reaction of endogenous cholesterol synthesis rate to an increased intake of cholesterol. No relation was found with age, sex, total caloric needs, or the ratio of primary to secondary fecal steroids. Upon multiple regression analysis, only habitual cholesterol intake and serum total and HDL2 cholesterol levels contributed significantly to the explanation of variance in responsiveness. Thus, a low habitual cholesterol intake, a high serum HDL2 cholesterol level, or a low body weight do not make one less susceptible to dietary cholesterol-induced hypercholesterolemia.

Status of non-HDL-cholesterol and LDL-cholesterol among subjects with and without metabolic syndrome.

Science.gov (United States)

Khan, Sikandar Hayat; Asif, Naveed; Ijaz, Aamir; Manzoor, Syed Mohsin; Niazi, Najumusaquib Khan; Fazal, Nadeem

2018-04-01

To to compare non-high-density lipoprotein and low-density lipoprotein cholesterol among subjects with or without metabolic syndrome, glycation status and nephropathic changes. The comparative cross-sectional study was carried out from Dec 21, 2015, to Nov 15, 2016, at the department of pathology and medicine PNS HAFEEZ and department of chemical pathology and clinical endocrinology (AFIP), and comprised patients of either gender visiting the out-patient department for routine screening. They were evaluated for anthropometric indices, blood pressure and sampled for lipid profile, fasting plasma glucose, glycated haemoglobin, insulin, and urine albumin-to-creatinine ratio. Subjects were segregated based upon presence (Group1) or absence (Group2) of metabolic syndrome based upon criteria of National Cholesterol Education Programme and the International Diabetes Federation. Differences in high and low density lipoprotein cholesterols were calculated between the groups. Of the 229 subjects, 120(52.4%) were women and 109(47.6%) were men. Overall, there were 107(46.7%) subjects in Group 1, and 122(53.3%) in Group 2. Non-high-density lipoprotein cholesterol was significantly different between subjects with and without metabolic syndrome as per both the study criteria (p<0.05 each). . Non-high-density lipoprotein cholesterol levels were higher in subjects with metabolic syndrome.

Dietary and biliary cholesterol absorption in rats. Effect of dietary cholesterol level and cholesterol saturation of bile

International Nuclear Information System (INIS)

Wilson, M.D.

1985-01-01

The principal objective of this research was to determine if cholesterol introduced into the duodenum of rats in a micellar form as occurs with bile, is absorbed more efficiently than cholesterol presented in a nonmicellar form, as occurs with dietary cholesterol. Cholesterol absorption was measured during the constant intraduodenal infusion of liquid diets ([ 14 C] cholesterol) and artificial biles ([ 3 H] cholesterol) in thoracic lymph duct cannulated rats. Percentage absorption was calculated by dividing the rate of appearance of radiolabeled cholesterol in lymph by its rate of infusion when lymph cholesterol specific activity was constant. Results provide strong evidence that under certain conditions biliary cholesterol is more efficiently absorbed than is dietary cholesterol, and that this differential must be considered when evaluating the influence of diet or drug therapy on cholesterol absorption

Effect of a high-fat-high-cholesterol diet on gallbladder bile acid composition and gallbladder motility in dogs.

Science.gov (United States)

Kakimoto, Toshiaki; Kanemoto, Hideyuki; Fukushima, Kenjiro; Ohno, Koichi; Tsujimoto, Hajime

2017-12-01

OBJCTIVE To investigate the effects of dietary lipid overload on bile acid metabolism and gallbladder motility in healthy dogs. ANIMALS 7 healthy Beagles. PROCEDURES In a crossover study, dogs were fed a high-fat-high-cholesterol diet (HFCD) or a low-fat diet (LFD) for a period of 2 weeks. After a 4-month washout period, dogs were fed the other diet for 2 weeks. Before and at the end of each feeding period, the concentrations of each of the gallbladder bile acids, cholecystokinin (CCK)-induced gallbladder motility, and bile acid metabolism-related hepatic gene expression were examined in all dogs. RESULTS The HFCD significantly increased plasma total cholesterol concentrations. The HFCD also increased the concentration of taurochenodeoxycholic acid and decreased the concentration of taurocholic acid in bile and reduced gallbladder contractility, whereas the LFD significantly decreased the concentration of taurodeoxycholic acid in bile. Gene expression analysis revealed significant elevation of cholesterol 7α-hydroxylase mRNA expression after feeding the HFCD for 2 weeks, but the expression of other genes was unchanged. CONCLUSIONS AND CLINICAL RELEVANCE Feeding the HFCD and LFD for 2 weeks induced changes in gallbladder bile acid composition and gallbladder motility in dogs. In particular, feeding the HFCD caused an increase in plasma total cholesterol concentration, an increase of hydrophobic bile acid concentration in bile, and a decrease in gallbladder sensitivity to CCK. These results suggested that similar bile acid compositional changes and gallbladder hypomotility might be evident in dogs with hyperlipidemia.

Cholesterol autoxidation in phospholipid membrane bilayers

International Nuclear Information System (INIS)

Sevanian, A.; McLeod, L.L.

1987-01-01

Lipid peroxidation in unilamellar liposomes of known cholesterol-phospholipid composition was monitored under conditions of autoxidation or as induced by a superoxide radical generating system, gamma-irradiation or cumene hydroperoxide. Formation of cholesterol oxidation products was indexed to the level of lipid peroxidation. The major cholesterol oxidation products identified were 7-keto-cholesterol, isomeric cholesterol 5,6-epoxides, isomeric 7-hydroperoxides and isomeric 3,7-cholestane diols. Other commonly encountered products included 3,5-cholestadiene-7-one and cholestane-3 beta, 5 alpha, 6 beta-triol. Superoxide-dependent peroxidation required iron and produced a gradual increase in 7-keto-cholesterol and cholesterol epoxides. Cholesterol oxidation was greatest in liposomes containing high proportions of unsaturated phospholipid to cholesterol (4:1 molar ratio), intermediate with low phospholipid to cholesterol ratios (2:1) and least in liposomes prepared with dipalmitoylphosphatidylcholine and cholesterol. This relationship held regardless of the oxidizing conditions used. Cumene hydroperoxide-dependent lipid peroxidation and/or more prolonged oxidations with other oxidizing systems yielded a variety of products where cholesterol-5 beta,6 beta-epoxide, 7-ketocholesterol and the 7-hydroperoxides were most consistently elevated. Oxyradical initiation of lipid peroxidation produced a pattern of cholesterol oxidation products distinguishable from the pattern derived by cumene hydroperoxide-dependent peroxidation

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

Science.gov (United States)

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

2012-04-15

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-affinity cholesterol-binding proteins present in hepatocyte cytosol, on HDL-mediated free cholesterol uptake were examined using gene-targeted mouse models, cultured primary hepatocytes, and 22-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-amino]-23,24-bisnor-5-cholen-3β-ol (NBD-cholesterol). While SCP-2 overexpression enhanced NBD-cholesterol uptake, counterintuitively, SCP-2/SCP-x gene ablation also 1) enhanced the rapid molecular phase of free sterol uptake detectable in rate and maximal uptake of HDL free cholesterol and 2) differentially enhanced free cholesterol uptake mediated by the HDL3, rather than the HDL2, subfraction. The increased HDL free cholesterol uptake was not due to increased expression or distribution of the HDL receptor [scavenger receptor B1 (SRB1)], proteins regulating SRB1 [postsynaptic density protein (PSD-95)/Drosophila disk large tumor suppressor (dlg)/tight junction protein (ZO1) and 17-kDa membrane-associated protein], or other intracellular cholesterol trafficking proteins (steroidogenic acute response protein D, Niemann Pick C, and oxysterol-binding protein-related proteins). However, expression of L-FABP, the single most prevalent hepatic cytosolic protein that binds cholesterol, was upregulated twofold in SCP-2/SCP-x null hepatocytes. Double-immunogold electron microscopy detected L-FABP sufficiently close to SRB1 for direct interaction, similar to SCP-2. These data suggest a role for L-FABP in HDL cholesterol uptake, a finding confirmed with SCP-2/SCP-x/L-FABP null

MooPoong (Gye Young Jeong) increases HDL-cholesterol but decreases LDL cholesterol and body-weight.

Science.gov (United States)

Chung, Hwan-Suck; Hong, Seung-Heon; Do, Keum-Rok; Rhee, Hyung-Koo; Jung, Sung-Ki; Hwang, Woo-Jun; Kim, Hyung-Min

2004-05-01

MooPoong (MP, Gye Young Jeong), a Korean traditional wine, has been used as a prevention and treatment agent of blood circulatory trouble. To evaluate such an effect of MP, we analyzed whether the plasma levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and body weight change after rats were fed on high fat diet with MP for 8 weeks. Plasma LDL cholesterol level decreased by 5.6% in 0.128% MP treated group and by 11.1% in 0.640% MP treated group. However, HDL cholesterol was increased by 6.7% in 0.128% MP diet group and 33.3% in 0.640% MP diet group. In addition, there was a significant weight loss in the MP treated group compared with the high-fat diet group (P < 0.05). Our findings indicate that MP may contain compounds with actions which can treat blood circulatory trouble as well as overweight.

The Comparison of Gemfibrozil and Lovastatin Therapy in Patients with High LDL and Low HDL Cholesterol Levels

Science.gov (United States)

1990-08-01

CLI ’T i-ITI2N 20. IM~IA~iN OF ASIRACTj OF REPORT OF TIIlS PAGF OF ARrsWiIlACT i The comparison of gemfibrozil and lovastatin therapy in patients...PRESENTATIONS/SEMINARS: Jun 1990 The comparison of gemfibrozil and lovastatin in a subpopulation of patients with high LDL and low HDL cholesterol levels...aggressive ndical treatment. 2 Gemfibrozil is known to increase HDL cholesterol, decrease VLDL cholesterol and triglycerides, as well as lower LDL

Utilizing food effects to overcome challenges in delivery of lipophilic bioactives: structural design of medical and functional foods.

Science.gov (United States)

McClements, David Julian

2013-12-01

The oral bioavailability of many lipophilic bioactives, such as pharmaceuticals and nutraceuticals, is relatively low due to their poor solubility, permeability and/or chemical stability within the human gastrointestinal tract (GIT). The oral bioavailability of lipophilic bioactives can be improved by designing food matrices that control their release, solubilization, transport and absorption within the GIT. This article discusses the challenges associated with delivering lipophilic bioactive components, the impact of food composition and structure on oral bioavailability and the design of functional and medical foods for improving the oral bioavailability of lipophilic bioactives. Food-based delivery systems can be used to improve the oral bioavailability of lipophilic bioactives. There are a number of potential advantages to delivering lipophilic bioactives using functional or medical foods: greater compliance than conventional delivery forms; increased bioavailability and efficacy; and reduced variability in biological effects. However, food matrices are structurally complex multicomponent materials and research is still needed to identify optimum structures and compositions for particular bioactives.

What's Cholesterol?

Science.gov (United States)

... LDL. Most cholesterol is LDL (low-density lipoprotein) cholesterol. LDL cholesterol is more likely to clog blood vessels because ... Here's a way to remember the difference: the LDL cholesterol is the bad kind, so call it "lousy" ...

Current guidelines for high-density lipoprotein cholesterol in therapy and future directions

Directory of Open Access Journals (Sweden)

Subedi BH

2014-04-01

Full Text Available Bishnu H Subedi,1,2 Parag H Joshi,1 Steven R Jones,1 Seth S Martin,1 Michael J Blaha,1 Erin D Michos1 1Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, 2Greater Baltimore Medical Center, Baltimore, MD, USA Abstract: Many studies have suggested that a significant risk factor for atherosclerotic cardiovascular disease (ASCVD is low high-density lipoprotein cholesterol (HDL-C. Therefore, increasing HDL-C with therapeutic agents has been considered an attractive strategy. In the prestatin era, fibrates and niacin monotherapy, which cause modest increases in HDL-C, reduced ASCVD events. Since their introduction, statins have become the cornerstone of lipoprotein therapy, the benefits of which are primarily attributed to decrease in low-density lipoprotein cholesterol. Findings from several randomized trials involving niacin or cholesteryl ester transfer protein inhibitors have challenged the concept that a quantitative elevation of plasma HDL-C will uniformly translate into ASCVD benefits. Consequently, the HDL, or more correctly, HDL-C hypothesis has become more controversial. There are no clear guidelines thus far for targeting HDL-C or HDL due to lack of solid outcomes data for HDL specific therapies. HDL-C levels are only one marker of HDL out of its several structural or functional properties. Novel approaches are ongoing in developing and assessing agents that closely mimic the structure of natural HDL or replicate its various functions, for example, reverse cholesterol transport, vasodilation, anti-inflammation, or inhibition of platelet aggregation. Potential new approaches like HDL infusions, delipidated HDL, liver X receptor agonists, Apo A-I upregulators, Apo A mimetics, and gene therapy are in early phase trials. This review will outline current therapies and describe future directions for HDL therapeutics. Keywords: high-density lipoprotein, lipids, cholesterol, atherosclerosis, cardiovascular disease, therapy

Lung surfactant microbubbles increase lipophilic drug payload for ultrasound-targeted delivery.

Science.gov (United States)

Sirsi, Shashank R; Fung, Chinpong; Garg, Sumit; Tianning, Mary Y; Mountford, Paul A; Borden, Mark A

2013-01-01

The cavitation response of circulating microbubbles to targeted ultrasound can be used for noninvasive, site-specific delivery of shell-loaded materials. One challenge for microbubble-mediated delivery of lipophilic compounds is the limitation of drug loading into the microbubble shell, which is commonly a single phospholipid monolayer. In this study, we investigated the use of natural lung surfactant extract (Survanta(®), Abbott Nutrition) as a microbubble shell material in order to improve drug payload and delivery. Pulmonary surfactant extracts such as Survanta contain hydrophobic surfactant proteins (SP-B and SP-C) that facilitate lipid folding and retention on lipid monolayers. Here, we show that Survanta-based microbubbles exhibit wrinkles in bright-field microscopy and increased lipid retention on the microbubble surface in the form of surface-associated aggregates observed with fluorescence microscopy. The payload of a model lipophilic drug (DiO), measured by flow cytometry, increased by over 2-fold compared to lipid-coated microbubbles lacking SP-B and SP-C. Lung surfactant microbubbles were highly echogenic to contrast enhanced ultrasound imaging at low acoustic intensities. At higher ultrasound intensity, excess lipid was observed to be acoustically cleaved for localized release. To demonstrate targeting, a biotinylated lipopolymer was incorporated into the shell, and the microbubbles were subjected to a sequence of radiation force and fragmentation pulses as they passed through an avidinated hollow fiber. Lung surfactant microbubbles showed a 3-fold increase in targeted deposition of the model fluorescent drug compared to lipid-only microbubbles. Our results demonstrate that lung surfactant microbubbles maintain the acoustic responsiveness of lipid-coated microbubbles with the added benefit of increased lipophilic drug payload.

Lack of P2Y(13) in mice fed a high cholesterol diet results in decreased hepatic cholesterol content, biliary lipid secretion and reverse cholesterol transport

NARCIS (Netherlands)

Lichtenstein, Laeticia; Serhan, Nizar; Annema, Wijtske; Combes, Guillaume; Robaye, Bernard; Boeynaems, Jean-Marie; Perret, Bertrand; Tietge, Uwe J. F.; Laffargue, Muriel; Martinez, Laurent O.

2013-01-01

Background: The protective effect of HDL is mostly attributed to their metabolic function in reverse cholesterol transport (RCT), a process whereby excess cellular cholesterol is taken up from peripheral cells, processed in HDL particles, and later delivered to the liver for further metabolism and

Increased cholinergic contractions of jejunal smooth muscle caused by a high cholesterol diet are prevented by the 5-HT4 agonist – tegaserod

Directory of Open Access Journals (Sweden)

Shaffer Eldon

2006-02-01

Full Text Available Abstract Background Excess cholesterol in bile and in blood is a major risk factor for the respective development of gallbladder disease and atherosclerosis. This lipid in excess negatively impacts the functioning of other smooth muscles, including the intestine. Serotonin is an important mediator of the contractile responses of the small intestine. Drugs targeting the serotonin receptor are used as prokinetic agents to manage intestinal motor disorders, in particular irritable bowel syndrome. Thus, tegaserod, acting on 5-HT4 receptor, ideally should obviate detrimental effects of excessive cholesterol on gastrointestinal smooth muscle. In this study we examined the effect of tegaserod on cholesterol-induced changes in the contractile responses of intestinal smooth muscle. Methods The effects of a high cholesterol (1% diet on the in vitro contractile responses of jejunal longitudinal smooth muscle from Richardson ground squirrels to the cholinergic agonist carbachol were examined in the presence or absence of tetrodrodotoxin (TTX. Two groups of animals, fed either low (0.03% or high cholesterol rat chow diet, were further divided into two subgroups and treated for 28 days with either vehicle or tegaserod. Results The high cholesterol diet increased, by nearly 2-fold, contractions of the jejunal longitudinal smooth muscle elicited by carbachol. These cholinergic contractions were mediated by muscarinic receptors since they were blocked by scopolamine, a muscarinic receptor antagonist, but not by the nicotinic receptor antagonist, hexamethonium. Tegaserod treatment, which did not affect cholinergic contractions of tissues from low cholesterol fed animals, abrogated the increase caused by the high cholesterol diet. With low cholesterol diet TTX enhanced carbachol-evoked contractions, whereas this action potential blocker did not affect the augmented cholinergic contractions seen with tissues from animals on the high cholesterol diet. Tegaserod

Hypolipidaemic and anti-oxidative potential of encapsulated herb (Terminalia arjuna) added vanilla chocolate milk in high cholesterol fed rats.

Science.gov (United States)

Sawale, Pravin Digambar; Pothuraju, Ramesh; Abdul Hussain, Shaik; Kumar, Anuj; Kapila, Suman; Patil, Girdhari Ramdas

2016-03-15

Atherosclerosis is associated with coronary artery disease and occurs in developing as well as developed countries. In the present investigation, hypolipidaemic and anti-oxidative properties of encapsulated herb (Terminalia arjuna, 1.8%) added vanilla chocolate dairy drink was evaluated in high cholesterol fed Wistar rats for 60 days. At the end of the experimental period, a significant decrease in the body weight gain by rats receiving the encapsulated herb extract was noted as compared to high cholesterol fed rats. Administration of microencapsulated herb showed a statistically significant decrease in organ weights (epididymal fat and liver). Moreover, a significant decrease in serum lipids such as triglycerides, total cholesterol, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol and atherogenic index was observed with encapsulated Terminalia arjuna extract in high cholesterol fed group. Increases in reduced glutathione and decreases in TBARS levels were also reported in both liver and red blood cell lysates with encapsulated herb supplementation. The results demonstrated that the bioactive components (phytosterols, flavanoids, saponins and tannins etc.) which are present in the encapsulated T. arjuna not only withstand the processing conditions but also are effectively released in the intestine and show their effects, such as hypolipidaemic and antioxidant activities, for better treating cardiovascular disease. © 2015 Society of Chemical Industry.

Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

DEFF Research Database (Denmark)

Chapman, M John; Ginsberg, Henry N; Amarenco, Pierre

2011-01-01

Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high......-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic...

Drugs targeting high-density lipoprotein cholesterol for coronary artery disease management.

Science.gov (United States)

Katz, Pamela M; Leiter, Lawrence A

2012-01-01

Many patients remain at high risk for future cardiovascular events despite levels of low-density lipoprotein cholesterol (LDL-C) at, or below, target while taking statin therapy. Much effort is therefore being focused on strategies to reduce this residual risk. High-density lipoprotein cholesterol (HDL-C) is a strong, independent, inverse predictor of coronary heart disease risk and is therefore an attractive therapeutic target. Currently available agents that raise HDL-C have only modest effects and there is limited evidence of additional cardiovascular risk reduction on top of background statin therapy associated with their use. It was hoped that the use of cholesteryl ester transfer protein (CETP) inhibitors would provide additional benefit, but the results of clinical outcome studies to date have been disappointing. The results of ongoing trials with other CETP inhibitors that raise HDL-C to a greater degree and also lower LDL-C, as well as with other emerging therapies are awaited. Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

The role of serum non-cholesterol sterols as surrogate markers of absolute cholesterol synthesis and absorption.

Science.gov (United States)

Miettinen, T A; Gylling, H; Nissinen, M J

2011-10-01

To study the whole-body cholesterol metabolism in man, cholesterol synthesis and absorption need to be measured. Because of the complicated methods of the measurements, new approaches were developed including the analysis of serum non-cholesterol sterols. In current lipidologic papers and even in intervention studies, serum non-cholesterol sterols are frequently used as surrogate markers of cholesterol metabolism without any validation to the absolute metabolic variables. The present review compares serum non-cholesterol sterols with absolute measurements of cholesterol synthesis and absorption in published papers to find out whether the serum markers are valid indicators of cholesterol metabolism in various conditions. During statin treatment, during interventions of dietary fat, and in type 2 diabetes the relative and absolute variables of cholesterol synthesis and absorption were frequently but not constantly correlated with each other. In some occasions, especially in subjects with apolipoprotein E3/4 and E4/4 phenotypes, the relative metabolic markers were even more sensitive than the absolute ones to reflect changes in cholesterol metabolism during dietary interventions. Even in general population at very high absorption the homeostasis of cholesterol metabolism is disturbed damaging the validity of the serum markers. It is worth using several instead of only one precursor and absorption sterol marker for making conclusions of altered synthesis or absorption of cholesterol, and even then the presence of at least some absolute measurement is valuable. During consumption of plant sterol-enriched diets and in situations of interfered cholesterol homeostasis the relative markers do not adequately reflect cholesterol metabolism. Accordingly, the validity of the relative markers of cholesterol metabolism should not be considered as self-evident. Copyright © 2011 Elsevier B.V. All rights reserved.

Physicochemical Properties and Lipophilicity of Polydatin-Lecithin ...

African Journals Online (AJOL)

Yang Liu, Baogang Wang, Qian Zhang, Kunfeng Liu, Quanxi Wu ... HPLC analysis found that the solubility of polydatin in n-octanol at 25 °C was enhanced from 0.41 mg/mL to 21.98 mg/mL by complexing with lecithin, indicating that the lipophilicity of polydatin was significantly improved. Conclusion: Polydatin and lecithin in ...

Effects of cations and cholesterol with sphingomyelin membranes investigated by high-resolution broadband sum frequency vibrational spectroscopy

Science.gov (United States)

Zhang, Zhen; Feng, Rong-juan; Li, Yi-yi; Liu, Ming-hua; Guo, Yuan

2017-08-01

Sphingomyelin(SM) is specifically enriched in the plasma membrane of mammalian cells. Its molecular structure is compose by N-acyl-Derythro-sphingosylphosphorylcholine. The function of the SM related to membrane signaling and protein trafficking are relied on the interactions of the SM, cations, cholesterol and proteins. In this report, the interaction of three different nature SMs, cations and cholesterol at air/aqueous interfaces studied by high-resolution broadband sum frequency vibrational spectroscopy, respectively. Our results shed lights on understanding the relationship between SMs monolayer, cholesterol and Cations.

Self-Reported Snoring Is Associated with Dyslipidemia, High Total Cholesterol, and High Low-Density Lipoprotein Cholesterol in Obesity: A Cross-Sectional Study from a Rural Area of China.

Science.gov (United States)

Zhang, Naijin; Chen, Yintao; Chen, Shuang; Jia, Pengyu; Guo, Xiaofan; Sun, Guozhe; Sun, Yingxian

2017-01-17

Studies to explore the relationship between self-reported snoring and dyslipidemia, especially high total cholesterol (TC) and high low-density lipoprotein cholesterol (LDL-C), in the general population are still lacking. Our study was designed to examine whether self-reported snoring is significantly associated with dyslipidemia and ascertain the effects of different snoring intensities on dyslipidemia. There were 10,139 participants in our study. After adjustment for all confounding factors, self-reported snoring (OR = 1.207; p = 0.003), moderate (OR = 1.229; p = 0.015), strong (OR = 1.222; p = 0.033), and very strong (OR = 1.467; p = 0.012) snoring intensity, but not low (OR = 1.110; p = 0.224) snoring intensity, were significantly associated with dyslipidemia among adults with BMI (body mass index) ≥ 25 kg/m². In addition, self-reported snoring was significantly associated with high TC (OR = 1.167; p = 0.048) and high LDL-C (OR = 1.228; p = 0.044), rather than low HDL-C (OR = 1.171; p = 0.057) and high triglyceride (TG) (OR = 1.110; p = 0.141). In conclusion, adults with BMI ≥ 25 kg/m² and who experience snoring, especially moderate, strong, and very strong intensity levels of snoring, should be on the alert regarding the possibility of dyslipidemia, especially high LDL-C and high TC.

Activity-guided identification of acetogenins as novel lipophilic antioxidants present in avocado pulp (Persea americana).

Science.gov (United States)

Rodríguez-Sánchez, Dariana; Silva-Platas, Christian; Rojo, Rocío P; García, Noemí; Cisneros-Zevallos, Luis; García-Rivas, Gerardo; Hernández-Brenes, Carmen

2013-12-30

Avocado fruit is a rich source of health-related lipophilic phytochemicals such as monounsaturated fatty acids, tocopherols, carotenes, acetogenins and sterols. However, limited information is available on the contribution of specific phytochemicals to the overall antioxidant capacity (AOC) of the fruit. Centrifugal partition chromatography was used as fractionation tool, guided by an in vitro chemical assay of oxygen radical absorbance capacity (ORAC). Subsequent experiments focused on isolation and characterization of the chemical nature of the main contributors to lipophilic AOC of avocado pulp. ORAC values obtained for acetogenins were contrasted with results from an isolated kidney mitochondria membrane lipid peroxidation bioassay. The present study established that lipophilic AOC of the pulp was significantly higher than its hydrophilic AOC. Our results confirmed the presence of acetogenins in the fractions with highest lipophilic AOC, and for the first time linked them as contributors to lipophilic-ORAC values. Further HPLC-PDA/MS-TOF analysis led to structural elucidation of two novel acetogenins, not previously reported as present in avocado pulp, along with five already known related-compounds. Antioxidant properties observed for avocado pulp acetogenins by the ORAC assay suggested that, in the presence of an emulsifying agent, acetogenins could serve as novel lipophilic antioxidants in a food matrix. Results from isolated mitochondria lipid peroxidation bioassay, indicated that L-ORAC values which may have relevance for food matrix applications, should not be interpreted to have a direct relevance in health-related claims, compounds need to be evaluated considering the complexity of biological systems. Copyright © 2013 Elsevier B.V. All rights reserved.

Minor lipophilic compounds in edible insects

OpenAIRE

Monika Sabolová; Anna Adámková; Lenka Kouřimská; Diana Chrpová; Jan Pánek

2016-01-01

Contemporary society is faced with the question how to ensure suffiecient nutrition (quantity and quality) for rapidly growing population. One solution can be consumption of edible insect, which can have very good nutritional value (dietary energy, protein, fatty acids, fibers, dietary minerals and vitamins composition). Some edible insects species, which contains a relatively large amount of fat, can have a potential to be a „good" (interesting, new) source of minor lipophilic compound...

Effects of chocolate supplementation on metabolic and cardiovascular parameters in ApoE3L mice fed a high-cholesterol atherogenic diet.

Science.gov (United States)

Yakala, Gopala K; Wielinga, Peter Y; Suarez, Manuel; Bunschoten, Annelies; van Golde, Jolanda M; Arola, Lluis; Keijer, Jaap; Kleemann, Robert; Kooistra, Teake; Heeringa, Peter

2013-11-01

Dietary intake of cocoa and/or chocolate has been suggested to exhibit protective cardiovascular effects although this is still controversial. The aim of this study was to investigate the effects of chocolate supplementation on metabolic and cardiovascular parameters. Four groups of ApoE*3Leiden mice were exposed to the following diet regimens. Group 1: cholesterol-free control diet (CO). Group 2: high-dose (1.0% w/w) control cholesterol (CC). Group 3: CC supplemented chocolate A (CCA) and Group 4: CC supplemented chocolate B (CCB). Both chocolates differed in polyphenol and fiber content, CCA had a relatively high-polyphenol and low-fiber content compared to CCB. Mice fed a high-cholesterol diet showed increased plasma-cholesterol and developed atherosclerosis. Both chocolate treatments, particularly CCA, further increased plasma-cholesterol and increased atherosclerotic plaque formation. Moreover, compared to mice fed a high-cholesterol diet, both chocolate-treated groups displayed increased liver injury. Mice on high-cholesterol diet had elevated plasma levels of sVCAM-1, sE-selectin and SAA, which was further increased in the CCB group. Similar effects were observed for renal inflammation markers. The two chocolate preparations showed unfavorable, but different effects on cardiometabolic health in E3L mice, which dissimilarities may be related to differences in chocolate composition. We conclude that discrepancies reported on the effects of chocolate on cardiometabolic health may at least partly be due to differences in chocolate composition. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A comparative study on the effect of high cholesterol diet on the hippocampal CA1 area of adult and aged rats.

Science.gov (United States)

Abo El-Khair, Doaa M; El-Safti, Fatma El-Nabawia A; Nooh, Hanaa Z; El-Mehi, Abeer E

2014-06-01

Dementia is one of the most important problems nowadays. Aging is associated with learning and memory impairments. Diet rich in cholesterol has been shown to be detrimental to cognitive performance. This work was carried out to compare the effect of high cholesterol diet on the hippocampus of adult and aged male albino rats. Twenty adult and twenty aged male rats were used in this study. According to age, the rats were randomly subdivided into balanced and high cholesterol diet fed groups. The diet was 15 g/rat/day for adult rats and 20 g/rat/day for aged rats for eight weeks. Serial coronal sections of hippocampus and blood samples were taken from each rat. For diet effect evaluation, Clinical, biochemical, histological, immunohistochemical, and morphometric assessments were done. In compare to a balanced diet fed rat, examination of Cornu Ammonis 1 (CA 1) area in the hippocampus of the high cholesterol diet adult rats showed degeneration, a significant decrease of the pyramidal cells, attenuation and/or thickening of small blood vessels, apparent increase of astrocytes and apparent decrease of Nissl's granules content. Moreover, the high cholesterol diet aged rats showed aggravation of senility changes of the hippocampus together with Alzheimer like pathological changes. In conclusion, the high cholesterol diet has a significant detrimental effect on the hippocampus and aging might pronounce this effect. So, we should direct our attention to limit cholesterol intake in our food to maintain a healthy life style for a successful aging.

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...

The total cholesterol to high-density lipoprotein cholesterol as a predictor of poor outcomes in a Chinese population with acute ischaemic stroke.

Science.gov (United States)

Chen, Lifang; Xu, Jianing; Sun, Hao; Wu, Hao; Zhang, Jinsong

2017-11-01

High admission cholesterol has been associated with better outcome after acute ischaemic stroke (AIS), but a paradox not completely illustrated. The purpose of this study was to investigate the effect of the total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) on short-term survival after AIS. Consecutive patients admitted in 2013 and 2015 were enrolled in the present study. The logistic regression analysis was conducted to evaluate predictors of 3-month outcomes. The primary endpoint was death. Secondary endpoint was good (modified Rankin Scale score 0-2 or equal to prestrike modified Rankin Scale score) at 3 months. Of 871 patients enrolled in the final analysis, 94 (10.8%) individuals died during 3 months of observation. The serum TC and TC/HDL-C levels at admission were significantly associated with stroke outcomes at 3 months, and the HDL-C level was only correlated with the good outcomes at 3 months. Mortality risk was markedly decreased for patients with high TC/HDL-C ratio (odds ratio: 0.23, 95% confidence interval [CI]: 0.10-0.50 for Q4:Q1; P-trend <.001) after adjustment. The effect of TC/HDL-C ratio on the probability of good outcomes was still obvious (odds ratio: 2.18, 95% CI: 1.40-3.39 for Q4:Q1; P-trend=.029). According to the receiver operating characteristic analyses, the best discriminating factor was a TG/HDL-C ≥3.37 (area under the ROC curve [AUC]=0.643, sensitivity 61.3%, specificity 61.7%) as well as the TC/HDL-C ≥4.09 for good outcomes (AUC: 0.587, sensitivity 63.9%, specificity 79.7%). High TC/HDL-C ratio may be associated with increased short-term survival and better outcomes after AIS. © 2017 Wiley Periodicals, Inc.

Are lipophilic beta-blockers preferable for peri-operative ...

African Journals Online (AJOL)

There is therefore doubt whether atenolol is the correct cardioprotective drug in the surgical setting. It is possible that some of the physiochemical properties of atenolol (hydrophilic and cardioselective) may decrease it's efficacy in comparison to its more lipophilic congeners (such as propranolol, metoprolol, bisoprolol and ...

Novel mutations in scavenger receptor BI associated with high HDL cholesterol in humans

NARCIS (Netherlands)

Brunham, Liam R.; Tietjen, Ian; Bochem, Andrea E.; Singaraja, Roshni R.; Franchini, Patrick L.; Radomski, Chris; Mattice, Maryanne; Legendre, Annick; Hovingh, G. Kees; Kastelein, John J. P.; Hayden, Michael R.

2011-01-01

The scavenger receptor class B, member 1 (SR-BI), is a key cellular receptor for high-density lipoprotein (HDL) in mice, but its relevance to human physiology has not been well established. Recently a family was reported with a mutation in the gene encoding SR-BI and high HDL cholesterol (HDL-C).

Cholesterol Levels: What You Need to Know: MedlinePlus Health Topic

Science.gov (United States)

... lipoprotein ( LDL ) cholesterol and high-density lipoprotein ( HDL ) cholesterol. LDL (bad) cholesterol - the main source of cholesterol buildup ... Teens How to Lower Cholesterol How to Lower Cholesterol with Diet LDL: The "Bad" Cholesterol Nutrition Statins Triglycerides VLDL Cholesterol ...

Extraction efficiency of hydrophilic and lipophilic antioxidants from lyophilized foods using pressurized liquid extraction and manual extraction.

Science.gov (United States)

Watanabe, Jun; Oki, Tomoyuki; Takebayashi, Jun; Takano-Ishikawa, Yuko

2014-09-01

The efficient extraction of antioxidants from food samples is necessary in order to accurately measure their antioxidant capacities. α-Tocopherol and gallic acid were spiked into samples of 5 lyophilized and pulverized vegetables and fruits (onion, cabbage, Satsuma mandarin orange, pumpkin, and spinach). The lipophilic and hydrophilic antioxidants in the samples were sequentially extracted with a mixed solvent of n-hexane and dichloromethane, and then with acetic acid-acidified aqueous methanol. Duplicate samples were extracted: one set was extracted using an automated pressurized liquid extraction apparatus, and the other set was extracted manually. Spiked α-tocopherol and gallic acid were recovered almost quantitatively in the extracted lipophilic and hydrophilic fractions, respectively, especially when pressurized liquid extraction was used. The expected increase in lipophilic oxygen radical absorbance capacity (L-ORAC) due to spiking with α-tocopherol, and the expected increase in 2,2-diphenyl-1-picrylhydrazyl radical scavenging activities and total polyphenol content due to spiking with gallic acid, were all recovered in high yield. Relatively low recoveries, as reflected in the hydrophilic ORAC (H-ORAC) value, were obtained following spiking with gallic acid, suggesting an interaction between gallic acid and endogenous antioxidants. The H-ORAC values of gallic acid-spiked samples were almost the same as those of postadded (spiked) samples. These results clearly indicate that lipophilic and hydrophilic antioxidants are effectively extracted from lyophilized food, especially when pressurized liquid extraction is used. © 2014 Institute of Food Technologists®

Electronegative LDL is linked to high-fat, high-cholesterol diet-induced nonalcoholic steatohepatitis in hamsters.

Science.gov (United States)

Lai, Yu-Sheng; Yang, Tzu-Ching; Chang, Po-Yuan; Chang, Shwu-Fen; Ho, Shu-Li; Chen, Hui-Ling; Lu, Shao-Chun

2016-04-01

The pathogenesis of nonalcoholic steatohepatitis (NASH), like that of atherosclerosis, involves lipid accumulation, inflammation and fibrosis. Recent studies suggest that oxidized LDL (oxLDL) may be a risk factor for NASH, but oxLDL levels were not directly measured in these studies. The aim of this study was to examine whether there was an association between electronegative LDL [LDL(-)], a mildly oxLDL found in the blood, and the development of NASH using two animal models. Golden Syrian hamsters and C57BL/6 mice were fed a high-fat, high-cholesterol (HFC) diet for 6 or 12weeks, then liver lipid and histopathology, plasma lipoprotein profile and LDL(-) levels were examined. The HFC-diet-fed hamsters and mice had similar levels of hepatic lipid but different histopathological changes, with microvesicular steatosis, hepatocellular hypertrophy, inflammation and bridging fibrosis in the hamsters, but only in mild steatohepatitis with low inflammatory cell infiltration in the mice. It also resulted in a significant increase in plasma levels of LDL cholesterol and LDL(-) in hamsters, but only a slight increase in mice. Moreover, enlarged Kupffer cells, LDL(-) and accumulation of unesterified cholesterol were detected in the portal area of HFC-diet-fed hamsters, but not HFC-diet-fed mice. An in vitro study showed that LDL(-) from HFC-diet-fed hamsters induced TNF-α secretion in rat Kupffer cell through a LOX-1-dependent pathway. Our results strongly suggest that LDL(-) is one of the underlying causes of hepatic inflammation and plays a critical role in the development of NASH. Copyright © 2015 Elsevier Inc. All rights reserved.

Different responsiveness to a high-fat/cholesterol diet in two inbred mice and underlying genetic factors: a whole genome microarray analysis

Directory of Open Access Journals (Sweden)

Jin Gang

2009-10-01

Full Text Available Abstract Background To investigate different responses to a high-fat/cholesterol diet and uncover their underlying genetic factors between C57BL/6J (B6 and DBA/2J (D2 inbred mice. Methods B6 and D2 mice were fed a high-fat/cholesterol diet for a series of time-points. Serum and bile lipid profiles, bile acid yields, hepatic apoptosis, gallstones and atherosclerosis formation were measured. Furthermore, a whole genome microarray was performed to screen hepatic genes expression profile. Quantitative real-time PCR, western blot and TUNEL assay were conducted to validate microarray data. Results After fed the high-fat/cholesterol diet, serum and bile total cholesterol, serum cholesterol esters, HDL cholesterol and Non-HDL cholesterol levels were altered in B6 but not significantly changed in D2; meanwhile, biliary bile acid was decreased in B6 but increased in D2. At the same time, hepatic apoptosis, gallstones and atherosclerotic lesions occurred in B6 but not in D2. The hepatic microarray analysis revealed distinctly different genes expression patterns between B6 and D2 mice. Their functional pathway groups included lipid metabolism, oxidative stress, immune/inflammation response and apoptosis. Quantitative real time PCR, TUNEL assay and western-blot results were consistent with microarray analysis. Conclusion Different genes expression patterns between B6 and D2 mice might provide a genetic basis for their distinctive responses to a high-fat/cholesterol diet, and give us an opportunity to identify novel pharmaceutical targets in related diseases in the future.

What Is Cholesterol?

Science.gov (United States)

... of Cholesterol There are two main types of cholesterol: LDL and HDL. The cholesterol blood test tells how much of each kind you have. Most cholesterol is LDL (low-density lipoprotein) cholesterol. This type is most ...

Food matrix and processing influence on carotenoid bioaccessibility and lipophilic antioxidant activity of fruit juice-based beverages.

Science.gov (United States)

Rodríguez-Roque, María Janeth; de Ancos, Begoña; Sánchez-Vega, Rogelio; Sánchez-Moreno, Concepción; Cano, M Pilar; Elez-Martínez, Pedro; Martín-Belloso, Olga

2016-01-01

The biological activity of carotenoids depends on their bioaccessibility and solubilization in the gastrointestinal tract. These compounds are poorly dispersed in the aqueous media of the digestive tract due to their lipophilic nature. Thus, it is important to analyze the extent to which some factors, such as the food matrix and food processing, may improve their bioaccessibility. Beverages formulated with a blend of fruit juices and water (WB), milk (MB) or soymilk (SB) were treated by high-intensity pulsed electric fields (HIPEF) (35 kV cm(-1) with 4 μs bipolar pulses at 200 Hz for 1800 μs), high-pressure processing (HPP) (400 MPa at 40 °C for 5 min) or thermal treatment (TT) (90 °C for 1 min) in order to evaluate the influence of food matrix and processing on the bioaccessibility of carotenoids and on the lipophilic antioxidant activity (LAA). The bioaccessibility of these compounds diminished after applying any treatment (HIPEF, HPP and TT), with the exception of cis-violaxanthin + neoxanthin, which increased by 79% in HIPEF and HPP beverages. The lowest carotenoid bioaccessibility was always obtained in TT beverages (losses up to 63%). MB was the best food matrix for improving the bioaccessibility of carotenoids, as well as the LAA. The results demonstrate that treatment and food matrix modulated the bioaccessibility of carotenoids as well as the lipophilic antioxidant potential of beverages. Additionally, HIPEF and HPP could be considered as promising technologies to obtain highly nutritional and functional beverages.

Reference intervals for serum total cholesterol, HDL cholesterol and ...

African Journals Online (AJOL)

Reference intervals of total cholesterol, HDL cholesterol and non-HDL cholesterol concentrations were determined on 309 blood donors from an urban and peri-urban population of Botswana. Using non-parametric methods to establish 2.5th and 97.5th percentiles of the distribution, the intervals were: total cholesterol 2.16 ...

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.

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

International Nuclear Information System (INIS)

Chawla, Sheetal; Rawal, Rachna; Sonia; Ramrati; Pundir, C. S.

2013-01-01

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 °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 °C

Rho kinase inhibitor fasudil mitigates high-cholesterol diet-induced hypercholesterolemia and vascular damage.

Science.gov (United States)

Abdali, Nibrass Taher; Yaseen, Awny H; Said, Eman; Ibrahim, Tarek M

2017-04-01

The current study was designed to investigate the potential beneficial therapeutic outcome of Rho kinase inhibitor (fasudil) against hypercholesterolemia-induced myocardial and vascular injury in rabbits together with diet modification. Sixteen male rabbits were randomly divided into four groups: normal control group which received standard rabbit chow, hypercholesterolemic control group, and treated groups which received cholesterol-rich rabbit chow (1.5% cholesterol) for 8 weeks. Treated groups received either fasudil (100 mg/kg/day) or rosuvastatin (2.5 mg/kg/day) starting from the ninth week for further 4 weeks with interruption of the cholesterol-rich chow. Biochemical assessment of serum cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and myocardial oxidative/antioxidant biomarkers malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH), besides biochemical assessment of serum nitric oxide (NO), creatine kinase (CK), and lactate dehydrogenase (LDH) activities and serum total antioxidant capacity (TAC), was conducted. Serum vascular cell adhesion molecule 1 (VCAM-1) and serum Rho-associated protein kinase 1 (ROCK-1) were also evaluated along with histopathological examination of aorta specimens. Fasudil administration significantly decreased serum cholesterol, triglyceride (TG), and LDL and significantly increased serum HDL, with concomitant decrease in serum CK and LDH activities, NO, and restoration of serum TAC. Myocardial MDA significantly declined; SOD activity and GSH contents were restored. Serum ROCK-1 and VCAM-1 levels significantly declined as well. Vascular improvement was confirmed with histopathological examination, which revealed normal aortic intema with the absence of atheromas. Fasudil has promising anti-atherogenic activity mediated primarily via alleviation of hypercholesterolemia-induced oxidative stress and modulation of inflammatory response.

Tuberculosis treatment raises total cholesterol level and restores ...

African Journals Online (AJOL)

aghomotsegin

2013-10-09

Oct 9, 2013 ... and restores high density lipoprotein cholesterol (HDL- ... cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and triglycerides (TG) were determined .... However, we found a strong negative correlation (r = - 0.96,.

Distribution and correlates of non-high-density lipoprotein cholesterol and triglycerides in Lebanese school children.

Science.gov (United States)

Gannagé-Yared, Marie-Hélène; Farah, Vanessa; Chahine, Elise; Balech, Nicole; Ibrahim, Toni; Asmar, Nadia; Barakett-Hamadé, Vanda; Jambart, Selim

2016-01-01

The prevalence of dyslipidelmia in pediatric Middle-Eastern populations is unknown. Our study aims to investigate the distribution and correlates of non-high-density lipoprotein cholesterol (non-HDL-C) and triglycerides among Lebanese school children. A total of 969 subjects aged 8-18 years were included in the study (505 boys and 464 girls). Recruitment was done from 10 schools located in the Great Beirut and Mount-Lebanon areas. Non-fasting total cholesterol, triglycerides, and HDL-cholesterol (HDL-C) were measured. Non-HDL-C was calculated. Schools were categorized into 3 socioeconomic statuses (SESs; low, middle, and high). In the overall population, the prevalence of high non-HDL-C (>3.8 mmol/L), very high non-HDL-C (>4.9 mmol/L), and high triglycerides (>1.5 mmol/l) are respectively 9.2%, 1.24%, and 26.6%. There is no significant gender difference for non-HDL-C or triglycerides. Non-HDL-C and triglycerides are inversely correlated with age in girls (P triglycerides are higher in children from lower SES schools. After adjustment for age and body mass index (BMI), testosterone is inversely associated with triglycerides in boys (P triglycerides are independently associated with BMI and schools' SES in both girls and boys. This study confirms, in our population, the association between obesity and both high non-HDL-C and triglycerides, and between high triglycerides and low SES. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

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.

Macrophage Activation by a Lipophilic Derivative of Muramyldipeptide within Nanocapsules: Investigation of the Mechanism of Drug Delivery

International Nuclear Information System (INIS)

Seyler, Isabelle; Appel, Martine; Devissaguet, Jean-Philippe; Legrand, Philippe; Barratt, Gillian

1999-01-01

Different colloidal formulations: nanocapsules (NC), emulsion and micelles, containing the lipophilic immunomodulator muramyltripeptide cholesterol (MTP-Chol) induce nitric oxide synthase activity in the RAW 264.7 cell line. The use of cytochalasin B, an inhibitor of cell movements, showed that phagocytosis was an important mechanism as far as NC and the emulsion were concerned. However, when the cells were separated from particles containing the immunomodulator by a membrane of 100 nm pore size, significant activity could still be obtained, provided that serum was included in the medium. To determine whether low-density lipoprotein (LDL) might act as an intermediate carrier for MTP-Chol, the transfer of the immunomodulator from NC to LDL was studied by an ultrafiltration/centrifugation method followed by HPLC analysis. Although MTP-Chol could be transferred to LDL, when purified human LDL was added to serum-free medium, activation by MTP-Chol NC was reduced, rather than increased. This suggests that intact LDL carrying MTP-Chol is not taken up to a great extent by these macrophages

Inhibition of angiotensin-1-converting enzyme activity by two varieties of ginger (Zingiber officinale) in rats fed a high cholesterol diet.

Science.gov (United States)

Akinyemi, Ayodele Jacob; Ademiluyi, Adedayo Oluwaseun; Oboh, Ganiyu

2014-03-01

Angiotensin-1-converting enzyme (ACE) inhibitors are widely used in the treatment of cardiovascular diseases. This study sought to investigate the inhibitory effect of two varieties of ginger (Zingiber officinale) commonly consumed in Nigeria on ACE activity in rats fed a high cholesterol diet. The inhibition of ACE activity of two varieties of ginger (Z. officinale) was investigated in a high cholesterol (2%) diet fed to rats for 3 days. Feeding high cholesterol diets to rats caused a significant (Pginger varieties. Rats that were fed 4% white ginger had the greatest inhibitory effect as compared with a control diet. Furthermore, there was a significant (Pginger (either 2% or 4%) caused a significant (Pginger had the greatest reduction as compared with control diet. In conclusion, both ginger varieties exhibited anti-hypercholesterolemic properties in a high cholesterol diet fed to rats. This activity of the gingers may be attributed to its ACE inhibitory activity. However, white ginger inhibited ACE better in a high cholesterol diet fed to rats than red ginger. Therefore, both gingers could serve as good functional foods/nutraceuticals in the management/treatment of hypertension and other cardiovascular diseases.

Anticholesterolemic effect of 3,4-di(OH)-phenylpropionic amides in high-cholesterol fed rats

International Nuclear Information System (INIS)

Kim, Soon-Ja; Bok, Song-Hae; Lee, Sangku; Kim, Hye-Jin; Lee, Mi-Kyung; Park, Yong Bok; Choi, Myung-Sook

2005-01-01

Two amide synthetic derivatives of 3,4-di(OH)-hydrocinnamate (HC), 3,4-dihydroxyphenylpropionic (L-serine methyl ester) amide (E030) and 3,4-dihydroxyphenylpropionic (L-aspartic acid) amide (E076), were investigated to compare their lipid-lowering efficacy with HC. Male rats were fed a 1 g/100 g high-cholesterol diet for 6 weeks with supplements of either clofibrate (0.02%, w/w), HC (0.025%, w/w), E030 (0.039%, w/w) or E076 (0.041%, w/w). The clofibrate supplement was used as a positive control for the lipid-lowering efficacy. The food intakes and body weight gains were not significantly different among the groups. The plasma and hepatic cholesterol and triglyceride levels were lower in clofibrate, HC, E030, and E076-supplemented groups compared to the control group. The supplementation of HC and its amide derivatives was as effective as clofibrate in increasing the ratio of HDL-cholesterol to total plasma cholesterol and reducing the atherogenic index (AI). The hepatic cholesterol level in the HC and E076 groups was significantly lower than that in the clofibrate group. The hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA reductase) and acyl-CoA:cholesterol acyltransferase (ACAT) activities were significantly lower in the all test groups than in the control group. The excretion of neutral sterol was significantly higher in the HC, E030, and E076-supplemented groups compared to the control group. The plasma AST and ALT activities, indirect indexes of hepatic toxicity, were significantly lower in the HC, E030, and E076-supplemented groups than in the control group. Accordingly, the current results suggest that E030 and E076, two amide synthetic derivatives of HC, are effective in lowering lipid activity

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

Simultaneous measurement of cholesterol 7 alpha-hydroxylase activity by reverse-phase high-performance liquid chromatography using both endogenous and exogenous [4-14C]cholesterol as substrate

International Nuclear Information System (INIS)

Hylemon, P.B.; Studer, E.J.; Pandak, W.M.; Heuman, D.M.; Vlahcevic, Z.R.; Chiang, J.Y.

1989-01-01

The HPLC-spectrophotometric method for measuring cholesterol 7 alpha-hydroxylase activity was modified by using a C-18 reverse-phase column to separate 7 alpha-hydroxy-4-cholesten-3-one and 4-cholesten-3-one and by adding 7 beta-hydroxycholesterol to each reaction mixture as an internal recovery standard. With this method, we were able to simultaneously measure cholesterol 7 alpha-hydroxylase activity using endogenous cholesterol and exogenous [4- 14 C]cholesterol as substrate. Rat liver cytosol differentially stimulated (286%) the 7 alpha-hydroxylation of exogenous [4- 14 C]-cholesterol. In contrast, total cholesterol 7 alpha-hydroxylase activity was stimulated only 35% by cytosol. This method should prove useful for studying mechanisms of cholesterol delivery to cholesterol 7 alpha-hydroxylase

Design of a serotonin 4 receptor radiotracer with decreased lipophilicity for single photon emission computed tomography.

Science.gov (United States)

Fresneau, Nathalie; Dumas, Noé; Tournier, Benjamin B; Fossey, Christine; Ballandonne, Céline; Lesnard, Aurélien; Millet, Philippe; Charnay, Yves; Cailly, Thomas; Bouillon, Jean-Philippe; Fabis, Frédéric

2015-04-13

With the aim to develop a suitable radiotracer for the brain imaging of the serotonin 4 receptor subtype (5-HT4R) using single photon emission computed tomography (SPECT), we synthesized and evaluated a library of di- and triazaphenanthridines with lipophilicity values which were in the range expected to favour brain penetration, and which demonstrated specific binding to the target of interest. Adding additional nitrogen atoms to previously described phenanthridine ligands exhibiting a high unspecific binding, we were able to design a radioiodinated compound [(125)I]14. This compound exhibited a binding affinity value of 0.094 nM toward human 5-HT4R and a high selectivity over other serotonin receptor subtypes (5-HTR). In vivo SPECT imaging studies and competition experiments demonstrated that the decreased lipophilicity (in comparison with our previously reported compounds 4 and 5) allowed a more specific labelling of the 5-HT4R brain-containing regions. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Protective potentials of wild rice (Zizania latifolia (Griseb) Turcz) against obesity and lipotoxicity induced by a high-fat/cholesterol diet in rats.

Science.gov (United States)

Han, Shu-Fen; Zhang, Hong; Zhai, Cheng-Kai

2012-07-01

The study evaluates the protective potentials of wild rice against obesity and lipotoxicity induced by a high-fat/cholesterol diet in rats. In addition to the rats of low-fat diet group, others animals were exposed to a high-fat/cholesterol diet condition for 8 weeks. The city diet (CD) is based on the diet consumed by urban residents in modern China, which is rich in fat/cholesterol and high in carbohydrates from white rice and processed wheat starch. The chief source of dietary carbohydrates of wild rice diet (WRD) is from Chinese wild rice and other compositions are the same with CD. Rats fed CD showed elevated body and liver organ weights, lipid profiles, free fatty acids (FFA) and leptin comparable with rats fed high-fat/cholesterol diet (HFD) known to induce obesity and hyperlipidaemia in this species. However, rats consuming WRD suppressed the increase of lipid droplets accumulation, FFA, and leptin, and the decrease of lipoprotein lipase and adipose triglyceride lipase. Meanwhile, WRD prevented high-fat/cholesterol diet-induced elevation in protein expression of sterol-regulatory element binding protein-1c, and gene expression of fatty acid synthase and acetyl-CoA carboxylase. These findings indicate that wild rice as a natural food has the potentials of preventing obesity and liver lipotoxicity induced by a high-fat/cholesterol diet in rats. Copyright © 2012 Elsevier Ltd. All rights reserved.

Lipophilized phenolics as antioxidants in fish oil enriched food systems

DEFF Research Database (Denmark)

Sørensen, Ann-Dorit Moltke; Nielsen, Nina Skall; Jacobsen, Charlotte

Food products containing long chain omega-3 PUFA are highly susceptible to oxidation, which causes undesirable flavors and loss of health beneficial fatty acids. Many omega-3 enriched food products on the market are oil-in-water emulsions. According to the so called “polar paradox”, polar compounds...... hypothesis is that lipophilization of such polar phenolic compounds may improve their efficacy in fish oil enriched food systems. Our study aimed at evaluating rutin and dihydrocaffeic acid and their esters as antioxidants in o/w emulsion model system and milk enriched with fish oil. Moreover, the effect...

Effect of Processing Methods on Cholesterol Contents and Cholesterol Oxides Formation in Some Dairy Products

International Nuclear Information System (INIS)

AlRowaily, Meshref A

2008-01-01

The effects of pasteurization, boiling, microwaving, processing and storage of milk and some locally produced dairy products on cholesterol contents and cholesterol oxides formation were studied and evaluated. The 7-ketocholesterol were not detected (ND) in all raw milk samples. On the contrary, heating of milk led to formation of cholesterol oxidation products (COPs), mostly, 7- ketocholesterol in different quantities. No significant effect of heating of milk on cholesterol level was observed with the exception of the ultra-high temperature (UHT) milk prepared from milk powder heated at 140 + - 1.0 degree C for 4 sec showed the highest value of 7-ketocholesterol (80.97 mgg-1), followed by microwave heated milk for 5 min (31.29 mgg-1), whereas the lowest value was in milk pasteurized at 85 + - 1.0 degree C for 16 sec (3.125 mgg-1). Commercial storage showed no significant effect on cholesterol and 7-ketocholestrol but lowered cholesterol concentration and increased 7-ketocholestrol level of UHT reconstituted milk. Cholesterol content of both yogurt and labaneh strained by centrifugal separator showed significant decrease while 7-ketochostrol level was increased significantly with refrigerated storage. The findings are discussed in the context with the results of previous similar studies. (author)

Nonlinear associations between plasma cholesterol levels and neuropsychological function.

Science.gov (United States)

Wendell, Carrington R; Zonderman, Alan B; Katzel, Leslie I; Rosenberger, William F; Plamadeala, Victoria V; Hosey, Megan M; Waldstein, Shari R

2016-11-01

Although both high and low levels of total and low-density lipoprotein (LDL) cholesterol have been associated with poor neuropsychological function, little research has examined nonlinear effects. We examined quadratic relations of cholesterol to performance on a comprehensive neuropsychological battery. Participants were 190 older adults (53% men, ages 54-83) free of major medical, neurologic, and psychiatric disease. Measures of fasting plasma total and high-density lipoprotein (HDL) cholesterol were assayed, and LDL cholesterol was calculated. Participants completed neuropsychological measures of attention, executive function, memory, visuospatial judgment, and manual speed and dexterity. Multiple regression analyses examined cholesterol levels as quadratic predictors of each measure of cognitive performance, with age (dichotomized as Reproduction II ( b = -.0020, p = .026) and log of the Trail Making Test, Part B (b = .0001, p = .044). Quadratic associations between HDL cholesterol and cognitive performance were nonsignificant. Results indicate differential associations between cholesterol and neuropsychological function across different ages and domains of function. High and low total and LDL cholesterol may confer both risk and benefit for suboptimal cognitive function at different ages. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

The role of cholesterol metabolism and cholesterol transport in carcinogenesis; A review of scientific findings, relevant to future cancer therapeutics.

Directory of Open Access Journals (Sweden)

Pedro Miguel Cruz

2013-09-01

Full Text Available While the unique metabolic activities of malignant tissues as potential targets for cancer therapeutics has been the subject of several recent reviews, the role of cholesterol metabolism in this context is yet to be fully explored. Cholesterol is an essential component of mammalian cell membranes as well as a precursor of bile acids and steroid hormones. The hypothesis that cancer cells need excess cholesterol and intermediates of the cholesterol biosynthesis pathway to maintain a high level of proliferation is well accepted, however the mechanisms by which malignant cells and tissues reprogram cholesterol synthesis, uptake and efflux are yet to be fully elucidated as potential therapeutic targets. High and low density plasma lipoproteins, area the likely major suppliers of cholesterol to cancer cells and tumors, potentially via receptor mediated mechanisms. This review is primarily focused on the role(s of lipoproteins in carcinogenesis, and their future roles as drug delivery vehicles for targeted cancer chemotherapy.

The cholesterol space of the rat; L'espace cholesterol du rat

Energy Technology Data Exchange (ETDEWEB)

Chevallier, F [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

1959-07-01

The experiments consisted in feeding daily to rats the same mass of radioactive cholesterol, over variable time intervals. From the evolution of the specific radioactivity of cholesterol carbon-14 in the organs as a function of time, information relative to the transport of cholesterol in the organism may be obtained. 1) The cholesterol space, defined as the group of molecules capable of being transferred from the organs into the serum and vice versa, represents at the most 50 per cent of the total cholesterol of the adult rat. 2) The incessant interchange between the tissual and the serum cholesterol renews entirely or for the most part the cholesterol molecules contained in the following organs: spleen, heart, adipose tissue, suprarenal glands, lungs, bone marrow, liver, erythrocytes. For a second group of organs: skin, testicles, kidneys, colon, bones, muscles, only a fraction of their cholesterol is renewable by this process. No transfer can be detected at the level of the brain. 3) The relative speeds of the various means of appearance (absorption, synthesis) and disappearance (excretion, transformation) of the cholesterol from its space are such that a stationary isotopic state is established around the eighth day, when the animal absorbs 5 milligrams of radioactive cholesterol daily. (author) [French] Les experiences ont consiste a faire ingerer quotidiennement une meme masse de cholesterol radioactif a des rats, durant des laps de temps variables. L'evolution de la radioactivite specifique du carbone-14 du cholesterol des organes en fonction du temps permet d'obtenir des renseignements relatifs au transport du cholesterol dans l'organisme. 1) L'espace cholesterol defini comme l'ensemble des molecules susceptibles d'etre transferees des organes dans le serum, et vice-versa, represente au plus 50 pour cent du cholesterol total du rat adulte. 2) Le va et vient incessant entre le cholesterol tissulaire et le cholesterol serique renouvelle en totalite ou en

Effect of the structure, solid state and lipophilicity on the solubility of novel bicyclic derivatives

International Nuclear Information System (INIS)

Blokhina, Svetlana V.; Ol’khovich, Marina V.; Sharapova, Angelica V.; Volkova, Tatyana V.; Proshin, Alexey N.; Perlovich, German L.

2014-01-01

Highlights: • The solubility in buffer pH 7.4 of novel bicyclo-derivatives of amine were measured. • The influence of melting parameters and lipophilicity on the solubility was studied. • The thermodynamic parameters of the solubility process were calculated. - Abstract: Novel bicyclic derivatives have been synthesized. The solubility of drug-like substances in phosphate buffer rH 7.4 has been measured within the range of (9.02 · 10 −5 to 1.05 · 10 −4 ) mol/l. The relationship between the chemical nature and the structure of the aryl substituents and the solubility parameter was investigated. The fusion temperatures, enthalpies and entropies have been determined experimentally. The influence of thermophysical characteristics and lipophilicity on the solubility was studied using regression analysis. The calculations by the solubility/lipophilicity equation showed an overall improvement of the predictions equal to 0.5 log units. It was concluded that the solvation has a considerable influence on the solubility of the compounds under consideration. It was also determined that the alkyl- and halogen-derivatives solubility values correlate with HYBOT descriptors characterizing the (donor + acceptor) properties of the substances. The thermodynamic parameters of the solubility process were calculated using the temperature dependences. The study also revealed that the solubility of the bicyclic compounds is characterized by high endothermicity of the processes and negative entropies

A Helix-Stabilizing Linker Improves Subcutaneous Bioavailability of a Helical Peptide Independent of Linker Lipophilicity

Science.gov (United States)

Zhang, Liang; Navaratna, Tejas; Thurber, Greg M.

2016-01-01

Stabilized peptides address several limitations to peptide-based imaging agents and therapeutics such as poor stability and low affinity due to conformational flexibility. There is also active research in developing these compounds for intracellular drug targeting, and significant efforts have been invested to determine the effects of helix stabilization on intracellular delivery. However, much less is known about the impact on other pharmacokinetic parameters such as plasma clearance and bioavailability. We investigated the effect of different fluorescent helix-stabilizing linkers with varying lipophilicity on subcutaneous (SC) bioavailability using the glucagon-like peptide-1 (GLP-1) receptor ligand exendin as a model system. The stabilized peptides showed significantly higher protease resistance and increased bioavailability independent of linker hydrophilicity, and all subcutaneously delivered conjugates were able to successfully target the islets of Langerhans with high specificity. The lipophilic peptide variants had slower absorption and plasma clearance than their respective hydrophilic conjugates, and the absolute bioavailability was also lower likely due to the longer residence times in the skin. The ease and efficiency of double-click helix stabilization chemistries is a useful tool for increasing the bioavailability of peptide therapeutics, many of which suffer from rapid in vivo protease degradation. Helix stabilization using linkers of varying lipophilicity can further control SC absorption and clearance rates to customize plasma pharmacokinetics. PMID:27327034

Clerodendron glandulosum Coleb., Verbenaceae, ameliorates high fat diet-induced alteration in lipid and cholesterol metabolism in rats

Directory of Open Access Journals (Sweden)

RN Jadeja

Full Text Available The present study was undertaken to evaluate the efficacy of freeze dried extract of Clerodendron glandulosum Coleb., Verbenaceae, leaves (FECG on alteration in lipid and cholesterol metabolism in high fat diet fed hyperlipidemic rats. Plasma and hepatic lipid profiles, lipid and cholesterol metabolizing enzymes in target tissues and fecal total lipids and bile acid contents were evaluated in FECG treated normolipidemic and hyperlipidemic rats. These results were compared with synthetic hypolipidemic drug Lovastatin (LVS. Results indicate that FECG was able to positively regulate induced experimental hyperlipidemia by significant alteration in plasma and tissue lipid profiles. These results can be attributed to reduced absorption, effective elimination and augmented catabolism of lipids and cholesterol possibly due to high content of saponin and phytosterols in C. glandulosum. Use of C. glandulosum extract as a potential therapeutic agent against hypercholesterolemia and hypertriglyceridemia is indicated.

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

The expression of cholesterol metabolism genes in monocytes from HIV-infected subjects suggests intracellular cholesterol accumulation.

Science.gov (United States)

Feeney, Eoin R; McAuley, Nuala; O'Halloran, Jane A; Rock, Clare; Low, Justin; Satchell, Claudette S; Lambert, John S; Sheehan, Gerald J; Mallon, Patrick W G

2013-02-15

Human immunodeficiency virus (HIV) infection is associated with increased cardiovascular risk and reduced high-density lipoprotein cholesterol (HDL-c). In vitro, HIV impairs monocyte-macrophage cholesterol efflux, a major determinant of circulating HDL-c, by increasing ABCA1 degradation, with compensatory upregulation of ABCA1 messenger RNA (mRNA). We examined expression of genes involved in cholesterol uptake, metabolism, and efflux in monocytes from 22 HIV-positive subjects on antiretroviral therapy (ART-Treated), 30 untreated HIV-positive subjects (ART-Naive), and 22 HIV-negative controls (HIV-Neg). HDL-c was lower and expression of ABCA1 mRNA was higher in ART-Naive subjects than in both ART-Treated and HIV-Neg subjects (both P ART-Treated and ART-Naive subjects than in HIV-Neg controls. In vivo, increased monocyte ABCA1 expression in untreated HIV-infected patients and normalization of ABCA1 expression with virological suppression by ART supports direct HIV-induced impairment of cholesterol efflux previously demonstrated in vitro. However, decreased expression of cholesterol sensing, uptake, and synthesis genes in both untreated and treated HIV infection suggests that both HIV and ART affect monocyte cholesterol metabolism in a pattern consistent with accumulation of intramonocyte cholesterol.

Trypanosoma cruzi Epimastigotes Are Able to Store and Mobilize High Amounts of Cholesterol in Reservosome Lipid Inclusions

Science.gov (United States)

Pereira, Miria G.; Nakayasu, Ernesto S.; Sant'Anna, Celso; De Cicco, Nuccia N. T.; Atella, Georgia C.; de Souza, Wanderley; Almeida, Igor C.; Cunha-e-Silva, Narcisa

2011-01-01

Background Reservosomes are lysosome-related organelles found in Trypanosoma cruzi epimastigotes. They represent the last step in epimastigote endocytic route, accumulating a set of proteins and enzymes related to protein digestion and lipid metabolism. The reservosome matrix contains planar membranes, vesicles and lipid inclusions. Some of the latter may assume rectangular or sword-shaped crystalloid forms surrounded by a phospholipid monolayer, resembling the cholesterol crystals in foam cells. Methodology/Principal Findings Using Nile Red fluorimetry and fluorescence microscopy, as well as electron microscopy, we have established a direct correlation between serum concentration in culture medium and the presence of crystalloid lipid inclusions. Starting from a reservosome purified fraction, we have developed a fractionation protocol to isolate lipid inclusions. Gas-chromatography mass-spectrometry (GC-MS) analysis revealed that lipid inclusions are composed mainly by cholesterol and cholesterol esters. Moreover, when the parasites with crystalloid lipid-loaded reservosomes were maintained in serum free medium for 48 hours the inclusions disappeared almost completely, including the sword shaped ones. Conclusions/Significance Taken together, our results suggest that epimastigote forms of T. cruzi store high amounts of neutral lipids from extracellular medium, mostly cholesterol or cholesterol esters inside reservosomes. Interestingly, the parasites are able to disassemble the reservosome cholesterol crystalloid inclusions when submitted to serum starvation. PMID:21818313

The effect of lipophilicity on the antibacterial activity of some 1-benzylbenzimidazole derivatives

Directory of Open Access Journals (Sweden)

D. J. BARNA

2008-10-01

Full Text Available In the present paper, the antibacterial activity of some 1-benzylbenzimidazole derivatives were evaluated against the Gram-negative bacteria Escherichia coli. The minimum inhibitory concentration was determined for all the compounds. Quantitative structure–activity relationship (QSAR was employed to study the effect of the lipophilicity parameters (log P on the inhibitory activity. Log P values for the target compounds were experimentally determined by the “shake-flask” method and calculated by using eight different software products. Multiple linear regression was used to correlate the log P values and antibacterial activity of the studied benzimidazole derivatives. The results are discussed based on statistical data. The most acceptable QSAR models for the prediction of the antibacterial activity of the investigated series of benzimidazoles were developed. High agreement between the experimental and predicted inhibitory values was obtained. The results of this study indicate that the lipophilicity parameter has a significant effect on the antibacterial activity of this class of compounds, which simplifies the design of new biologically active molecules.

High Blood Pressure and Cholesterol—What You Need to Know

Centers for Disease Control (CDC) Podcasts

This podcast is based on the February, 2011 CDC Vital Signs report which indicates that two out of three U.S. adults with high cholesterol and half of U.S. adults with high blood pressure don't have their condition under control which puts them at risk for heart disease and stroke. Listen to this program for ways to reduce your risk for heart disease and stroke.

Melanocortin signaling in the CNS directly regulates circulating cholesterol

OpenAIRE

Perez-Tilve, Diego; Hofmann, Susanna M; Basford, Joshua; Nogueiras, Ruben; Pfluger, Paul T; Patterson, James T; Grant, Erin; Wilson-Perez, Hilary E; Granholm, Norman A; Arnold, Myrtha; Trevaskis, James L; Butler, Andrew A; Davidson, William S; Woods, Stephen C; Benoit, Stephen C

2010-01-01

Cholesterol circulates in the blood in association with triglycerides and other lipids, and elevated blood low-density lipoprotein cholesterol carries a risk for metabolic and cardiovascular disorders, whereas high-density lipoprotein (HDL) cholesterol in the blood is thought to be beneficial. Circulating cholesterol is the balance among dietary cholesterol absorption, hepatic synthesis and secretion, and the metabolism of lipoproteins by various tissues. We found that the CNS is also an impo...

Pairing of cholesterol with oxidized phospholipid species in lipid bilayers

DEFF Research Database (Denmark)

Khandelia, Himanshu; Loubet, Bastien; Olzynska, Agnieszka

2014-01-01

We claim that (1) cholesterol protects bilayers from disruption caused by lipid oxidation by sequestering conical shaped oxidized lipid species such as 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PZPC) away from phospholipid, because cholesterol and the oxidized lipid have complementary...... shapes and (2) mixtures of cholesterol and oxidized lipids can self-assemble into bilayers much like lysolipid–cholesterol mixtures. The evidence for bilayer protection comes from molecular dynamics (MD) simulations and dynamic light scattering (DLS) measurements. Unimodal size distributions of extruded...... vesicles (LUVETs) made up of a mixture of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and PZPC containing high amounts of PZPC are only obtained when cholesterol is present in high concentrations. In simulations, bilayers containing high amounts of PZPC become porous, unless cholesterol is also present...

2013 Cholesterol Guidelines Revisited: Percent LDL Cholesterol Reduction or Attained LDL Cholesterol Level or Both for Prognosis?

NARCIS (Netherlands)

Bangalore, Sripal; Fayyad, Rana; Kastelein, John J.; Laskey, Rachel; Amarenco, Pierre; Demicco, David A.; Waters, David D.

2016-01-01

The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guideline on the treatment of blood cholesterol recommends moderate- to high-intensity statins for patients with atherosclerotic cardiovascular disease but departs from the traditional treat-to-target approach. Whether

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

, 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...... was associated with an 18% increase in risk of MI. S208T associated with a 13% (0.21 mmol/liter) decrease in HDL cholesterol levels but not with increased risk of MI or other ischemic end points. The causal odds ratio for MI for a 50% reduction in plasma HDL cholesterol due to S208T genotype in both studies......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...

Effects of lipophilic components on the compatibility of lipid-based formulations with hard gelatin capsules.

Science.gov (United States)

Chen, Feng-Jing; Etzler, Frank M; Ubben, Johanna; Birch, Amy; Zhong, Li; Schwabe, Robert; Dudhedia, Mayur S

2010-01-01

The present study investigated the effect of lipophilic components on the compatibility of propylene glycol (PG)-containing lipid-based drug delivery system (LBDDS) formulations with hard gelatin capsules. The presence of a lipophilic active pharmaceutical ingredient (API) (log P approximately 6.1) and an additional lipophilic excipient (Capmul MCM) significantly affected the activity of PG in the fills and the equilibrium of PG between capsule shells and fills. These changes in activity and equilibrium of PG were furthermore correlated to the mechanical and thermal properties of the liquid-filled capsules and subsequently linked to the shelf-life of the capsules on stability with respect to capsule deformation. The present study also investigated the mechanism by which lipophilic component(s) might affect the activity of PG in the fill formulations and the equilibrium of PG between capsule shells and fills. The activities of PG in two series of "binary" mixtures with Capmul MCM and with Cremophor EL were measured, respectively. The mixtures of PG containing Capmul MCM were found to be more nearly ideal than those containing Cremophor EL. The observed negative deviation from Rauolt's law indicates that the excess free energies of mixing are less then zero indicating favorable interaction between PG and the other component. It is speculated that enhanced hydrogen bonding opportunities with Cremophor EL are responsible for the decreased excess free energy of mixing. Replacement of Cremophor EL with lipophilic API also reduces the hydrogen bonding opportunities for PG in the mixtures. This hypothesis may further explain the increased activity of PG in the fills and the shifted equilibrium of PG toward the capsule shells. Activity determination utilizing headspace gas chromatography (GC) using short 30 min incubation time seems to be a time-efficient approach for assessing capsule-fill compatibility. Direct measurements of PG migration and other physical properties of

Cholesterol testing and results

Science.gov (United States)

... your cholesterol is in this normal range. LDL (Bad) Cholesterol LDL cholesterol is sometimes called "bad" cholesterol. ... to 3.3 mmol/l) are desired. VLDL (Bad) Cholesterol VLDL contains the highest amount of triglycerides. ...

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

International Nuclear Information System (INIS)

Dallongeville, J.; Davignon, J.; Lussier-Cacan, S.

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 [ 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

Lipophilic organic pollutants induce changes in phospholipid and membrane protein composition leading to Vero cell morphological change.

Science.gov (United States)

Liao, Ting T; Wang, Lei; Jia, Ru W; Fu, Xiao H; Chua, Hong

2014-01-01

Membrane damage related to morphological change in Vero cells is a sensitive index of the composite biotoxicity of trace lipophilic chemicals. However, judging whether the morphological change in Vero cells happens and its ratio are difficult because it is not a quantitative characteristic. To find biomarkers of cell morphological change for quantitatively representing the ratio of morphological changed cell, the mechanism of cell membrane damage driven by typical lipophilic chemicals, such as trichlorophenol (TCP) and perfluorooctanesulphonate (PFOS), was explored. The ratio of morphologically changed cells generally increased with increased TCP or PFOS concentrations, and the level of four major components of phospholipids varied with concentrations of TCP or PFOS, but only the ratio of phosphatidylcholine (PC)/phosphatidylethanolamine (PE) decreased regularly as TCP or PFOS concentrations increased. Analysis of membrane proteins showed that the level of vimentin in normal cell membranes is high, while it decreases or vanishes after TCP exposure. These variations in phospholipid and membrane protein components may result in membrane leakage and variation in rigid structure, which leads to changes in cell morphology. Therefore, the ratio of PC/PE and amount of vimentin may be potential biomarkers for representing the ratio of morphological changed Vero cell introduced by trace lipophilic compounds, thus their composite bio-toxicity.

Studies on the lipophilicity of vehicles (or co-vehicles) and botanical oils used in cosmetic products.

Science.gov (United States)

Mbah, C J

2007-05-01

The lipophilic character of five vehicles (or co-vehicles): diethylhexylmaleate, dimethicone, light mineral oil, octyldodecanol and oleyl alcohol and eight botanical oils: Aloe vera oil, coconut oil, extra virgin olive oil, grape leaf oil, grape seed oil, hazelnut oil, jojoba oil and safflower oil was determined by partitioning esters of p-hydroxybenzoic acid (parabens) between them and phosphate buffer (pH 7.4). The results were compared to those obtained with 1-octanol. The most lipophilic effects were observed with octyldodecanol and oleyl alcohol for the vehicles (or co-vehicles), coconut oil, jojoba oil and safflower oil for botanical oils. Light mineral oil showed the least lipophilic effect. With butylparaben, it was observed that oleyl alcohol, octyldodecanol, coconut oil and jojoba oil were 0.94, 0.91, 0.74 and 0.68 times as lipophilic as 1-octanol respectively. The study indicates that octyldodecanol and oleyl alcohol could be good substitutes for 1-octanol in partition coefficient determination. The estimated permeability coefficients of the parabens suggest that octyldodecanol, oleyl alcohol, coconut oil and jojoba oil could be potential dermal permeation enhancers.

Genetic analysis of long-lived families reveals novel variants influencing high density-lipoprotein cholesterol

DEFF Research Database (Denmark)

Feitosa, Mary F; Wojczynski, Mary K; Straka, Robert

2014-01-01

The plasma levels of high-density lipoprotein cholesterol (HDL) have an inverse relationship to the risks of atherosclerosis and cardiovascular disease (CVD), and have also been associated with longevity. We sought to identify novel loci for HDL that could potentially provide new insights...

Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

NARCIS (Netherlands)

Chapman, M. John; Ginsberg, Henry N.; Amarenco, Pierre; Andreotti, Felicita; Borén, Jan; Catapano, Alberico L.; Descamps, Olivier S.; Fisher, Edward; Kovanen, Petri T.; Kuivenhoven, Jan Albert; Lesnik, Philippe; Masana, Luis; Nordestgaard, Børge G.; Ray, Kausik K.; Reiner, Zeljko; Taskinen, Marja-Riitta; Tokgözoglu, Lale; Tybjærg-Hansen, Anne; Watts, Gerald F.

2011-01-01

Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density

Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

DEFF Research Database (Denmark)

Chapman, M John; Ginsberg, Henry N; Amarenco, Pierre

2011-01-01

Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipop...

Effects of Food Based Yeast on Oxidant-Antioxidant Systems in Rats fed by High Cholesterol Diet

OpenAIRE

Savaş, Hasan Basri; Yüksel, Özlem; Şanlıdere Aloğlu, Hatice; Öner, Zübeyde; Demir Özer, Ezgi; Gültekin, Fatih

2013-01-01

In living organisms, oxidant and antioxidant systems are in a balance. In the present study, our aim was to study the effects of Cryptococcus humicola, which is a food based yeast whose cholesterol lowering activity is under investigation, on oxidant and antioxidant systems.31 adult male, Wistar albino rats weighing 200-250 gr were included in the study. Rats were divided into four groups based on their diets. Group 1(Control Group) was fed a normal diet, Group 2 was fed a high cholesterol di...

Remnant cholesterol as a cause of ischemic heart disease

DEFF Research Database (Denmark)

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

2014-01-01

This review focuses on remnant cholesterol as a causal risk factor for ischemic heart disease (IHD), on its definition, measurement, atherogenicity, and levels in high risk patient groups; in addition, present and future pharmacological approaches to lowering remnant cholesterol levels...... are considered. Observational studies show association between elevated levels of remnant cholesterol and increased risk of cardiovascular disease, even when remnant cholesterol levels are defined, measured, or calculated in different ways. In-vitro and animal studies also support the contention that elevated...... 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...

Cholesterol Check (A Minute of Health with CDC)

Centers for Disease Control (CDC) Podcasts

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.

Cholesterol and Health

Indian Academy of Sciences (India)

fats and oil in the diet on the other hand. Gallstones result from ... such factors as high levels of estrogens, multiple pregnancies, obesity, genetic factors and certain ... protein with an inner core of cholesterol and triglycerides. Lipoproteins are ...

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

KAUST Repository

Mandal, Pritam; Noutsi, Bakiza Kamal; Chaieb, Saharoui

2016-01-01

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

Cold labelled substrate and estimation of cholesterol esterification rate in lecithin cholesterol acyltransferase radioassay

International Nuclear Information System (INIS)

Dobiasova, M.; Schuetzova, M.

1986-01-01

A new method is described of cold labelling of blood serum, plasma and body fluids containing lecithin cholesterol acyltransferase (LCAT) and/or lipoproteins for radioassay to assess the cholesterol esterification rate. The method uses the principle of transfer, in refrigeration conditions, of 14 C-cholesterol from filter paper discs to the fluids. The preparation of the disc guarantees homogeneous labelling and high stability. The use of the labelling disc was shown to be reliable, easy and fast and suitable for accurate assessment of LCAT reaction, applicable in the widest possible enzyme concentration range. It was also, found suited for the measurement of the esterification rate of rabbit intraocular fluid which is a medium with the lowest contents of the substrate and LCAT. (L.O.)

Sex Differences in the Hepatic Cholesterol Sensing Mechanisms in Mice

Directory of Open Access Journals (Sweden)

Ingemar Björkhem

2013-09-01

Full Text Available Cholesterol is linked to many multifactorial disorders, including different forms of liver disease where development and severity depend on the sex. We performed a detailed analysis of cholesterol and bile acid synthesis pathways at the level of genes and metabolites combined with the expression studies of hepatic cholesterol uptake and transport in female and male mice fed with a high-fat diet with or without cholesterol. Lack of dietary cholesterol led to a stronger response of the sterol sensing mechanism in females, resulting in higher expression of cholesterogenic genes compared to males. With cholesterol in the diet, the genes were down-regulated in both sexes; however, males maintained a more efficient hepatic metabolic flux through the pathway. Females had higher content of hepatic cholesterol but this was likely not due to diminished excretion but rather due to increased synthesis and absorption. Dietary cholesterol and sex were not important for gallbladder bile acids composition. Neither sex up-regulated Cyp7a1 upon cholesterol loading and there was no compensatory up-regulation of Abcg5 or Abcg8 transporters. On the other hand, females had higher expression of the Ldlr and Cd36 genes. These findings explain sexual dimorphism of cholesterol metabolism in response to dietary cholesterol in a high-fat diet in mice, which contributes to understanding the sex-basis of cholesterol-associated liver diseases.

Enzymatic lipophilization of epicatechin with free fatty acids and its effect on antioxidative capacity in crude camellia seed oil.

Science.gov (United States)

Chen, Sa-Sa; Luo, Shui-Zhong; Zheng, Zhi; Zhao, Yan-Yan; Pang, Min; Jiang, Shao-Tong

2017-02-01

Crude camellia seed oil is rich in free fatty acids, which must be removed to produce an oil of acceptable quality. In the present study, we reduced the free fatty acid content of crude camellia seed oil by lipophilization of epicatechin with these free fatty acids in the presence of Candida antarctica lipase B (Novozym 435), and this may enhance the oxidative stability of the oil at the same time. The acid value of crude camellia seed oil reduced from 3.7 to 2.5 mgKOH g -1 after lipophilization. Gas chomatography-mass spectrometry analysis revealed that epicatechin oleate and epicatechin palmitate were synthesized in the lipophilized oil. The peroxide, p-anisidine, and total oxidation values during heating of the lipophilized oil were much lower than that of the crude oil and commercially available camellia seed oil, suggesting that lipophilized epicatechin derivatives could help enhance the oxidative stability of edible oil. The enzymatic process to lipophilize epicatechin with the free fatty acids in crude camellia seed oil described in the present study could decrease the acid value to meet the quality standards for commercial camellia seed oil and, at the same time, obtain a new edible camellia seed oil product with good oxidative stability. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Remnant cholesterol as a causal risk factor for ischemic heart disease

DEFF Research Database (Denmark)

Varbo, Anette; Benn, Marianne; Tybjærg-Hansen, Anne

2013-01-01

The aim of this study was to test the hypothesis that elevated nonfasting remnant cholesterol is a causal risk factor for ischemic heart disease independent of reduced high-density lipoprotein (HDL) cholesterol.......The aim of this study was to test the hypothesis that elevated nonfasting remnant cholesterol is a causal risk factor for ischemic heart disease independent of reduced high-density lipoprotein (HDL) cholesterol....

Cholesterol: a novel regulatory role in myelin formation.

Science.gov (United States)

Saher, Gesine; Quintes, Susanne; Nave, Klaus-Armin

2011-02-01

Myelin consists of tightly compacted membranes that form an insulating sheath around axons. The function of myelin for rapid saltatory nerve conduction is dependent on its unique composition, highly enriched in glycosphingolipids and cholesterol. Cholesterol emerged as the only integral myelin component that is essential and rate limiting for the development of CNS and PNS myelin. Experiments with conditional mouse mutants that lack cholesterol biosynthesis in oligodendrocytes revealed that only minimal changes of the CNS myelin lipid composition are tolerated. In Schwann cells of the PNS, protein trafficking and myelin compaction depend on cholesterol. In this review, the authors summarize the role of cholesterol in myelin biogenesis and myelin disease.

Association between non-high-density lipoprotein cholesterol concentrations and mortality from coronary heart disease among Japanese men and women: the Ibaraki Prefectural Health Study.

Science.gov (United States)

Noda, Hiroyuki; Iso, Hiroyasu; Irie, Fujiko; Sairenchi, Toshimi; Ohtaka, Emiko; Ohta, Hitoshi

2010-02-01

The aim of this study was to examine whether non-high-density lipoprotein cholesterol (non-HDL-cholesterol) raises the risk of coronary heart disease in a dose-response fashion in a non-obese population with low total cholesterol levels and high HDL-cholesterol levels, such as Japanese. A total of 30,802 men and 60,417 women, aged 40 to 79 years with no history of stroke or coronary heart disease, completed a baseline risk factor survey in 1993 under the auspices of the Ibaraki Prefectural Health Study. Systematic mortality surveillance through 2003 identified 539 coronary heart disease deaths. The mean values for non-HDL-cholesterol were 140 mg/dL for men and 151 mg/dL for women. The corresponding mean values were 193 mg/dL and 208 mg/dL total cholesterol and 52 mg/dL and 57 mg/dL HDL-cholesterol, respectively. Men with non-HDL-cholesterol > or = 180 mg/dL had a two-fold higher age-adjusted risk of mortality from coronary heart disease than did those with non-HDL-cholesterol or = 180 mg/dL versus <100 mg/dL of non-HDL-cholesterol was 2.22 (95% confidence interval: 1.37 to 3.62) for men and 0.71 (0.37 to 1.34) for women. Higher concentrations of non-HDL-cholesterol were associated with an increased risk of mortality from coronary heart disease for men, but not for women.

Changes in plasma low-density lipoprotein (LDL)- and high-density lipoprotein cholesterol in hypo- and hyperthyroid patients are related to changes in free thyroxine, not to polymorphisms in LDL receptor or cholesterol ester transfer protein genes

NARCIS (Netherlands)

Diekman, M. J.; Anghelescu, N.; Endert, E.; Bakker, O.; Wiersinga, W. M.

2000-01-01

Thyroid function disorders lead to changes in lipoprotein metabolism. Both plasma low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) increase in hypothyroidism and decrease in hyperthyroidism. Changes in LDL-C relate to altered clearance of LDL particles

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

Science.gov (United States)

Corral, Pablo; Schreier, Laura

2014-01-01

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

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.

Cholesterol and myelin biogenesis.

Science.gov (United States)

Saher, Gesine; Simons, Mikael

2010-01-01

Myelin consists of several layers of tightly compacted membranes wrapped around axons in the nervous system. The main function of myelin is to provide electrical insulation around the axon to ensure the rapid propagation of nerve conduction. As the myelinating glia terminally differentiates, they begin to produce myelin membranes on a remarkable scale. This membrane is unique in its composition being highly enriched in lipids, in particular galactosylceramide and cholesterol. In this review we will summarize the role of cholesterol in myelin biogenesis in the central and peripheral nervous system.

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

Science.gov (United States)

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

2008-11-04

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

Cholesterol metabolism and serum non-cholesterol sterols: summary of 13 plant stanol ester interventions.

Science.gov (United States)

Hallikainen, Maarit; Simonen, Piia; Gylling, Helena

2014-04-27

The efficacy and safety of plant stanols added to food products as serum cholesterol lowering agents have been demonstrated convincingly, but their effects on cholesterol metabolism and on serum non-cholesterol sterols is less evaluated. The aim of this study was to assess the validity of serum non-cholesterol sterols and squalene as bioindices of cholesterol synthesis and absorption, and to examine how the individual serum non-cholesterol sterols respond to consumption of plant stanols. We collected all randomized, controlled plant stanol ester (STAEST) interventions in which serum cholestanol, plant sterols campesterol and sitosterol, and at least two serum cholesterol precursors had been analysed. According to these criteria, there was a total of 13 studies (total 868 subjects without lipid-lowering medication; plant stanol doses varied from 0.8 to 8.8 g/d added in esterified form; the duration of the studies varied from 4 to 52 weeks). Serum non-cholesterol sterols were assayed with gas-liquid chromatography, cholesterol synthesis with the sterol balance technique, and fractional cholesterol absorption with the dual continuous isotope feeding method. The results demonstrated that during the control and the STAEST periods, the serum plant sterol/cholesterol- and the cholestanol/cholesterol-ratios reflected fractional cholesterol absorption, and the precursor sterol/cholesterol-ratios reflected cholesterol synthesis. Plant sterol levels were dose-dependently reduced by STAEST so that 2 g of plant stanols reduced serum campesterol/cholesterol-ratio on average by 32%. Serum cholestanol/cholesterol-ratio was reduced less frequently than those of the plant sterols by STAEST, and the cholesterol precursor sterol ratios did not change consistently in the individual studies emphasizing the importance of monitoring more than one surrogate serum marker. Serum non-cholesterol sterols are valid markers of cholesterol absorption and synthesis even during cholesterol

Cholesterol lipoproteins and prevalence of dyslipidemias in urban Asian Indians: A cross sectional study

Directory of Open Access Journals (Sweden)

Soneil Guptha

2014-05-01

Conclusions: Mean cholesterol and LDL cholesterol are low and triglycerides were high in urban Asian Indians. Most prevalent dyslipidemias are borderline high LDL, low HDL and high triglycerides. Subjects with high socioeconomic status, high fat intake and greater adiposity have higher total and LDL cholesterol and triglyceride and lower HDL cholesterol.

Inhibition of serum cholesterol oxidation by dietary vitamin C and selenium intake in high fat fed rats.

Science.gov (United States)

Menéndez-Carreño, M; Ansorena, D; Milagro, F I; Campión, J; Martínez, J A; Astiasarán, I

2008-04-01

Cholesterol oxidation products (COPs) have been considered as specific in vivo markers of oxidative stress. In this study, an increased oxidative status was induced in Wistar rats by feeding them a high-fat diet (cafeteria diet). Another group of animals received the same diet supplemented with a combination of two different antioxidants, ascorbic acid (100 mg/kg rat/day) and sodium selenite (200 microg/kg rat/day) and a third group fed on a control diet. Total and individual COPs analysis of the different diets showed no differences among them. At the end of the experimental trial, rats were sacrificed and serum cholesterol, triglycerides and COPs were measured. None of the diets induced changes in rats body weight, total cholesterol and triglycerides levels. Serum total COPs in rats fed on the high-fat diet were 1.01 microg/ml, two times the amount of the control rats (0.47 microg/ml). When dietary antioxidant supplementation was given, serum total COPs concentration (0.44 microg/ml) showed the same levels than those of the rats on control diet. 7beta-hydroxycholesterol, formed non-enzymatically via cholesterol peroxidation in the presence of reactive oxygen species, showed slightly lower values in the antioxidant-supplemented animals compared to the control ones. This study confirms the importance of dietary antioxidants as protective factors against the formation of oxysterols.

Changes in the serum profiles of lipids and cholesterol in sheep ...

African Journals Online (AJOL)

The samples were used for haematological and parasitological analyses and determination of serum concentrations of total cholesterol, triglycerides, high density lipoprotein-cholesterol (HDL-cholesterol) and low density lipoproteincholesterol (LDL-cholesterol). All animals in the infected group showed parasitaemia by day ...

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) ...

Plasma cholesterol and related lipid levels of seemingly healthy ...

African Journals Online (AJOL)

The purpose of this study was achieved through analysis of fasting plasma samples for the following: Total cholesterol (TC), Triacylglycerols (TG), High density lipoprotein cholesterol (HDL), Low density lipoprotein cholesterol (LDL), and molar ratios of LDL/HDL, TC/ HDL, and TC/TG. Methods: One hundred and seventy four ...

Survival of adult neurons lacking cholesterol synthesis in vivo.

Science.gov (United States)

Fünfschilling, Ursula; Saher, Gesine; Xiao, Le; Möbius, Wiebke; Nave, Klaus-Armin

2007-01-02

Cholesterol, an essential component of all mammalian plasma membranes, is highly enriched in the brain. Both during development and in the adult, brain cholesterol is derived from local cholesterol synthesis and not taken up from the circulation. However, the contribution of neurons and glial cells to total brain cholesterol metabolism is unknown. Using conditional gene inactivation in the mouse, we disrupted the squalene synthase gene (fdft1), which is critical for cholesterol synthesis, in cerebellar granule cells and some precerebellar nuclei. Mutant mice showed no histological signs of neuronal degeneration, displayed ultrastructurally normal synapses, and exhibited normal motor coordination. This revealed that these adult neurons do not require cell-autonomous cholesterol synthesis for survival or function. We conclude that at least some adult neurons no longer require endogenous cholesterol synthesis and can fully meet their cholesterol needs by uptake from their surrounding. Glia are a likely source of cholesterol in the central nervous system.

Survival of adult neurons lacking cholesterol synthesis in vivo

Directory of Open Access Journals (Sweden)

Möbius Wiebke

2007-01-01

Full Text Available Abstract Background Cholesterol, an essential component of all mammalian plasma membranes, is highly enriched in the brain. Both during development and in the adult, brain cholesterol is derived from local cholesterol synthesis and not taken up from the circulation. However, the contribution of neurons and glial cells to total brain cholesterol metabolism is unknown. Results Using conditional gene inactivation in the mouse, we disrupted the squalene synthase gene (fdft1, which is critical for cholesterol synthesis, in cerebellar granule cells and some precerebellar nuclei. Mutant mice showed no histological signs of neuronal degeneration, displayed ultrastructurally normal synapses, and exhibited normal motor coordination. This revealed that these adult neurons do not require cell-autonomous cholesterol synthesis for survival or function. Conclusion We conclude that at least some adult neurons no longer require endogenous cholesterol synthesis and can fully meet their cholesterol needs by uptake from their surrounding. Glia are a likely source of cholesterol in the central nervous system.

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

Science.gov (United States)

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

2017-10-01

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

Interaction of pathogens with host cholesterol metabolism.

Science.gov (United States)

Sviridov, Dmitri; Bukrinsky, Michael

2014-10-01

Pathogens of different taxa, from prions to protozoa, target cellular cholesterol metabolism to advance their own development and to impair host immune responses, but also causing metabolic complications, for example, atherosclerosis. This review describes recent findings of how pathogens do it. A common theme in interaction between pathogens and host cholesterol metabolism is pathogens targeting lipid rafts of the host plasma membrane. Many intracellular pathogens use rafts as an entry gate, taking advantage of the endocytic machinery and high abundance of outward-looking molecules that can be used as receptors. At the same time, disruption of the rafts' functional capacity, achieved by the pathogens through a number of various means, impairs the ability of the host to generate immune response, thus helping pathogen to thrive. Pathogens cannot synthesize cholesterol, and salvaging host cholesterol helps pathogens build advanced cholesterol-containing membranes and assembly platforms. Impact on cholesterol metabolism is not limited to the infected cells; proteins and microRNAs secreted by infected cells affect lipid metabolism systemically. Given an essential role that host cholesterol metabolism plays in pathogen development, targeting this interaction may be a viable strategy to fight infections, as well as metabolic complications of the infections.

A Statistical Study of Serum Cholesterol Level by Gender and Race.

Science.gov (United States)

Tharu, Bhikhari Prasad; Tsokos, Chris P

2017-07-25

Cholesterol level (CL) is growing concerned as health issue in human health since it is considered one of the causes in heart diseases. A study of cholesterol level can provide insight about its nature and characteristics. A cross-sectional study. National Health and Nutrition Examination Survey (NHANS) II was conducted on a probability sample of approximately 28,000 persons in the USA and cholesterol level is obtained from laboratory results. Samples were selected so that certain population groups thought to be at high risk of malnutrition. Study included 11,864 persons for CL cases with 9,602 males and 2,262 females with races: whites, blacks, and others. Non-parametric statistical tests and goodness of fit test have been used to identify probability distributions. The study concludes that the cholesterol level exhibits significant racial and gender differences in terms of probability distributions. The study has concluded that white people are relatively higher at risk than black people to have risk line and high risk cholesterol. The study clearly indicates that black males normally have higher cholesterol. Females have lower variation in cholesterol than males. There exists gender and racial discrepancies in cholesterol which has been identified as lognormal and gamma probability distributions. White individuals seem to be at a higher risk of having high risk cholesterol level than blacks. Females tend to have higher variation in cholesterol level than males.

Bioavailability assessment of the lipophilic benfotiamine as compared to a water-soluble thiamin derivative.

Science.gov (United States)

Bitsch, R; Wolf, M; Möller, J; Heuzeroth, L; Grüneklee, D

1991-01-01

The bioequivalence of thiamin in 2 therapeutically used preparations was tested in 10 healthy young men. Thiamin was orally administered either as lipophilic benfotiamine or as water-soluble thiamin mononitrate. Biokinetic data, measured as area under the curve and maximal concentration in plasma and hemolysate after ingestion, demonstrated a significantly improved bioavailability from the lipophilic derivative despite an ingested dose of only 40% as compared with the water-soluble salt. A superior cellular efficacy of benfotiamine was also concluded from the short-term stimulation of the thiamin-dependent transketolase activity in erythrocytes.

Can non-cholesterol sterols and lipoprotein subclasses distribution predict different patterns of cholesterol metabolism and statin therapy response?

Science.gov (United States)

Gojkovic, Tamara; Vladimirov, Sandra; Spasojevic-Kalimanovska, Vesna; Zeljkovic, Aleksandra; Vekic, Jelena; Kalimanovska-Ostric, Dimitra; Djuricic, Ivana; Sobajic, Sladjana; Jelic-Ivanovic, Zorana

2017-03-01

Cholesterol homeostasis disorders may cause dyslipidemia, atherosclerosis progression and coronary artery disease (CAD) development. Evaluation of non-cholesterol sterols (NCSs) as synthesis and absorption markers, and lipoprotein particles quality may indicate the dyslipidemia early development. This study investigates associations of different cholesterol homeostasis patterns with low-density (LDL) and high-density lipoproteins (HDL) subclasses distribution in statin-treated and statin-untreated CAD patients, and potential use of aforementioned markers for CAD treatment optimization. The study included 78 CAD patients (47 statin-untreated and 31 statin-treated) and 31 controls (CG). NCSs concentrations were quantified using gas chromatography- flame ionization detection (GC-FID). Lipoprotein subclasses were separated by gradient gel electrophoresis. In patients, cholesterol-synthesis markers were significantly higher comparing to CG. Cholesterol-synthesis markers were inversely associated with LDL size in all groups. For cholesterol homeostasis estimation, each group was divided to good and/or poor synthetizers and/or absorbers according to desmosterol and β-sitosterol median values. In CG, participants with reduced cholesterol absorption, the relative proportion of small, dense LDL was higher in those with increased cholesterol synthesis compared to those with reduced synthesis (p<0.01). LDL I fraction was significantly higher in poor synthetizers/poor absorbers subgroup compared to poor synthetizers/good absorbers (p<0.01), and good synthetizers/poor absorbers (p<0.01). Statin-treated patients with increased cholesterol absorption had increased proportion of LDL IVB (p<0.05). The results suggest the existence of different lipoprotein abnormalities according to various patterns of cholesterol homeostasis. Desmosterol/β-sitosterol ratio could be used for estimating individual propensity toward dyslipidemia development and direct the future treatment.

Effect of different fat-enriched meats on non-cholesterol sterols and oxysterols as markers of cholesterol metabolism: Results of a randomized and cross-over clinical trial.

Science.gov (United States)

Baila-Rueda, L; Mateo-Gallego, R; Pérez-Calahorra, S; Lamiquiz-Moneo, I; de Castro-Orós, I; Cenarro, A; Civeira, F

2015-09-01

Different kinds of fatty acids can affect the synthesis, absorption, and elimination of cholesterol. This study was carried out to assess the associations of cholesterol metabolism with the intake of two meats with different fatty acid composition in healthy volunteers. The study group was composed of 20 subjects (12 males and eight females; age, 34.4 ± 11.6 years; body mass index (BMI), 23.5 ± 2.3 kg/m(2); low-density lipoprotein (LDL) cholesterol, 2.97 ± 0.55 mmol/l; high-density lipoprotein (HDL) cholesterol, 1.61 ± 0.31 mmol/l; triglycerides (TG), 1.06 ± 0.41 mmol/l) who completed a 30-day randomized and cross-over study to compare the cholesterol metabolism effect of 250 g of low-fat lamb versus 250 g of high-fat lamb per day in their usual diet. Cholesterol absorption, synthesis, and elimination were estimated from the serum non-cholesterol sterol and oxysterol concentrations analyzed by a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). No changes in weight, plasma lipids, or physical activity were observed across the study. Cholesterol intestinal absorption was decreased with both diets. Cholesterol synthesis and elimination decreased during the low-fat lamb dietary intervention (ρ = 0.048 and ρ = 0.005, respectively). Acute changes in the diet fat content modify the synthesis, absorption, and biliary elimination of cholesterol. These changes were observed even in the absence of total and LDL cholesterol changes in plasma. ClinicalTrials.gov PRS, NCT02259153. Copyright © 2015 Elsevier B.V. All rights reserved.

Cholesterol Transport Revisited : A New Turbo Mechanism to Drive Cholesterol Excretion

NARCIS (Netherlands)

de Boer, Jan Freark; Kuipers, Folkert; Groen, Albert K.

A fine-tuned balance between cholesterol uptake and excretion by the body is pivotal to maintain health and to remain free from the deleterious consequences of cholesterol accumulation such as cardiovascular disease. The pathways involved in intracellular and extracellular cholesterol transport are

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 ...

High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies.

Science.gov (United States)

Gordon, D J; Probstfield, J L; Garrison, R J; Neaton, J D; Castelli, W P; Knoke, J D; Jacobs, D R; Bangdiwala, S; Tyroler, H A

1989-01-01

The British Regional Heart Study (BRHS) reported in 1986 that much of the inverse relation of high-density lipoprotein cholesterol (HDLC) and incidence of coronary heart disease was eliminated by covariance adjustment. Using the proportional hazards model and adjusting for age, blood pressure, smoking, body mass index, and low-density lipoprotein cholesterol, we analyzed this relation separately in the Framingham Heart Study (FHS), Lipid Research Clinics Prevalence Mortality Follow-up Study (LRCF) and Coronary Primary Prevention Trial (CPPT), and Multiple Risk Factor Intervention Trial (MRFIT). In CPPT and MRFIT (both randomized trials in middle-age high-risk men), only the control groups were analyzed. A 1-mg/dl (0.026 mM) increment in HDLC was associated with a significant coronary heart disease risk decrement of 2% in men (FHS, CPPT, and MRFIT) and 3% in women (FHS). In LRCF, where only fatal outcomes were documented, a 1-mg/dl increment in HDLC was associated with significant 3.7% (men) and 4.7% (women) decrements in cardiovascular disease mortality rates. The 95% confidence intervals for these decrements in coronary heart and cardiovascular disease risk in the four studies overlapped considerably, and all contained the range 1.9-2.9%. HDLC levels were essentially unrelated to non-cardiovascular disease mortality. When differences in analytic methodology were eliminated, a consistent inverse relation of HDLC levels and coronary heart disease event rates was apparent in BRHS as well as in the four American studies.

Photoaffinity labeling with cholesterol analogues precisely maps a cholesterol-binding site in voltage-dependent anion channel-1.

Science.gov (United States)

Budelier, Melissa M; Cheng, Wayland W L; Bergdoll, Lucie; Chen, Zi-Wei; Janetka, James W; Abramson, Jeff; Krishnan, Kathiresan; Mydock-McGrane, Laurel; Covey, Douglas F; Whitelegge, Julian P; Evers, Alex S

2017-06-02

Voltage-dependent anion channel-1 (VDAC1) is a highly regulated β-barrel membrane protein that mediates transport of ions and metabolites between the mitochondria and cytosol of the cell. VDAC1 co-purifies with cholesterol and is functionally regulated by cholesterol, among other endogenous lipids. Molecular modeling studies based on NMR observations have suggested five cholesterol-binding sites in VDAC1, but direct experimental evidence for these sites is lacking. Here, to determine the sites of cholesterol binding, we photolabeled purified mouse VDAC1 (mVDAC1) with photoactivatable cholesterol analogues and analyzed the photolabeled sites with both top-down mass spectrometry (MS), and bottom-up MS paired with a clickable, stable isotope-labeled tag, FLI -tag. Using cholesterol analogues with a diazirine in either the 7 position of the steroid ring (LKM38) or the aliphatic tail (KK174), we mapped a binding pocket in mVDAC1 localized to Thr 83 and Glu 73 , respectively. When Glu 73 was mutated to a glutamine, KK174 no longer photolabeled this residue, but instead labeled the nearby Tyr 62 within this same binding pocket. The combination of analytical strategies employed in this work permits detailed molecular mapping of a cholesterol-binding site in a protein, including an orientation of the sterol within the site. Our work raises the interesting possibility that cholesterol-mediated regulation of VDAC1 may be facilitated through a specific binding site at the functionally important Glu 73 residue. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Cholesterol efflux is differentially regulated in neurons and astrocytes: implications for brain cholesterol homeostasis

Science.gov (United States)

Chen, Jing; Zhang, Xiaolu; Kusumo, Handojo; Costa, Lucio G.; Guizzetti, Marina

2012-01-01

Disruption of cholesterol homeostasis in the central nervous system (CNS) has been associated with neurological, neurodegenerative, and neurodevelopmental disorders. The CNS is a closed system with regard to cholesterol homeostasis, as cholesterol-delivering lipoproteins from the periphery cannot pass the blood-brain-barrier and enter the brain. Different cell types in the brain have different functions in the regulation of cholesterol homeostasis, with astrocytes producing and releasing apolipoprotein E and lipoproteins, and neurons metabolizing cholesterol to 24(S)-hydroxycholesterol. We present evidence that astrocytes and neurons adopt different mechanisms also in regulating cholesterol efflux. We found that in astrocytes cholesterol efflux is induced by both lipid-free apolipoproteins and lipoproteins, while cholesterol removal from neurons is triggered only by lipoproteins. The main pathway by which apolipoproteins induce cholesterol efflux is through ABCA1. By upregulating ABCA1 levels and by inhibiting its activity and silencing its expression, we show that ABCA1 is involved in cholesterol efflux from astrocytes but not from neurons. Furthermore, our results suggest that ABCG1 is involved in cholesterol efflux to apolipoproteins and lipoproteins from astrocytes but not from neurons, while ABCG4, whose expression is much higher in neurons than astrocytes, is involved in cholesterol efflux from neurons but not astrocytes. These results indicate that different mechanisms regulate cholesterol efflux from neurons and astrocytes, reflecting the different roles that these cell types play in brain cholesterol homeostasis. These results are important in understanding cellular targets of therapeutic drugs under development for the treatments of conditions associated with altered cholesterol homeostasis in the CNS. PMID:23010475

Acute Effects of Apple Cider Vinegar Intake on Some Biochemical Risk Factors of Atherosclerosis in Rabbits Fed with a High Cholesterol Diet

Directory of Open Access Journals (Sweden)

M Setorki

2012-05-01

Full Text Available

Background and Objectives: Metabolic changes in postprandial stage, especially after consumption of high fat meal cause atherosclerosis and increase the risk of cardiovascular diseases. Apple cider vinegar is an acidic juice with useful medicinal effects. In this research; we investigated acute effects of apple cider vinegar intake on some of the biochemical atherosclerosis risk factors in high cholesterol fed rabbits.

Methods: Thirty two male New Zealand rabbits were randomly divided into four groups: normal diet group, high cholesterol diet group (%1cholesterol, %1 cholesterol with 5ml apple cider vinegar group, %1 cholesterol with 10ml apple cider vinegar group. The C-Reactive Protein (CRP, low density lipoprotein (LDL-C, high density lipoprotein (HDL-C, total cholesterol (TC, malondialdehyde (MDA, oxidized-LDL (OxLDL, serum glutamic pyruvic transaminase (SGPT, serum glutamic oxaloacetate transaminase (SGOT, nitrite, nitrate, glucose, fibrinogen triacylglycerol (TG, apolipoprotein A (ApoA1, apolipoprotein B (ApoB100 were all measured before the experiment and three hours after feeding with these treatment diets.

Results: In high cholesterol diet fibrinogen, nitrite, glucose, OxLDL, MDA and CRP showed a significant increase compared to normal diet. Significant differences were observed between both groups of apple cider vinegar by fibrinogen in comparison with hypercholesterolemic diet. Using 10ml apple cider vinegar with cholesterolemic diet caused a significant reduction in Ox-LDL, MDA and glucose in comparison with hypercholesterolemic diet. Moreover, the consumption of 5ml apple cider vinegar with cholesterolemic diet caused a significant decrease in LDL-C and TC compared to hypercholesterolemic diet. No significant difference was found between apple cider vinegar taking groups and

Normal Non-HDL Cholesterol, Low Total Cholesterol, and HDL Cholesterol Levels in Sickle Cell Disease Patients in the Steady State: A Case-Control Study of Tema Metropolis.

Science.gov (United States)

Ephraim, Richard K D; Adu, Patrick; Ake, Edem; Agbodzakey, Hope; Adoba, Prince; Cudjoe, Obed; Agoni, Clement

2016-01-01

Background. Abnormal lipid homeostasis in sickle cell disease (SCD) is characterized by defects in plasma and erythrocyte lipids and may increase the risk of cardiovascular disease. This study assessed the lipid profile and non-HDL cholesterol level of SCD patients. Methods. A hospital-based cross-sectional study was conducted in 50 SCD patients, in the steady state, aged 8-28 years, attending the SCD clinic, and 50 healthy volunteers between the ages of 8-38 years. Serum lipids were determined by enzymatic methods and non-HDL cholesterol calculated by this formula: non-HDL-C = TC-HDL-C. Results. Total cholesterol (TC) ( p = 0.001) and high-density lipoprotein cholesterol (HDL-C) ( p < 0.0001) were significantly decreased in cases compared to controls. The levels of non-HDL-C, low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were similar among the participants. The levels of decrease in TC and HDL were associated with whether a patient was SCD-SS or SCD-SC. Systolic blood pressure and diastolic blood pressure were each significantly associated with increased VLDL [SBP, p = 0.01, OR: 0.74 (CI: 0.6-0.93); DBP, p = 0.023, OR: 1.45 (CI: 1.05-2.0)]. Conclusion. Dyslipidemia is common among participants in this study. It was more pronounced in the SCD-SS than in SCD-SC. This dyslipidemia was associated with high VLDL as well as increased SBP and DBP.

Cholesterol biosynthesis in polychlorinated biphenyl-treated rats

International Nuclear Information System (INIS)

Kling, D.; Gamble, W.

1982-01-01

After administration of polychlorinated biphenly (PCB) at 0.055 (w/w) of the diet to Wistar rats for 30 days, followed by intraperitioneal injection of tritiated water, [ 14 C]mevalonate, and [ 14 C]acetate, there was a decrease in cholesterol biosynthesis in rat liver. No significant change in cholesterol formation was observed when PCB was administered at 0.01% (w/w) of the diet. In vitro inhibition of cholesterol synthesis by rat liver microsomes was observed with PCB. Squalene 2,3-oxidocyclase activity of rat liver microsomes was not significantly altered. Desmosterol delta 24 reductase activity was inhibited only at relatively high concentrations of PCB. There was increased incorporation of radioactivity into squalene and lanosterol, in vitro, in the presence of PCB. The primary inhibition of cholesterol biosynthesis appears to be at the demethylation and rearrangement reactions between lanosterol and cholesterol in the biosynthetic pathway

Community cholesterol screening. Impact of labeling on participant behavior.

Science.gov (United States)

Gordon, R L; Klag, M J; Whelton, P K

1990-09-01

To investigate the effect of screening for an elevated cholesterol level and compliance with follow-up recommendations, we surveyed 375 participants in a free screening program at a shopping mall walk-in clinic. One hundred thirty-nine participants (37%) had desirable (less than 5.17 mmol/L [less than 200 mg/dL]), 135 (36%) had borderline (5.17 to 6.18 mmol/L [200 to 239 mg/dL]), and 101 (27%) had high (greater than 6.18 mmol/L [greater than 239 mg/dL]) cholesterol levels. Persons in the borderline and high categories were instructed to see their physicians within 2 months for confirmation of their levels. Of the 338 (90%) who responded to a follow-up questionnaire at 3 months, 8 (7%) in the desirable, 23 (22%) in the borderline, and 44 (50%) in the high group had been to see physicians concerning their cholesterol levels since the screening. In multiple logistic regression analyses only cholesterol category at time of screening, current use of antihypertensive drugs, history of coronary heart disease, and history of a high cholesterol level were associated with physician follow-up. Our results suggest that labeling persons as being at high rather than borderline risk results in greater physician follow-up.

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.

Cholesterol Test

Science.gov (United States)

... artery disease. Other names for a cholesterol test: Lipid profile, Lipid panel What is it used for? If you ... Clinic [Internet]. Mayo Foundation for Medical Education and Research; c1998-2017.Cholesterol Test: Overview; 2016 Jan 12 [ ...

Cholesterol synthesis by human fetal hepatocytes: effect of lipoproteins

International Nuclear Information System (INIS)

Carr, B.R.; Simpson, E.R.

1984-01-01

The purpose of the present investigation was to determine the effect of various lipoproteins on the rate of cholesterol synthesis of human fetal liver cells maintained in culture. This was accomplished by measuring the rate of incorporation of tritium from tritiated water or carbon 14-labeled acetate into cholesterol in human fetal liver cells. Optimal conditions for each assay were determined. When human fetal liver cells were maintained in the presence of low-density lipoprotein, cholesterol synthesis was inhibited in a concentration-dependent fashion. Intermediate--density lipoprotein and very-low-density lipoprotein also suppressed cholesterol synthesis in human fetal liver cells. In contrast, high-density lipoprotein stimulated cholesterol synthesis in human fetal liver cells. The results of the present as well as our previous investigations suggest that multiple interrelationships exist between fetal liver cholesterol synthesis and lipoprotein-cholesterol utilization by the human fetal adrenal gland and that these processes serve to regulate the lipoprotein-cholesterol levels in fetal plasma

Controlling for high-density lipoprotein cholesterol does not affect the magnitude of the relationship between alcohol and coronary heart disease.

Science.gov (United States)

Magnus, Per; Bakke, Eirin; Hoff, Dominic A; Høiseth, Gudrun; Graff-Iversen, Sidsel; Knudsen, Gun Peggy; Myhre, Ronny; Normann, Per Trygve; Næss, Øyvind; Tambs, Kristian; Thelle, Dag S; Mørland, Jørg

2011-11-22

This study tested the hypothesis that moderate alcohol intake exerts its cardioprotective effect mainly through an increase in the serum level of high-density lipoprotein cholesterol. In the Cohort of Norway (CONOR) study, 149 729 adult participants, recruited from 1994 to 2003, were followed by linkage to the Cause of Death Registry until 2006. At recruitment, questionnaire data on alcohol intake were collected, and the concentration of high-density lipoprotein cholesterol in serum was measured. Using Cox regression, we found that the adjusted hazard ratio for men for dying from coronary heart disease was 0.52 (95% confidence interval, 0.39-0.69) when consuming alcohol more than once a week compared with never or rarely. The ratio changed only slightly, to 0.55 (0.41-0.73), after the regression model included the serum level of high-density cholesterol. For women, the corresponding hazard ratios were 0.62 (0.32-1.23) and 0.68 (0.34-1.34), respectively. Alcohol intake is related to a reduced risk of death from coronary heart disease in the follow-up of a large, population-based Norwegian cohort study with extensive control for confounding factors. Our findings suggest that the serum level of high-density cholesterol is not an important intermediate variable in the possible causal pathway between moderate alcohol intake and coronary heart disease.

Plasma HDL-cholesterol and triglycerides, but not LDL-cholesterol, are associated with insulin secretion in non-diabetic subjects.

Science.gov (United States)

Natali, Andrea; Baldi, Simona; Bonnet, Fabrice; Petrie, John; Trifirò, Silvia; Tricò, Domenico; Mari, Andrea

2017-04-01

Experimental data support the notion that lipoproteins might directly affect beta cell function, however clinical data are sparse and inconsistent. We aimed at verifying whether, independently of major confounders, serum lipids are associated with alterations in insulin secretion or clearance non-diabetic subjects. Cross sectional and observational prospective (3.5yrs), multicentre study in which 1016 non-diabetic volunteers aged 30-60yrs. and with a wide range of BMI (20.0-39.9kg/m 2 ) were recruited in a setting of University hospital ambulatory care (RISC study). baseline fasting lipids, fasting and OGTT-induced insulin secretion and clearance (measured by glucose and C-peptide modeling), peripheral insulin sensitivity (by the euglycemic clamp). Lipids and OGTT were repeated in 980 subjects after 3.5years. LDL-cholesterol did not show independent associations with fasting or stimulated insulin secretion or clearance. After accounting for potential confounders, HDL-cholesterol displayed negative and triglycerides positive independent associations with fasting and OGTT insulin secretion; neither with insulin clearance. Low HDL-cholesterol and high triglycerides were associated with an increase in glucose-dependent and a decrease in non-glucose-dependent insulin secretion. Over 3.5years both an HDL-cholesterol decline and a triglycerides rise were associated with an increase in fasting insulin secretion independent of changes in body weight or plasma glucose. LDL-cholesterol does not seem to influence any major determinant of insulin bioavailability while low HDL-cholesterol and high triglycerides might contribute to sustain the abnormalities in insulin secretion that characterize the pre-diabetic state. Copyright © 2017 Elsevier Inc. All rights reserved.

Intestinal cholesterol transport: Measuring cholesterol absorption and its reverse

NARCIS (Netherlands)

Jakulj, L.

2013-01-01

Intestinal cholesterol transport might serve as an attractive future target for cardiovascular disease reduction, provided that underlying molecular mechanisms are more extensively elucidated, combined with improved techniques to measure changes in cholesterol fluxes and their possible

The Relationship between the Triglyceride to High-Density Lipoprotein Cholesterol Ratio and Metabolic Syndrome.

Science.gov (United States)

Shin, Hyun-Gyu; Kim, Young-Kwang; Kim, Yong-Hwan; Jung, Yo-Han; Kang, Hee-Cheol

2017-11-01

Metabolic syndrome is associated with cardiovascular diseases and is characterized by insulin resistance. Recent studies suggest that the triglyceride/high-density lipoprotein cholesterol (TG/HDLC) ratio predicts insulin resistance better than individual lipid levels, including TG, total cholesterol, low-density lipoprotein cholesterol (LDLC), or HDLC. We aimed to elucidate the relationship between the TG/HDLC ratio and metabolic syndrome in the general Korean population. We evaluated the data of adults ≥20 years old who were enrolled in the Korean National Health and Nutrition Examination Survey in 2013 and 2014. Subjects with angina pectoris, myocardial infarction, stroke, or cancer were excluded. Metabolic syndrome was defined by the harmonized definition. We examined the odds ratios (ORs) of metabolic syndrome according to TG/HDLC ratio quartiles using logistic regression analysis (SAS ver. 9.4; SAS Institute Inc., Cary, NC, USA). Weighted complex sample analysis was also conducted. We found a significant association between the TG/HDLC ratio and metabolic syndrome. The cutoff value of the TG/HDLC ratio for the fourth quartile was ≥3.52. After adjustment, the OR for metabolic syndrome in the fourth quartile compared with that of the first quartile was 29.65 in men and 20.60 in women (Pmetabolic syndrome.

Biogenesis of plasma membrane cholesterol

International Nuclear Information System (INIS)

Lange, Y.

1986-01-01

A striking feature of the molecular organization of eukaryotic cells is the singular enrichment of their plasma membranes in sterols. The authors studies are directed at elucidating the mechanisms underlying this inhomogeneous disposition. Cholesterol oxidase catalyzes the oxidation of plasma membrane cholesterol in intact cells, leaving intracellular cholesterol pools untouched. With this technique, the plasma membrane was shown to contain 95% of the unesterified cholesterol of cultured human fibroblasts. Cholesterol synthesized from [ 3 H] acetate moved to the plasma membrane with a half-time of 1 h at 37 0 C. They used equilibrium gradient centrifugation of homogenates of biosynthetically labeled, cholesterol oxidase treated cells to examine the distribution of newly synthesized sterols among intracellular pools. Surprisingly, lanosterol, a major precursor of cholesterol, and intracellular cholesterol both peaked at much lower buoyant density than did 3-hydroxy-3-methylglutaryl-CoA reductase. This suggests that cholesterol biosynthesis is not taken to completion in the endoplasmic reticulum. The cholesterol in the buoyant fraction eventually moved to the plasma membrane. Digitonin treatment increased the density of the newly synthesized cholesterol fractions, indicating that nascent cholesterol in transit is associated with cholesterol-rich membranes. The authors are testing the hypothesis that the pathway of cholesterol biosynthesis is spatially organized in various intracellular membranes such that the sequence of biosynthetic steps both concentrates the sterol and conveys it to the plasma membrane

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.

Bioactive Phytochemicals from Wild Arbutus unedo L. Berries from Different Locations in Portugal: Quantification of Lipophilic Components.

Science.gov (United States)

Fonseca, Daniela F S; Salvador, Ângelo C; Santos, Sónia A O; Vilela, Carla; Freire, Carmen S R; Silvestre, Armando J D; Rocha, Sílvia M

2015-06-23

The lipophilic composition of wild Arbutus unedo L. berries, collected from six locations in Penacova (center of Portugal), as well as some general chemical parameters, namely total soluble solids, pH, titratable acidity, total phenolic content and antioxidant activity was studied in detail to better understand its potential as a source of bioactive compounds. The chemical composition of the lipophilic extracts, focused on the fatty acids, triterpenoids, sterols, long chain aliphatic alcohols and tocopherols, was investigated by gas chromatography-mass spectrometry (GC-MS) analysis of the dichloromethane extracts. The lipophilic extractives of the ripe A. unedo berries ranged from 0.72% to 1.66% (w/w of dry weight), and consisted mainly of triterpenoids, fatty acids and sterols. Minor amounts of long chain aliphatic alcohols and tocopherols were also identified. Forty-one compounds were identified and among these, ursolic acid, lupeol, α-amyrin, linoleic and α-linolenic acids, and β-sitosterol were highlighted as the major components. To the best of our knowledge the current research study provides the most detailed phytochemical repository for the lipophilic composition of A. unedo, and offers valuable information for future valuation and exploitation of these berries.

Bioactive Phytochemicals from Wild Arbutus unedo L. Berries from Different Locations in Portugal: Quantification of Lipophilic Components

Directory of Open Access Journals (Sweden)

Daniela F. S. Fonseca

2015-06-01

Full Text Available The lipophilic composition of wild Arbutus unedo L. berries, collected from six locations in Penacova (center of Portugal, as well as some general chemical parameters, namely total soluble solids, pH, titratable acidity, total phenolic content and antioxidant activity was studied in detail to better understand its potential as a source of bioactive compounds. The chemical composition of the lipophilic extracts, focused on the fatty acids, triterpenoids, sterols, long chain aliphatic alcohols and tocopherols, was investigated by gas chromatography–mass spectrometry (GC–MS analysis of the dichloromethane extracts. The lipophilic extractives of the ripe A. unedo berries ranged from 0.72% to 1.66% (w/w of dry weight, and consisted mainly of triterpenoids, fatty acids and sterols. Minor amounts of long chain aliphatic alcohols and tocopherols were also identified. Forty-one compounds were identified and among these, ursolic acid, lupeol, α-amyrin, linoleic and α-linolenic acids, and β-sitosterol were highlighted as the major components. To the best of our knowledge the current research study provides the most detailed phytochemical repository for the lipophilic composition of A. unedo, and offers valuable information for future valuation and exploitation of these berries.

Atherosclerosis in familial lines of pigeons fed exogenous cholesterol.

Science.gov (United States)

Patton, N M; Brown, R V; Middleton, C C

1975-01-01

Exogenous cholesterol was fed to F1 pigeons of high and low serum cholesterol differentiated lines of White Carneau and Racing Homer pigeons that had previously been developed by selection and positive assortive mating. The serum cholesterol response of the various high and low lines was dependent upon the breed and the amount of cholesterol in the diet. Racing Homer pigeons were found to be more resistant to aortic atherosclerosis and more susceptible to coronary atherosclerosis than White Carneau pigeons. Data from necropsy examinations showed significant differences in both aortic and coronary atherosclerosis between lines within the White Carneau breed, but no differences between lines of the Racing Homer breed. Mean organ weights for the 4 lines of pigeons were reported.

The analysis of lipophilic marine toxins : development of an alternative method

NARCIS (Netherlands)

Gerssen, A.

2010-01-01

Lipophilic marine toxins are produced by certain algae species and can accumulate in filter feeding shellfish such as mussels, scallops and oysters. Consumption of contaminated shellfish can lead to severe intoxications such as diarrhea, abdominal cramps and vomiting. Methods described in

Enhancing mechanism of intestinal absorption of highly lipophilic compounds using microemulsion – Quantitative analysis of the partitioning to the mesenteric lymph in intestinal cells

Directory of Open Access Journals (Sweden)

Kazunori Iwanaga

2015-06-01

Full Text Available The purpose of this study was to quantify the effect of the fatty acid alkyl-chain length of a polyethylene glycol (PEG glyceryl ester, which was used as a microemulsion oil component, on the partitioning of highly lipophilic compounds to the mesenteric lymph after oral administration. Oil blue N, a highly lipophilic anthraquinone derivative, was orally administered to lymph duct-cannulated and untreated rats in two kinds of different microemulsions. Gelucire® 50/13 and Gelucire® 44/14 were used as the oil component with long chain and medium chain fatty acid portions, respectively, of PEG glyceryl esters in microemulsions. The cumulative amount of oil blue N in lymph fluid was almost the same between the two microemulsions, although the transferred amount of oil component (triglyceride in the lymph after administration of the Gelucire® 50/13 microemulsion was significantly higher than that of the Gelucire® 44/14 microemulsion. On the other hand, the solubility of oil blue N in Gelucire® 44/14 was much higher than that in Gelucire® 50/13. No significant differences were observed between microemulsions in the bioavailability of oil blue N. From these data, the partitioning of oil blue N to the lymph was calculated using a mathematical model, showing that the partitioning ratios of oil blue N to the lymph fluid were almost the same for both microemulsions. The solubility of oil blue N to the oil component of the microemulsions and the transfer of triglycerides to the lymph after administration of the microemulsions counteract each other, leading to similar partitioning ratios of oil blue N to the lymph.

Effects of apolipoproteins on the kinetics of cholesterol exchange

International Nuclear Information System (INIS)

Letizia, J.Y.; Phillips, M.C.

1991-01-01

The effects of apolipoproteins on the kinetics of cholesterol exchange have been investigated by monitoring the transfer of [ 14 C]cholesterol from donor phospholipid/cholesterol complexes containing human apolipoproteins A, B, or C. Negatively charged discoidal and vesicular particles containing purified apolipoproteins complexed with lipid and a trace of [ 14 C]cholesterol were incubated with a 10-fold excess of neutral, acceptor, small unilamellar vesicles. The donor and acceptor particles were separated by chromatogrphy of DEAE-Sepharose, and the rate of movement of labeled cholesterol was analyzed as a first-order exchange process. The kinetics of exchange of cholesterol from both vesicular and discoidal complexes that contain apoproteins are consistent with an aqueous diffusion mechanism, as has been established previously for PC/cholesterol SUV. Apolipoproteins A-I, A-II, reduced and carboxymethylated A-11, and B-100 present in SUV at the same lipid/protein (w/w) ratio all enhance the rate of cholesterol exchange to about the same degree. Cholesterol molecules exchange more rapidly from discoidal complexes. Generally, as the diameter of apoprotein/phospholipid/cholesterol discs decreases, t 1/2 for cholesterol exchange decreases. Since small bilayer discs have a relatively high ratio of boundary to face surface area, cholesterol molecules desorb more rapidly than from larger discs. The modulation of lipid packing by the apoprotein molecules present at the surface of lipoprotein particles affects the rate of cholesterol exchange from such particles

[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. © 2014 médecine/sciences – Inserm.

Reduction in lipophilicity improved the solubility, plasma–protein binding, and permeability of tertiary sulfonamide RORc inverse agonists

Energy Technology Data Exchange (ETDEWEB)

Fauber, Benjamin P.; René, Olivier; de Leon Boenig, Gladys; Burton, Brenda; Deng, Yuzhong; Eidenschenk, Céline; Everett, Christine; Gobbi, Alberto; Hymowitz, Sarah G.; Johnson, Adam R.; La, Hank; Liimatta, Marya; Lockey, Peter; Norman, Maxine; Ouyang, Wenjun; Wang, Weiru; Wong, Harvey (Genentech); (Argenta)

2014-08-01

Using structure-based drug design principles, we identified opportunities to reduce the lipophilicity of our tertiary sulfonamide RORc inverse agonists. The new analogs possessed improved RORc cellular potencies with >77-fold selectivity for RORc over other nuclear receptors in our cell assay suite. The reduction in lipophilicity also led to an increased plasma–protein unbound fraction and improvements in cellular permeability and aqueous solubility.

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

EFFECT OF ASCORBIC ACID ON THE RIGHT AND LEFT CORONARY ARTERIES OF MALE RABBITS FED WITH HIGH-CHOLESTEROL DIET

Directory of Open Access Journals (Sweden)

Gholamreza Dashti

2010-12-01

Full Text Available   Abstract INTRODUCTION: Atherosclerosis and cardiovascular diseases are the most common causes of death in western countries. The beneficial effect of ascorbic acid on various organs has been reported. The present study was conducted to determine the effect of ascorbic acid on the right and left coronary arteries of male rabbits fed with high-cholesterol diet. methods: Twenty white male rabbits (mean weight: 950 g were weighed and randomly divided into two groups. For 40 days, group 1 (n=10 was given a high-cholesterol (1% diet, group 2 (n=10 was fed with a high-cholesterol diet and ascorbic acid (100 mg/kg. Then both of the groups were weighed and the animals were sacrificed. The right and left coronary arteries were dissected and then fixation, tissue processing, histological sectioning and H & E staining were carried out and sections were studied by light microscopy. The results were analyzed by using the Mann Whitney test. results: Group 2 which received ascorbic acid had no fatty streaks in their coronary arteries. Significant difference in mean weight was observed before and after the diet in both groups (P<0.05. CONCLUSIONS: Histopathological study of the coronary arteries showed that the rabbits which received ascorbic acid diet did not develop fatty streaks. Thus ascorbic acid exerts an apparently inhibitory effect on fatty streak formation and may slow down or prevent atherosclerosis by countering the side effects of a high-fat meal.     Keywords: Ascorbic acid, cholesterol, coronary arteries.

Consumption of a liquid high-fat meal increases triglycerides but decreases high-density lipoprotein cholesterol in abdominally obese subjects with high postprandial insulin resistance.

Science.gov (United States)

Wang, Feng; Lu, Huixia; Liu, Fukang; Cai, Huizhen; Xia, Hui; Guo, Fei; Xie, Yulan; Huang, Guiling; Miao, Miao; Shu, Guofang; Sun, Guiju

2017-07-01

Abdominal obesity is associated with an increased risk of insulin resistance, which may be a potential contributor to dyslipidemia. However, the relationship between postprandial insulin resistance and lipid metabolism in abdominally obese subjects remains unknown. We hypothesized that postprandial dyslipidemia would be exaggerated in abdominally obese subjects with high postprandial insulin resistance. To test this hypothesis, serum glucose, insulin, triglycerides, total cholesterol, high-density lipoprotein cholesterol, and apolipoprotein B were measured at baseline and postprandial state at 0.5, 1, 2, 4, 6, and 8 hours after a liquid high-fat meal in non-abdominally obese controls (n=44) and abdominally obese subjects with low (AO-LPIR, n=40), middle (n=40), and high postprandial insulin resistance (AO-HPIR, n=40) based on the tertiles ratio of the insulin to glucose areas under the curve (AUC). Their serum adipokines were tested at baseline only. Fasting serum leptin was higher (Pinsulin resistance and controls. The present study indicated that the higher degree of postprandial insulin resistance, the more adverse lipid profiles in abdominally obese subjects, which provides insight into opportunity for screening in health. Copyright © 2017 Elsevier Inc. All rights reserved.

High Blood Pressure and Cholesterol—What You Need to Know

Centers for Disease Control (CDC) Podcasts

2011-02-01

This podcast is based on the February, 2011 CDC Vital Signs report which indicates that two out of three U.S. adults with high cholesterol and half of U.S. adults with high blood pressure don't have their condition under control which puts them at risk for heart disease and stroke. Listen to this program for ways to reduce your risk for heart disease and stroke.  Created: 2/1/2011 by Centers for Disease Control and Prevention (CDC).   Date Released: 2/1/2011.

Comparison of cardiovascular protective effects of tropical seaweeds, Kappaphycus alvarezii, Caulerpa lentillifera, and Sargassum polycystum, on high-cholesterol/high-fat diet in rats.

Science.gov (United States)

Matanjun, Patricia; Mohamed, Suhaila; Muhammad, Kharidah; Mustapha, Noordin Mohamed

2010-08-01

This study was designed to investigate the comparative in vivo cardiovascular protective effects of red, green, and brown tropical seaweeds, namely, Kappaphycus alvarezii (or Eucheuma cottonii), Caulerpa lentillifera, and Sargassum polycystum, in rats fed on high-cholesterol/high-fat (HCF) diets. Male Sprague-Dawley rats (weighing 260-300 g) on the HCF diet had significantly increased body weight, plasma total cholesterol (TC), plasma low-density lipoprotein cholesterol (LDL-C), plasma triglycerides (TG), lipid peroxidation, and erythrocyte glutathione peroxidase (GSH-Px) and superoxide dismutase levels after 16 weeks. Supplementing 5% seaweeds to HCF diet significantly reduced plasma TC (-11.4% to -18.5%), LDL-C (-22% to -49.3%), and TG (-33.7% to -36.1%) levels and significantly increased HDL-C levels (16.3-55%). Among the seaweeds, S. polycystum showed the best anti-obesity and blood GSH-Px properties, K. alvarezii showed the best antihyperlipemic and in vivo antioxidation effects, and C. lentillifera was most effective at reducing plasma TC. All seaweeds significantly reduced body weight gain, erythrocyte GSH-Px, and plasma lipid peroxidation of HCF diet rats towards the values of normal rats.

Active site-directed alkylation of Na+-K+-ATPase by digitalis sulphonate derivatives of different lipophilicity.

Science.gov (United States)

Fricke, U.; Klaus, W.; Rogatti, M.

1981-01-01

1 Sulphonate derivatives of k-strophanthidin and digitoxigenin were tested as active site-directed labels of Na+-K+-adenosine triphosphatase (Na+-ATPase) from guinea-pig heart. 2 Lipophilicity ranged between P = 93 for strophanthidin-3-tosyloxy-acetate (STA) and P = 3028 for digitoxigenin-3-tosyloxy-acetate (DTA). 3 Although the alkylating moiety of STA and DTA was identical, the reversibility of Na+-K+-ATPase inhibition varied appreciably (82% and 35% respectively). 4 It is concluded that lipophilicity contributes considerably to the irreversible binding of alkylating cardiotonic steroids to myocardial Na+-K+-ATPase. PMID:6261865

The tuber extract and flour of Dioscorea alatanormalize the blood lipid profile of rabbits treated with high cholesterol diets

Directory of Open Access Journals (Sweden)

Nelis Imanningsih

2014-08-01

rabbits treated with high cholesterol diets.Methods:DA tuber extract and flour were administrated to the rabbits for 60 days using completely randomised design. The ration treatment are as follows: 1 Basal ration as negative control (K0, 2 Basal ration + 0.5% cholesterol, as positive control (K1, 3 Basal ration + 0.5% cholesterol + DA extract 1.8 g/100 g (KE1, 4 Basal ration + cholesterol 0.5% + DA extract 3.6 g/100 g (KE2, 5 Basal ration with 15% DA flour + 0.5% cholesterol (KT1 and 6 Basal ration with 30% DA flour + 0.5% cholesterol (KT2. The Total cholesterol, HDL, LDL cholesterol in serum were analysed at baseline, days 28, days 56 and at the end of study.Results:The administration of high cholesterol (1% ration increased blood lipid levels by 16 fold compared to that of control. The administration of 15% and 30% of DA flour could maintain blood lipid profile to normal condition, in particular at 30% substitution DA flour. However the water extract of DA can not maintain a normal blood lipids of high cholesterol treated rabbitsConclusion: Dioscorea alata flour has suggested to have anti-hyperlipidemia effect. (Health Science Indones 2014;1:23-9Key words: Dioscorea alata, hyperlipidemia, atherosclerosis

Functional characteristics of a renal H+/lipophilic cation antiport system in porcine LLC-PK1 cells and rats.

Science.gov (United States)

Matsui, Ryutaro; Hattori, Ryutaro; Usami, Youhei; Koyama, Masumi; Hirayama, Yuki; Matsuba, Emi; Hashimoto, Yukiya

2018-02-01

We have recently found an H + /quinidine (a lipophilic cation, QND) antiport system in Madin-Darby canine kidney (MDCK) cells. The primary aim of the present study was to evaluate whether the H + /lipophilic cation antiport system is expressed in porcine LLC-PK 1 cells. That is, we investigated uptake and/or efflux of QND and another cation, bisoprolol, in LLC-PK 1 cells. In addition, we studied the renal clearance of bisoprolol in rats. Uptake of QND into LLC-PK 1 cells was decreased by acidification of the extracellular pH or alkalization of the intracellular pH. Cellular uptake of QND from the apical side was much greater than from the basolateral side. In addition, apical efflux of QND from LLC-PK 1 cells was increased by acidification of the extracellular pH. Furthermore, lipophilic cationic drugs significantly reduced uptake of bisoprolol in LLC-PK 1 cells. Renal clearance of bisoprolol in rats was approximately 7-fold higher than that of creatinine, and was markedly decreased by alkalization of the urine pH. The present study suggests that the H + /lipophilic cation antiport system is expressed in the apical membrane of LLC-PK 1 cells. Moreover, the H + /lipophilic cation antiport system may be responsible for renal tubular secretion of bisoprolol in rats. Copyright © 2017 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Portulaca oleracea reduces triglyceridemia, cholesterolemia, and improves lecithin: cholesterol acyltransferase activity in rats fed enriched-cholesterol diet.

Science.gov (United States)

Zidan, Y; Bouderbala, S; Djellouli, F; Lacaille-Dubois, M A; Bouchenak, M

2014-10-15

The effects of Portulaca oleracea (Po) lyophilized aqueous extract were determined on the serum high-density lipoproteins (HDL2 and HDL3) amounts and composition, as well as on lecithin: cholesterol acyltansferase (LCAT) activity. Male Wistar rats (n = 12) were fed on 1% cholesterol-enriched diet for 10 days. After this phase, hypercholesterolemic rats (HC) were divided into two groups fed the same diet supplemented or not with Portulaca oleracea (Po-HC) (0.5%) for four weeks. Serum total cholesterol (TC) and triacylglycerols (TG), and liver TG values were respectively 1.6-, 1.8-, and 1.6-fold lower in Po-HC than in HC group. Cholesterol concentrations in LDL-HDL1, HDL2, and HDL3 were respectively 1.8, 1.4-, and 2.4-fold decreased in Po-HC group. HDL2 and HDL3 amounts, which were the sum of apolipoproteins (apos), TG, cholesteryl esters (CE), unesterified cholesterol (UC), and phospholipids (PL) contents, were respectively 4.5-fold higher and 1.2-fold lower with Po treatment. Indeed, enhanced LCAT activity (1.2-fold), its cofactor-activator apo A-I (2-fold) and its reaction product HDL2-CE (2.1-fold) were observed, whereas HDL3-PL (enzyme substrate) and HDL3-UC (acyl group acceptor) were 1.2- and 2.4-fold lower. Portulaca oleracea reduces triglyceridemia, cholesterolemia, and improves reverse cholesterol transport in rat fed enriched-cholesterol diet, contributing to anti-atherogenic effects. Copyright © 2014 Elsevier GmbH. All rights reserved.

LDL-Cholesterol Increases the Transcytosis of Molecules through Endothelial Monolayers.

Science.gov (United States)

Magalhaes, Ana; Matias, Inês; Palmela, Inês; Brito, Maria Alexandra; Dias, Sérgio

2016-01-01

Cholesterol has been identified as a causative factor in numerous pathologies including atherosclerosis and cancer. One of the frequent effects of elevated cholesterol levels in humans is the compromise of endothelial function due to activation of pro-inflammatory signalling pathways. While the mechanisms involved in endothelial activation by cholesterol during an inflammatory response are well established, less is known about the mechanisms by which cholesterol may affect endothelial barrier function, which were the subject of the present study. Here we show that low density lipoprotein (LDL) increases the permeability of endothelial monolayers to high molecular weight dextrans in an LDL receptor and cholesterol-dependent manner. The increased permeability seen upon LDL treatment was not caused by disruption of cell-to-cell junctions as determined by a normal localization of VE-Cadherin and ZO-1 proteins, and no major alterations in transendothelial electrical resistance or permeability to fluorescein. We show instead that LDL increases the level of high molecular weight transcytosis and that this occurs in an LDL receptor, cholesterol and caveolae-dependent way. Our findings contribute to our understanding of the systemic pathological effects of elevated cholesterol and the transport of cargo through endothelial monolayers.

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 A.; Tietge, Uwe J. F.; Brufau, Gemma; Groen, Albert K.

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

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 A.; Tietge, Uwe J. F.; Brufau, 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

Application of GC-MS for the detection of lipophilic compounds in diverse plant tissues

Directory of Open Access Journals (Sweden)

Hellmann Hanjo

2009-04-01

Full Text Available Abstract Background The concept of metabolite profiling has been around for decades and technical innovations are now enabling it to be carried out on a large scale with respect to the number of both metabolites measured and experiments carried out. However, studies are generally confined to polar compounds alone. Here we describe a simple method for lipophilic compounds analysis in various plant tissues. Results We choose the same preparative and instrumental platform for lipophilic profiling as that we routinely use for polar metabolites measurements. The method was validated in terms of linearity, carryover, reproducibility and recovery rates, as well as using various plant tissues. As a first case study we present metabolic profiling of Arabidopsis root and shoot tissue of wild type (C24 and mutant (rsr4-1 plants deficient on vitamin B6. We found significant alterations in lipid constituent contents, especially in the roots, which were characterised by dramatic increases in several fatty acids, thus providing further hint for the role of pyridoxine in oxidative stress and lipid peroxidation. The second example is the lipophilic profiling of red and green tomato fruit cuticles of wild type (Alisa Craig and the DFD (delayed fruit deterioration mutant, which we compared and contrasted with the more focused wax analysis of these plants reported before. Conclusion We can rapidly and reliably detect and quantify over 40 lipophilic metabolites including fatty acids, fatty alcohols, alkanes, sterols and tocopherols. The method presented here affords a simple and rapid, yet robust complement to previously validated methods of polar metabolite profiling by gas-chromatography mass-spectrometry.

Cholesterol - what to ask your doctor

Science.gov (United States)

... your doctor; What to ask your doctor about cholesterol ... What is my cholesterol level? What should my cholesterol level be? What are HDL ("good") cholesterol and LDL ("bad") cholesterol? Does my cholesterol ...

How to Lower Cholesterol

Science.gov (United States)

... includes high triglyceride levels, low HDL (good) cholesterol levels, and being overweight with a large waist measurement (more than 40 inches for men and more than 35 inches for women). Physical Activity. Everyone should get regular physical activity (30 minutes ...

Nonenzymatic free-cholesterol detection via a modified highly sensitive macroporous gold electrode with platinum nanoparticles.

Science.gov (United States)

Lee, Yi-Jae; Park, Jae-Yeong

2010-12-15

A sensitive macroporous Au electrode with a highly rough surface obtained through the use of with Pt nanoparticles (macroporous Au-/nPts) is reported. It has been designed for nonenzymatic free-cholesterol biosensor applications. A macroporous Au-/nPts electrode was fabricated by electroplating Pt nanoparticles onto a coral-like shaped macroporous Au electrode structure. The macroporous Au-/nPts electrode was physically characterized by field emission scanning electron microscopy (FESEM). It was confirmed that the Pt nanoparticles were well deposited on the surface of the macroporous Au electrode. The porosity and window pore size of the macroporous Au electrode were 50% and 100-300 nm, respectively. The electroplated Pt nanoparticle size was approximately 10-20 nm. Electrochemical experiments showed that the macroporous Au-/nPts exhibited a much larger surface activation area (roughness factor (RF)=2024.7) than the macroporous Au electrode (RF=46.07). The macroporous Au-/nPts also presented a much stronger electrocatalytic activity towards cholesterol oxidation than does the macroporous Au electrode. At 0.2 V, the electrode responded linearly up to a 5 mM cholesterol concentration in a neutral media, with a detection limit of 0.015 mM and detection sensitivity of 226.2 μA mM(-1) cm(-2). Meanwhile, interfering species such as ascorbic acid (AA), acetaminophen (AP), and uric acid (UA), were effectively avoided. This novel nonenzymatic detection electrode has strong applications as an electrochemically based cholesterol biosensor. Copyright © 2010 Elsevier B.V. All rights reserved.

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

Physical inactivity interacts with an endothelial lipase polymorphism to modulate high density lipoprotein cholesterol in the GOLDN study

Science.gov (United States)

BACKGROUND: Plasma high density lipoprotein (HDL) cholesterol (HDL-C) concentration is highly heritable but is also modifiable by environmental factors including physical activity. HDL-C response to exercise varies among individuals, and this variability may be associated with genetic polymorphism...

Effects of Lactobacillus plantarum MA2 isolated from Tibet kefir on lipid metabolism and intestinal microflora of rats fed on high-cholesterol diet.

Science.gov (United States)

Wang, Yanping; Xu, Nv; Xi, Aodeng; Ahmed, Zaheer; Zhang, Bin; Bai, Xiaojia

2009-08-01

The objective of this study was to evaluate the effects of Lactobacillus plantarum MA2, an isolate from Chinese traditional Tibet kefir, on cholesterol-lowering and microflora of rat in vivo. Rats were fed on cholesterol-enriched experimental diet, supplemented with lyophilized L. plantarum MA2 powder, with a dose of 10(11) cells/day per mice. The results showed that L. plantarum MA2 feeding significantly lowered serum total cholesterol, low-density lipoprotein cholesterol, and triglycerides level, while there was no change in high-density lipoprotein cholesterol. In addition, liver total cholesterol and triglycerides was also decreased. However, fecal cholesterol and triglycerides was increased significantly (P MA2 increased the population of lactic acid bacteria and bifidobacteria in the fecal, but it did not change the number of Escherichia coli as compared to control. Moreover, pH, moisture, and organic acids in the fecal were also measured. The present results indicate the probiotic potential of the L. plantarum MA2 strain in hypocholesterolemic effect and also increasing the probiotic count in the intestine.

Low plasma lecithin : cholesterol acyltransferase and lipid transfer protein activities in growth hormone deficient and acromegalic men: role in altered high density lipoproteins

NARCIS (Netherlands)

Beentjes, JAM; van Tol, A; Sluiter, WJ; Dullaart, RPF

2000-01-01

Growth hormone (GH) deficiency and acromegaly may be associated with increased cardiovascular risk. Little is known about alterations in high density lipoproteins (HDL) in these conditions. Lecithin:cholesterol acyl transferase (LCAT) has the ability to esterify free cholesterol (FC) in HDL.

Impact of a public cholesterol screening program.

Science.gov (United States)

Fischer, P M; Guinan, K H; Burke, J J; Karp, W B; Richards, J W

1990-12-01

The National Cholesterol Education Program (NCEP) has endorsed physician case finding as the primary method to detect individuals with elevated cholesterol levels. Despite this recommendation, promotional and for-profit public screening programs have flourished. We surveyed participants of a mall-based cholesterol screening program 1 year after their screening. Sixty-four percent of those screened had not previously known their cholesterol levels. Those who were newly screened were less likely to benefit from this testing than the general public, since they were older (mean age, 55.3 years), more likely to be female (67.4%), and nonsmokers (88%). Screenees had excellent recall of their cholesterol level (mean absolute reporting error, 0.24 mmol/L [9 mg/dL]) and a good understanding of cholesterol as a coronary heart disease risk. Those with elevated cholesterol levels reported high distress from screening but no reduction in overall psychosocial well-being and an actual decrease in absenteeism. Only 53.7% of all who were advised to seek follow-up because of an elevated screening value had done so within the year following the screening program. However, of those with values greater than 6.2 mmol/L (240 mg/dL), 68% had sought follow-up. Many of those who participate in public screening programs have been previously tested, fall into low-benefit groups, or fail to comply with recommended follow-up. We therefore conclude that cholesterol screening programs of the type now commonly offered are unlikely to contribute greatly to the national efforts to further reduce coronary heart disease.

Covalent immobilization of cholesterol esterase and cholesterol oxidase on polyaniline films for application to cholesterol biosensor

Energy Technology Data Exchange (ETDEWEB)

Singh, Suman [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi-110012 (India); Solanki, Pratima R. [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi-110012 (India); Pandey, M.K. [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@mail.nplindia.ernet.in

2006-05-24

Cholesterol esterase (ChEt) and cholesterol oxidase (ChOx) have been covalently immobilized on electrochemically prepared polyaniline (PANI) films. These PANI/ChEt/ChOx enzyme films have been characterized using UV-visible, Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). Electrochemical behavior of these films has been studied using cyclic voltammetry (CV) and amperometric techniques, respectively. The PANI/ChEt/ChOx enzyme films show broad oxidation peak from 0.2 to 0.5 V. These PANI/ChEt/ChOx biosensing electrodes have a response time of about 40 s, linearity from 50 to 500 mg/dl of cholesterol oleate concentration. These PANI/ChEt/ChOx films are thermally stable up to 46 deg. C. This polyaniline based cholesterol biosensor has optimum pH in the range of 6.5-7.5, sensitivity as 7.5 x 10{sup -4} nA/mg dl and a lifetime of about 6 weeks.

Lecithin Cholesterol Acyltransferase: An Anti- or Pro-atherogenic Factor?

OpenAIRE

Rousset, Xavier; Shamburek, Robert; Vaisman, Boris; Amar, Marcelo; Remaley, Alan T.

2011-01-01

Lecithin cholesterol acyl transferase (LCAT) is a plasma enzyme that esterifies cholesterol and raises high-density lipoprotein cholesterol, but its role in atherosclerosis is not clearly established. Studies of various animal models have yielded conflicting results, but studies done in rabbits and non-human primates, which more closely simulate human lipoprotein metabolism, indicate that LCAT is likely atheroprotective. Although suggestive, there are also no biomarker studies that mechanisti...

Dietary Rhus coriaria L. powder reduces the blood cholesterol ...

African Journals Online (AJOL)

Dietary Rhus coriaria L. powder reduces the blood cholesterol, VLDL-c and ... of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL-c), low ... birds had higher feed conversion ratio compared with birds in the other treatments.

Self-Reported High-Cholesterol Prevalence in the Brazilian Population: Analysis of the 2013 National Health Survey.

Science.gov (United States)

Lotufo, Paulo A; Santos, Raul D; Sposito, Andrei C; Bertolami, Marcelo; Rocha-Faria, Jose; Izar, M Cristina; Szwarcwald, Celia; Prado, Rogério R; Stoppa, Sheila R; Malta, Deborah C; Bensenor, Isabela M

2017-05-01

Data on the prevalence of dyslipidemia in Brazil are scarce, with surveys available only for some towns. To evaluate the prevalence of the self-reported medical diagnosis of high cholesterol in the Brazilian adult population by use of the 2013 National Health Survey data. Descriptive study assessing the 2013 National Health Survey data, a household-based epidemiological survey with a nationally representative sample and self-reported information. The sample consisted of 60,202 individuals who reported a medical diagnosis of dyslipidemia. The point prevalence and 95% confidence interval (95%CI) for the medical diagnosis of high cholesterol/triglyceride by gender, age, race/ethnicity, geographic region and educational level were calculated. Adjusted odds ratio was calculated. Of the 60,202 participants, 14.3% (95%CI=13.7-14.8) never had their cholesterol or triglyceride levels tested, but a higher frequency of women, white individuals, elderly and those with higher educational level had their cholesterol levels tested within the last year. The prevalence of the medical diagnosis of high cholesterol was 12.5% (9.7% in men and 15.1% in women), and women had 60% higher probability of a diagnosis of high cholesterol than men. The frequency of the medical diagnosis of high cholesterol increased up to the age of 59 years, being higher in white individuals or those of Asian heritage, in those with higher educational level and in residents of the Southern and Southeastern regions. The importance of dyslipidemia awareness in the present Brazilian epidemiological context must be emphasized to guide actions to control and prevent coronary heart disease, the leading cause of death in Brazil and worldwide. A prevalência de hipercolesterolemia no Brasil não é conhecida para todo o país, havendo somente inquéritos em algumas cidades. Avaliar a prevalência de diagnóstico médico de colesterol alto autorreferido na população adulta brasileira, utilizando-se dos dados da

On-treatment non-high-density lipoprotein cholesterol, apolipoprotein B, triglycerides, and lipid ratios in relation to residual vascular risk after treatment with potent statin therapy

DEFF Research Database (Denmark)

Mora, Samia; Glynn, Robert J; Boekholdt, S Matthijs

2012-01-01

The goal of this study was to determine whether residual risk after high-dose statin therapy for primary prevention individuals with reduced levels of low-density lipoprotein cholesterol (LDL-C) is related to on-treatment apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C), tri...

Phaleria macrocarpa Boerl. (Thymelaeaceae Leaves Increase SR-BI Expression and Reduce Cholesterol Levels in Rats Fed a High Cholesterol Diet

Directory of Open Access Journals (Sweden)

Yosie Andriani

2015-03-01

Full Text Available In vitro and in vivo studies of the activity of Phaleria macrocarpa Boerl (Thymelaeaceae leaves against the therapeutic target for hypercholesterolemia were done using the HDL receptor (SR-BI and hypercholesterolemia-induced Sprague Dawley rats. The in vitro study showed that the active fraction (CF6 obtained from the ethyl acetate extract (EMD and its component 2',6',4-trihydroxy-4'-methoxybenzophenone increased the SR-BI expression by 95% and 60%, respectively. The in vivo study has proven the effect of EMD at 0.5 g/kgbw dosage in reducing the total cholesterol level by 224.9% and increasing the HDL cholesterol level by 157% compared to the cholesterol group. In the toxicity study, serum glutamate oxalate transaminase (SGOT and serum glutamate pyruvate transaminase (SGPT activity were observed to be at normal levels. The liver histology also proved no toxicity and abnormalities in any of the treatment groups, so it can be categorized as non-toxic to the rat liver. The findings taken together show that P. macrocarpa leaves are safe and suitable as an alternative control and prevention treatment for hypercholesterolemia in Sprague Dawley rats.

Antitumoral and antioxidant activities of lipophilic and phenolic extracts from Cynara cardunculus L. var. altilis (DC)

OpenAIRE

Ramos, P.; Guerra, A.; Guerreiro, O.; Santos, S.; Oliveira, H.; Freire, C.; Rocha, S.; Silvestre, A.; Duarte, M. F.

2014-01-01

Cynara cardunculus L. var. altilis (DC) (Cca) grows under the semi-arid conditions as those of south of Portugal. Given to high cellulose and hemicelluloses contents, paper pulp production has been proposed [1]. Moreover, the extraction of bioactive compounds could also be considered for an integrated valorization of Cca. Sesquiterpene lactones (SL) and pentacyclic triterpenes, the major constituents of Cca leaves and capitula lipophilic fractions [2] showed lower tryglyceride levels in rat s...

On the Solubility and Lipophilicity of Metallacarborane Pharmacophores

Czech Academy of Sciences Publication Activity Database

Rak, J.; Dejlová, B.; Lampová, H.; Kaplánek, R.; Matějíček, P.; Cígler, Petr; Král, V.

2013-01-01

Roč. 10, č. 5 (2013), s. 1751-1759 ISSN 1543-8384 R&D Projects: GA MŠk(CZ) LH11027; GA TA ČR(CZ) TE01020028; GA AV ČR IAAX00320901 Grant - others:GA ČR(CZ) GAP303/11/1291; Biomedreg Project(XE) CZ.1.05/2.1.00/01.0030 Program:GA Institutional support: RVO:61388963 Keywords : metallacarborane * cobalt bis(dicarbollide) * serum albumin * HIV protease * inhibitor * lipophilicity * P-ow * solubility Subject RIV: CC - Organic Chemistry Impact factor: 4.787, year: 2013

Phytosterol and cholesterol precursor levels indicate increased cholesterol excretion and biosynthesis in gallstone disease.

Science.gov (United States)

Krawczyk, Marcin; Lütjohann, Dieter; Schirin-Sokhan, Ramin; Villarroel, Luis; Nervi, Flavio; Pimentel, Fernando; Lammert, Frank; Miquel, Juan Francisco

2012-05-01

In hepatocytes and enterocytes sterol uptake and secretion is mediated by Niemann-Pick C1-like 1 (NPC1L1) and ATP-binding cassette (ABC)G5/8 proteins, respectively. Whereas serum levels of phytosterols represent surrogate markers for intestinal cholesterol absorption, cholesterol precursors reflect cholesterol biosynthesis. Here we compare serum and biliary sterol levels in ethnically different populations of patients with gallstone disease (GSD) and stone-free controls to identify differences in cholesterol transport and synthesis between these groups. In this case-control study four cohorts were analyzed: 112 German patients with GSD and 152 controls; two distinct Chilean ethnic groups: Hispanics (100 GSD, 100 controls), and Amerindians (20 GSD, 20 controls); additionally an 8-year follow-up of 70 Hispanics was performed. Serum sterols were measured by gas chromatography / mass spectrometry. Gallbladder bile sterol levels were analyzed in cholesterol GSD and controls. Common ABCG5/8 variants were genotyped. Comparison of serum sterols showed lower levels of phytosterols and higher levels of cholesterol precursors in GSD patients than in controls. The ratios of phytosterols to cholesterol precursors were lower in GSD patients, whereas biliary phytosterol and cholesterol concentrations were elevated as compared with controls. In the follow-up study, serum phytosterol levels were significantly lower even before GSD was detectable by ultrasound. An ethnic gradient in the ratios of phytosterols to cholesterol precursors was apparent (Germans > Hispanics > Amerindians). ABCG5/8 variants did not fully explain the sterol metabolic trait of GSD in any of the cohorts. Individuals predisposed to GSD display increased biliary output of cholesterol in the setting of relatively low intestinal cholesterol absorption, indicating enhanced whole-body sterol clearance. This metabolic trait precedes gallstone formation and is a feature of ethnic groups at higher risk of cholesterol

Cholesterol in the retina: the best is yet to come

Science.gov (United States)

Pikuleva, Irina A.; Curcio, Christine A.

2014-01-01

Historically understudied, cholesterol in the retina is receiving more attention now because of genetic studies showing that several cholesterol-related genes are risk factors for age-related macular degeneration (AMD) and because eye pathology studies showing high cholesterol content of drusen, aging Bruch's membrane, and newly found subretinal lesions. The challenge before us is determining how the cholesterol-AMD link is realized. Meeting this challenge will require an excellent understanding these genes’ roles in retinal physiology and how chorioretinal cholesterol is maintained. In the first half of this review, we will succinctly summarize physico-chemical properties of cholesterol, its distribution in the human body, general principles of maintenance and metabolism, and differences in cholesterol handling in human and mouse that impact on experimental approaches. This information will provide a backdrop to the second part of the review focusing on unique aspects of chorioretinal cholesterol homeostasis, aging in Bruch's membrane, cholesterol in AMD lesions, a model for lesion biogenesis, a model for macular vulnerability based on vascular biology, and alignment of AMD-related genes and pathobiology using cholesterol and an atherosclerosis-like progression as unifying features. We conclude with recommendations for the most important research steps we can take towards delineating the cholesterol-AMD link. PMID:24704580

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.

Steady-state oxidation of cholesterol catalyzed by cholesterol oxidase in lipid bilayer membranes on platinum electrodes

International Nuclear Information System (INIS)

Bokoch, Michael P.; Devadoss, Anando; Palencsar, Mariela S.; Burgess, James D.

2004-01-01

Cholesterol oxidase is immobilized in electrode-supported lipid bilayer membranes. Platinum electrodes are initially modified with a self-assembled monolayer of thiolipid. A vesicle fusion method is used to deposit an outer leaflet of phospholipids onto the thiolipid monolayer forming a thiolipid/lipid bilayer membrane on the electrode surface. Cholesterol oxidase spontaneously inserts into the electrode-supported lipid bilayer membrane from solution and is consequently immobilized to the electrode surface. Cholesterol partitions into the membrane from buffer solutions containing cyclodextrin. Cholesterol oxidase catalyzes the oxidation of cholesterol by molecular oxygen, forming hydrogen peroxide as a product. Amperometric detection of hydrogen peroxide for continuous solution flow experiments are presented, where flow was alternated between cholesterol solution and buffer containing no cholesterol. Steady-state anodic currents were observed during exposures of cholesterol solutions ranging in concentration from 10 to 1000 μM. These data are consistent with the Michaelis-Menten kinetic model for oxidation of cholesterol as catalyzed by cholesterol oxidase immobilized in the lipid bilayer membrane. The cholesterol detection limit is below 1 μM for cholesterol solution prepared in buffered cyclodextrin. The response of the electrodes to low density lipoprotein solutions is increased upon addition of cyclodextrin. Evidence for adsorption of low density lipoprotein to the electrode surface is presented

Hypolipidemic activity of Phellinus rimosus against triton WR-1339 and high cholesterol diet induced hyperlipidemic rats.

Science.gov (United States)

Rony, K A; Ajith, T A; Nima, N; Janardhanan, K K

2014-03-01

Patients with the risk for atherosclerotic disease will be targeted to reduce the existing hyperlipidemia. The hypolipidemic activity of Phellinus rimosus was studied using triton WR-1339 and high cholesterol diet (HCD) induced models. The triton induced elevated lipid profile was attenuated by P. rimosus or standard drug atorvastatin. Similarly, administration of P. rimosus along with HCD significantly decline serum triglyceride, total cholesterol, low-density lipoprotein, with elevating the high-density lipoprotein. Thiobarbituric acid reacting substances in heart and liver significantly decreased; where as activity of enzymatic antioxidants and level of reduced glutathione were significantly increased. In both models, P. rimosus extract showed a significant ameliorative effect on the elevated atherogenic index as well as LDL/HDL-C ratio. The hypolipidemic activity of P. rimosus can be ascribed to its inhibitory effect on the liver HMG CoA reductase activity. The results suggest the possible therapeutic potential of this fungus as hypolipidemic agent. Copyright © 2014 Elsevier B.V. All rights reserved.

Amperometric cholesterol biosensor based on the direct electrochemistry of cholesterol oxidase and catalase on a graphene/ionic liquid-modified glassy carbon electrode.

Science.gov (United States)

Gholivand, Mohammad Bagher; Khodadadian, Mehdi

2014-03-15

Cholesterol oxidase (ChOx) and catalase (CAT) were co-immobilized on a graphene/ionic liquid-modified glassy carbon electrode (GR-IL/GCE) to develop a highly sensitive amperometric cholesterol biosensor. The H2O2 generated during the enzymatic reaction of ChOx with cholesterol could be reduced electrocatalytically by immobilized CAT to obtain a sensitive amperometric response to cholesterol. The direct electron transfer between enzymes and electrode surface was investigated by cyclic voltammetry. Both enzymes showed well-defined redox peaks with quasi-reversible behaviors. An excellent sensitivity of 4.163 mA mM(-1)cm(-2), a response time less than 6s, and a linear range of 0.25-215 μM (R(2)>0.99) have been observed for cholesterol determination using the proposed biosensor. The apparent Michaelis-Menten constant (KM(app)) was calculated to be 2.32 mM. The bienzymatic cholesterol biosensor showed good reproducibility (RSDsascorbic acid and uric acid. The CAT/ChOx/GR-IL/GCE showed excellent analytical performance for the determination of free cholesterol in human serum samples. © 2013 Elsevier B.V. All rights reserved.

Ursodeoxycholic Acid for the Treatment of Cholesterol Gallstones

International Nuclear Information System (INIS)

Zaater, M.K.

2011-01-01

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.

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.

High Pre-β1 HDL Concentrations and Low Lecithin: Cholesterol Acyltransferase Activities Are Strong Positive Risk Markers for Ischemic Heart Disease and Independent of HDL-Cholesterol

Science.gov (United States)

Sethi, Amar A.; Sampson, Maureen; Warnick, Russell; Muniz, Nehemias; Vaisman, Boris; Nordestgaard, Børge G.; Tybjærg-Hansen, Anne; Remaley, Alan T.

2016-01-01

BACKGROUND We hypothesized that patients with high HDL-cholesterol (HDL-C) and ischemic heart disease (IHD) may have dysfunctional HDL or unrecognized nonconventional risk factors. METHODS Individuals with IHD (Copenhagen University Hospital) and either high HDL-C (n = 53; women ≥735 mg/L; men ≥619 mg/L) or low HDL-C (n = 42; women ≤387 mg/L; men ≤341 mg/L) were compared with individuals without IHD (Copenhagen City Heart Study) matched by age, sex, and HDL-C concentrations (n = 110). All participants had concentrations within reference intervals for LDL-C (lecithin:cholesterol acyltransferase (LCAT) activity by using a proteoliposome cholesterol esterification assay. RESULTS Pre-β1 HDL concentrations were 2-fold higher in individuals with IHD vs no IHD in both the high [63 (5.7) vs 35 (2.3) mg/L; P < 0.0001] and low HDL-C [49 (5.0) vs 27 (1.5) mg/L; P = 0.001] groups. Low LCAT activity was also associated with IHD in the high [95.2 (6.7) vs 123.0 (5.3) μmol · L−1 · h−1; P = 0.002] and low [93.4 (8.3) vs 113.5 (4.9) μmol · L−1 · h−1; P = 0.03] HDL-C groups. ROC curves for pre-β1 HDL in the high–HDL-C groups yielded an area under the curve of 0.71 (95% CI: 0.61–0.81) for predicting IHD, which increased to 0.92 (0.87–0.97) when LCAT was included. Similar results were obtained for low HDL-C groups. An inverse correlation between LCAT activity and pre-β1 HDL was observed (r2 = 0.30; P < 0.0001) in IHD participants, which was stronger in the low HDL-C group (r2 = 0.56; P < 0.0001). CONCLUSIONS IHD was associated with high pre-β1 HDL concentrations and low LCAT levels, yielding correct classification in more than 90% of the IHD cases for which both were measured, thus making pre-β1 HDL concentration and LCAT activity level potentially useful diagnostic markers for cardiovascular disease. PMID:20511449

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, ...

Free cholesterol and cholesterol esters in bovine oocytes: Implications in survival and membrane raft organization after cryopreservation.

Directory of Open Access Journals (Sweden)

Jorgelina Buschiazzo

Full Text Available Part of the damage caused by cryopreservation of mammalian oocytes occurs at the plasma membrane. The addition of cholesterol to cell membranes as a strategy to make it more tolerant to cryopreservation has been little addressed in oocytes. In order to increase the survival of bovine oocytes after cryopreservation, we proposed not only to increase cholesterol level of oocyte membranes before vitrification but also to remove the added cholesterol after warming, thus recovering its original level. Results from our study showed that modulation of membrane cholesterol by methyl-β-cyclodextrin (MβCD did not affect the apoptotic status of oocytes and improved viability after vitrification yielding levels of apoptosis closer to those of fresh oocytes. Fluorometric measurements based on an enzyme-coupled reaction that detects both free cholesterol (membrane and cholesteryl esters (stored in lipid droplets, revealed that oocytes and cumulus cells present different levels of cholesterol depending on the seasonal period. Variations at membrane cholesterol level of oocytes were enough to account for the differences found in total cholesterol. Differences found in total cholesterol of cumulus cells were explained by the differences found in both the content of membrane cholesterol and of cholesterol esters. Cholesterol was incorporated into the oocyte plasma membrane as evidenced by comparative labeling of a fluorescent cholesterol. Oocytes and cumulus cells increased membrane cholesterol after incubation with MβCD/cholesterol and recovered their original level after cholesterol removal, regardless of the season. Finally, we evaluated the effect of vitrification on the putative raft molecule GM1. Cholesterol modulation also preserved membrane organization by maintaining ganglioside level at the plasma membrane. Results suggest a distinctive cholesterol metabolic status of cumulus-oocyte complexes (COCs among seasons and a dynamic organizational structure

Direct chromatographic analysis of metabolites of lipophilic tracers in whole blood by ISRP chromatography

International Nuclear Information System (INIS)

Rosenspire, K.C.; Hirth, W.; Jurisson, S.; Nowotnik, D.P.; Eckelman, W.C.; Nunn, A.D.

1991-01-01

HPLC using columns packed with 5 μ Internal Surface Reverse Phase (ISRP) resin have shown utility in the analysis of lipophilic drugs and their metabolites by direct injection of serum or plasma samples. We have developed a method for rapid on-line separation of small hydrophobic components from cellular whole blood components. This is achieved through the use of 75 μ GFF (glycine-phenylalanine-phenylalanine) glass bead ISRP chromatographic material packed into a small HPLC column, and used in conjunction with an HPLC system containing a switching valve and a second analytical column. When heparinized whole blood is applied to a 75 μ GFF ISRP column, and the column eluted with an isotonic eluent, lipophilic compounds free in plasma are retained by the column, while plasma proteins, blood cells, and compounds bound to these blood components pass through the ISRP column. Following the elution of these components, the lipophilic compounds retained on the ISRP column are eluted by increasing the percentage of organic solvent in the eluent, and are further resolved (if required) by the analytical column. We have applied this analytical method to the study of metabolism of the 99m Tc-BATO (Boronic acid Adducts of Technetium diOxime) cerebral and myocardial perfusion tracers. (author)

Examination of the relation between periodontal health status and cardiovascular risk factors: serum total and high density lipoprotein cholesterol, C-reactive protein, and plasma fibrinogen.

Science.gov (United States)

Wu, T; Trevisan, M; Genco, R J; Falkner, K L; Dorn, J P; Sempos, C T

2000-02-01

Using data from the Third National Health and Nutrition Examination Survey (1988-1994), the authors examined the relation between periodontal health and cardiovascular risk factors: serum total and high density lipoprotein cholesterol, C-reactive protein, and plasma fibrinogen. A total of 10,146 participants were included in the analyses of cholesterol and C-reactive protein and 4,461 in the analyses of fibrinogen. Periodontal health indicators included the gingival bleeding index, calculus index, and periodontal disease status (defined by pocket depth and attachment loss). While cholesterol and fibrinogen were analyzed as continuous variables, C-reactive protein was dichotomized into two levels. The results show a significant relation between indicators of poor periodontal status and increased C-reactive protein and fibrinogen. The association between periodontal status and total cholesterol level is much weaker. No consistent association between periodontal status and high density lipoprotein cholesterol was detectable. Similar patterns of association were observed for participants aged 17-54 years and those 55 years and older. In conclusion, this study suggests that total cholesterol, C-reactive protein, and fibrinogen are possible intermediate factors that may link periodontal disease to elevated cardiovascular risk.

Discovery of a novel acyl-CoA: cholesterol acyltransferase inhibitor: the synthesis, biological evaluation, and reduced adrenal toxicity of (4-phenylcoumarin)acetanilide derivatives with a carboxylic acid moiety.

Science.gov (United States)

Ogino, Masaki; Nakada, Yoshihisa; Negoro, Nobuyuki; Itokawa, Shigekazu; Nishimura, Satoshi; Sanada, Tsukasa; Satomi, Tomoko; Kita, Shunbun; Kubo, Kazuki; Marui, Shogo

2011-01-01

As a part of our research for novel potent and orally available acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors that can be used as anti-atherosclerotic agents, we recently reported the discovery of the (4-phenylcoumarine)acetanilide derivative 1. However, compound 1 showed adrenal toxicity in animal models. In order to search for safer ACAT inhibitors that do not have adrenal toxicity, we examined the inhibitory activity of ACAT in human macrophage and adrenal cells. The introduction of a carboxylic acid moiety on the pendant phenyl ring and the adjustment of the lipophilicity led to the discovery of (2E)-3-[7-chloro-3-[2-[[4-fluoro-2-(trifluoromethyl)phenyl]amino]-2-oxoethyl]-6-methyl-2-oxo-2H-chromen-4-yl]phenyl]acrylic acid (21e), which showed potent ACAT inhibitory activity in macrophages and a selectivity of around 30-fold over adrenal cells. In addition, compound 21e showed high adrenal safety in guinea pigs.

Human Intestinal Fluid Layer Separation: The Effect On Colloidal Structures & Solubility Of Lipophilic Compounds.

Science.gov (United States)

Danny, Riethorst; Amitava, Mitra; Filippos, Kesisoglou; Wei, Xu; Jan, Tack; Joachim, Brouwers; Patrick, Augustijns

2018-05-23

In addition to individual intestinal fluid components, colloidal structures are responsible for enhancing the solubility of lipophilic compounds. The present study investigated the link between as well as the variability in the ultrastructure of fed state human intestinal fluids (FeHIF) and their solubilizing capacity for lipophilic compounds. For this purpose, FeHIF samples from 10 healthy volunteers with known composition and ultrastructure were used to determine the solubility of four lipophilic compounds. In light of the focus on solubility and ultrastructure, the study carefully considered the methodology of solubility determination in relation to colloid composition and solubilizing capacity of FeHIF. To determine the solubilizing capacity of human and simulated intestinal fluids, the samples were saturated with the compound of interest, shaken for 24 h, and centrifuged. When using FeHIF, solubilities were determined in the micellar layer of FeHIF, i.e. after removing the upper (lipid) layer (standard procedure), as well as in 'full' FeHIF (without removal of the upper layer). Compound concentrations were determined using HPLC-UV/fluorescence. To link the solubilizing capacity with the ultrastructure, all human and simulated fluids were imaged using transmission electron microscopy (TEM) before and after centrifugation and top layer (lipid) removal. Comparing the ultrastructure and solubilizing capacity of individual FeHIF samples demonstrated a high intersubject variability in postprandial intestinal conditions. Imaging of FeHIF after removal of the upper layer clearly showed that only micellar structures remain in the lower layer. This observation suggests that larger colloids such as vesicles and lipid droplets are contained in the upper, lipid layer. The solubilizing capacity of most FeHIF samples substantially increased with inclusion of this lipid layer. The relative increase in solubilizing capacity upon inclusion of the lipid layer was most pronounced

Dynamic SPECT of the brain using a lipophilic technetium-99m complex, PnAO

DEFF Research Database (Denmark)

Holm, S; Andersen, A R; Vorstrup, S

1985-01-01

m PnAO was injected i.v. as a bolus of 15 to 25 mCi. The distribution was followed over 10-sec intervals using a highly sensitive, rapidly rotating SPECT (Tomomatic 64) and compared to 133Xe flow maps. Upon arrival of the PnAO bolus to the brain, a high uptake was found in brain tissue with high......The lipophilic 99mTc-labeled oxime propylene amine oxime (PnAO) should, according to recent reports behave like 133Xe in the human brain. This study compares SPECT images of the two tracers in six subjects: four stroke cases, one transitory ischemic attack case and one normal subject. Technetium-99......AO has a high yet incomplete brain extraction yielding a flow dominated initial distribution with limitations mentioned....

Mechanism of allosteric regulation of β2-adrenergic receptor by cholesterol

DEFF Research Database (Denmark)

Manna, Moutusi; Niemelä, Miia; Tynkkynen, Joona

2016-01-01

) - a prototypical G protein-coupled receptor - is modulated by cholesterol in an allosteric fashion. Extensive atomistic simulations show that cholesterol regulates b2AR by limiting its conformational variability. The mechanism of action is based on the binding of cholesterol at specific high-affinity sites located...... near the transmembrane helices 5-7 of the receptor. The alternative mechanism, where the β2AR conformation would be modulated by membrane-mediated interactions, plays only a minor role. Cholesterol analogues also bind to cholesterol binding sites and impede the structural flexibility of β2AR, however...... cholesterol generates the strongest effect. The results highlight the capacity of lipids to regulate the conformation of membrane receptors through specific interactions....

Chemical composition of barks from Quercus faginea trees and characterization of their lipophilic and polar extracts.

Science.gov (United States)

Ferreira, Joana P A; Miranda, Isabel; Sousa, Vicelina B; Pereira, Helena

2018-01-01

The bark from Quercus faginea mature trees from two sites was chemically characterized for the first time. The barks showed the following composition: ash 14.6%, total extractives 13.2%, suberin 2.9% and lignin 28.2%. The polysaccharides were composed mainly of glucose and xylose (50.3% and 35.1% of all monosaccharides respectively) with 4.8% of uronic acids. The suberin composition was: ω-hydroxyacids 46.3% of total compounds, ɑ,ω-alkanoic diacids 22.3%, alkanoic acids 5.9%, alkanols 6.7% and aromatics 6.9% (ferulic acid 4.0%). Polar extracts (ethanol-water) had a high phenolic content of 630.3 mg of gallic acid equivalents (GAE)/g of extract, condensed tannins 220.7 mg of catechin equivalents (CE)/g extract, and flavonoids 207.7 mg CE/g of extract. The antioxidant activity was very high corresponding to 1567 mg Trolox equivalents/g of extract, and an IC50 of 2.63 μg extract/ml. The lipophilic extracts were constituted mainly by glycerol and its derivatives (12.3% of all compounds), alkanoic acids (27.8%), sterols (11.5%) and triterpenes (17.8%). In view of an integrated valorization, Quercus faginea barks are interesting sources of polar compounds including phenols and polyphenols with possible interesting bioactivities, while the sterols and triterpenes contained in the lipophilic extracts are also valuable bioactive compounds or chemical intermediates for specific high-value market niches, such as cosmetics, pharmaceuticals and biomedicine.

Exploration of molecular interactions in cholesterol superlattices: effect of multibody interactions.

Science.gov (United States)

Huang, Juyang

2002-08-01

Experimental evidences have indicated that cholesterol may adapt highly regular lateral distributions (i.e., superlattices) in a phospholipid bilayer. We investigated the formations of superlattices at cholesterol mole fraction of 0.154, 0.25, 0.40, and 0.5 using Monte Carlo simulation. We found that in general, conventional pairwise-additive interactions cannot produce superlattices. Instead, a multibody (nonpairwise) interaction is required. Cholesterol superlattice formation reveals that although the overall interaction between cholesterol and phospholipids is favorable, it contains two large opposing components: an interaction favoring cholesterol-phospholipid mixing and an unfavorable acyl chain multibody interaction that increases nonlinearly with the number of cholesterol contacts. The magnitudes of interactions are in the order of kT. The physical origins of these interactions can be explained by our umbrella model. They most likely come from the requirement for polar phospholipid headgroups to cover the nonpolar cholesterol to avoid the exposure of cholesterol to water and from the sharp decreasing of acyl chain conformation entropy due to cholesterol contact. This study together with our previous work demonstrate that the driving force of cholesterol-phospholipid mixing is a hydrophobic interaction, and multibody interactions dominate others over a wide range of cholesterol concentration.

Comparison of soymilk and probiotic soymilk effects on serum high-density lipoprotein cholesterol and low-density lipoprotein cholesterol in diabetic Wistar rats

Directory of Open Access Journals (Sweden)

Mina Babashahi

2015-04-01

Full Text Available BACKGROUND: Soy milk (SM and its fermented products are identified as rich sources of bioactive compounds helping to manage and to reduce the risk of chronic disease. This study aimed to compare the effects of SM and probiotic SM (PSM consumption on serum low-density lipoprotein cholesterol (LDL-C and high-density lipoprotein cholesterol (HDL-C in diabetic Wistar rats. METHODS: Probiotic SM was prepared by fermentation of the plain SM with a native strain of Lactobacillus plantarum. 20 streptozotocin-nicotinamide-induced diabetic Wistar rats were divided into two groups based on the type of administered SM (SM group and PSM group. The animals were fed with 1 ml/day of either soy or PSM for 21 days. The serum lipoprotein levels were analyzed at baseline and the end of the intervention period. RESULTS: HDL-C increased significantly in PSM group. Furthermore, this group showed more percent of change in increased HDL-C in compression with SM group (P < 0.050. Regarding LDL-C level, rats fed with SM was not significantly different from the PSM group (P < 0.050; though, this biomarker was reduced in both group. CONCLUSION: Probiotic SM could modulate blood lipoprotein levels. Thus, it may be considered in managing diabetes complications and atherosclerotic risks. 

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......-rich lipoproteins) as a contributor to the development of atherosclerosis and IHD. Observational studies show association between elevated remnant cholesterol and IHD, and mechanistic studies show remnant cholesterol accumulation in the arterial wall like LDL-cholesterol (LDL-C) accumulation. Furthermore, large...... genetic studies show evidence of remnant cholesterol as a causal risk factor for IHD independent of HDL-cholesterol levels. Genetic studies also show that elevated remnant cholesterol is associated with low-grade inflammation, whereas elevated LDL-C is not. There are several pharmacologic ways of lowering...

Thermodynamic studies of bilirubin/cholesterol mixtures at the air/water interface

International Nuclear Information System (INIS)

Xie Anjian; Shen Yuhua; Xia Bing; Chen Hongbo; Ouyang Jianming

2005-01-01

Mixed monolayers of cholesterol and bilirubin spread at the air/water interface were used as model systems to examine the cholesterol effect on bilirubin. Miscibility and interactions between cholesterol and bilirubin were studied based on the analysis of the surface pressure-molecular area isotherms. From the isotherm data differentiated with respect to area, the condensing effect of cholesterol on the mixed monolayers could be observed distinctly. By studying surface compressibility modulus of bilirubin/cholesterol binary system vs. molecule area, we show that the liquid expanded-condensed phase transition (LE-C) of bilirubin was eliminated by cholesterol. In monolayers, bilirubin and cholesterol were found to be miscible at low surface pressure and immiscible at high surface pressure by studying the excess molecular areas of bilirubin/cholesterol system vs. mole fraction of bilirubin. The results from excess free energy of bilirubin/cholesterol system vs. mole fraction of bilirubin (X BR ) show that the maximum negative value of ΔG exc appeared at X BR =0.6, which indicates the formation of a bilirubin/cholesterol complex (M B-C ) of 3:2 stoichiometry as a result of the strong hydrogen bond between the polar groups of cholesterol and bilirubin and the self-assembly characteristics of cholesterol

Recombinant high-density lipoprotein nanoparticles containing gadolinium-labeled cholesterol for morphologic and functional magnetic resonance imaging of the liver

Directory of Open Access Journals (Sweden)

Rui M

2012-07-01

Full Text Available Mengjie Rui,1 Wei Guo,2 Qian Ding,2 Xiaohui Wei,2 Jianrong Xu,3 Yuhong Xu21School of Life Science and Biotechnology, 2School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People's Republic of China; 3Department of Radiology, Renji Hospital Affiliation with Medical School of Shanghai Jiao Tong University, Shanghai, People's Republic of ChinaBackground: Natural high-density lipoproteins (HDL possess important physiological functions to the transport of cholesterol from the peripheral tissues to the liver for metabolic degradation and excretion in the bile.Methods and results: In this work, we took advantage of this pathway and prepared two different gadolinium (Gd-DTPA-labeled cholesterol-containing recombinant HDL nanoparticles (Gd-chol-HDL and Gd-(chol2-HDL as liver-specific magnetic resonance imaging (MRI contrast agents. The reconstituted HDL nanoparticles had structural similarity to native HDL, and could be taken up by HepG2 cells via interaction with HDL receptors in vitro. In vivo MRI studies in rats after intravenous injections of 10 µmol gadolinium per kg of recombinant HDL nanoparticles indicated that both nanoparticles could provide signal enhancement in the liver and related organs. However, different T1-weighted image details suggested that they participated in different cholesterol metabolism and excretion pathways in the liver.Conclusion: Such information could be highly useful to differentiate functional changes as well as anatomic differences in the liver. These cholesterol-derived contrast agents and their recombinant HDL preparations may warrant further development as a new class of contrast agents for MRI of the liver and related organs.Keywords: magnetic resonance imaging, apolipoprotein, high-density lipoprotein, contrast agent, gadolinium, liver

Role of cholesterol on the transfection barriers of cationic lipid/DNA complexes

Science.gov (United States)

Pozzi, Daniela; Cardarelli, Francesco; Salomone, Fabrizio; Marchini, Cristina; Amenitsch, Heinz; Barbera, Giorgia La; Caracciolo, Giulio

2014-08-01

Most lipid formulations need cholesterol for efficient transfection, but the precise motivation remains unclear. Here, we have investigated the effect of cholesterol on the transfection efficiency (TE) of cationic liposomes made of 1,2-dioleoyl-3-trimethylammonium-propane and dioleoylphosphocholine in Chinese hamster ovary cells. The transfection mechanisms of cholesterol-containing lipoplexes have been investigated by TE, synchrotron small angle X-ray scattering, and laser scanning confocal microscopy experiments. We prove that cholesterol-containing lipoplexes enter the cells using different endocytosis pathways. Formulations with high cholesterol content efficiently escape from endosomes and exhibit a lamellar-nonlamellar phase transition in mixture with biomembrane mimicking lipid formulations. This might explain both the DNA release ability and the high transfection efficiency. These studies highlight the enrichment in cholesterol as a decisive factor for transfection and will contribute to the rational design of lipid nanocarriers with superior TE.

Lathosterol to cholesterol ratio in serum predicts cholesterol lowering response to plant sterol consumption in a dual center, randomized, single-blind placebo controlled trial

Science.gov (United States)

Benefits of plant sterols (PS) for cholesterol lowering are compromised by large variability in efficacy across individuals. High fractional cholesterol synthesis measured by deuterium incorporation has been associated with non-response to PS consumption; however, prospective studies showing this as...

Cholesterol as a Causative Factor in Alzheimer Disease: A Debatable Hypothesis

Science.gov (United States)

Wood, W. Gibson; Li, Ling; Müller, Walter E.; Eckert, Gunter P.

2014-01-01

High serum/plasma cholesterol levels have been suggested as a risk factor for Alzheimer disease (AD). Some reports, mostly retrospective epidemiological studies, have observed a decreased prevalence of AD in patients taking the cholesterol lowering drugs, statins. The strongest evidence causally linking cholesterol to AD is provided by experimental studies showing that adding/reducing cholesterol alters amyloid precursor protein (APP) and amyloid beta-protein (Aβ) levels. However, there are problems with the cholesterol-AD hypothesis. Cholesterol levels in serum/plasma and brain of AD patients do not support cholesterol as a causative factor in AD. Prospective studies on statins and AD have largely failed to show efficacy. Even the experimental data are open to interpretation given that it is well-established that modification of cholesterol levels has effects on multiple proteins, not only APP and Aβ. The purpose of this review, therefore, is to examine the above-mentioned issues and discuss the pros and cons of the cholesterol-AD hypothesis, and the involvement of other lipids in the mevalonate pathway, such as isoprenoids and oxysterols, in AD. PMID:24329875

The ABCG5/8 Cholesterol Transporter and Myocardial Infarction Versus Gallstone Disease

DEFF Research Database (Denmark)

Stender, Stefan; Frikke-Schmidt, Ruth; Nordestgaard, Børge G

2014-01-01

OBJECTIVES: The study sought to test the hypothesis that genetic variation in ABCG5/8, the transporter responsible for intestinal and hepatobiliary cholesterol efflux, may simultaneously influence plasma and biliary cholesterol levels, and hence risk of myocardial infarction (MI) and gallstone...... disease in opposite directions. BACKGROUND: High plasma levels of low-density lipoprotein (LDL) cholesterol are a causal risk factor for MI, whereas high levels of biliary cholesterol promote gallstone formation. METHODS: A total of 60,239 subjects from Copenhagen were included, including 5,647 with MI...... and 3,174 with symptomatic gallstone disease. Subjects were genotyped for 6 common, nonsynonymous and functional variants in ABCG5/8, and a combined weighted genotype score was calculated. RESULTS: Combined, weighted genotype scores were associated with stepwise decreases in LDL cholesterol of up to 5...

Cellular Cholesterol Regulates Ubiquitination and Degradation of the Cholesterol Export Proteins ABCA1 and ABCG1*

Science.gov (United States)

Hsieh, Victar; Kim, Mi-Jurng; Gelissen, Ingrid C.; Brown, Andrew J.; Sandoval, Cecilia; Hallab, Jeannette C.; Kockx, Maaike; Traini, Mathew; Jessup, Wendy; Kritharides, Leonard

2014-01-01

The objective of this study was to examine the influence of cholesterol in post-translational control of ABCA1 and ABCG1 protein expression. Using CHO cell lines stably expressing human ABCA1 or ABCG1, we observed that the abundance of these proteins is increased by cell cholesterol loading. The response to increased cholesterol is rapid, is independent of transcription, and appears to be specific for these membrane proteins. The effect is mediated through cholesterol-dependent inhibition of transporter protein degradation. Cell cholesterol loading similarly regulates degradation of endogenously expressed ABCA1 and ABCG1 in human THP-1 macrophages. Turnover of ABCA1 and ABCG1 is strongly inhibited by proteasomal inhibitors and is unresponsive to inhibitors of lysosomal proteolysis. Furthermore, cell cholesterol loading inhibits ubiquitination of ABCA1 and ABCG1. Our findings provide evidence for a rapid, cholesterol-dependent, post-translational control of ABCA1 and ABCG1 protein levels, mediated through a specific and sterol-sensitive mechanism for suppression of transporter protein ubiquitination, which in turn decreases proteasomal degradation. This provides a mechanism for acute fine-tuning of cholesterol transporter activity in response to fluctuations in cell cholesterol levels, in addition to the longer term cholesterol-dependent transcriptional regulation of these genes. PMID:24500716

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 ...

Blood cholesterol level in Sudanese females with hyperthyroidism

International Nuclear Information System (INIS)

Ahmed, N. M.

2004-08-01

In view to high incidence of thyroid dis function among Sudanese females, this study was conducted, essentially to study the effect of thyroid disorders on lipids metabolism, mainly on total cholesterol. In this study samples were collected from RIA laboratory in Sudan Atomic Energy Commission. 50 hyperthyroidism females were selected as a study group of age range (20-55) years. In addition 47 samples were collected with same age of study group used as control group. Thyroid related hormones thyroxine T4, triiodothyronine T3, thyroid stimulating hormone TSH using the sensitive radioimmunoassay method and cholesterol were measured for the two groups using enzymatic-calorimetric test. Statistical analysis were done with SPSS computer program to compare the cholesterol levels in the control subjects with the patients levels. The results showed significantly decreased cholesterol level of patient group when compared with the control group (p<0.01). At the end of this study the result was agreed well with previous results concerning cholesterol level as affected by thyroid disorder. (Author)

Effect of dietary cholesterol and plant sterol consumption on plasma lipid responsiveness and cholesterol trafficking in healthy individuals.

Science.gov (United States)

Alphonse, Peter A S; Ramprasath, Vanu; Jones, Peter J H

2017-01-01

Dietary cholesterol and plant sterols differentially modulate cholesterol kinetics and circulating cholesterol. Understanding how healthy individuals with their inherent variabilities in cholesterol trafficking respond to such dietary sterols will aid in improving strategies for effective cholesterol lowering and alleviation of CVD risk. The objectives of this study were to assess plasma lipid responsiveness to dietary cholesterol v. plant sterol consumption, and to determine the response in rates of cholesterol absorption and synthesis to each sterol using stable isotope approaches in healthy individuals. A randomised, double-blinded, crossover, placebo-controlled clinical trial (n 49) with three treatment phases of 4-week duration were conducted in a Manitoba Hutterite population. During each phase, participants consumed one of the three treatments as a milkshake containing 600 mg/d dietary cholesterol, 2 g/d plant sterols or a control after breakfast meal. Plasma lipid profile was determined and cholesterol absorption and synthesis were measured by oral administration of [3, 4-13C] cholesterol and 2H-labelled water, respectively. Dietary cholesterol consumption increased total (0·16 (sem 0·06) mmol/l, P=0·0179) and HDL-cholesterol (0·08 (sem 0·03) mmol/l, P=0·0216) concentrations with no changes in cholesterol absorption or synthesis. Plant sterol consumption failed to reduce LDL-cholesterol concentrations despite showing a reduction (6 %, P=0·0004) in cholesterol absorption. An over-compensatory reciprocal increase in cholesterol synthesis (36 %, P=0·0026) corresponding to a small reduction in absorption was observed with plant sterol consumption, possibly resulting in reduced LDL-cholesterol lowering efficacy of plant sterols. These data suggest that inter-individual variability in cholesterol trafficking mechanisms may profoundly impact plasma lipid responses to dietary sterols in healthy individuals.

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

Science.gov (United States)

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

2015-02-13

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

Effect of methanolic extract of Piper sarmentosum leaves on neointimal foam cell infiltration in rabbits fed with high cholesterol diet

Science.gov (United States)

Amran, Adel A.; Zakaria, Zaiton; Othman, Faizah; Das, Srijit; Al-Mekhlafi, Hesham M.; Raj, Santhana; Nordin, Nor-Anita MM

2012-01-01

Previous research has shown the beneficial effects of aqueous extract of Piper sarmentosum (P.s) on atherosclerosis. The first stage in atherosclerosis is the formation of foam cell. The aim of this study was to investigate the effect of the methanol extract of P.s on fatty streaks by calculating neointimal foam cell infiltration in rabbits fed with high cholesterol diet. Thirty six male New Zealand white rabbits were divided equally into six groups: (i) C: control group fed normal rabbit chow; (ii) CH: cholesterol diet (1 % cholesterol); (iii) PM1: 1 % cholesterol with methanol extract of P.s (62.5 mg/kg); (iv) PM2: 1 % cholesterol with methanol extract of P.s (125 mg/kg); (v) PM3: 1 % cholesterol with methanol extract of P.s (250 mg/kg); (vi) SMV group fed 1 % cholesterol supplemented with Simvistatin drug (1.2 mg/kg). All animals were treated for 10 weeks. At the end of the treatment, the rabbits were fasted and sacrificed and the aortic tissues were collected for histological studies to measure the area of the neointimal foam cell infiltration using software. The thickening of intima ratio of atherosclerosis and morphological changes by scanning electron microscope were measured. The results showed that the atherosclerotic group had significantly bigger area of fatty streak compared to the control group. The area of fatty streak in the abdominal aorta was significantly reduced in the treatment groups which were similar with the SMV group. Similarly, there was a reduction in the number of foam cell in the treatment groups compared to the atherosclerotic group as seen under scanning microscope. In conclusion, histological study demonstrated that the methanol extract of the P.s could reduce the neointimal foam cell infiltration in the lumen of the aorta and the atherosclerotic lesion. PMID:27366140

Evaluation of ACE inhibitors lipophilicity using in silico and chromatographically obtained hydrophobicity parameters

Directory of Open Access Journals (Sweden)

Odović Jadranka V.

2013-01-01

Full Text Available The aim of this study was to compare different calculation methods to determine lipophilicity, expressed as logP value, of seven ACE inhibitors (enalapril, quinapril, fosinopril, lisinopril, cilazapril, ramipril, and benazapril with significantly different structure. Experimentally determined n-octanol/water partition coefficients, logPO/W values, were obtained from relevant literature. The correlations between all collected logP values were studied and the best agreements between calculated logP and experimentally determined logPO/W values, were observed for KOWWINlogP or MilogP values (r = 0.999 or r = 0.974, respectively. The correlations between all collected logP values and chromatographically (reversed-phase thin-layer chromatography obtained hydrophobicity parameters, RM0 and C0, were established. The good correlations (r > 0.90 were obtained in the majority of relationships. The KOWWINlogP was established as the most suitable hydrophobicity parameter of investigated group of ACE inhibitors with r = 0.981 for correlation with RM0 and r = 0.977 for correlation with C0 parameters (water-methanol mobile phase. Using multiple linear regressions, it was established that application of two selected logP, calculated by different mathematical approaches, led to very good correlation due to the benefits of both calculation methods. The good relationships indicate that the computed logP, with careful selection of method calculation, can be useful in ACE inhibitors lipophilicity evaluation, as high-throughput screening technique.

Ezetimibe Increases Endogenous Cholesterol Excretion in Humans.

Science.gov (United States)

Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Ostlund, Richard E

2017-05-01

Ezetimibe improves cardiovascular outcomes when added to optimum statin treatment. It lowers low-density lipoprotein cholesterol and percent intestinal cholesterol absorption, but the exact cardioprotective mechanism is unknown. We tested the hypothesis that the dominant effect of ezetimibe is to increase the reverse transport of cholesterol from rapidly mixing endogenous cholesterol pool into the stool. In a randomized, placebo-controlled, double-blind parallel trial in 24 healthy subjects with low-density lipoprotein cholesterol 100 to 200 mg/dL, we measured cholesterol metabolism before and after a 6-week treatment period with ezetimibe 10 mg/d or placebo. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d 7 in a lipid emulsion and dietary cholesterol with cholesterol-d 5 and sitostanol-d 4 solubilized in oil. Plasma and stool samples collected during a cholesterol- and phytosterol-controlled metabolic kitchen diet were analyzed by mass spectrometry. Ezetimibe reduced intestinal cholesterol absorption efficiency 30±4.3% (SE, P <0.0001) and low-density lipoprotein cholesterol 19.8±1.9% ( P =0.0001). Body cholesterol pool size was unchanged, but fecal endogenous cholesterol excretion increased 66.6±12.2% ( P <0.0001) and percent cholesterol excretion from body pools into the stool increased 74.7±14.3% ( P <0.0001), whereas plasma cholesterol turnover rose 26.2±3.6% ( P =0.0096). Fecal bile acids were unchanged. Ezetimibe increased the efficiency of reverse cholesterol transport from rapidly mixing plasma and tissue pools into the stool. Further work is needed to examine the potential relation of reverse cholesterol transport and whole body cholesterol metabolism to coronary events and the treatment of atherosclerosis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01603758. © 2017 American Heart Association, Inc.

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......, at least initially, an intralayer cholesterol rearrangement in a single-crystal-to-single-crystal transition. The preferred nucleation of the monoclinic phase of cholesterol . H2O followed by transformation to the stable monohydrate phase may be associated with an energetically more stable cholesterol...... bilayer arrangement of the former and a more favorable hydrogen-bonding arrangement of the latter. The relevance of this nucleation process of cholesterol monohydrate to pathological crystallization of cholesterol from cell biomembranes is discussed....

Characterization of placental cholesterol transport

DEFF Research Database (Denmark)

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

2008-01-01

Patients with Smith-Lemli-Opitz syndrome (SLOS) are born with multiple congenital abnormalities. Postnatal cholesterol supplementation is provided; however, it cannot correct developmental malformations due to in utero cholesterol deficit. Increased transport of cholesterol from maternal to fetal...... 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...

Increased hepatic cholesterol esterification with essential fatty acid deficiency (EFAD): relationship to plasma lipoprotein (LP) cholesterol content

International Nuclear Information System (INIS)

Ney, D.M.; Ziboh, V.A.; Schneeman, B.O.

1986-01-01

EFAD in the rat is associated with hepatic accumulation of esterified cholesterol and altered distribution of cholesterol between plasma and hepatic tissue. Little is known regarding the impact of EFAD on LP composition. To determine the relationship between hepatic cholesterol esterification and plasma lP composition in control (C) and EFAD male Wistar rats, the authors induced EFAD with continuous intragastric (IG) infusion of EFA-free solutions containing 3.5% of calories as triolein for 7 and 14 days. C animals received IG infusion of solutions containing 3.5% of calories as linoleic acid. Data in the EFAD groups reveal: (i) marked decreases in hepatic EFAs and increases in monoenoic acids; (ii) progressive increases in hepatic content of triglyceride and esterified cholesterol with 7 and 14 days of feeding; (iii) assay of acyl CoA:cholesterol acyltransferase activity in hepatic tissue using 14 C-cholesterol demonstrates an increase in hepatic cholesterol esterification when compared to C animals. Increased hepatic cholesterol esterification correlates with elevated levels of esterified cholesterol in plasma VLDL and HDL particles. These data indicate that the elevated levels of cholesterol esters in LP particles is due, at least in part, to increased hepatic cholesterol esterification with EFAD

Chlordecone altered hepatic disposition of [14C]cholesterol and plasma cholesterol distribution but not SR-BI or ABCG8 proteins in livers of C57BL/6 mice

International Nuclear Information System (INIS)

Lee, Junga; Scheri, Richard C.; Curtis, Lawrence R.

2008-01-01

Organochlorine (OC) insecticides continue to occur in tissues of humans and wildlife throughout the world although they were banned in the United States a few decades ago. Low doses of the OC insecticide chlordecone (CD) alter hepatic disposition of lipophilic xenobiotics and perturb lipid homeostasis in rainbow trout, mice and rats. CD pretreatment altered tissue and hepatic subcellular distribution of exogenous [ 14 C]cholesterol (CH) equivalents 4 and 16 h after a bolus intraperitoneal (ip) injection of 5 ml corn oil/kg that contained 10 mg CH/kg. CD pretreatment altered tissue distribution of exogenously administered [ 14 C]CH by decreased hepatic and renal accumulation, and increased biliary excretion up to 300%. Biliary excretion of polar [ 14 C]CH metabolites was not altered by CD. CD pretreatment decreased subcellular distribution of [ 14 C]CH equivalents in hepatic cytosol and microsomes and lipoprotein-rich fraction-to-homogenate ratio. CD pretreatment increased the ratio of [ 14 C]CH equivalents in high density lipoprotein (HDL) to that in plasma and reduced [ 14 C]CH equivalents in the non-HDL fraction 4 h after a bolus lipid dose. CD pretreatment increased plasma non-HDL total CH by 80% 4 h after a bolus lipid dose. Scavenger receptor class B type I (SR-BI) and ATP-binding cassette transporter G8 (ABCG8) proteins were quantified by western blotting in hepatic membranes from control and CD treated mice. Liver membrane contents of SR-BI and ABCG8 proteins were unchanged by CD pretreatment. The data demonstrated that a single dose of CD altered CH homeostasis and lipoprotein metabolism

Chlordecone altered hepatic disposition of [14C]cholesterol and plasma cholesterol distribution but not SR-BI or ABCG8 proteins in livers of C57BL/6 mice.

Science.gov (United States)

Lee, Junga; Scheri, Richard C; Curtis, Lawrence R

2008-06-15

Organochlorine (OC) insecticides continue to occur in tissues of humans and wildlife throughout the world although they were banned in the United States a few decades ago. Low doses of the OC insecticide chlordecone (CD) alter hepatic disposition of lipophilic xenobiotics and perturb lipid homeostasis in rainbow trout, mice and rats. CD pretreatment altered tissue and hepatic subcellular distribution of exogenous [(14)C]cholesterol (CH) equivalents 4 and 16 h after a bolus intraperitoneal (ip) injection of 5 ml corn oil/kg that contained 10 mg CH/kg. CD pretreatment altered tissue distribution of exogenously administered [(14)C]CH by decreased hepatic and renal accumulation, and increased biliary excretion up to 300%. Biliary excretion of polar [(14)C]CH metabolites was not altered by CD. CD pretreatment decreased subcellular distribution of [(14)C]CH equivalents in hepatic cytosol and microsomes and lipoprotein-rich fraction-to-homogenate ratio. CD pretreatment increased the ratio of [(14)C]CH equivalents in high density lipoprotein (HDL) to that in plasma and reduced [(14)C]CH equivalents in the non-HDL fraction 4 h after a bolus lipid dose. CD pretreatment increased plasma non-HDL total CH by 80% 4 h after a bolus lipid dose. Scavenger receptor class B type I (SR-BI) and ATP-binding cassette transporter G8 (ABCG8) proteins were quantified by western blotting in hepatic membranes from control and CD treated mice. Liver membrane contents of SR-BI and ABCG8 proteins were unchanged by CD pretreatment. The data demonstrated that a single dose of CD altered CH homeostasis and lipoprotein metabolism.

Inulin and Fibersol-2 Combined Have Hypolipidemic Effects on High Cholesterol Diet-Induced Hyperlipidemia in Hamsters

Directory of Open Access Journals (Sweden)

Wen-Ching Huang

2016-03-01

Full Text Available The resistant carbohydrates, inulin, and Fibersol-2, belong to soluble dietary fibers and are considered important prebiotics that maintain biological functions, including glucose homeostasis, lipid regulation, colon disease prevention, and prebiotics characteristics. However, few studies have investigated Fibersol-2 alone or in combination with inulin to assess a pooled effect on modulation of hyperlipidemia. We aimed to investigate the effects of this combined supplement (defined as InF on hamsters fed a 0.2% cholesterol and 10% lard diet (i.e., high-cholesterol diet, HCD to induce hyperlipidemia. A total of 40 male hamsters were randomly assigned to five groups (n = 8 per group for treatment: standard diet, vehicle (control; or vehicle or InF supplementation by oral gavage at 0, 864, 1727, or 2591 mg/kg/day for eight weeks, designated HCD, InF-1X, InF-2X, and InF-3X groups, respectively. The hypolipidemic efficacy and safety of InF supplementation was assessed by serum lipid indexes, hepatic and fecal lipid content, and histology. InF supplementation significantly improved serum levels of triacylglycerol (TG and low-density lipoprotein cholesterol (LDL-C and the ratio of LDL-C/HDL-C after two-week treatment, and reduced serum total cholesterol (TC levels after four-week administration. After eight-week supplementation, InF supplementation dose-dependently improved serum levels of TC, TG, HDL-C, and LDL-C; LDL-C/HDL-C ratio; and hepatic TC and TG levels. It inhibited TC absorption by feces elimination. Our study provides experiment-based evidence to support that this prebiotics remedy may be useful in preventing or treating hyperlipidemia.

The anti-inflammatory effect of kaempferol on early atherosclerosis in high cholesterol fed rabbits

Science.gov (United States)

2013-01-01

Background Atherosclerosis has been widely accepted as an inflammatory disease of vascular, adhesion molecules play an important role in the early progression of it. The aim of the present study was to evaluate the effect of kaempferol on the inflammatory molecules such as E-selectin (E-sel), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesionmolecule-1 (VCAM-1) and monocyte chemotactic protein-1 (MCP-1) in high cholesterol induced atherosclerosis rabbit models. Methods Thirty male New Zealand white (NZW) rabbits were randomly divided into five groups, control group, model group, fenofibrate (12mg/kg) group and kaempferol groups (150 mg/kg and 30 mg/kg). The rabbits were fed with a normal diet or a high cholesterol diet for 10 weeks. Levels of blood lipids, serum tumour-necrosis factor-alpha (TNF-α) and serum interleukin-1beta (IL-1β) were detected at the end of the sixth and tenth week. Malonaldehyde (MDA) level and superoxide dismutase (SOD) activity in serum were also determined. Lesion areas of the aorta were measured with morphometry analysis after ten weeks. Gene expression of E-sel, ICAM-1, VCAM-1 and MCP-1 in aortas was determined by RT-PCR (reverse transcription-polymerase chain reaction). Immunohistochemical staining was employed to measure protein expression of E-sel, ICAM-1, VCAM-1 and MCP-1. Results Model rabbits fed with ten weeks of high-cholesterol diet developed significant progression of atherosclerosis. Compared with the control, levels of blood lipids, TNF-α, IL-1β and MDA increased markedly in serum of model rabbits, while SOD levels decreased. Gene and protein expressions of E-sel, ICAM-1, VCAM-1 and MCP-1 in atherosclerotic aortas increased remarkably in model group. However, comparing to the model rabbits, levels of TNF-α, IL-1β and MDA decreased significantly and serum SOD activity increased, gene and protein expressions of E-sel, ICAM-1, VCAM-1 and MCP-1 in aortas decreased significantly with the treatment of

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

Science.gov (United States)

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

1993-12-01

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

Immobilization of cholesterol oxidase in LbL films and detection of cholesterol using ac measurements

International Nuclear Information System (INIS)

Moraes, Marli L.; Souza, Nara C. de; Hayasaka, Caio O.; Ferreira, Marystela; Rodrigues Filho, Ubirajara P.; Riul, Antonio; Zucolotto, Valtencir; Oliveira, Osvaldo N.

2009-01-01

The preserved activity of immobilized biomolecules in layer-by-layer (LbL) films can be exploited in various applications, including biosensing. In this study, cholesterol oxidase (COX) layers were alternated with layers of poly(allylamine hydrochloride) (PAH) in LbL films whose morphology was investigated with atomic force microscopy (AFM). The adsorption kinetics of COX layers comprised two regimes, a fast, first-order kinetics process followed by a slow process fitted with a Johnson-Mehl-Avrami (JMA) function, with exponent ∼ 2 characteristic of aggregates growing as disks. The concept based on the use of sensor arrays to increase sensitivity, widely employed in electronic tongues, was extended to biosensing with impedance spectroscopy measurements. Using three sensing units, made of LbL films of PAH/COX and PAH/PVS (polyvinyl sulfonic acid) and a bare gold interdigitated electrode, we were able to detect cholesterol in aqueous solutions down to the 10 -6 M level. This high sensitivity is attributed to the molecular-recognition interaction between COX and cholesterol, and opens the way for clinical tests to be made with low cost, fast experimental procedures

Plasma lecithin : cholesterol acyltransferase activity modifies the inverse relationship of C-reactive protein with HDL cholesterol in nondiabetic men

NARCIS (Netherlands)

Dullaart, R. P. F.; Perton, F.; Kappelle, P.J.W.H.; de Vries, R.; Sluiter, W. J.; van Tol, A.

Lecithin:cholesterol acyltransferase (LCAT) is instrumental in high-density lipoprotein (HDL) maturation, but high LCAT levels do not predict low cardiovascular risk. LCAT may affect antioxidative or anti-inflammatory properties of HDL We determined the relationship of plasma high-sensitivity

High Sensitivity Electrochemical Cholesterol Sensor Utilizing a Vertically Aligned Carbon Nanotube Electrode with Electropolymerized Enzyme Immobilization

Directory of Open Access Journals (Sweden)

Ditsayut Phokharatkul

2009-10-01

Full Text Available In this report, a new cholesterol sensor is developed based on a vertically aligned CNT electrode with two-step electrochemical polymerized enzyme immobilization. Vertically aligned CNTs are selectively grown on a 1 mm2 window of gold coated SiO2/Si substrate by thermal chemical vapor deposition (CVD with gravity effect and water-assisted etching. CNTs are then simultaneously functionalized and enzyme immobilized by electrochemical polymerization of polyaniline and cholesterol enzymes. Subsequently, ineffective enzymes are removed and new enzymes are electrochemically recharged. Scanning electron microscopic characterization indicates polymer-enzyme nanoparticle coating on CNT surface. Cyclic voltammogram (CV measurements in cholesterol solution show the oxidation and reduction peaks centered around 450 and −220 mV, respectively. An approximately linear relationship between the cholesterol concentration and the response current could be observed in the concentration range of 50–300 mg/dl with a sensitivity of approximately 0.22 μA/mg·dl−1, which is considerably higher compared to previously reported CNT bioprobe. In addition, good specificity toward glucose, uric acid acetaminophen and ascorbic acid have been obtained. Moreover, sensors have satisfactory stability, repeatability and life time. Therefore, the electropolymerized CNT bioprobe is promising for cholesterol detection in normal cholesterol concentration in human blood.

Pitfalls in the detection of cholesterol in Huntington's disease models.

Science.gov (United States)

Marullo, Manuela; Valenza, Marta; Leoni, Valerio; Caccia, Claudio; Scarlatti, Chiara; De Mario, Agnese; Zuccato, Chiara; Di Donato, Stefano; Carafoli, Ernesto; Cattaneo, Elena

2012-10-11

Background Abnormalities in brain cholesterol homeostasis have been reported in Huntington's disease (HD), an adult-onset neurodegenerative disorder caused by an expansion in the number of CAG repeats in the huntingtin (HTT) gene. However, the results have been contradictory with respect to whether cholesterol levels increase or decrease in HD models. Biochemical and mass spectrometry methods show reduced levels of cholesterol precursors and cholesterol in HD cells and in the brains of several HD animal models. Abnormal brain cholesterol homeostasis was also inferred from studies in HD patients. In contrast, colorimetric and enzymatic methods indicate cholesterol accumulation in HD cells and tissues. Here we used several methods to investigate cholesterol levels in cultured cells in the presence or absence of mutant HTT protein. Results Colorimetric and enzymatic methods with low sensitivity gave variable results, whereas results from a sensitive analytical method, gas chromatography-mass spectrometry, were more reliable. Sample preparation, high cell density and cell clonality also influenced the detection of intracellular cholesterol. Conclusions Detection of cholesterol in HD samples by colorimetric and enzymatic assays should be supplemented by detection using more sensitive analytical methods. Care must be taken to prepare the sample appropriately. By evaluating lathosterol levels using isotopic dilution mass spectrometry, we confirmed reduced cholesterol biosynthesis in knock-in cells expressing the polyQ mutation in a constitutive or inducible manner. *Correspondence should be addressed to Elena Cattaneo: elena.cattaneo@unimi.it.

Taurocholate Deconjugation and Cholesterol Binding by Indigenous Dadih Lactic Acid Bacteria

Directory of Open Access Journals (Sweden)

USMAN PATO

2005-09-01

Full Text Available High serum cholesterol levels have been associated with an increased risk for human coronary heart disease. Lowering of serum cholesterol has been suggested to prevent the heart disease. To reduce serum cholesterol levels one may consumed diet supplementat of fermented dairy product such as dadih. Lactic acid bacteria present in dadih may alter serum cholesterol by directly bind to dietary cholesterol and/or deconjugation of bile salts. Acid and bile tolerance, deconjugation of sodium taurocholate, and the cholesterol-binding ability of lactic acid bacteria from dadih were examined. Among ten dadih lactic acid bacteria tested, six strains namely I-11, I-2775, K-5, I-6257, IS-7257, and B-4 could bind cholesterol and deconjugate sodium taurocholate. However, the last four strains were very sensitive to bile. Therefore, Lactobacillus fermentum I-11 and Leuconostoc lactis subsp. lactis I-2775 those were tolerant to acid and oxgall (bile and deconjugated sodium taurocholate and bound cholesterol could be recommended as probiotic to prevent coronary heart disease.

Expression profiles of miRNA-122 and its target CAT1 in minipigs (Sus scrofa) fed a high-cholesterol diet

DEFF Research Database (Denmark)

Cirera Salicio, Susanna; Birck, Malene Muusfeldt; Busk, Peter Kamp

2010-01-01

The Göttingen minipig is an excellent model for studying effects of dietary high-fat intake on obesity. In this study, we analyzed the expression level of microRNA-122 (miRNA-122) and its target mRNA, CAT1, in intact young male minipigs fed either high-cholesterol or standard diet for 11 wk. Mi...... with a decrease in the expression of miRNA-122, confirming the implication of this microRNA in obesity. Gene expression levels of CAT1 did not differ between groups.......RNA-122 and CAT1 are known to be important regulators of lipid metabolism. The weight of the young minipigs was monitored once a week during the feeding period; measurements of total cholesterol, triglycerides, high-density lipoproteins, and low-density lipoproteins were recorded at 4 time points (8, 14...

Recovery and purification of cholesterol from cholesterol-β-cyclodextrin inclusion complex using ultrasound-assisted extraction.

Science.gov (United States)

Li, Yong; Chen, Youliang; Li, Hua

2017-01-01

Response surface methodology was used to optimize ultrasound-assisted ethanol extraction (UAE) of cholesterol from cholesterol-β-cyclodextrin (C-β-CD) inclusion complex prepared from duck yolk oil. The best extraction conditions were solvent-solid ratio 10mL/g, ultrasonic power 251W, extraction temperature 56°C and sonication time 36min. Under these conditions, the highest cholesterol extraction yield and cholesterol content obtained 98.12±0.25% and 43.38±0.61mg/g inclusion complex, respectively. As compared with Reflux extraction and Soxhlet extraction, the UAE was more efficient and economical. To increase the purity of crude cholesterol extraction, silica gel column chromatography and crystallization were carried out. Finally, cholesterol was obtained at 95.1% purity, 71.7% recovery and 22.0% yield. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of +G_z exposure on gallbladder emptying function,cholecystokinin,and somatostatin in rabbits with high cholesterol diets

Directory of Open Access Journals (Sweden)

Guo-feng XIAO

2011-12-01

Full Text Available Objective The present study explores the effects of +Gz exposure on the gallbladder emptying function,cholecystokinin(CCK,and somatostatin(SS in rabbits with high cholesterol diets and investigates its mechanism in the occurrence of cholecystolithiasis.Methods Twenty-four male New Zealand rabbits were randomly divided into the high cholesterol diet(control group,n=8 and high cholesterol diet plus +Gz exposure groups.The latter was divided into the four-and six-week +Gz exposure groups(n=8 based on the exposure time.Radioimmunoassay was used to determine the CCK and SS contents of the gallbladder at the end of the experiment in the fourth and sixth weeks and to calculate the gallbladder volume and maximum emptying ratio.A microcomputer biodynamic pressure monitor was used to record the hydrostatic pressure in the gallbladder to measure its capacity.Moreover,the bile properties and formation of concretion were observed with the naked eye,and polarized light microscopy was used to observe cholesterin crystallization on the gallbladder wall.Results The gallbladder capacity increased upon +Gz exposure for four and six weeks,indicating that the maximum emptying ratio(E% decreased,the empty and residual volumes improved,and the pressure increased(P < 0.05.After +Gz exposure for four and six weeks,the CCK contents in the experimental groups were evidently lower than that in the control group and gradually decreased(P < 0.05 as the +Gz exposure time increased.On the other hand,after +Gz exposure for four and six weeks,the SS contents in the experimental groups were higher than that in the control group and gradually improved(P < 0.05 as the +Gz exposure time increased.After +Gz exposure for four and six weeks,bile was turbid and sticky with cholesterol crystals and without visible concretion.Conclusions Therefore,+Gz exposure may cause abnormal gallbladder emptying functions,decrease CCK content,increase SS content,and thus cause bile stasis

Clinical relevance of non-fasting and postprandial hypertriglyceridemia and remnant cholesterol

DEFF Research Database (Denmark)

Nordestgaard, Børge G; Freiberg, Jacob J

2011-01-01

Non-fasting triglycerides are measured at any time within up to 8 h (14 h) after any normal meal, while postprandial triglycerides are measured at a fixed time point within up to 8 h (14 h) of a standardised fat tolerance test. The simplest possible way of evaluating remnant cholesterol is non......-fasting/postprandial total cholesterol minus low-density lipoprotein (LDL) cholesterol minus high-density lipoprotein (HDL) cholesterol. Elevated levels of non-fasting/postprandial triglycerides directly correlate with elevated remnant cholesterol. In the general population, 38% of men have non......-fasting/postprandial triglycerides > 2mmol/L (>176 mg/dL) while 45% of men have non-fasting/postprandial triglyceride levels of 1-2 mmol/L (89-176 mg/dL); corresponding fractions in women are 20% and 47%. Also, 31% of men have remnant cholesterol levels > 1mmol/L (>39 mg/dL) while 46% of men have remnant cholesterol levels of 0...

The cholesterol space of the rat

International Nuclear Information System (INIS)

Chevallier, F.

1959-01-01

The experiments consisted in feeding daily to rats the same mass of radioactive cholesterol, over variable time intervals. From the evolution of the specific radioactivity of cholesterol carbon-14 in the organs as a function of time, information relative to the transport of cholesterol in the organism may be obtained. 1) The cholesterol space, defined as the group of molecules capable of being transferred from the organs into the serum and vice versa, represents at the most 50 per cent of the total cholesterol of the adult rat. 2) The incessant interchange between the tissual and the serum cholesterol renews entirely or for the most part the cholesterol molecules contained in the following organs: spleen, heart, adipose tissue, suprarenal glands, lungs, bone marrow, liver, erythrocytes. For a second group of organs: skin, testicles, kidneys, colon, bones, muscles, only a fraction of their cholesterol is renewable by this process. No transfer can be detected at the level of the brain. 3) The relative speeds of the various means of appearance (absorption, synthesis) and disappearance (excretion, transformation) of the cholesterol from its space are such that a stationary isotopic state is established around the eighth day, when the animal absorbs 5 milligrams of radioactive cholesterol daily. (author) [fr

Strategies for increasing house staff management of cholesterol with inpatients.

Science.gov (United States)

Boekeloo, B O; Becker, D M; Levine, D M; Belitsos, P C; Pearson, T A

1990-01-01

This study tested the effectiveness of two conceptually different chart audit-based approaches to modifying physicians' clinical practices to conform with quality-assurance standards. The objective was to increase intern utilization of cholesterol management opportunities in the inpatient setting. Using a clinical trial study design, 29 internal medicine interns were randomly assigned to four intervention groups identified by the intervention they received: control, reminder checklists (checklists), patient-specific feedback (feedback), or both interventions (combined). Over a nine-month period, intern management of high blood cholesterol levels in internal medicine inpatients (n = 459) was monitored by postdischarge chart audit. During both a baseline and subsequent intervention period, interns documented significantly more cholesterol management for inpatients with coronary artery disease (CAD) than without CAD. During baseline, 27.3%, 24.3%, 21.7%, 12.4%, 5.4%, and 2.7% of all inpatient charts had intern documentation concerning a low-fat hospital diet, cholesterol history, screening blood cholesterol level assessment, follow-up lipid profile, nutritionist consult, and preventive cardiology consult, respectively. The feedback intervention significantly increased overall intern-documented cholesterol management among inpatients with CAD. The checklists significantly decreased overall intern-documented cholesterol management. Feedback appears to be an effective approach to increasing intern cholesterol management in inpatients.

Transintestinal cholesterol excretion in humans

NARCIS (Netherlands)

Reeskamp, Laurens F.; Meessen, Emma C. E.; Groen, Albert K.

2018-01-01

Purpose of review To discuss recent insights into the measurement and cellular basis of transintestinal cholesterol excretion (TICE) in humans and to explore TICE as a therapeutic target for increasing reverse cholesterol transport. Recent findings TICE is the net effect of cholesterol excretion by

Cholesterol Absorption and Synthesis in Vegetarians and Omnivores.

Science.gov (United States)

Lütjohann, Dieter; Meyer, Sven; von Bergmann, Klaus; Stellaard, Frans

2018-03-01

Vegetarian diets are considered health-promoting; however, a plasma cholesterol lowering effect is not always observed. We investigate the link between vegetarian-diet-induced alterations in cholesterol metabolism. We study male and female omnivores, lacto-ovo vegetarians, lacto vegetarians, and vegans. Cholesterol intake, absorption, and fecal sterol excretion are measured as well as plasma concentrations of cholesterol and noncholesterol sterols. These serve as markers for cholesterol absorption, synthesis, and catabolism. The biliary cholesterol secretion rate is estimated. Flux data are related to body weight. Individual vegetarian diet groups are statistically compared to the omnivore group. Lacto vegetarians absorb 44% less dietary cholesterol, synthesized 22% more cholesterol, and show no differences in plasma total and LDL cholesterol. Vegan subjects absorb 90% less dietary cholesterol, synthesized 35% more cholesterol, and have a similar plasma total cholesterol, but a 13% lower plasma LDL cholesterol. No diet-related differences in biliary cholesterol secretion and absorption are observed. Total cholesterol absorption is lower only in vegans. Total cholesterol input is similar under all vegetarian diets. Unaltered biliary cholesterol secretion and higher cholesterol synthesis blunt the lowered dietary cholesterol intake in vegetarians. LDL cholesterol is significantly lower only in vegans. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Serum cholesterol as a risk factor for coronary heart disease revisited

African Journals Online (AJOL)

2014-08-04

Aug 4, 2014 ... levels to low-density lipoprotein (LDL) cholesterol levels, and high- density ... intestinal absorption of triglycerides and cholesterol, plus very low- ... These relationships are present across the age spectrum and in both sexes.

Effect of Ascorbic Acid on Serum Cholesterol Levels and on Die ...

African Journals Online (AJOL)

1974-06-12

Jun 12, 1974 ... Myasnikova' was the first to show that vitamin Chad the ability to influence ~erum cholesterol levels of patients. She observed that the intravenous administration of high doses of vitamin C to patients with high levels of serum cholesterol resulted in a distinct decrease, whereas in patients with low values it ...

Prevalence of obesity and high level of cholesterol in hypertension ...

African Journals Online (AJOL)

This study was undertaken to determine what proportion of patients with hypertension are obese and or have elevated serum cholesterol. The data of two hundred and fifty patients who attended the outpatient clinics of the University College Hospital, Ibadan from January 1998 to December 2001 were analysed. Almost half ...

The Chemical Potential of Plasma Membrane Cholesterol: Implications for Cell Biology.

Science.gov (United States)

Ayuyan, Artem G; Cohen, Fredric S

2018-02-27

Cholesterol is abundant in plasma membranes and exhibits a variety of interactions throughout the membrane. Chemical potential accounts for thermodynamic consequences of molecular interactions, and quantifies the effective concentration (i.e., activity) of any substance participating in a process. We have developed, to our knowledge, the first method to measure cholesterol chemical potential in plasma membranes. This was accomplished by complexing methyl-β-cyclodextrin with cholesterol in an aqueous solution and equilibrating it with an organic solvent containing dissolved cholesterol. The chemical potential of cholesterol was thereby equalized in the two phases. Because cholesterol is dilute in the organic phase, here activity and concentration were equivalent. This equivalence allowed the amount of cholesterol bound to methyl-β-cyclodextrin to be converted to cholesterol chemical potential. Our method was used to determine the chemical potential of cholesterol in erythrocytes and in plasma membranes of nucleated cells in culture. For erythrocytes, the chemical potential did not vary when the concentration was below a critical value. Above this value, the chemical potential progressively increased with concentration. We used standard cancer lines to characterize cholesterol chemical potential in plasma membranes of nucleated cells. This chemical potential was significantly greater for highly metastatic breast cancer cells than for nonmetastatic breast cancer cells. Chemical potential depended on density of the cancer cells. A method to alter and fix the cholesterol chemical potential to any value (i.e., a cholesterol chemical potential clamp) was also developed. Cholesterol content did not change when cells were clamped for 24-48 h. It was found that the level of activation of the transcription factor STAT3 increased with increasing cholesterol chemical potential. The cholesterol chemical potential may regulate signaling pathways. Copyright © 2018. Published by

Promotive effect of Bofutsushosan (Fangfengtongshengsan) on lipid and cholesterol excretion in feces in mice treated with a high-fat diet.

Science.gov (United States)

Akaki, Junji; Tachi, Shiori; Nakamura, Naoki; Arai, Tetsuya; Yamasaki, Hiroo; Inoue, Makoto; Makino, Toshiaki

2018-06-28

Bofutsushosan (fangfengtongshengsan in Chinese, BTS) is a formula in traditional Japanese Kampo medicine and Chinese medicine comprising 18 crude drugs that is used for treating obesity and metabolic syndrome. We evaluated the promotive effects of BTS on lipid and cholesterol elimination in mice. Mice were reared with a high-fat diet containing boiled water extract of BTS for 30 days, and their biochemical parameters as well as the weight and lipid content of feces were measured. We also measured cholesterol uptake into Caco-2 cells cultured with or without BTS extract. The body weight and amounts of visceral fat and subcutaneous fat on day 28; the weights of epididymal, perirenal, and mesenteric fat; and the serum concentrations of triglyceride, glucose, and hemoglobin A1c on day 30 were significantly lower in the BTS extract-treated groups than in the control in a dose-dependent manner. The amounts of lipid and cholesterol in the feces collected from day 6-23 were significantly greater than in the control. When Caco-2 cells were incubated with BTS extract, the uptake of cholesterol into cells was significantly reduced in a concentration-dependent manner. Among the components of BTS, the methanol extracts of Platycodi Radix and Zingiberis Rhizoma contribute but the extracts of Ephedrae Herba and Rhei Rhizoma counteract the suppressive effect of BTS on cholesterol uptake into Caco-2 cells. BTS has beneficial effects on obesity and metabolic syndrome, and its mechanisms of action include the promotion of lipid elimination and the inhibition of cholesterol absorption in the intestine. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Estimation hydrophilic-lipophilic balance number of surfactants

Energy Technology Data Exchange (ETDEWEB)

Pawignya, Harsa, E-mail: harsa-paw@yahoo.co.id [Chemical Engineering Department Diponegoro University (Indonesia); Chemical Engineering Departement University of Pembangunan Nasional Yogyakarta (Indonesia); Prasetyaningrum, Aji, E-mail: ajiprasetyaningrum@gmail.com; Kusworo, Tutuk D.; Pramudono, Bambang, E-mail: Pramudono2004@yahoo.com [Chemical Engineering Department Diponegoro University (Indonesia); Dyartanti, Endah R. [Chemical Engineering Department Diponegoro University (Indonesia); Chemical Enginering Departement Sebelas Maret University (Indonesia)

2016-02-08

Any type of surfactant has a hydrophilic-lipophilic balance number (HLB number) of different. There are several methods for determining the HLB number, with ohysical properties of surfactant (solubility cloud point and interfacial tension), CMC methods and by thermodynamics properties (Free energy Gibbs). This paper proposes to determined HLB numbers from interfelation methods. The result of study indicated that the CMC method described by Hair and Moulik espesially for nonionic surfactant. The application of exess Gibbs free energy and by implication activity coefficient provides the ability to predict the behavior of surfactants in multi component mixtures of different concentration. Determination of HLB number by solubility and cloud point parameter is spesific for anionic and nonionic surfactant but this methods not available for cationic surfactants.

Inclusion of Almonds in a Cholesterol-Lowering Diet Improves Plasma HDL Subspecies and Cholesterol Efflux to Serum in Normal-Weight Individuals with Elevated LDL Cholesterol.

Science.gov (United States)

Berryman, Claire E; Fleming, Jennifer A; Kris-Etherton, Penny M

2017-08-01

Background : Almonds may increase circulating HDL cholesterol when substituted for a high-carbohydrate snack in an isocaloric diet, yet little is known about the effects on HDL biology and function. Objective: The objective was to determine whether incorporating 43 g almonds/d in a cholesterol-lowering diet would improve HDL subspecies and function, which were secondary study outcomes. Methods: In a randomized, 2-period, crossover, controlled-feeding study, a diet with 43 g almonds/d (percentage of total energy: 51% carbohydrate, 16% protein, and 32% total and 8% saturated fat) was compared with a similar diet with an isocaloric muffin substitution (58% carbohydrate, 15% protein, and 26% total and 8% saturated fat) in men and women with elevated LDL cholesterol. Plasma HDL subspecies and cholesterol efflux from J774 macrophages to human serum were measured at baseline and after each diet period. Diet effects were examined in all participants ( n = 48) and in normal-weight (body mass index: almond diet, compared with the control diet, increased α-1 HDL [mean ± SEM: 26.7 ± 1.5 compared with 24.3 ± 1.3 mg apolipoprotein A-I (apoA-I)/dL; P = 0.001]. In normal-weight participants, the almond diet, relative to the control diet, increased α-1 HDL (33.7 ± 3.2 compared with 28.4 ± 2.6 mg apoA-I/dL), the α-1 to pre-β-1 ratio [geometric mean (95% CI): 4.3 (3.3, 5.7) compared with 3.1 (2.4, 4.0)], and non-ATP-binding cassette transporter A1 cholesterol efflux (8.3% ± 0.4% compared with 7.8% ± 0.3%) and decreased pre-β-2 (3.8 ± 0.4 compared with 4.6 ± 0.4 mg apoA-I/dL) and α-3 (23.5 ± 0.9 compared with 26.9 ± 1.1 mg apoA-I/dL) HDL ( P almonds for a carbohydrate-rich snack within a lower-saturated-fat diet may be a simple strategy to maintain a favorable circulating HDL subpopulation distribution and improve cholesterol efflux in normal-weight individuals with elevated LDL cholesterol. This trial was registered at clinicaltrials.gov as NCT01101230. © 2017

Influence of the membrane environment on cholesterol transfer.

Science.gov (United States)

Breidigan, Jeffrey Michael; Krzyzanowski, Natalie; Liu, Yangmingyue; Porcar, Lionel; Perez-Salas, Ursula

2017-12-01

Cholesterol, an essential component in biological membranes, is highly unevenly distributed within the cell, with most localized in the plasma membrane while only a small fraction is found in the endoplasmic reticulum, where it is synthesized. Cellular membranes differ in lipid composition and protein content, and these differences can exist across their leaflets too. This thermodynamic landscape that cellular membranes impose on cholesterol is expected to modulate its transport. To uncover the role the membrane environment has on cholesterol inter- and intra-membrane movement, we used time-resolved small angle neutron scattering to study the passive movement of cholesterol between and within membranes with varying degrees of saturation content. We found that cholesterol moves systematically slower as the degree of saturation in the membranes increases, from a palmitoyl oleyl phosphotidylcholine membrane, which is unsaturated, to a dipalmitoylphosphatidylcholine (DPPC) membrane, which is fully saturated. Additionally, we found that the energetic barrier to move cholesterol in these phosphatidylcholine membranes is independent of their relative lipid composition and remains constant for both flip-flop and exchange at ∼100 kJ/mol. Further, by replacing DPPC with the saturated lipid palmitoylsphingomyelin, an abundant saturated lipid of the outer leaflet of the plasma membrane, we found the rates decreased by a factor of two. This finding is in stark contrast with recent molecular dynamic simulations that predict a dramatic slow-down of seven orders of magnitude for cholesterol flipping in membranes with a similar phosphocholine and SM lipid composition. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Levels of high-density lipoprotein cholesterol (HDL-C among children with steady-state sickle cell disease

Directory of Open Access Journals (Sweden)

Seixas Magda O

2010-08-01

Full Text Available Abstract Background The search for sickle cell disease (SCD prognosis biomarkers is a challenge. These markers identification can help to establish further therapy, later severe clinical complications and with patients follow-up. We attempted to study a possible involvement of levels of high-density lipoprotein cholesterol (HDL-C in steady-state children with SCD, once that this lipid marker has been correlated with anti-inflammatory, anti-oxidative, anti-aggregation, anti-coagulant and pro-fibrinolytic activities, important aspects to be considered in sickle cell disease pathogenesis. Methods We prospectively analyzed biochemical, inflammatory and hematological biomarkers of 152 steady-state infants with SCD and 132 healthy subjects using immunochemistry, immunoassay and electronic cell counter respectively. Clinical data were collected from patient medical records. Results Of the 152 infants investigated had a significant positive association of high-density lipoprotein cholesterol with hemoglobin (P Conclusions We hypothesize that some SCD patients can have a specific dyslipidemic subphenotype characterized by low HDL-C with hypertriglyceridemia and high VLDL-C in association with other biomarkers, including those related to inflammation. This represents an important step toward a more reliable clinical prognosis. Additional studies are warranted to test this hypothesis and the probably mechanisms involved in this complex network of markers and their role in SCD pathogenesis.

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.

Antioxidative effect of lipophilized caffeic acid in fish oil enriched mayonnaise and milk

DEFF Research Database (Denmark)

Alemán, Mercedes; Bou, Ricard; Guardiola, Francesc

2015-01-01

The antioxidative effect of lipophilized caffeic acid was assessed in two different fish oil enriched food products: mayonnaise and milk. In both emulsion systems, caffeic acid esterified with fatty alcohols of different chain lengths (C1–C20) were better antioxidants than the original phenolic c...

Meta-analysis of genome-wide association studies of HDL cholesterol response to statins

DEFF Research Database (Denmark)

Postmus, Iris; Warren, Helen R; Trompet, Stella

2016-01-01

BACKGROUND: In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation. METHODS AND RESULTS: We performed...... a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p

Cholesterol Assimilation with Isolated lactobacilli Strains of Fars’ Local Dairy Products

Directory of Open Access Journals (Sweden)

A Emami

2008-12-01

Full Text Available ABSTRACT: Introduction & Objective: Cholesterol is an important compound in most of the biological reactions which the excess of it can be seen as a harmful compound of causing heart diseases. The aim of the present study was to evaluate the cholesterol removal property and also its pathway by dairy lactobacillus in in vitro condition under different bile salts concentration. Materials & Methods: After isolation of lactobacillus strains from dairy products, they were identified with chemical tests and their growths were evaluated under presence of cholesterol and bile salts. The method of action of the bacillus in cholesterol removal was assayed by spectrophotometer method. Collected data was analyzed by SPSS software. Results: result of this study showed that any strains of the bacteria had the ability of cholesterol removal (7.82-34.69 µg/ml. L.casei had more competence for removal of cholesterol in compare to the rest of bacilli. The evaluation of cholesterol cell wall attachment revealed that most of removed cholesterols have been changed to the other products. Conclusion: Considering the result of this study, it can be concluded that cholesterol removal has a direct association with growth of bacteria where the L. casei with high growth rate had more capability of cholesterol removal. Whereas the Lactobacillus can remove the cholesterol with different methods, results of this study showed that dairy products, especially yogurt, can remove the harmful substances such as cholesterol using non chemical methods. The results of this study could be expanded on human use if more study and research could be carried out.

Modulation of cholesterol transport by maternal hypercholesterolemia in human full-term placenta.

Directory of Open Access Journals (Sweden)

Ran Zhang

Full Text Available The significance of maternal cholesterol transporting to the fetus under normal as well as pathological circumstances is less understood. The objective of this study was to observe the effects of maternal hypercholesterolemia on placental cholesterol transportation. Human full-time placenta, maternal and venous cord blood were sampled at delivery from the pregnant women with serum total cholesterol (TC concentrations at third trimester higher than 7.25 mM (n = 19 and the pregnant women with normal TC concentrations (n = 19. Serum lipids and expression of genes related to cholesterol transportation were measured by western blot or real-time PCR. The results indicated that serum TC, high density lipoprotein cholesterol (HDL-C, and low density lipoprotein cholesterol (LDL-C levels were significantly increased, in pregnancies, but decreased in cord blood in hypercholesterolemic group compared to the matched control group. All the subjects were no-drinking, non-smoker, and gestational disease free. The mRNA expression of lipoprotein receptors, including LDLR and VLDLR were significantly increased, while the protein expression of PCSK9 was significantly increased in hypercholesterolemic placenta. In conclusion, maternal hypercholesterolemia might decrease the transportation of cholesterol from mother to fetus because of the high levels of PCSK9 protein expression.

Tissue sterol composition in Atlantic salmon (Salmo salar L.) depends on the dietary cholesterol content and on the dietary phytosterol:cholesterol ratio, but not on the dietary phytosterol content.

Science.gov (United States)

Sissener, Nini H; Rosenlund, Grethe; Stubhaug, Ingunn; Liland, Nina S

2018-03-01

The aim of the study was to investigate how the dietary sterol composition, including cholesterol, phytosterol:cholesterol ratio and phytosterols, affect the absorption, biliary excretion, retention, tissue storage and distribution of cholesterol and individual phytosterols in Atlantic salmon (Salmo salar L.). A feeding trial was conducted at two different temperatures (6 and 12°C), using nine different diets with varying contents of phytosterols, cholesterol and phytosterol:cholesterol ratio. Cholesterol retention values were clearly dependent on dietary cholesterol, and showed that fish fed cholesterol levels phytosterol:cholesterol ratio, but not on the dietary phytosterol content in itself. Campesterol and brassicasterol appeared to be the phytosterols with the highest intestinal absorption in Atlantic salmon. There was a high biliary excretion of campesterol, but not of brassicasterol, which accumulated in tissues and particularly in adipose tissue, with 2-fold-higher retention at 12°C compared with 6°C. Campesterol had the second highest retention of the phytosterols in the fish, but with no difference between the two temperatures. Other phytosterols had very low retention. Although brassicasterol retention decreased with increasing dietary phytosterols, campesterol retention decreased with increasing dietary cholesterol, indicating differences in the uptake mechanisms for these two sterols.

Controlling Cholesterol with Statins

Science.gov (United States)

... For Consumers Home For Consumers Consumer Updates Controlling Cholesterol with Statins Share Tweet Linkedin Pin it More ... not, the following tips can help keep your cholesterol in check: Talk with your healthcare provider about ...

Low-carbohydrate diets reduce lipid accumulation and arterial inflammation in guinea pigs fed a high-cholesterol diet.

Science.gov (United States)

Leite, Jose O; DeOgburn, Ryan; Ratliff, Joseph; Su, Randy; Smyth, Joan A; Volek, Jeff S; McGrane, Mary M; Dardik, Alan; Fernandez, Maria Luz

2010-04-01

Low-carbohydrate diets (LCD) efficiently induce weight loss and favorably affect plasma lipids, however, the effect of LCD on atherosclerosis is still argued. To evaluate the effect of LCD on the prevention of atherosclerosis. Twenty guinea pigs were fed either a LCD or a low-fat diet (LFD) in combination with high-cholesterol (0.25g/100g) for 12 weeks. The percentage energy of macronutrient distribution was 10:65:25 for carbohydrate:fat:protein for the LCD, and 55:20:25 for the LFD. Plasma lipids were measured using colorimetric assays. Plasma and aortic oxidized (oxLDL) were quantified using ELISA methods. Inflammatory cytokines were measured in aortic homogenates using an immunoassay. H&E stained sections of aortic sinus and Schultz stained sections of carotid arteries were examined. LDL cholesterol was lower in the LCD compared to the LFD group (71.9+/-34.8 vs. 81.7+/-26.9mg/dL; p=0.039). Aortic cholesterol was also lower in the LCD (4.98+/-1.3mg/g) compared to the LFD group (6.68+/-2.0mg/g); p<0.05. The Schultz staining method confirmed less aortic cholesterol accumulation in the LCD group. Plasma oxLDL did not differ between groups, however, aortic oxLDL was 61% lower in the LCD compared to the LFD group (p=0.045). There was a positive correlation (r=0.63, p=0.03) between oxLDL and cholesterol concentration in the aorta of LFD group, which was not observed in LCD group (r=-0.05, p=0.96). Inflammatory markers were reduced in guinea pigs from the LCD group (p<0.05) and they were correlated with the decreases in oxLDL in aorta. These results suggest that LCD not only decreases lipid deposition, but also prevents the accumulation of oxLDL and reduces inflammatory cytokines within the arterial wall and may prevent atherosclerosis. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Electrical and optical properties of gold nanoparticles: applications in gold nanoparticles-cholesterol oxidase integrated systems for cholesterol sensing

Energy Technology Data Exchange (ETDEWEB)

Saxena, Urmila; Goswami, Pranab, E-mail: pgoswami@iitg.ernet.in [Indian Institute of Technology Guwahati, Department of Biotechnology (India)

2012-03-15

We describe here the application of electrical and optical properties of gold nanoparticles (AuNPs) in conjunction with cholesterol oxidase (ChOx) for cholesterol estimation. The electrocatalytic property of AuNPs was studied with spectrophotometric technique using a redox dye 2,6-dichloroindophenol (DCPIP), where AuNPs found to increase the electron transfer rate between ChOx and DCPIP by {approx}1.68-fold. This study demonstrated AuNPs as efficient electron transfer mediator for ChOx based electrochemical cholesterol biosensors. Optocatalytic property of AuNPs was used in the AuNPs seed mediated enlargement system to develop an optical detection path for cholesterol. This optical method exhibited a linear detection range of 0.01-0.1 mM and a detection limit of 10 {mu}M cholesterol. The effect of AuNPs size (13-21 nm) on the catalytic properties of AuNPs was also studied. Spectrophotometric analysis of the electron transfer process between ChOx and DCPIP with different sized AuNPs showed highest electron transfer efficiency with smaller (13 nm) AuNPs. The electrochemical bioelectrode fabricated with AuNPs and ChOx gave consensus results. Contrastingly, AuNPs size did not affect its optocatalytic activity and eventually the performance of the optical method based on the growth of AuNPs. The findings of the present study offer useful insight and perspectives for fabricating highly sensitive analytical systems based on AuNPs-ChOx complexes.

The Interpretation of Cholesterol Balance Derived Synthesis Data and Surrogate Noncholesterol Plasma Markers for Cholesterol Synthesis under Lipid Lowering Therapies

Directory of Open Access Journals (Sweden)

Frans Stellaard

2017-01-01

Full Text Available The cholesterol balance procedure allows the calculation of cholesterol synthesis based on the assumption that loss of endogenous cholesterol via fecal excretion and bile acid synthesis is compensated by de novo synthesis. Under ezetimibe therapy hepatic cholesterol is diminished which can be compensated by hepatic de novo synthesis and hepatic extraction of plasma cholesterol. The plasma lathosterol concentration corrected for total cholesterol concentration (R_Lath as a marker of de novo cholesterol synthesis is increased during ezetimibe treatment but unchanged under treatment with ezetimibe and simvastatin. Cholesterol balance derived synthesis data increase during both therapies. We hypothesize the following. (1 The cholesterol balance data must be applied to the hepatobiliary cholesterol pool. (2 The calculated cholesterol synthesis value is the sum of hepatic de novo synthesis and the net plasma—liver cholesterol exchange rate. (3 The reduced rate of biliary cholesterol absorption is the major trigger for the regulation of hepatic cholesterol metabolism under ezetimibe treatment. Supportive experimental and literature data are presented that describe changes of cholesterol fluxes under ezetimibe, statin, and combined treatments in omnivores and vegans, link plasma R_Lath to liver function, and define hepatic de novo synthesis as target for regulation of synthesis. An ezetimibe dependent direct hepatic drug effect cannot be excluded.

Effect of sardine proteins on hyperglycaemia, hyperlipidaemia and lecithin:cholesterol acyltransferase activity, in high-fat diet-induced type 2 diabetic rats.

Science.gov (United States)

Benaicheta, Nora; Labbaci, Fatima Z; Bouchenak, Malika; Boukortt, Farida O

2016-01-14

Type 2 diabetes (T2D) is a major risk factor of CVD. The effects of purified sardine proteins (SP) were examined on glycaemia, insulin sensitivity and reverse cholesterol transport in T2D rats. Rats fed a high-fat diet (HFD) for 5 weeks, and injected with a low dose of streptozotocin, were used. The diabetic rats were divided into four groups, and they were fed casein (CAS) or SP combined with 30 or 5% lipids, for 4 weeks. HFD-induced hyperglycaemia, insulin resistance and hyperlipidaemia in rats fed HFD, regardless of the consumed protein. In contrast, these parameters lowered in rats fed SP combined with 5 or 30% lipids, and serum insulin values reduced in SP v. CAS. HFD significantly increased total cholesterol and TAG concentrations in the liver and serum, whereas these parameters decreased with SP, regardless of lipid intake. Faecal cholesterol excretion was higher with SP v. CAS, combined with 30 or 5% lipids. Lecithin:cholesterol acyltransferase (LCAT) activity and HDL3-phospholipids (PL) were higher in CAS-HF than in CAS, whereas HDL2-cholesteryl esters (CE) were lower. Otherwise, LCAT activity and HDL2-CE were higher in the SP group than in the CAS group, whereas HDL3-PL and HDL3-unesterified cholesterol were lower. Moreover, LCAT activity lowered in the SP-HF group than in the CAS-HF group, when HDL2-CE was higher. In conclusion, these results indicate the potential effects of SP to improve glycaemia, insulin sensitivity and reverse cholesterol transport, in T2D rats.

Nanoscale Membrane Domain Formation Driven by Cholesterol

DEFF Research Database (Denmark)

Javanainen, Matti; Martinez-Seara, Hector; Vattulainen, Ilpo

2017-01-01

Biological membranes generate specific functions through compartmentalized regions such as cholesterol-enriched membrane nanodomains that host selected proteins. Despite the biological significance of nanodomains, details on their structure remain elusive. They cannot be observed via microscopic...... dipalmitoylphosphatidylcholine and cholesterol - the "minimal standard" for nanodomain formation. The simulations reveal how cholesterol drives the formation of fluid cholesterol-rich nanodomains hosting hexagonally packed cholesterol-poor lipid nanoclusters, both of which show registration between the membrane leaflets....... The complex nanodomain substructure forms when cholesterol positions itself in the domain boundary region. Here cholesterol can also readily flip-flop across the membrane. Most importantly, replacing cholesterol with a sterol characterized by a less asymmetric ring region impairs the emergence of nanodomains...

Importance of measuring Non-HDL cholesterol in type 2 diabetes patients

International Nuclear Information System (INIS)

Ram, N.; Hashmi, F.; Jabbar, A

2014-01-01

Objective: To study the correlation between Non-high-density lipoprotein and low-density lipoprotein cholesterol in patients with Type 2 diabetes mellitus and the proportion of patients achieving Adult Treatment Panel III recommended goals. Methods: The cross sectional study was conducted at the Diabetic Clinic, Aga Khan University Hospital, Karachi. Data of Type 2 diabetes mellitus patients who attended the clinic between 2007 and 2011 was reviewed. All Type 2 diabetic patients of either gender with fasting lipid profile irrespective of taking lipid lowering therapy were included. Type-1 DM, gestational diabetes, type 2 diabetes patients with pregnancy and those with incomplete data were excluded. Correlation between the low-density lipoprotein and Non- high-density lipoprotein was assessed by applying Cramer V and phi. Proportion of patients achieving Adult Treatment Panel III recommended goals was checked. Multivariable regression was done to identify common factors associated with elevated Non- high-density lipoprotein cholesterol. Results: A total of 1352 patients fulfilling the eligibility criteria were included in the study. Mean age of the patients was 54.5+-11.3 years; 797 (59%) were males; 1122 (83%) had Body Mass Index above 25; and 1016 (75%) had HbA1c >7%. Mean Non-high-density lipoprotein cholesterol was 129+-42mg/dl. Mean low-density lipoprotein cholesterol was 100+-37mg/dl. Both low-density lipoprotein 130mg/dl (p 100mg/dl was independently associated with having Non-high-density lipoprotein cholesterol >130mg/dl (Adjusted Odds Ratio 38.6; 95% Confidance Interval 28.1-53.1). Similarly, age 130 mg/dl (Adjusted Odds Ratio 1.6; 95% Confidance Interval = 1.01 - 2.3). Whereas having obesity Body Mass Index >25 was 3.6 times more associated to have Non-high-density lipoprotein >130mg/dl (Adjusted Odds Ratio 3.6; 95% Confidance Interval = 1.6-7.7). In patients with coronary artery disease, combined goal achievement of low-density lipoprotein 100mg/dl (p <0

Barley β-glucan reduces blood cholesterol levels via interrupting bile acid metabolism.

Science.gov (United States)

Wang, Yanan; Harding, Scott V; Thandapilly, Sijo J; Tosh, Susan M; Jones, Peter J H; Ames, Nancy P

2017-11-01

Underlying mechanisms responsible for the cholesterol-lowering effect of β-glucan have been proposed, yet have not been fully demonstrated. The primary aim of this study was to determine whether the consumption of barley β-glucan lowers cholesterol by affecting the cholesterol absorption, cholesterol synthesis or bile acid synthesis. In addition, this study was aimed to assess whether the underlying mechanisms are related to cholesterol 7α hydroxylase (CYP7A1) SNP rs3808607 as proposed by us earlier. In a controlled, randomised, cross-over study, participants with mild hypercholesterolaemia (n 30) were randomly assigned to receive breakfast containing 3 g high-molecular weight (HMW), 5 g low-molecular weight (LMW), 3 g LMW barley β-glucan or a control diet, each for 5 weeks. Cholesterol absorption was determined by assessing the enrichment of circulating 13C-cholesterol over 96 h following oral administration; fractional rate of synthesis for cholesterol was assessed by measuring the incorporation rate of 2H derived from deuterium oxide within the body water pool into the erythrocyte cholesterol pool over 24 h; bile acid synthesis was determined by measuring serum 7α-hydroxy-4-cholesten-3-one concentrations. Consumption of 3 g HMW β-glucan decreased total cholesterol (TC) levels (P=0·029), but did not affect cholesterol absorption (P=0·25) or cholesterol synthesis (P=0·14). Increased bile acid synthesis after consumption of 3 g HMW β-glucan was observed in all participants (P=0·049), and more pronounced in individuals carrying homozygous G of rs3808607 (P=0·033). In addition, a linear relationship between log (viscosity) of β-glucan and serum 7α-HC concentration was observed in homozygous G allele carriers. Results indicate that increased bile acid synthesis rather than inhibition of cholesterol absorption or synthesis may be responsible for the cholesterol-lowering effect of barley β-glucan. The pronounced TC reduction in G allele carriers of rs

Determination of the variability of both hydrophilic and lipophilic toxins in endemic wild bivalves and carnivorous gastropods from the southern part of Chile.

Science.gov (United States)

Zamorano, Ruben; Marín, Michelle; Cabrera, Fabiola; Figueroa, Diego; Contreras, Cristóbal; Barriga, Andrés; Lagos, Néstor; García, Carlos

2013-01-01

The aim of this study was to analyse and determine the composition of paralytic shellfish poisoning (PSP) toxins and lipophilic toxins in the Region of Aysén, Chile, in wild endemic mussels (Mytilus chilensis, Venus antiqua, Aulacomya ater, Choromytilus chorus, Tagelus dombeii and Gari solida) and in two endemic carnivorous molluscs species (Concholepas concholepas and Argobuccinum ranelliforme). PSP-toxin contents were determined by using HPLC with fluorescence detection, while lipophilic toxins were determined by using LC-MS/MS. Mean concentrations for the total of PSP toxins were in the range 55-2505 μg saxitoxin-equivalent/100 g. The two most contaminated samples for PSP toxicity were bivalve Gari solida and carnivorous Argobuccinum ranelliforme with 2505 ± 101 and 1850 ± 137 μg saxitoxin-equivalent/100 g, respectively (p < 0.05). The lipophilic toxins identified were okadaic acid, dinophysistoxin-1 (DTX-1), azaspiracid-1 (AZA-1), pectenotoxin-2 (PTX-2) and yessotoxins (YTX). All analysed molluscs contained lipophilic toxins at levels ranging from 56 ± 4.8 to 156.1 ± 8.2 μg of okadaic acid-equivalent/kg shellfish together with YTX at levels ranging from 1.0 ± 0.1 to 18 ± 0.9 μg of YTX-equivalent/kg shellfish and AZA at levels ranging from 3.6 ± 0.2 to 31 ± 2.1 μg of AZA-equivalent/kg shellfish. Furthermore, different bivalves and gastropods differ in their capacity of retention of lipophilic toxins, as shown by the determination of their respective lipophilic toxins levels. In all the evaluated species, the presence of lipophilic toxins associated with biotransformation in molluscs and carnivorous gastropods was not identified, in contrast to the identification of PSP toxins, where the profiles identified in the different species are directly related to biotransformation processes. Thus, this study provides evidence that the concentration of toxins in the food intake of the evaluated species (Bivalvia and Gastropoda class) determines the degree of

Cholesterol crystallization within hepatocyte lipid droplets and its role in murine NASH.

Science.gov (United States)

Ioannou, George N; Subramanian, Savitha; Chait, Alan; Haigh, W Geoffrey; Yeh, Matthew M; Farrell, Geoffrey C; Lee, Sum P; Savard, Christopher

2017-06-01

We recently reported that cholesterol crystals form in hepatocyte lipid droplets (LDs) in human and experimental nonalcoholic steatohepatitis. Herein, we assigned WT C57BL/6J mice to a high-fat (15%) diet for 6 months, supplemented with 0%, 0.25%, 0.5%, 0.75%, or 1% dietary cholesterol. Increasing dietary cholesterol led to cholesterol loading of the liver, but not of adipose tissue, resulting in fibrosing steatohepatitis at a dietary cholesterol concentration of ≥0.5%, whereas mice on lower-cholesterol diets developed only simple steatosis. Hepatic cholesterol crystals and crown-like structures also developed at a dietary cholesterol concentration ≥0.5%. Crown-like structures consisted of activated Kupffer cells (KCs) staining positive for NLRP3 and activated caspase 1, which surrounded and processed cholesterol crystal-containing remnant LDs of dead hepatocytes. The KCs processed LDs at the center of crown-like structures in the extracellular space by lysosomal enzymes, ultimately transforming into lipid-laden foam cells. When HepG2 cells were exposed to LDL cholesterol, they developed cholesterol crystals in LD membranes, which caused activation of THP1 cells (macrophages) grown in coculture; upregulation of TNF-alpha , NLRP3, and interleukin 1beta ( IL1β ) mRNA; and secretion of IL-1beta. In conclusion, cholesterol crystals form on the LD membrane of hepatocytes and cause activation and cholesterol loading of KCs that surround and process these LDs by lysosomal enzymes.

Intracellular transport of cholesterol in mammalian cells

International Nuclear Information System (INIS)

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 [ 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

marital status and occupation versus serum total cholesterol and hdl

African Journals Online (AJOL)

DR. AMIN

ABSTRACT. The influence of marital status and occupation on serum total cholesterol (TC) and high density lipoprotein cholesterol (HDL – CH) concentrations was studied in sixty one (61) adult male and female Hausa subjects aged 20 – 50 years. Irrespective of marital status and occupation, female subjects had higher ...

Prevalence of coronary heart disease risk factors and screening for high cholesterol levels among young adults, United States, 1999-2006.

Science.gov (United States)

Kuklina, Elena V; Yoon, Paula W; Keenan, Nora L

2010-01-01

Previous studies have reported low rates of screening for high cholesterol levels among young adults in the United States. Although recommendations for screening young adults without risk factors for coronary heart disease (CHD) differ, all guidelines recommend screening adults with CHD, CHD equivalents, or 1 or more CHD risk factors. This study examined national prevalence of CHD risk factors and compliance with the cholesterol screening guidelines among young adults. National estimates were obtained using results for 2,587 young adults (men aged 20 to 35 years; women aged 20 to 45 years) from the 1999-2006 National Health and Nutrition Examination Surveys. We defined high low-density lipoprotein cholesterol (LDL-C) as levels higher than the goal specific for each CHD risk category outlined in the National Cholesterol Education Program Adult Treatment Panel III guidelines. About 59% of young adults had CHD or CHD equivalents, or 1 or more of the following CHD risk factors: family history of early CHD, smoking, hypertension, or obesity. In our study, the overall screening rate in this population was less than 50%. Moreover, no significant difference in screening rates between young adults with no risk factors and their counterparts with 1 or more risk factors was found even after adjustment for sociodemographic and health care factors. Approximately 65% of young adults with CHD or CHD equivalents, 26% of young adults with 2 or more risk factors, 12% of young adults with 1 risk factor, and 7% with no risk factor had a high level of LDL-C. CHD risk factors are common in young adults but do not appear to alter screening rates. Improvement of risk assessment and management for cardiovascular disease among young adults is warranted.

The relationship between cholesterol and cognitive function is homocysteine-dependent

Directory of Open Access Journals (Sweden)

Cheng YB

2014-10-01

Full Text Available Yibin Cheng,1 Yinlong Jin,1 Frederick W Unverzagt,2 Liqin Su,1 Lili Yang,3 Feng Ma,1 Ann M Hake,4,5 Carla Kettler,3 Chen Chen,1 Jingyi Liu,1 Jianchao Bian,6 Ping Li,7 Jill R Murrell,8 Hugh C Hendrie,2,9,10 Sujuan Gao3 1Institute for Environmental Health and Related Product Safety, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 2Department of Psychiatry, 3Department of Biostatistics, 4Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA; 5Eli Lilly and Company, Indianapolis, Indiana, USA; 6Shandong Institute for Prevention and Treatment of Endemic Disease in China, Jinan, People’s Republic of China; 7Sichuan Provincial Center for Disease Control and Prevention in China, Chengdu, People’s Republic of China; 8Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 9Indiana University Center for Aging Research, 10Regenstrief Institute, Inc., Indianapolis, Indiana, USA Introduction: Previous studies have identified hyperlipidemia as a potential risk factor for dementia and Alzheimer’s disease. However, studies on cholesterol measured in late-life and cognitive function have been inconsistent. Few studies have explored nonlinear relationships or considered interactions with other biomarker measures.Methods: A cross-sectional sample of 1,889 participants from four rural counties in the People’s Republic of China was included in this analysis. Serum total cholesterol, high-density lipoprotein, triglycerides, and homocysteine levels were measured in fasting blood samples. A composite cognitive score was derived based on nine standardized cognitive test scores. Analysis of covariance models were used to investigate the association between biomarker measures and the composite cognitive scores.Results: There was a significant interaction between the homocysteine quartile group and the cholesterol quartile group on cognitive scores (P=0

Correlation of lipophilicity with mosquito larvicidal and repellent activities of novel trifluoromethylphenyl amides

Science.gov (United States)

For a chemical to have a biological impact on an organism, the molecules must be capable of being transported across the membranes of cells. Lipophilic insecticides that can pass through lipid bilayers and penetrate the insect cuticle can lead to rapid intoxication or mortality by acting on the nerv...

Tympanomastoid cholesterol granulomas: Immunohistochemical evaluation of angiogenesis.

Science.gov (United States)

Iannella, Giannicola; Di Gioia, Cira; Carletti, Raffaella; Magliulo, Giuseppe

2017-08-01

This study investigates the immunohistochemical expression of vascular endothelial growth factor (VEGF) and CD34 in patients treated for middle ear and mastoid cholesterol granulomas to evaluate the angiogenesis and vascularization of this type of lesion. A correlation between the immunohistochemical data and the radiological and intraoperative evidence of temporal bone marrow invasion and blood source connection was performed to validate this hypothesis. Retrospective study. Immunohistochemical expression of VEGF and CD34 in a group of 16 patients surgically treated for cholesterol granuloma was examined. Middle ear cholesteatomas with normal middle ear mucosa and external auditory canal skin were used as the control groups. The radiological and intraoperative features of cholesterol granulomas were also examined. In endothelial cells, there was an increased expression of angiogenetic growth factor receptors in all the cholesterol granulomas in this study. The quantitative analysis of VEGF showed a mean value of 37.5, whereas the CD34 quantitative analysis gave a mean value of 6.8. Seven patients presented radiological or intraoperative evidence of bone marrow invasion, hematopoietic potentialities, or blood source connections that might support the bleeding theory. In all of these cases there was computed tomography or intraoperative evidence of bone erosion of the middle ear and/or temporal bone structures. The mean values of VEGF and CD34 were 41.1 and 7.7, respectively. High values of VEGF and CD34 are present in patients with cholesterol granulomas. Upregulation of VEGF and CD34 is indicative of a remarkable angiogenesis and a widespread vascular concentration in cholesterol granulomas. 3b. Laryngoscope, 127:E283-E290, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Severe hypertriglyceridemia and hypercholesterolemia accelerating renal injury: a novel model of type 1 diabetic hamsters induced by short-term high-fat / high-cholesterol diet and low-dose streptozotocin.

Science.gov (United States)

He, Liang; Hao, Lili; Fu, Xin; Huang, Mingshu; Li, Rui

2015-04-11

Hyperlipidemia is thought to be a major risk factor for the progression of renal diseases in diabetes. Recent studies have shown that lipid profiles are commonly abnormal early on type 2 diabetes mellitus (T2DM) with diabetic nephropathy. However, the early effects of triglyceride and cholesterol abnormalities on renal injury in type 1 diabetes mellitus (T1DM) are not fully understood and require reliable animal models for exploration of the underlying mechanisms. Hamster models are important tools for studying lipid metabolism because of their similarity to humans in terms of lipid utilization and high susceptibility to dietary cholesterol and fat. Twenty-four male Golden Syrian hamsters (100-110 g) were rendered diabetes by intraperitoneal injections of streptozotocin (STZ) on consecutive 3 days at dose of 30 mg/kg, Ten days after STZ injections, hamsters with a plasma Glu concentration more than 12 mmol/L were selected as insulin deficient ones and divided into four groups (D-C, D-HF, D-HC, and D-HFHC), and fed with commercially available standard rodent chow, high-fat diet, high-cholesterol diet, high-fat and cholesterol diet respectively, for a period of four weeks. After an induction phase, a stable model of renal injury was established with the aspects of early T1DM kidney disease, These aspects were severe hypertriglyceridemia, hypercholesterolemia, proteinuria with mesangial matrix accumulation, upgraded creatinine clearance, significant cholesterol and triglyceride deposition, and increasing glomerular surface area, thickness of basement membrane and mesangial expansion. The mRNA levels of sterol regulatory element binding protein-1c, transforming growth factors-β, plasminogen activator inhibitor-1, tumor necrosis factor-α and interleukin-6 in the D-HFHC group were significantly up-regulated compared with control groups. This study presents a novel, non-transgenic, non-surgical method for induction of renal injury in hamsters, which is an important

Effectiveness of water-air and octanol-air partition coefficients to predict lipophilic flavor release behavior from O/W emulsions.

Science.gov (United States)

Tamaru, Shunji; Igura, Noriyuki; Shimoda, Mitsuya

2018-01-15

Flavor release from food matrices depends on the partition of volatile flavor compounds between the food matrix and the vapor phase. Thus, we herein investigated the relationship between released flavor concentrations and three different partition coefficients, namely octanol-water, octanol-air, and water-air, which represented the oil, water, and air phases present in emulsions. Limonene, 2-methylpyrazine, nonanal, benzaldehyde, ethyl benzoate, α-terpineol, benzyl alcohol, and octanoic acid were employed. The released concentrations of these flavor compounds from oil-in-water (O/W) emulsions were measured under equilibrium using static headspace gas chromatography. The results indicated that water-air and octanol-air partition coefficients correlated with the logarithms of the released concentrations in the headspace for highly lipophilic flavor compounds. Moreover, the same tendency was observed over various oil volume ratios in the emulsions. Our findings therefore suggest that octanol-air and water-air partition coefficients can be used to predict the released concentration of lipophilic flavor compounds from O/W emulsions. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Comparative Study of Molecular Structure, pKa, Lipophilicity, Solubility, Absorption and Polar Surface Area of Some Antiplatelet Drugs

Directory of Open Access Journals (Sweden)

Milan Remko

2016-03-01

Full Text Available Theoretical chemistry methods have been used to study the molecular properties of antiplatelet agents (ticlopidine, clopidogrel, prasugrel, elinogrel, ticagrelor and cangrelor and several thiol-containing active metabolites. The geometries and energies of most stable conformers of these drugs have been computed at the Becke3LYP/6-311++G(d,p level of density functional theory. Computed dissociation constants show that the active metabolites of prodrugs (ticlopidine, clopidogrel and prasugrel and drugs elinogrel and cangrelor are completely ionized at pH 7.4. Both ticagrelor and its active metabolite are present at pH = 7.4 in neutral undissociated form. The thienopyridine prodrugs ticlopidine, clopidogrel and prasugrel are lipophilic and insoluble in water. Their lipophilicity is very high (about 2.5–3.5 logP values. The polar surface area, with regard to the structurally-heterogeneous character of these antiplatelet drugs, is from very large interval of values of 3–255 Å2. Thienopyridine prodrugs, like ticlopidine, clopidogrel and prasugrel, with the lowest polar surface area (PSA values, exhibit the largest absorption. A high value of polar surface area (PSA of cangrelor (255 Å2 results in substantial worsening of the absorption in comparison with thienopyridine drugs.

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).

Cholesterol in unusual places

International Nuclear Information System (INIS)

Kucerka, N; Nieh, M P; Marquardt, D; Harroun, T A; Wassail, S R; Katsaras, J

2010-01-01

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).

Endogenous Cholesterol Excretion Is Negatively Associated With Carotid Intima-Media Thickness in Humans.

Science.gov (United States)

Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Dávila-Román, Victor G; Ostlund, Richard E

2017-12-01

Epidemiological studies strongly suggest that lipid factors independent of low-density lipoprotein cholesterol contribute significantly to cardiovascular disease risk. Because circulating lipoproteins comprise only a small fraction of total body cholesterol, the mobilization and excretion of cholesterol from plasma and tissue pools may be an important determinant of cardiovascular disease risk. Our hypothesis is that fecal excretion of endogenous cholesterol is protective against atherosclerosis. Cholesterol metabolism and carotid intima-media thickness were quantitated in 86 nondiabetic adults. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d 7 solubilized in a lipid emulsion and dietary cholesterol by cholesterol-d 5 and the nonabsorbable stool marker sitostanol-d 4 . Plasma and stool samples were collected while subjects consumed a cholesterol- and phytosterol-controlled metabolic kitchen diet and were analyzed by mass spectrometry. Carotid intima-media thickness was negatively correlated with fecal excretion of endogenous cholesterol ( r =-0.426; P cholesterol ( r =-0.472; P ≤0.0001), and daily percent excretion of cholesterol from the rapidly mixing cholesterol pool ( r =-0.343; P =0.0012) and was positively correlated with percent cholesterol absorption ( r =+0.279; P =0.0092). In a linear regression model controlling for age, sex, systolic blood pressure, hemoglobin A1c, low-density lipoprotein, high-density lipoprotein cholesterol, and statin drug use, fecal excretion of endogenous cholesterol remained significant ( P =0.0008). Excretion of endogenous cholesterol is strongly, independently, and negatively associated with carotid intima-media thickness. The reverse cholesterol transport pathway comprising the intestine and the rapidly mixing plasma, and tissue cholesterol pool could be an unrecognized determinant of cardiovascular disease risk not reflected in circulating lipoproteins. Further work is needed to relate measures of

Lipophilic versus hydrophilic statin therapy for heart failure: a protocol for an adjusted indirect comparison meta-analysis

Science.gov (United States)

2013-01-01

Background Statins are known to reduce cardiovascular morbidity and mortality in primary and secondary prevention studies. Subsequently, a number of nonrandomised studies have shown statins improve clinical outcomes in patients with heart failure (HF). Small randomised controlled trials (RCT) also show improved cardiac function, reduced inflammation and mortality with statins in HF. However, the findings of two large RCTs do not support the evidence provided by previous studies and suggest statins lack beneficial effects in HF. Two meta-analyses have shown statins do not improve survival, whereas two others showed improved cardiac function and reduced inflammation in HF. It appears lipophilic statins produce better survival and other outcome benefits compared to hydrophilic statins. But the two types have not been compared in direct comparison trials in HF. Methods/design We will conduct a systematic review and meta-analysis of lipophilic and hydrophilic statin therapy in patients with HF. Our objectives are: 1. To determine the effects of lipophilic statins on (1) mortality, (2) hospitalisation for worsening HF, (3) cardiac function and (4) inflammation. 2. To determine the effects of hydrophilic statins on (1) mortality, (2) hospitalisation for worsening HF, (3) cardiac function and (4) inflammation. 3. To compare the efficacy of lipophilic and hydrophilic statins on HF outcomes with an adjusted indirect comparison meta-analysis. We will conduct an electronic search of databases for RCTs that evaluate statins in patients with HF. The reference lists of all identified studies will be reviewed. Two independent reviewers will conduct the search. The inclusion criteria include: 1. RCTs comparing statins with placebo or no statin in patients with symptomatic HF. 2. RCTs that employed the intention-to-treat (ITT) principle in data analysis. 3. Symptomatic HF patients of all aetiologies and on standard treatment. 4. Statin of any dose as intervention. 5. Placebo or no

Break the fast? Update on patient preparation for cholesterol testing.

Science.gov (United States)

Naugler, Christopher; Sidhu, Davinder

2014-10-01

To provide an update on the clinical usefulness of nonfasting versus fasting lipid testing to improve patient compliance, patient safety, and clinical assessment in cholesterol testing. Recommendations are identified as supported by good, fair, and poor (conflicting or insufficient) evidence, according to the classifications adopted by the Canadian Task Force on Preventive Health Care. Screening for dyslipidemia as a risk factor for coronary artery disease and management of lipid-lowering medications are key parts of primary care. Recent evidence has questioned the fasting requirement for lipid testing. In population-based studies, total cholesterol, high-density lipoprotein cholesterol, and non-low-density lipoprotein cholesterol all varied by an average of 2% with fasting status. For routine screening, nonfasting cholesterol measurement is now a reasonable alternative to a fasting cholesterol measurement. For patients with diabetes, the fasting requirement might be an important safety issue because of problems with hypoglycemia. For the monitoring of triglyceride and low-density lipoprotein cholesterol levels in patients taking lipid-lowering medications, fasting becomes more important. Fasting for routine lipid level determinations is largely unnecessary and unlikely to affect patient clinical risk stratification, while nonfasting measurement might improve patient compliance and safety. Copyright© the College of Family Physicians of Canada.

Low HDL cholesterol is correlated to the acute ischemic stroke with diabetes mellitus.

Science.gov (United States)

Luo, Yun; Li, Jingwei; Zhang, Junfeng; Xu, Yun

2014-11-14

To clarify the role of lipid composition in the occurrence of acute ischemic stroke (AIS) with diabetes mellitus (DM) and its influence factors. Data was collected from the patients hospitalization in Affiliated Drum Tower Hospital of Nanjing University Medical School from October 2008 to May 2012, which included AIS and non-AIS consist of transient ischemic attack (TIA) and Vertigo or dizzy. Lipid and other risk factors including blood glucose (BG), uric acid (UA), hypertension, DM and atrial fibrillation (AF) were investigated in relation to occurrence of AIS. The level of high density lipoprotein (HDL) cholesterol was decreased obviously in the DM group compared to the non-DM group and low level of HDL cholesterol was prevalent in the AIS patients with DM. logistic regression demonstrated that decreased HDL cholesterol was correlated to the AIS with DM, not all AIS, and the relative risk of ischemic stroke in low HDL cholesterol level group was 2.113 (95% CI = 1.191-3.749, P = 0.011) compared to the high level group. Furthermore, age has the obviously impact on it. HDL cholesterol was correlated to the AIS with DM just in the populations of aged ≦70 years (OR = 0.192, P = 0.000), low level of HDL cholesterol had more high risk of ischemic stroke than that in the high level group (OR = 6.818, P = 0.002). Decreased HDL cholesterol was correlated to the occurrence of AIS with DM, especially in the populations of aged ≦70 years.

Pitfalls in the detection of cholesterol in Huntington’s disease models

Science.gov (United States)

Marullo, Manuela; Valenza, Marta; Leoni, Valerio; Caccia, Claudio; Scarlatti, Chiara; De Mario, Agnese; Zuccato, Chiara; Di Donato, Stefano; Carafoli, Ernesto; Cattaneo, Elena

2012-01-01

Background Abnormalities in brain cholesterol homeostasis have been reported in Huntington’s disease (HD), an adult-onset neurodegenerative disorder caused by an expansion in the number of CAG repeats in the huntingtin (HTT) gene. However, the results have been contradictory with respect to whether cholesterol levels increase or decrease in HD models. Biochemical and mass spectrometry methods show reduced levels of cholesterol precursors and cholesterol in HD cells and in the brains of several HD animal models. Abnormal brain cholesterol homeostasis was also inferred from studies in HD patients. In contrast, colorimetric and enzymatic methods indicate cholesterol accumulation in HD cells and tissues. Here we used several methods to investigate cholesterol levels in cultured cells in the presence or absence of mutant HTT protein. Results Colorimetric and enzymatic methods with low sensitivity gave variable results, whereas results from a sensitive analytical method, gas chromatography-mass spectrometry, were more reliable. Sample preparation, high cell density and cell clonality also influenced the detection of intracellular cholesterol. Conclusions Detection of cholesterol in HD samples by colorimetric and enzymatic assays should be supplemented by detection using more sensitive analytical methods. Care must be taken to prepare the sample appropriately. By evaluating lathosterol levels using isotopic dilution mass spectrometry, we confirmed reduced cholesterol biosynthesis in knock-in cells expressing the polyQ mutation in a constitutive or inducible manner. *Correspondence should be addressed to Elena Cattaneo: elena.cattaneo@unimi.it PMID:23145355

Cholesterol-Lowering Effect of Allicin on Hypercholesterolemic ICR Mice

Directory of Open Access Journals (Sweden)

Yin Lu

2012-01-01

Full Text Available Allicin was discussed as an active compound with regard to the beneficial effects of garlic in atherosclerosis. The aim of this study was to investigate the cholesterol-lowering properties of allicin. In order to examine its effects on hypercholesterolemia in male ICR mice, this compound with doses of 5, 10, or 20 mg/kg body weight was given orally daily for 12 weeks. Changes in body weight and daily food intake were measured regularly during the experimental period. Final contents of serum cholesterol, triglyceride, glucose, and hepatic cholesterol storage were determined. Following a 12-week experimental period, the body weights of allicin-fed mice were less than those of control mice on a high-cholesterol diet by 38.24±7.94% (P<0.0001 with 5 mg/kg allicin, 39.28±5.03% (P<0.0001 with 10 mg/kg allicin, and 41.18±5.00% (P<0.0001 with 20 mg/kg allicin, respectively. A decrease in daily food consumption was also noted in most of the treated animals. Meanwhile, allicin showed a favorable effect in reducing blood cholesterol, triglycerides, and glucose levels and caused a significant decrease in lowering the hepatic cholesterol storage. Accordingly, both in vivo and in vitro results demonstrated a potential value of allicin as a pronounced cholesterol-lowering candidate, providing protection against the onset of atherosclerosis.

Adzuki bean ameliorates hepatic lipogenesis and proinflammatory mediator expression in mice fed a high-cholesterol and high-fat diet to induce nonalcoholic fatty liver disease.

Science.gov (United States)

Kim, Sera; Hong, Jihye; Jeon, Raok; Kim, Hyun-Sook

2016-01-01

Nonalcoholic fatty liver disease (NAFLD) is a simple steatosis, in which fat accumulates more than 5% in the liver, and regarded as most common liver diseases worldwide. Because NAFLD can be developed to severe liver disease and correlated with metabolic disease, its importance is currently emphasized. Occurrence of NAFLD is strongly related to dietary patterns and lifestyles; therefore, the suggestion of physiologically beneficial food is essential. Based on these, adzuki beans containing anthocyanin, catechin, and adzukisaponin are suggested as a health-beneficial food. Moreover, the effects of adzuki beans on metabolic improvement are not well established through the in vivo studies. Therefore, this study hypothesized that adzuki beans can alleviate lipid accumulation and oxidative stress-mediated inflammation in high-cholesterol and high-fat diet-induced NALFD mice. To demonstrate its effects, 6-week-old C57BL/6 male mice were allocated into 4 groups and fed a normal diet (ND), a high-cholesterol and high-fat diet (HCD), and HCD with 10% and 20% adzuki bean for 10 weeks. The result shows that fasting blood glucose, serum and hepatic triglyceride and cholesterol levels, and antioxidative enzyme activity ameliorated in the adzuki bean groups (P hepatic lipogenesis, such as adiponectin, AMP-activated protein kinase α, sterol regulatory element-binding protein 1c, fatty acid synthase, carnitine palmitoyltransferase 1, 3-hydroxy-3-methyl-glutaryl-CoA reductase, and apolipoprotein B, as well as proinflammatory mediators, such as tumor necrosis factor α, nuclear factor κB, and caspase-3, improved in both experimental groups (P hepatic messenger RNA expression of lipogenic and inflammatory mediators in NAFLD. Copyright © 2016 Elsevier Inc. All rights reserved.

Influence of chronic stress on the compositions of hepatic cholesterol and triglyceride in male Wistar rats fed a high fat diet.

Science.gov (United States)

Gao, Siyuan; Han, Xue; Fu, Jihua; Yuan, Xiaoling; Sun, Xing; Li, Qiang

2012-07-01

  We determined the influence of chronic stress (CS) on the compositions of hepatic cholesterol and triglyceride (TG) in rats fed a high fat diet (HFD).   Male Wistar rats were fed either a standard diet or a HFD and half of the HFD fed rats were given CS (electric foot shock assisted with noise) for 8 weeks.   Compared with the control group, the levels of hepatic total cholesterol (TC) and TG were significantly elevated in the HFD and HFD with chronic stress (HFD+CS) groups, and the more severe elevations of them were found in the HFD group. Inversely, the more severe elevations of hepatic water-soluble parts of TC and TG were found in the HFD+CS group, as the elevations of low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol in liver and serum, tumor necrosis factor-α, interleukin-1β and malondialdehyde in liver. Meanwhile, downregulated mRNA expressions of hepatic liver X receptor-α (LXR-α) and peroxisome proliferator-activated receptor-γ (PPAR-γ) were also more severe in the HFD+CS group.   CS can aggravate the high levels of water-soluble compositions of hepatic TC and TG induced by HFD as it aggravates hepatic inflammation and oxidative stress; in spite of that, however, it cannot further promote hepatic lipidosis. This is consistent with the downregulated mRNA expressions of LXR-α and PPAR-γ. © 2012 The Japan Society of Hepatology.

Polygenic determinants in extremes of high-density lipoprotein cholesterol.

Science.gov (United States)

Dron, Jacqueline S; Wang, Jian; Low-Kam, Cécile; Khetarpal, Sumeet A; Robinson, John F; McIntyre, Adam D; Ban, Matthew R; Cao, Henian; Rhainds, David; Dubé, Marie-Pierre; Rader, Daniel J; Lettre, Guillaume; Tardif, Jean-Claude; Hegele, Robert A

2017-11-01

HDL cholesterol (HDL-C) remains a superior biochemical predictor of CVD risk, but its genetic basis is incompletely defined. In patients with extreme HDL-C concentrations, we concurrently evaluated the contributions of multiple large- and small-effect genetic variants. In a discovery cohort of 255 unrelated lipid clinic patients with extreme HDL-C levels, we used a targeted next-generation sequencing panel to evaluate rare variants in known HDL metabolism genes, simultaneously with common variants bundled into a polygenic trait score. Two additional cohorts were used for validation and included 1,746 individuals from the Montréal Heart Institute Biobank and 1,048 individuals from the University of Pennsylvania. Findings were consistent between cohorts: we found rare heterozygous large-effect variants in 18.7% and 10.9% of low- and high-HDL-C patients, respectively. We also found common variant accumulation, indicated by extreme polygenic trait scores, in an additional 12.8% and 19.3% of overall cases of low- and high-HDL-C extremes, respectively. Thus, the genetic basis of extreme HDL-C concentrations encountered clinically is frequently polygenic, with contributions from both rare large-effect and common small-effect variants. Multiple types of genetic variants should be considered as contributing factors in patients with extreme dyslipidemia. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Optimizing solubility and permeability of a biopharmaceutics classification system (BCS) class 4 antibiotic drug using lipophilic fragments disturbing the crystal lattice.

Science.gov (United States)

Tehler, Ulrika; Fagerberg, Jonas H; Svensson, Richard; Larhed, Mats; Artursson, Per; Bergström, Christel A S

2013-03-28

Esterification was used to simultaneously increase solubility and permeability of ciprofloxacin, a biopharmaceutics classification system (BCS) class 4 drug (low solubility/low permeability) with solid-state limited solubility. Molecular flexibility was increased to disturb the crystal lattice, lower the melting point, and thereby improve the solubility, whereas lipophilicity was increased to enhance the intestinal permeability. These structural changes resulted in BCS class 1 analogues (high solubility/high permeability) emphasizing that simple medicinal chemistry may improve both these properties.

Nori- and sea spaghetti- but not wakame-restructured pork decrease the hypercholesterolemic and liver proapototic short-term effects of high-dietary cholesterol consumption.

Science.gov (United States)

Schultz Moreira, Adriana R; Benedi, Juana; Bastida, Sara; Sánchez-Reus, Isabel; Sánchez-Muniz, Francisco J

2013-01-01

Restructured pork (RP) enriched in Seaweeds are potential functional foods. The antiapoptotic and hypocholesterolemic effects of consuming cholesterol enriched diets containing Wakame-RP (CW), Nori-RP (CN) and Sea Spaghetti (CS) were tested in a 1-wk study. Groups of six rats per group were fed a mix of 85% AIN-93M rodent-diet containing cholesterol and cholic acid as a cholesterol rising agent plus 15% RP containing alga. These diets were compared to control-RP diets enriched or not in cholesterol (CC and C, respectively). After 1-wk, cholesterol feeding significantly increased liver apoptosis markers which were significantly reduced by CS (cellular cycle DNA, caspase-3, and cytochrome c), CN (caspase-3 and cytochrome c) and CW (caspase-3) diets. CN and CS diets significantly blocked the cholesterolaemic rising effect observed in the CC group but no protective effect was observed in the CW group. Differences in seaweed composition added to RP appear responsible for blocking or not the proapoptotic and hypercholesterolemic effects of high cholesterol-RP consumption; thus, any generalization on seaweed effects or food containing seaweeds must be avoided. Although present results are worthy, future studies are demanded to ascertain the utility of consuming algal-RP as part of usual diets. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

Red Cabbage Microgreens Lower Circulating Low-Density Lipoprotein (LDL), Liver Cholesterol, and Inflammatory Cytokines in Mice Fed a High-Fat Diet.

Science.gov (United States)

Huang, Haiqiu; Jiang, Xiaojing; Xiao, Zhenlei; Yu, Lu; Pham, Quynhchi; Sun, Jianghao; Chen, Pei; Yokoyama, Wallace; Yu, Liangli Lucy; Luo, Yaguang Sunny; Wang, Thomas T Y

2016-12-07

Cardiovascular disease (CVD) is the leading cause of death in the United States, and hypercholesterolemia is a major risk factor. Population studies, as well as animal and intervention studies, support the consumption of a variety of vegetables as a means to reduce CVD risk through modulation of hypercholesterolemia. Microgreens of a variety of vegetables and herbs have been reported to be more nutrient dense compared to their mature counterparts. However, little is known about the effectiveness of microgreens in affecting lipid and cholesterol levels. The present study used a rodent diet-induced obesity (DIO) model to address this question. C57BL/6NCr mice (n = 60, male, 5 weeks old) were randomly assigned to six feeding groups: (1) low-fat diet; (2) high-fat diet; (3) low-fat diet + 1.09% red cabbage microgreens; (4) low-fat diet + 1.66% mature red cabbage; (5) high-fat diet + 1.09% red cabbage microgreens; (6) high-fat diet + 1.66% mature red cabbage. The animals were on their respective diets for 8 weeks. We found microgreen supplementation attenuated high-fat diet induced weight gain. Moreover, supplementation with microgreens significantly lowered circulating LDL levels in animals fed the high-fat diet and reduced hepatic cholesterol ester, triacylglycerol levels, and expression of inflammatory cytokines in the liver. These data suggest that microgreens can modulate weight gain and cholesterol metabolism and may protect against CVD by preventing hypercholesterolemia.

Vertically aligned carbon nanotube probes for monitoring blood cholesterol

Science.gov (United States)

Roy, Somenath; Vedala, Harindra; Choi, Wonbong

2006-02-01

Detection of blood cholesterol is of great clinical significance. The amperometric detection technique was used for the enzymatic assay of total cholesterol. Multiwall carbon nanotubes (MWNTs), vertically aligned on a silicon platform, promote heterogeneous electron transfer between the enzyme and the working electrode. Surface modification of the MWNT with a biocompatible polymer, polyvinyl alcohol (PVA), converted the hydrophobic nanotube surface into a highly hydrophilic one, which facilitates efficient attachment of biomolecules. The fabricated working electrodes showed a linear relationship between cholesterol concentration and the output signal. The efficacy of the multiwall carbon nanotubes in promoting heterogeneous electron transfer was evident by distinct electrochemical peaks and higher signal-to-noise ratio as compared to the Au electrode with identical enzyme immobilization protocol. The selectivity of the cholesterol sensor in the presence of common interferents present in human blood, e.g. uric acid, ascorbic acid and glucose, is also reported.

Supercritical Carbon Dioxide and Microwave-Assisted Extraction of Functional Lipophilic Compounds from Arthrospira platensis

Directory of Open Access Journals (Sweden)

Diego A. Esquivel-Hernández

2016-05-01

Full Text Available Arthrospira platensis biomass was used in order to obtain functional lipophilic compounds through green extraction technologies such as supercritical carbon dioxide fluid extraction (SFE and microwave-assisted extraction (MAE. The temperature (T factor was evaluated for MAE, while for SFE, pressure (P, temperature (T, and co-solvent (ethanol (CS were evaluated. The maximum extraction yield of the obtained oleoresin was (4.07% ± 0.14% and (4.27% ± 0.10% for SFE and MAE, respectively. Extracts were characterized by gas chromatography mass spectrometry (GC-MS and gas chromatography flame ionization detector (GC-FID. The maximum contents of functional lipophilic compounds in the SFE and MAE extracts were: for carotenoids 283 ± 0.10 μg/g and 629 ± 0.13 μg/g, respectively; for tocopherols 5.01 ± 0.05 μg/g and 2.46 ± 0.09 μg/g, respectively; and for fatty acids 34.76 ± 0.08 mg/g and 15.88 ± 0.06 mg/g, respectively. In conclusion, the SFE process at P 450 bar, T 60 °C and CS 53.33% of CO2 produced the highest yield of tocopherols, carotenoids and fatty acids. The MAE process at 400 W and 50 °C gives the best extracts in terms of tocopherols and carotenoids. For yield and fatty acids, the MAE process at 400 W and 70 °C produced the highest values. Both SFE and MAE showed to be suitable green extraction technologies for obtaining functional lipophilic compounds from Arthrospira platensis.

Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol

NARCIS (Netherlands)

Ray, Kausik K.; Landmesser, Ulf; Leiter, Lawrence A.; Kallend, David; Dufour, Robert; Karakas, Mahir; Hall, Tim; Troquay, Roland P. T.; Turner, Traci; Visseren, Frank L. J.; Wijngaard, Peter; Wright, R. Scott; Kastelein, John J. P.

2017-01-01

BACKGROUND In a previous study, a single injection of inclisiran, a chemically synthesized small interfering RNA designed to target PCSK9 messenger RNA, was found to produce sustained reductions in low-density lipoprotein (LDL) cholesterol levels over the course of 84 days in healthy volunteers.

Effect of Atorvastatin on Serum Levels of Total Cholesterol and High-Sensitivity C-reactive Protein in High-Risk Patients with Atrial Fibrillation in Asia.

Science.gov (United States)

Shi, Ming Yu; Xue, Feng Hua; Teng, Shi Chao; Jiang, Li; Zhu, Jing; Yin, Feng; Gu, Hong Yue

2015-08-01

The aim of this meta-analysis was to investigate the effects of atorvastatin on serum levels of high-sensitivity C-reactive protein (hs-CRP) and total cholesterol in atrial fibrillation (AF) patients in Asia. By searching English and Chinese language-based electronic databases (ie, PubMed, EBSCO, Ovid, SpringerLink, Wiley, Web of Science, Wanfang database, China National Knowledge Infrastructure, and VIP database), we identified 13 studies relevant to our topic of interest. Data were collected from the 13 studies and analyzed with Comprehensive Meta-Analysis software (version 2.0, Biostat Inc., Englewood, New Jersey). Initially, our database searches retrieved 356 studies (45 in English, 311 in Chinese). Thirteen studies were selected for the meta-analysis following stringent criteria. The data included 1239 patients with AF, of whom 634 were treated with atorvastatin and included in the treatment group, and 605 patients were treated with conventional treatment and included in the control group. The results of our meta-analysis suggested that the serum levels of hs-CRP (mg/L) and total cholesterol (mmol/L) in the treatment group were significantly lower than those of the control group (hs-CRP: standardized mean difference = 0.962; 95% CI, 0.629-1.295, P < 0.001; total cholesterol: standardized mean difference = 1.400; 95% CI, 0.653-2.146, P < 0.001). The findings of this study suggest that atorvastatin may be very effective in decreasing serum levels of hs-CRP and total cholesterol to prevent cardiovascular events. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

A matrix of cholesterol crystals, but not cholesterol alone, primes human monocytes/macrophages for excessive endotoxin-induced production of tumor necrosis factor-alpha. Role in atherosclerotic inflammation?

DEFF Research Database (Denmark)

Bendtzen, Klaus; Christensen, Ole; Nielsen, Claus Henrik

2014-01-01

When exposed to small amounts of bacterial endotoxin, matrices of cholesterol crystals, but not cholesterol itself, primed human monocytes/macrophages to a highly augmented (>10-fold) production of inflammatory tumor necrosis factor-α. Priming also sensitized the cells, as 10- to 100-fold lower...

[Lipids and cerebrovascular disease - New therapeutic options in lowering LDL-cholesterol].

Science.gov (United States)

Lovadi, Emese; Csécsei, Péter; Lovig, Csenge; Karádi, Zsófia; Szapáry, László

2016-12-01

Stroke is the third most common cause of death worldwide following myocardial infaction and malignancies, furthermore, its functional outcome is the worst of all conditions. Cholesterol, especially LDL-cholesterol plays a key role in the formation of atherosclerotic plaques. It has been verified recently that escalating incidence and mortality of cerebrovascular diseases are proportional to increased levels of LDL-cholesterol. Statin therapy undeniably reduces the risk of stroke, however other methods for decreasing lipid levels have not been proved significantly effective. Preventive effect of high-dose statin treatment is without doubt, although administration of such high dosage might require special precautions for patients with prior intracerebral hemorrhage and it also risks development of incident diabetes. The recently published IMPROVE-IT study is the first to prove that the addition of ezetimibe as a non-statin type drug, to statin treatment contributes to further reduction of LDL-cholesterol. The combination treatment results in additional decrease in the incidence and mortality of cerebrovascular events, without any expansion in the number or adverse effects. These results confirm the importance of any further reduction of LDL-cholesterol levels. Achieving target values with statin-ezetimibe combination allows administration of low to moderate dose of statin, which decreases risks of adverse effects related to high-dose statin therapy. Orv. Hetil., 2016, 157(52), 2059-2065.

Lung Surfactant Microbubbles Increase Lipophilic Drug Payload for Ultrasound-Targeted Delivery

OpenAIRE

Sirsi, Shashank R.; Fung, Chinpong; Garg, Sumit; Tianning, Mary Y.; Mountford, Paul A.; Borden, Mark A.

2013-01-01

The cavitation response of circulating microbubbles to targeted ultrasound can be used for noninvasive, site-specific delivery of shell-loaded materials. One challenge for microbubble-mediated delivery of lipophilic compounds is the limitation of drug loading into the microbubble shell, which is commonly a single phospholipid monolayer. In this study, we investigated the use of natural lung surfactant extract (Survanta?, Abbott Nutrition) as a microbubble shell material in order to improve dr...

Agonistic Human Antibodies Binding to Lecithin-Cholesterol Acyltransferase Modulate High Density Lipoprotein Metabolism*

Science.gov (United States)

Gunawardane, Ruwanthi N.; Fordstrom, Preston; Piper, Derek E.; Masterman, Stephanie; Siu, Sophia; Liu, Dongming; Brown, Mike; Lu, Mei; Tang, Jie; Zhang, Richard; Cheng, Janet; Gates, Andrew; Meininger, David; Chan, Joyce; Carlson, Tim; Walker, Nigel; Schwarz, Margrit; Delaney, John; Zhou, Mingyue

2016-01-01

Drug discovery opportunities where loss-of-function alleles of a target gene link to a disease-relevant phenotype often require an agonism approach to up-regulate or re-establish the activity of the target gene. Antibody therapy is increasingly recognized as a favored drug modality due to multiple desirable pharmacological properties. However, agonistic antibodies that enhance the activities of the target enzymes are rarely developed because the discovery of agonistic antibodies remains elusive. Here we report an innovative scheme of discovery and characterization of human antibodies capable of binding to and agonizing a circulating enzyme lecithin cholesterol acyltransferase (LCAT). Utilizing a modified human LCAT protein with enhanced enzymatic activity as an immunogen, we generated fully human monoclonal antibodies using the XenoMouseTM platform. One of the resultant agonistic antibodies, 27C3, binds to and substantially enhances the activity of LCAT from humans and cynomolgus macaques. X-ray crystallographic analysis of the 2.45 Å LCAT-27C3 complex shows that 27C3 binding does not induce notable structural changes in LCAT. A single administration of 27C3 to cynomolgus monkeys led to a rapid increase of plasma LCAT enzymatic activity and a 35% increase of the high density lipoprotein cholesterol that was observed up to 32 days after 27C3 administration. Thus, this novel scheme of immunization in conjunction with high throughput screening may represent an effective strategy for discovering agonistic antibodies against other enzyme targets. 27C3 and other agonistic human anti-human LCAT monoclonal antibodies described herein hold potential for therapeutic development for the treatment of dyslipidemia and cardiovascular disease. PMID:26644477

Cardiovascular disease markers responses in male receiving improved-fat meat-products vary by initial LDL-cholesterol levels.

Directory of Open Access Journals (Sweden)

Paloma Celada

2016-11-01

Full Text Available Objectives: Cardiovascular disease (CVD is prevalent in people at high meat-product consumption. To study the effect of consuming different Pâté and Frankfurter formulations on clinical/emergent CVD biomarkers in male volunteers with different initial LDL-cholesterol levels (< and ³ 3.36 mmol/L. Method: Eighteen male volunteers with at least two CVD risk factors were enrolled in a crossover controlled study. Pork-products were consumed during 4wk: reduced-fat (RF, omega-3-enriched-RF (n-3RF, and normal-fat (NF. Pork-products were separated by 4wk washout. Lipids, lipoproteins, oxidized LDL (oxLDL, apolipoproteins (apo and their ratios, homocysteine (tHcys, arylesterase (AE, C-reactive protein (CRP, tumor necrotic factor (TNFa were tested. Results: The rate of change for AE, oxLDL, Lp(a, AE/HDL-cholesterol, LDL/apo B and AE/oxLDL ratios varied (p<0.05 among periods only in volunteers with LDLcholesterol ³3.36 mmol/L. TNFa decreased (p<0.05 among volunteers with low-normal LDL-cholesterol values while AE increased (p<0.01 in high LDL-cholesterol volunteers during the RF-period. AE increased while CRP decreased (both p<0.01 in low-normal LDL-cholesterol volunteers while AE (p<0.001 and apo B (p<0.01 increased in the high LDL-cholesterol group during the n-3RF-period. Total cholesterol (p<0.05 increased in the low/normal LDL-cholesterol group while tHcys decreased (p<0.05 in the high LDL-cholesterol group during the NF-period. Differences in response in volunteers with low-normal vs. high initial LDL-cholesterol levels to the n-3RF but not to the RF meat-products seem evident. Conclusions: Subjects with high LDL-cholesterol seem target for n-3RF products while subjects with LDL-cholesterol <3.36 mmol/L were more negatively affected by NF-products. Any generalization about functional meat product or consumption should be avoided.

Association of Air Pollution Exposures With High-Density Lipoprotein Cholesterol and Particle Number: The Multi-Ethnic Study of Atherosclerosis.

Science.gov (United States)

Bell, Griffith; Mora, Samia; Greenland, Philip; Tsai, Michael; Gill, Ed; Kaufman, Joel D

2017-05-01

The relationship between air pollution and cardiovascular disease may be explained by changes in high-density lipoprotein (HDL). We examined the cross-sectional relationship between air pollution and both HDL cholesterol and HDL particle number in the MESA Air study (Multi-Ethnic Study of Atherosclerosis Air Pollution). Study participants were 6654 white, black, Hispanic, and Chinese men and women aged 45 to 84 years. We estimated individual residential ambient fine particulate pollution exposure (PM 2.5 ) and black carbon concentrations using a fine-scale likelihood-based spatiotemporal model and cohort-specific monitoring. Exposure periods were averaged to 12 months, 3 months, and 2 weeks prior to examination. HDL cholesterol and HDL particle number were measured in the year 2000 using the cholesterol oxidase method and nuclear magnetic resonance spectroscopy, respectively. We used multivariable linear regression to examine the relationship between air pollution exposure and HDL measures. A 0.7×10 - 6 m - 1 higher exposure to black carbon (a marker of traffic-related pollution) averaged over a 1-year period was significantly associated with a lower HDL cholesterol (-1.68 mg/dL; 95% confidence interval, -2.86 to -0.50) and approached significance with HDL particle number (-0.55 mg/dL; 95% confidence interval, -1.13 to 0.03). In the 3-month averaging time period, a 5 μg/m 3 higher PM 2.5 was associated with lower HDL particle number (-0.64 μmol/L; 95% confidence interval, -1.01 to -0.26), but not HDL cholesterol (-0.05 mg/dL; 95% confidence interval, -0.82 to 0.71). These data are consistent with the hypothesis that exposure to air pollution is adversely associated with measures of HDL. © 2017 American Heart Association, Inc.

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

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

DIETARY-CHOLESTEROL INDUCED DOWN-REGULATION OF INTESTINAL 3-HYDROXY-3-METHYLGLUTARYL COENZYME-A REDUCTASE-ACTIVITY IS DIMINISHED IN RABBITS WITH HYPERRESPONSE OF SERUM-CHOLESTEROL TO DIETARY-CHOLESTEROL

NARCIS (Netherlands)

MEIJER, GW; SMIT, MJ; VANDERPALEN, JGP; KUIPERS, F; VONK, RJ; VANZUTPHEN, BFM; BEYNEN, AC

Key enzymes of cholesterol metabolism were studied in two inbred strains of rabbits with hyper- or hyporesponse of serum cholesterol to dietary cholesterol. Baseline 3-hydroxy-3-methylglutaryl (HMG)CoA reductase activity in liver was similar in hypo- and hyperresponders, but that in intestine was