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Sample records for affect serum cholesterol

  1. Lactic acid bacteria affect serum cholesterol levels, harmful fecal enzyme activity, and fecal water content

    PubMed Central

    Lee, Do Kyung; Jang, Seok; Baek, Eun Hye; Kim, Mi Jin; Lee, Kyung Soon; Shin, Hea Soon; Chung, Myung Jun; Kim, Jin Eung; Lee, Kang Oh; Ha, Nam Joo

    2009-01-01

    Background Lactic acid bacteria (LAB) are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as lower cholesterol. Although present in many foods, most trials have been in spreads or dairy products. Here we tested whether Bifidobacteria isolates could lower cholesterol, inhibit harmful enzyme activities, and control fecal water content. Methods In vitro culture experiments were performed to evaluate the ability of Bifidobacterium spp. isolated from healthy Koreans (20~30 years old) to reduce cholesterol-levels in MRS broth containing polyoxyethanylcholesterol sebacate. Animal experiments were performed to investigate the effects on lowering cholesterol, inhibiting harmful enzyme activities, and controlling fecal water content. For animal studies, 0.2 ml of the selected strain cultures (108~109 CFU/ml) were orally administered to SD rats (fed a high-cholesterol diet) every day for 2 weeks. Results B. longum SPM1207 reduced serum total cholesterol and LDL levels significantly (p < 0.05), and slightly increased serum HDL. B. longum SPM1207 also increased fecal LAB levels and fecal water content, and reduced body weight and harmful intestinal enzyme activities. Conclusion Daily consumption of B. longum SPM1207 can help in managing mild to moderate hypercholesterolemia, with potential to improve human health by helping to prevent colon cancer and constipation. PMID:19515264

  2. Compounds affecting cholesterol absorption

    NASA Technical Reports Server (NTRS)

    Hua, Duy H. (Inventor); Koo, Sung I. (Inventor); Noh, Sang K. (Inventor)

    2004-01-01

    A class of novel compounds is described for use in affecting lymphatic absorption of cholesterol. Compounds of particular interest are defined by Formula I: ##STR1## or a pharmaceutically acceptable salt thereof.

  3. Serum cholesterol concentrations in parasuicide.

    PubMed Central

    Gallerani, M.; Manfredini, R.; Caracciolo, S.; Scapoli, C.; Molinari, S.; Fersini, C.

    1995-01-01

    OBJECTIVE--To evaluate whether people who have committed parasuicide have low serum cholesterol concentrations. DESIGN--Results of blood tests in subjects admitted to hospital for parasuicide compared with those of a control group of non-suicidal subjects; comparison in subgroup of parasuicide subjects of two sets of blood test results (one set from admission for parasuicide and the other from admission for some other illness). SETTING--General hospital, Ferrara, Italy. SUBJECTS--331 parasuicide subjects aged 44 (SD 21) years (109 with two sets of blood test results) and 331 controls. MAIN OUTCOME MEASURES--Serum cholesterol concentrations and possible association with parasuicide, considering sex, violence of method of parasuicide, and underlying psychiatric disorder. RESULTS--Lower serum cholesterol concentrations (4.96 (SD 1.16) mmol/l) were found in the parasuicide subjects than in the controls (5.43 (1.30); P < 0.001), regardless of sex and degree of violence of parasuicide method. Both men and women with two sets of blood test results had lower cholesterol concentrations after parasuicide. Linear regression analysis showed that the difference in cholesterol concentrations was significantly related to the length of time between the taking of the two sets of blood samples. CONCLUSION--The study showed low cholesterol concentrations after parasuicide. This finding agrees with previous studies, which suggest an association between low cholesterol concentration and suicide. PMID:7795448

  4. Reduction of blood serum cholesterol

    NASA Technical Reports Server (NTRS)

    Winitz, M. (Inventor)

    1974-01-01

    By feeding a human subject as the sole source of sustenance a defined diet wherein the carbohydrate consists substantially entirely of glucose, maltose or a polysaccharide of glucose, the blood serum cholesterol level of the human subject is substantially reduced. If 25 percent of the carbohydrate is subsequently supplied in the form of sucrose, an immediate increase from the reduced level is observed. The remainder of the defined diet normally includes a source of amino acids, such as protein or a protein hydrolysate, vitamins, minerals and a source of essential fatty acid.

  5. Glutamate supply positively affects serum cholesterol concentrations without increases in total protein and urea around the onset of puberty in goats.

    PubMed

    Meza-Herrera, C A; Calderón-Leyva, G; Soto-Sanchez, M J; Serradilla, J M; García-Martinez, A; Mellado, M; Veliz-Deras, F G

    2014-06-30

    Different neurotransmitter and neuromodulatory systems regulate synthesis and secretion of GnRH. Whereas the endocrine and neural systems are activated in response to the metabolic status and the circulating levels of specific blood metabolites, glutamate receptors have been reported at hepatic level. This study evaluated the possible effect of glutamate supplementation upon changes in serum concentrations across time for total protein (TP), urea (UR) and cholesterol (CL) around the onset of puberty in goats. Prepuberal female goats (n=18) were randomly assigned to: (1) excitatory amino acids group, GLUT, n=10; 16.52±1.04kg live weight (LW), 3.4±0.12 body condition score (BCS) receiving an i.v. infusion of 7mgkg(-1) LW of l-glutamate, and (2) Control group, CONT, n=8; 16.1±1.04kg LW, 3.1±0.12 BCS. General averages for LW (23.2±0.72kg), BCS (3.37±0.10 units), serum TP (65.28±2.46mgdL(-1)), UR (23.42±0.95mgdL(-1)), CL (77.89±1.10mgdL(-1)) as well as the serum levels for TP and UR across time did not differ (P>0.05) between treatments. However, while GLUT positively affected (P<0.05) both the onset (207±9 vs. 225±12 d) and the percentage (70 vs. 25%) of females showing puberty, a treatment×time interaction effect (P<0.05) was observed in the GLUT group, with increases in serum cholesterol, coincident with the onset of puberty. Therefore, in peripuberal glutamate supplemented goats, serum cholesterol profile could act as a metabolic modulator for the establishment of puberty, denoting also a potential role of glutamate as modulator of lipid metabolism. PMID:24811839

  6. High intake of fatty fish, but not of lean fish, affects serum concentrations of TAG and HDL-cholesterol in healthy, normal-weight adults: a randomised trial.

    PubMed

    Hagen, Ingrid V; Helland, Anita; Bratlie, Marianne; Brokstad, Karl A; Rosenlund, Grethe; Sveier, Harald; Mellgren, Gunnar; Gudbrandsen, Oddrun A

    2016-08-01

    The aim of the present study was to examine whether high intake of lean or fatty fish (cod and farmed salmon, respectively) by healthy, normal-weight adults would affect risk factors of type 2 diabetes and CVD when compared with lean meat (chicken). More knowledge is needed concerning the potential health effects of high fish intake (>300 g/week) in normal-weight adults. In this randomised clinical trial, thirty-eight young, healthy, normal-weight participants consumed 750 g/week of lean or fatty fish or lean meat (as control) for 4 weeks at dinner according to provided recipes to ensure similar ways of preparations and choices of side dishes between the groups. Energy and macronutrient intakes at baseline and end point were similar in all groups, and there were no changes in energy and macronutrient intakes within any of the groups during the course of the study. High intake of fatty fish, but not lean fish, significantly reduced TAG and increased HDL-cholesterol concentrations in fasting serum when compared with lean meat intake. When compared with lean fish intake, fatty fish intake increased serum HDL-cholesterol. No differences were observed between lean fish, fatty fish and lean meat groups regarding fasting and postprandial glucose regulation. These findings suggest that high intake of fatty fish, but not of lean fish, could beneficially affect serum concentrations of TAG and HDL-cholesterol, which are CVD risk factors, in healthy, normal-weight adults, when compared with high intake of lean meat. PMID:27363518

  7. Fluorimetric determination of cholesterol in hypercholesterolemia serum

    NASA Astrophysics Data System (ADS)

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

    2005-01-01

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

  8. Amperometric determination of serum total cholesterol with nanoparticles of cholesterol esterase and cholesterol oxidase.

    PubMed

    Aggarwal, V; Malik, J; Prashant, A; Jaiwal, P K; Pundir, C S

    2016-05-01

    We describe the preparation of glutaraldehyde cross-linked and functionalized cholesterol esterase nanoparticles (ChENPs) and cholesterol oxidase nanoparticles (ChOxNPs) aggregates and their co-immobilization onto Au electrode for improved amperometric determination of serum total cholesterol. Transmission electron microscope (TEM) images of ChENPs and ChOxNPs showed their spherical shape and average size of 35.40 and 56.97 nm, respectively. Scanning electron microscope (SEM) studies of Au electrode confirmed the co-immobilization of enzyme nanoparticles (ENPs). The biosensor exhibited optimal response at pH 5.5 and 40 °C within 5 s when polarized at +0.25 V versus Ag/AgCl. The working/linear range of the biosensor was 10-700 mg/dl for cholesterol. The sensor showed high sensitivity and measured total cholesterol as low as 0.1 mg/dl. The biosensor was evaluated and employed for total cholesterol determination in sera of apparently healthy and diseased persons. The analytical recovery of added cholesterol was 90%, whereas the within-batch and between-batch coefficients of variation (CVs) were less than 2% and less than 3%. There was a good correlation (r = 0.99) between serum cholesterol values as measured by the standard enzymic colorimetric method and the current method. The initial activity of ENPs/working electrode was reduced by 50% during its regular use (200 times) over a period of 60 days when stored dry at 4 °C. PMID:26853742

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

    PubMed Central

    Oluwole, Ayodeji A.; Adegbesan-Omilabu, Maymunah A.; Okunade, Kehinde S.

    2014-01-01

    Background: The study assessed whether low maternal serum cholesterol during early pregnancy is associated with preterm delivery. Patients and Methods: It was a prospective observational cohort study involving pregnant women at gestational age of 14-20 weeks over a period of 12 months. Blood samples were obtained to measure total serum cholesterol concentrations and the sera were then analysed enzymatically by the cholesterol oxidase: p-aminophenazone (CHOD PAP) method. Results: The study showed an incidence of 5.0% for preterm delivery in the low risk study patients. Preterm birth was 4.83-times more common with low total maternal cholesterol than with midrange total cholesterol (11.8% versus 2.2%, P = 0.024). Conclusion: Low maternal serum cholesterol (hypocholesterolaemia) is associated with preterm delivery. Optimal maternal serum cholesterol during pregnancy may have merit, therefore pregnant women should be encouraged to follow a healthy, balanced diet. PMID:25298606

  10. Serum cholesterol concentration and coronary heart disease in population with low cholesterol concentrations.

    PubMed Central

    Chen, Z; Peto, R; Collins, R; MacMahon, S; Lu, J; Li, W

    1991-01-01

    OBJECTIVE--To examine the relation between serum cholesterol concentration and mortality (from coronary heart disease and from other causes) below the range of cholesterol values generally seen in Western populations. DESIGN--Prospective observational study based on 8-13 years of follow up of subjects in a population with low cholesterol concentrations. SETTING--Urban Shanghai, China. SUBJECTS--9021 Chinese men and women aged 35-64 at baseline. MAIN OUTCOME MEASURE--Death from coronary heart disease and other causes. RESULTS--The average serum cholesterol concentration was 4.2 mmol/l at baseline examination, and only 43 (7%) of the deaths that occurred during 8-13 years of follow up were attributed to coronary heart disease. There was a strongly positive, and apparently independent, relation between serum cholesterol concentration and death from coronary heart disease (z = 3.47, p less than 0.001), and within the range of usual serum cholesterol concentration studied (3.8-4.7 mmol/l) there was no evidence of any threshold. After appropriate adjustment for the regression dilution bias, a 4 (SD 1)% difference in usual cholesterol concentration was associated with a 21 (SD 6)% (95% confidence interval 9% to 35%) difference in mortality from coronary heart disease. There was no significant relation between serum cholesterol concentration and death from stroke or all types of cancer. The 79 deaths due to liver cancer or other chronic liver disease were inversely related to cholesterol concentration at baseline. CONCLUSION--Blood cholesterol concentration was directly related to mortality from coronary heart disease even in those with what was, by Western standards, a "low" cholesterol concentration. There was no good evidence of an adverse effect of cholesterol on other causes of death. PMID:1888927

  11. Effects of zinc and cholesterol/choleate on serum lipoproteins and the liver in rats

    SciTech Connect

    Cho, C.H.; Chen, S.M.; Ogle, C.W.; Young, T.K.

    1989-01-01

    The effects of short-term treatment with orally-administered zinc sulfate and/or a mixture of cholesterol/choleate on serum lipoprotein and hepatic enzyme levels were studied. Administration of graded doses of zinc sulfate for 5 days, dose-dependently increased serum and hepatic zinc levels but depressed the serum high-density lipoprotein-cholesterol (HDL-C) concentration and liver cytochrome P-450 activity. However, it did not affect hepatic concentrations of malondialdehyde and free {beta}-glucuronidase. Cholesterol/choleate treatment for 5 days markedly damaged the liver, as reflected by elevations of hepatic concentrations of malondialdehyde (both in the mitochondrial and microsomal fractions) and of free {beta}-glucuronidase; total cholesterol and low-density lipoprotein-cholesterol in the blood were increased, whereas HDL-C was decreased significantly. Concomitant administration of zinc sulfate with cholesterol/choleate further lowered HDL-C levels, but reversed the high hepatic concentrations of both malondialdehyde and free {beta}-glucuronidase. The present study indicates that both zinc ions and cholesterol can decrease circulatory HDL-C levels and that zinc protects against cholesterol-induced hepatic damage by reducing lysosomal enzyme release and preventing lipid peroxidation in the liver.

  12. Yolk and serum cholesterol and production traits, as affected by incorporating a supraoptimal amount of copper in the diet of the leghorn hen.

    PubMed

    al Ankari, A; Najib, H; al Hozab, A

    1998-07-01

    1. An experiment was conducted to investigate the possibility of lowering the yolk cholesterol of the egg by supplementing the diet with supraoptimal amounts of copper (50, 150 or 250 mg/kg) as sulphate or acetate. 2. A significant reduction in egg production and a negative effect on food conversion was found when 250 mg/kg of copper was added compared to the control (no added copper). Acetate seemed significantly less harmful in both cases. 3. A significant linear reduction was found in plasma and yolk cholesterol (20% and 14%) and in plasma and yolk triglycerides (24% and 30%) as the dietary copper content was increased from 0 to 250 mg/kg. 4. Regardless of type or quantity of copper, cholesterol and lipids were decreased linearly as birds remained longer on the treatments. A significant interaction between quantity and period showed a greater reduction at a later time. 5. If slightly lower egg production can be accepted, the addition of 250 mg/kg copper might be beneficial in reducing the cholesterol content of the yolk. PMID:9693820

  13. Cholesterol in serum lipoprotein fractions after spaceflight

    NASA Technical Reports Server (NTRS)

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

    1988-01-01

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

  14. Lowering of serum cholesterol in hypercholesterolemic humans by tocotrienols (palmvitee).

    PubMed

    Qureshi, A A; Qureshi, N; Wright, J J; Shen, Z; Kramer, G; Gapor, A; Chong, Y H; DeWitt, G; Ong, A; Peterson, D M

    1991-04-01

    A double-blind, crossover, 8-wk study was conducted to compare effects of the tocotrienol-enriched fraction of palm oil (200 mg palmvitee capsules/day) with those of 300 mg corn oil/d on serum lipids of hypercholesterolemic human subjects (serum cholesterol 6.21-8.02 mmol/L). Concentrations of serum total cholesterol (-15%), LDL cholesterol (-8%), Apo B (-10%), thromboxane (-25%), platelet factor 4 (-16%), and glucose (-12%) decreased significantly only in the 15 subjects given palmvitee during the initial 4 wk. The crossover confirmed these actions of palmvitee. There was a carry over effect of palmvitee. Serum cholesterol concentrations of seven hypercholesterolemic subjects (greater than 7.84 mmol/L) decreased 31% during a 4-wk period in which they were given 200 mg gamma-tocotrienol/d. This indicates that gamma-tocotrienol may be the most potent cholesterol inhibitor in palmvitee capsules. The results of this pilot study are very encouraging. PMID:2012010

  15. Mechanism of serum cholesterol reduction by oat bran.

    PubMed

    Marlett, J A; Hosig, K B; Vollendorf, N W; Shinnick, F L; Haack, V S; Story, J A

    1994-12-01

    Nine normolipidemic young men consumed a constant diet for 2 mo into which oat bran was incorporated during the second month so that we might test the hypotheses that oats lower serum cholesterol concentrations by decreasing bile acid and fat absorption and increasing bile acid synthesis. Bile acid kinetics were determined by measuring the 13C enrichment of serum cholic and chenodeoxycholic acids. Oat bran consumption decreased serum cholesterol levels (p < 0.01) and cholic acid pool size (p < 0.05). Deoxycholic acid pool size (p < 0.01) and the synthesis and fractional turnover rates of both primary bile acids (p < 0.05) increased. Total bile acid pool size did not change. Fecal excretion of total bile acids, the two secondary bile acids and fat increased significantly. The results demonstrate that oat bran lowers serum cholesterol levels in part by altering bile acid metabolism. In addition, the substantial increase in the proportion of the total bile acid pool that was deoxycholic acid is consistent with the hypothesis that oat bran also decreases cholesterol synthesis. PMID:7982644

  16. Serum cholesterol and variant in cholesterol-related gene CETP predict white matter microstructure.

    PubMed

    Warstadt, Nicholus M; Dennis, Emily L; Jahanshad, Neda; Kohannim, Omid; Nir, Talia M; McMahon, Katie L; de Zubicaray, Greig I; Montgomery, Grant W; Henders, Anjali K; Martin, Nicholas G; Whitfield, John B; Jack, Clifford R; Bernstein, Matt A; Weiner, Michael W; Toga, Arthur W; Wright, Margaret J; Thompson, Paul M

    2014-11-01

    Several common genetic variants influence cholesterol levels, which play a key role in overall health. Myelin synthesis and maintenance are highly sensitive to cholesterol concentrations, and abnormal cholesterol levels increase the risk for various brain diseases, including Alzheimer's disease. We report significant associations between higher serum cholesterol (CHOL) and high-density lipoprotein levels and higher fractional anisotropy in 403 young adults (23.8 ± 2.4 years) scanned with diffusion imaging and anatomic magnetic resonance imaging at 4 Tesla. By fitting a multi-locus genetic model within white matter areas associated with CHOL, we found that a set of 18 cholesterol-related, single-nucleotide polymorphisms implicated in Alzheimer's disease risk predicted fractional anisotropy. We focused on the single-nucleotide polymorphism with the largest individual effects, CETP (rs5882), and found that increased G-allele dosage was associated with higher fractional anisotropy and lower radial and mean diffusivities in voxel-wise analyses of the whole brain. A follow-up analysis detected white matter associations with rs5882 in the opposite direction in 78 older individuals (74.3 ± 7.3 years). Cholesterol levels may influence white matter integrity, and cholesterol-related genes may exert age-dependent effects on the brain. PMID:24997672

  17. Serum Cholesterol and Variant in Cholesterol-Related Gene CETP Predict White Matter Microstructure

    PubMed Central

    Warstadt, Nicholus M.; Dennis, Emily L.; Jahanshad, Neda; Kohannim, Omid; Nir, Talia M.; McMahon, Katie L.; de Zubicaray, Greig I.; Montgomery, Grant W.; Henders, Anjali K.; Martin, Nicholas G.; Whitfield, John B.; Jack, Clifford R.; Bernstein, Matt A.; Weiner, Michael W.; Toga, Arthur W.; Wright, Margaret J.; Thompson, Paul M.

    2014-01-01

    Several common genetic variants influence cholesterol levels, which play a key role in overall health. Myelin synthesis and maintenance are highly sensitive to cholesterol concentrations, and abnormal cholesterol levels increase the risk for various brain diseases, including Alzheimer's disease (AD). We report significant associations between higher serum cholesterol (CHOL) levels and high-density lipoproteins (HDL) and higher fractional anisotropy in 403 young adults (23.8±2.4 years) scanned with diffusion imaging and anatomical MRI at 4 Tesla. By fitting a multi-locus genetic model within white matter areas associated with CHOL, we found that a set of 18 cholesterol-related SNPs implicated in AD risk predicted FA. We focused on the SNP with the largest individual effects - CETP (rs5882) – and found that increased G-allele dosage was associated with higher FA and lower radial and mean diffusivities in voxel-wise analyses of the whole brain. A follow-up analysis detected WM associations with rs5882 in the opposite direction in 78 older individuals (74.3±7.3 years). Cholesterol levels may influence WM integrity, and cholesterol-related genes may exert age-dependent effects. PMID:24997672

  18. Effect of honey on serum cholesterol and lipid values.

    PubMed

    Münstedt, Karsten; Hoffmann, Sven; Hauenschild, Annette; Bülte, Michael; von Georgi, Richard; Hackethal, Andreas

    2009-06-01

    Small studies have suggested that honey benefits patients with high cholesterol concentrations. The present study aimed to confirm this finding in a larger group of subjects. Sixty volunteers with high cholesterol, stratified according to gender and hydroxymethylglutaryl-coenzyme A reductase inhibitor (statin) treatment (yes/no), were randomized to receive 75 g of honey solution or a honey-comparable sugar solution once daily over a period of 14 days. Baseline measurements, including body mass index (BMI) and lipid profile, were obtained, and subjects also completed dietary questionnaires and the Inventory for the Assessment of Negative Bodily Affect-Trait form (INKA-h) questionnaire. Measurements were repeated 2 weeks later. BMI and high-density lipoprotein (HDL) cholesterol values were significantly correlated (r = -0.487; P < .001) as were BMI and a lower ratio of low-density lipoprotein (LDL) cholesterol to HDL cholesterol (r = 0.420; P < .001), meaning that subjects with a high BMI had a lower HDL cholesterol value. INKA-h scores and LDL cholesterol values were also significantly correlated (r = 0.273, P = .042). Neither solution influenced significantly cholesterol or triglyceride values in the total group; in women, however, the LDL cholesterol value increased in the sugar solution subgroup but not in the women taking honey. Although ingesting honey did not reduce LDL cholesterol values in general, women may benefit from substituting honey for sugar in their diet. Reducing the BMI lowers the LDL cholesterol value, and psychological interventions also seem important and merit further investigation. PMID:19627212

  19. Fitness, Fatness, and Serum Cholesterol: An Epidemiological Study of an Entire Community

    ERIC Educational Resources Information Center

    Montoye, Henry J.; And Others

    1976-01-01

    Research on relationships between serum cholesterol, heart rate, and exercise in age-and sex-specific groups suggests a positive relationship between fatness on the one hand and serum cholesterol and heart rate, but eliminating the effect of body fatness results in no relationship between heart rate and serum total cholesterol. (MB)

  20. Combined dietary and exercise intervention for control of serum cholesterol in the workplace

    NASA Technical Reports Server (NTRS)

    Angotti, C. M.; Chan, W. T.; Sample, C. J.; Levine, M. S.

    2000-01-01

    PURPOSE: To elucidate a potential combined dietary and exercise intervention affect on cardiovascular risk reduction of the National Aeronautics and Space Administration Headquarters employees. DESIGN: A nonexperimental, longitudinal, clinical-chart review study (1987 to 1996) of an identified intervention group and a reference (not a control) group. SETTING: The study group worked in an office environment and participated in the annual medical examinations. SUBJECTS: An intervention group of 858 people with initially elevated serum cholesterol, and a reference group of 963 people randomly sampled from 10% of the study group. MEASURES: Serum cholesterol data were obtained for both groups, respectively, from pre- and postintervention and annual examinations. The reference group was adjusted by statistical exclusion of potential intervention participants. Regression equations (cholesterol vs. study years) for the unadjusted/adjusted reference groups were tested for statistical significance. INTERVENTION: An 8-week individualized, combined dietary and exercise program was instituted with annual follow-ups and was repeated where warranted. RESULTS: Only the unadjusted (but not the adjusted) reference group with initial mean total serum cholesterol levels above 200 mg/dL shows a significant 9-year decline trend and significant beta coefficient tests. An intervention effect is suggested. Mean high density lipoprotein cholesterol rose slightly in the intervention group but was maintained in the reference group. CONCLUSION: With potential design limitations, the NASA intervention program focusing on a high risk group may be associated to some degree, if not fully, with an overall cardiovascular risk profile improvement.

  1. The association between abdominal obesity and serum cholesterol level

    PubMed Central

    Veghari, Gholamreza; Sedaghat, Mehdi; Maghsodlo, Siavash; Banihashem, Samieh; Moharloei, Pooneh; Angizeh, Abdolhamid; Tazik, Ebrahim; Moghaddami, Abbas; Joshaghani, Hamidreza

    2015-01-01

    Background: The main aim of this study is to evaluate the association between serum cholesterol level and abdominal obesity in adult men and women in the north of Iran. Materials and Methods: This cross-sectional and analytical study was conducted on the 1956 subjects (990 men and 966 women) between 25 and 65 years old chosen by cluster sampling. Plasma cholesterol was measured in the morning after a 12 h fast and determined by auto-analyzer. Hypercholesterolemia (HC) was defined by a total plasma cholesterol level over 200 mg/dl. Waist circumference ≥102 cm and ≥88 cm in men and women were defined as abdominal obesity. SPSS 16.0 software was used for statistical analysis and P < 0.05 considered as statistical significance. Results: Averagely, the mean of age was 44.2 years and mean ± standard deviation of plasma total cholesterol level was 203 ± 11.3 mg/dl. The HC was seen in 50.8% of subjects with a more common in women than in men. Compared with normal subjects, in abdominal obese people, the odds ratio (OR) of HC was (OR = 4.208 [95% confidence interval [CI]: 1.939–9.130]) and (OR = 3.956 [95% CI: 1.821–8.592]) in men aged 25–35 and 35–45 years, respectively. In women aged 25–35 years, it was (OR = 3.444 [95% CI: 1.959–6.056]) in abdominal obese compared with normal subjects. Conclusion: Hypercholesterolemia was revealed as a major health problem among adults, and it was associated with abdominal obesity especially in the early middle-age in the north of Iran. This association was not significant in men and women after the age of 45 and 35, respectively. PMID:26097812

  2. Combined effect of Lactobacillus acidophilus and β-cyclodextrin on serum cholesterol in pigs.

    PubMed

    Alonso, L; Fontecha, J; Cuesta, P

    2016-01-14

    A total of twenty-four Yorkshire gilt pigs of 6-7 weeks of age were used in a 2×2 factorial experiment to determine the individual and combined effects of the inclusion of two dietary factors (cholesterol rich, 3% β-cyclodextrin (BCD) and Lactobacillus acidophilus cultures) on total cholesterol and LDL-cholesterol levels in blood serum. Pigs were assigned randomly to treatment groups (n 6). Total serum cholesterol concentrations decreased after 3 weeks in all the experimental treatment groups, including diets with BCD, L. acidophilus or both. Similar trends were observed for serum LDL-cholesterol concentrations among the experimental treatments. No statistically significant differences from the control group were observed in either total serum cholesterol or LDL-cholesterol concentrations (P<0·05) for each of the individual treatment groups: BCD or L. acidophilus. However, significant differences in total serum cholesterol concentrations were observed when comparing the combined treatment group (BCD and L. acidophilus) with the control group, which consisted of a basal diet and sterile milk. The combined treatment group exhibited 17·9% lower total serum cholesterol concentration after 3 weeks. Similar significant differences were observed when comparing the combined effect experimental group with the control group after 3 weeks. The combined treatment group exhibited 27·9% lower serum LDL-cholesterol concentrations. PMID:26467089

  3. Total serum cholesterol, atherogenic indices and their longitudinal association with depressive symptoms among US adults

    PubMed Central

    Beydoun, M A; Beydoun, H A; Dore, G A; Fanelli-Kuczmarski, M T; Evans, M K; Zonderman, A B

    2015-01-01

    Serum cholesterol, both total and lipoprotein fractions, has been associated with mid- and late-life depression. Using longitudinal data on a large and ethnically diverse sample of urban adults, the associations of serum lipid profile measured by high or low total cholesterol (TC; >200 mg dl−1; <160 mg dl−1) and by atherogenic indices, namely high total cholesterol and low-density lipoprotein cholesterol relative to high-density lipoprotein cholesterol, with change in total and domain-specific depressive symptoms over time were examined. Findings were compared by sex. (Hypothesis 1) In addition, baseline depressive symptoms as predictors for longitudinal change in lipid profile trajectory were tested. (Hypothesis 2) Mixed-effects regression analyses stratified by sex was used. Sample sizes of participants (n) and repeated observations (n') were: Hypothesis 1 (Men: n=826 ; n'=1319; Women: n=1099 ; n'=1817); Hypothesis 2 (Men: n=738; n'=1230; Women: n=964; n'=1678). As hypothesized, a higher level of atherogenic indices was linked to faster increase in depressive symptom scores, particularly depressed affect and interpersonal problems, though this relationship was found only among women. Among men a U-shaped relationship between baseline TC and longitudinal increase in somatic complaints and a direct link between low TC and longitudinal putative improvement in positive affect was found. On excluding statin users among women, low TC was associated with slower increase in depressed affect over time, whereas high TC was associated with faster increase in interpersonal problems. In summary, atherogenic indices were directly linked to faster increase in depressive symptoms among women only. More studies are needed to explain these sex-specific associations. PMID:25734511

  4. Effects of different fibre sources and fat addition on cholesterol and cholesterol-related lipids in blood serum, bile and body tissues of growing pigs.

    PubMed

    Kreuzer, M; Hanneken, H; Wittmann, M; Gerdemann, M M; Machmuller, A

    2002-04-01

    Knowledge is limited on the efficacy of hindgut-fermentable dietary fibre to reduce blood, bile and body tissue cholesterol levels. In three experiments with growing pigs the effects of different kinds and levels of bacterially fermentable fibre (BFS) on cholesterol metabolism were examined. Various diets calculated to have similar contents of metabolizable energy were supplied for complete fattening periods. In the first experiment, a stepwise increase from 12 to 20% BFS was performed by supplementing diets with fermentable fibre from sugar beet pulp (modelling hemicelluloses and pectin). Beet pulp, rye bran (modelling cellulose) and citrus pulp (pectin) were offered either independently or in a mixture in the second experiment. These diets were opposed to rations characterized in carbohydrate type by starch either mostly non-resistant (cassava) or partly resistant (maize) to small intestinal digestion. The third experiment was planned to explore the interactions of BFS from citrus pulp with fat either through additional coconut oil/palm kernel oil blend or full-fat soybeans. In all experiments the increase of the BFS content was associated with a constant (cellulose) or decreasing (hemicelluloses, pectin) dietary proportion of non-digestible fibre. In experiment 1 an inverse dose-response relationship between BFS content and cholesterol in blood serum and adipose tissue as well as bile acid concentration in bile was noted while muscle cholesterol did not respond. In experiment 2 the ingredients characterized by cellulose and hemicelluloses/pectin reduced cholesterol-related traits relative to the low-BFS-high-starch controls whereas, except in adipose tissue cholesterol content, the pectinous ingredient had the opposite effect. However, the changes in serum cholesterol mainly affected HDL and not LDL cholesterol. Adipose tissue cholesterol also was slightly lower with partly resistant starch compared to non-resistant starch in the diet. Experiment 3 showed that

  5. Associations between Serum 25-hydroxyvitamin D and Lipids, Lipoprotein Cholesterols, and Homocysteine

    PubMed Central

    Glueck, Charles J.; Jetty, Vybhav; Rothschild, Matan; Duhon, Gregory; Shah, Parth; Prince, Marloe; Lee, Kevin; Goldenberg, Michael; Kumar, Ashwin; Goldenberg, Naila; Wang, Ping

    2016-01-01

    Background: Serum 25(OH) vitamin D levels are inversely associated with cardiovascular disease (CVD) mortality, mediated in part by independent positive relationships with high-density lipoprotein cholesterol (HDLC) and inverse relationships with low-density lipoprotein cholesterol (LDLC), triglyceride, and homocysteine. Aims: In this study, we assessed relationships between fasting serum vitamin D and lipids, lipoprotein cholesterols, and homocysteine. Materials and Methods: We studied 1534 patients sequentially referred to our center from 2007 to 2016. Fasting serum total 25(OH) vitamin D, plasma cholesterol, triglyceride, HDLC, LDLC, and homocysteine were measured. Stepwise regression models were used with total cholesterol, triglyceride, HDLC, LDLC, and homocysteine as dependent variables and explanatory variables age, race, gender, body mass index (BMI), and serum vitamin D levels. Relationships between quintiles of serum vitamin D and triglycerides, HDLC, LDLC, and homocysteine were assessed after covariance adjusting for age, race, gender, and BMI. Results: Fasting serum vitamin D was positively correlated with age, HDLC, and White race, and was inversely correlated with BMI, total and LDL cholesterol, triglyceride, and fasting serum homocysteine (P ≤ 0.0001 for all). Serum vitamin D was a significant independent inverse explanatory variable for total cholesterol, triglyceride, and LDL cholesterol, and accounted for the largest amount of variance in serum total cholesterol (partial R2 =3.6%), triglyceride (partial R2 =3.1%), and LDLC (partial R2 =2.9%) (P < 0.0001 for all). Serum vitamin D was a significant positive explanatory variable for HDLC (partial R2 = 1.4%, P < 0.0001), and a significant inverse explanatory variable for homocysteine (partial R2 = 6.0–12.6%). Conclusions: In hyperlipidemic patients, serum vitamin D was a significant independent inverse determinant of total cholesterol, LDLC, triglyceride, and homocysteine, and a significant

  6. Effect of serum, cholesterol and low density lipoprotein on the functionality and structure of lung surfactant films.

    PubMed

    Nahak, Prasant; Nag, Kaushik; Hillier, Ashley; Devraj, Ravi; Thompson, David W; Manna, Kausik; Makino, Kimiko; Ohshima, Hiroyuki; Nakahara, Hiromichi; Shibata, Osamu; Panda, Amiya Kumar

    2014-01-01

    Lung surfactant is a complex mixture of lipid and protein, responsible for alveolar stability, becomes dysfunctional due to alteration of its structure and function by leaked serum materials in disease. Serum proteins, cholesterol and low density lipoprotein (LDL) were studied with bovine lipid extract surfactant (BLES) using Langmuir films, and bilayer dispersions using Raman spectroscopy. While small amount of cholesterol (10 wt%) and LDL did not significantly affect the adsorption and surface tension lowering properties of BLES. However serum lipids, whole serum as well as higher amounts of cholesterol, and LDL dramatically altered the surface properties of BLES films, as well as gel-fluid structures formed in such films observed using atomic force microscopy (AFM). Raman-spectroscopic studies revealed that serum proteins, LDL and excess cholesterol had fluidizing effects on BLES bilayers dispersion, monitored from the changes in hydrocarbon vibrational modes during gel-fluid thermal phase transitions. This study clearly suggests that patho-physiological amounts of serum lipids (and not proteins) significantly alter the molecular arrangement of surfactant in films and bilayers, and can be used to model lung disease. PMID:25409691

  7. Is the serum cholesterol-coronary heart disease relationship modified by activity level in older persons?

    PubMed

    Harris, T B; Makuc, D M; Kleinman, J C; Gillum, R F; Curb, J D; Schatzkin, A; Feldman, J J

    1991-08-01

    Although coronary heart disease remains a leading cause of death and disability in old age, the relationship of serum cholesterol level to risk of coronary heart disease in old age is controversial. Data for 2,388 white persons aged 65-74 who participated in the National Health and Nutrition Examination Survey (NHANES) I Epidemiologic Follow-up Study (NHEFS) were examined to determine the relationship of serum cholesterol level to coronary heart disease incidence and whether activity level would modify this relationship. While there was no overall relationship between serum cholesterol level and coronary heart disease risk in either men or women, the relationship between serum cholesterol level and coronary heart disease differed within activity groups. For persons who were more active, serum cholesterol level was associated with a graded increase in risk of coronary heart disease, from 1.3 (95% CI 0.7, 2.3) in those with serum cholesterol level of 4.7-5.1 to 1.7 in those with serum cholesterol level of 6.2 mmol/L or more (95% CI 1.0, 2.7), when compared with those with serum cholesterol level below 4.7. For the least active persons, all levels of cholesterol were associated with a significant inverse relative risk, including cholesterol of 6.2 mmol/L or more (Relative risk = 0.4 (95% CI 0.2, 0.7]. These data suggest that factors such as activity level may modify the serum cholesterol-coronary heart disease association in old age. The serum cholesterol-coronary heart disease association in more active older persons resembles that seen in younger populations, whereas the association in less active persons is that of serum cholesterol level and risk of cancer or death. The modification of the serum cholesterol-coronary heart disease association by activity level may have implications for appropriate clinical management as well as appropriate design of research studies of this association. PMID:2071804

  8. Effects of stress on serum triglycerides, nonsterified fatty acids, and total cholesterol levels in male rats after ethanol administration

    SciTech Connect

    Hershock, D.; Vogel, W.H. )

    1989-02-09

    Serum triglycerides, nonesterified fatty acids (NEFA), and total cholesterol were determined during one hour immobilization stress in adult male Sprague-Dawley rats after ethanol administration (2g/kg, i.p.). Stress and ethanol effects were evaluated in two experiments: (1) rats maintained on Purina Rodent Chow for six weeks and fasted for 24 hours; and (2) rats maintained on the same diet supplemented with 1% cholesterol and 10% peanut oil for six weeks and nonfasted prior to experimentation. Blood was obtained from indwelling jugular catheters. In each experiment, differences were seen in triglyceride and NEFA levels but not in total cholesterol. In the regular diet-fed rats (1), serum triglyceride levels were not affected by either stress or ethanol. However, NEFA levels did show differences in the response to ethanol and stress. A 63% decrease from baseline after 5{prime} of stress was partially abolished by ethanol; instead, a 24% increase was observed. Also, a stress-induced increase in NEFA which occurred after 15{prime} was not observed in the ethanol treated rats; rather, a decrease in NEFA was noted. Total cholesterol did not change in response to stress or ethanol. In the high cholesterol diet-fed rats (2), ethanol did not suppress a stress-induced increase in triglyceride levels. NEFA levels in ethanol-treated rats were higher during the first 15{prime} of stress as compared to stress alone. A decrease in NEFA was however seen in the ethanol-treated rats after 30{prime} of stress and these levels remained lower than the stress alone group. A diet-induced increase in total cholesterol levels was observed; however, no changes were seen due to either or ethanol. Thus, ethanol administration prior to acute immobilization stress did affect serum triglyceride and NEFA levels but did not change total cholesterol.

  9. Transport of circulating serum cholesterol by human renal cell carcinoma

    SciTech Connect

    Clayman, R.V.; Figenshau, R.S.; Prigge, W.F.; Forstrom, L.; Gebhard, R.L.

    1987-06-01

    Clear cell renal cancer contains a large quantity of cholesterol ester (300-mg./gm. protein). To determine whether abnormalities in cholesterol transport could account for this sterol accumulation, the uptake, release, and imaging capabilities of intravenously injected /sup 131/I-6-iodomethyl-29-norcholesterol, a cholesterol analogue, were studied preoperatively in five patients with clear cell renal cancer. At surgery, samples of the liver, tumor, adrenal, and non-tumor kidney were obtained for analysis. /sup 131/I-sterol uptake by the tumor, when normalized for cholesterol content, was less than for adrenal, liver or kidney. In contrast, release of preloaded /sup 131/I-sterol from the human tumors was consistently slower than for normal kidney. The reduced release of free cholesterol from renal cancer cells may, in part, be responsible for the accumulation of cholesterol in human renal cancer.

  10. Review of 5 years of a combined dietary and physical fitness intervention for control of serum cholesterol

    NASA Technical Reports Server (NTRS)

    Angotti, C. M.; Levine, M. S.

    1994-01-01

    A chart review covering the first 5 years of clinical experience with a combined dietary and exercise intervention program for the reduction of hypercholesterolemia at the National Aeronautics and Space Administration headquarters demonstrated the program's success in maintaining high-density lipoprotein cholesterol (HDL-C) levels while significantly lowering total serum cholesterol levels. This combined program also resulted in improved ratios of total serum cholesterol to HDL-C and lowered levels of low-density lipoprotein cholesterol, thus further reducing the risk for cardiovascular disease. The National Aeronautics and Space Administration Cardiovascular Risk Reduction Program was developed after it was determined that although dietary intervention alone improved total cholesterol levels, it often resulted in a more than proportionate decrease in HDL-C and a worsening of the ratio of cholesterol to HDL-C. An approach was needed that would positively affect all factors of the lipid profile. The findings from the program indicate that reduction of cardiovascular risk can be accomplished easily and effectively at the worksite through dietary intervention, personal monitoring, and a reasonable exercise program.

  11. Epiberberine reduces serum cholesterol in diet-induced dyslipidemia Syrian golden hamsters via network pathways involving cholesterol metabolism.

    PubMed

    Zou, Zong-Yao; Hu, Yin-Ran; Ma, Hang; Feng, Min; Li, Xue-Gang; Ye, Xiao-Li

    2016-03-01

    This study aimed to evaluate the cholesterol-lowering effect of epiberberine in dyslipidemia Syrian golden hamsters induced by high fat and high cholesterol (HFHC) diet and its regulation mechanism on some key genes involved in cholesterol metabolism. Hamsters were divided into six groups: normal control group (NC), HFHC group, simvastatin (Sim) and three doses of epiberberine group. The body weight, organs weight and serum lipid levels, as well as total cholesterol (TC) and total bile acids (TBA) levels in liver and feces were determined. Furthermore, the antidyslipidemia effect of epiberberine on key genes involved in cholesterol biosynthesis, uptake, conversion and elimination such as 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), low density lipoprotein receptor (LDL receptor), 7-alpha-hydroxylase (CYP7A1) and apical sodium dependent bile acid transporter (ASBT) were investigated. The results showed that epiberberine at high dosage significantly reduced serum TC, low density lipoprotein cholesterol (LDL-c) and TBA levels by 20.2%, 22.3% and 43.8%, respectively, and increased TBA and TC levels in feces. Epiberberine inhibited HMGCR mRNA and protein expressions and slightly reduced the protein level of ASBT, as well as dramatically up-regulated mRNA and protein expressions of CYP7A1 and LDL receptor. These findings suggested that the antidyslipidemia effects of epiberberine can be achieved via inhibiting the synthesis of cholesterol, promoting the uptake and conversion of TC in liver and increasing the excretion of TC and TBA in feces. Thus, epiberberine should be considered as one of the promising natural drugs for the treatment of dyslipidemia. PMID:26593426

  12. Prognostic Usefulness of Serum Cholesterol Efflux Capacity in Patients With Coronary Artery Disease.

    PubMed

    Zhang, Jianhua; Xu, Jia; Wang, Jingfeng; Wu, Changhao; Xu, Yan; Wang, Yueguo; Deng, Fengfeng; Wang, Zhe; Chen, Xuhua; Wu, Mengzuo; Chen, Yangxin

    2016-02-15

    Cholesterol efflux capacity has been shown to have an inverse relation with coronary artery disease (CAD) and may overcome the limitations of high-density lipoprotein (HDL) cholesterol levels as a predictor for CAD risks. We investigated the predictive value of cholesterol efflux capacity for the prognosis of CAD. Serum cholesterol efflux capacity in 313 patients newly diagnosed with CAD by coronary angiography was measured, and all patients completed a 3-year follow-up. The primary clinical end points were nonfatal myocardial infarction, nonfatal stroke, and cardiovascular mortality. The secondary clinical end points were class IV heart failure requiring hospitalization and coronary artery revascularization. Cholesterol efflux capacity was lower in patients with CAD compared with control group, and decreased cholesterol efflux capacity was associated with an increased risk of acute coronary syndrome (odds ratios, 0.25; 95% confidence interval, 0.14 to 0.46; p <0.01). There was no association between cholesterol efflux capacity and serum HDL cholesterol levels. Follow-up data showed that patients with CAD with lower cholesterol efflux capacity had higher primary clinical end point events (26 of 158 vs 8 of 155, p <0.01). Cox regression and Kaplan-Meier analysis further showed that a decreased cholesterol efflux capacity was associated with an increased risk of the primary end point events regardless of adjustment. There was no association between cholesterol efflux capacity and the secondary end point events. In conclusion, the results provide the important clinical evidence that cholesterol efflux capacity is a predictive index for plaque stability and the prognosis of CAD, independent of HDL cholesterol levels. PMID:26718234

  13. Serum cholesterol level in a typical suburban commercial community in Nigeria.

    PubMed

    Ahaneku, J E; Ndefo, J C; Dioka, C E

    1996-07-15

    Forty-one apparently healthy businessmen and -women and an equal number of government workers matched for age and sex underwent serum cholesterol determinations. The mean serum cholesterol levels of businessmen and -women were significantly higher than those of their government worker counterparts (p < 0.001). The marked increase in the serum cholesterol of the business subjects was attributed to their overindulgence and/or eating habits and lack of physical activity. The cardiovascular risk implications of the high cholesterol value and other risk co-factors such as obesity and alcoholism observed among the business subjects are highlighted. We advise that for communities similar to the one described here, public enlightenment programmes about the health benefits of periodic medical assessment and recreational physical activities are necessary. A further comprehensive study of lipid, lipoprotein and other risk factors in these subjects should be encouraged. PMID:8698110

  14. INTERINDIVIDUAL VARIATION IN SERUM CHOLESTEROL IS ASSOCIATED WITH REGIONAL WHITE MATTER TISSUE INTEGRITY IN OLDER ADULTS

    PubMed Central

    Williams, Victoria J.; Leritz, Elizabeth C.; Shepel, Juli; McGlinchey, Regina E.; Milberg, William P.; Rudolph, James L.; Lipsitz, Lewis A.; Salat, David H.

    2013-01-01

    Prior research has demonstrated links among vascular health and the occurrence of stroke, mild cognitive decline, and dementia in older adults. However, little is known about whether normal variation in vascular indicators may be related to changes in neural tissue integrity. Even less is known about how the brain is affected by cholesterol levels in the normal to moderate risk range, leading up to overt disease pathology. This study examined associations between serum lipid levels and DTI indicators of white matter (WM) structural integrity in a sample of 125 generally healthy older adults aged 43–87 years. Whole-brain voxelwise analysis, controlling for age and gender, revealed low density lipoprotein levels (LDL) as the most robust correlate of regional WM structural integrity of the measured lipids. Higher LDL was associated with decreased WM integrity in right frontal and temporal regions, the superior longitudinal fasciculus and internal/external capsules. Increasing LDL was associated with increased radial and axial diffusivity; however, more widespread statistical effects were found for radial diffusivity. These findings suggest that normal inter-individual variation in lipid levels is associated with compromised regional WM integrity, even in individuals below clinical thresholds for hyperlipidemia. Given the prevalence of cholesterol-associated sequelae in older adults, and mounting evidence suggesting a vascular role in the etiology of dementia, the current data suggest that understanding the relationship between cholesterol and brain tissue microstructure may have important clinical implications for early detection of vascular-related cognitive disorders and optimal regulation of serum lipids to maintain neural health in older adults. PMID:22438182

  15. Tea Dietary Fiber Improves Serum and Hepatic Lipid Profiles in Mice Fed a High Cholesterol Diet.

    PubMed

    Guo, Wenxin; Shu, Yang; Yang, Xiaoping

    2016-06-01

    Tea dietary fiber (TDF) was prepared from tea residues and modified to get cellulose-modified TDF (CTDF) by cellulase or micronized TDF (MTDF) by ultrafine grinding. The in vitro lipid-binding capacities of the three fibers and their effects on serum and hepatic lipid profiles in mice fed a high cholesterol diet were evaluated. The results showed that the three fibers had excellent lipid-binding capacities, and the cholesterol- and sodium cholate-binding capacities of CTDF and MTDF were significantly higher than those of TDF. Animal studies showed that, compared to model control, the three fibers significantly decreased mice average daily gain, gain: feed, and liver index, reduced total cholesterol (TC), triglyceride, and low density lipoprotein-cholesterol of serum and liver, increased serum and hepatic high density lipoprotein-cholesterol to TC ratio, and promoted the excretion of fecal lipids, and they also significantly increased the activities of superoxide dismutase and glutathione peroxidase of serum and liver, and decreased lipid peroxidation; moreover, the effects of CTDF and MTDF were better than that of TDF. It was concluded that the three fibers could improve serum and hepatic lipid profiles in mice fed a high cholesterol diet and the mechanism of action might be due to the promotion of fecal excretion of lipids through their lipid-binding ability and the inhibition of lipid peroxidation. These findings suggest that tea dietary fiber has the potential to be used as a functional ingredient to control cardiovascular disease. PMID:27040277

  16. Freeze-dried strawberries lower serum cholesterol and lipid peroxidation in adults with abdominal adiposity and elevated serum lipids.

    PubMed

    Basu, Arpita; Betts, Nancy M; Nguyen, Angel; Newman, Emily D; Fu, Dongxu; Lyons, Timothy J

    2014-06-01

    Dietary flavonoid intake, especially berry flavonoids, has been associated with reduced risks of cardiovascular disease (CVD) in large prospective cohorts. Few clinical studies have examined the effects of dietary berries on CVD risk factors. We examined the hypothesis that freeze-dried strawberries (FDS) improve lipid and lipoprotein profiles and lower biomarkers of inflammation and lipid oxidation in adults with abdominal adiposity and elevated serum lipids. In a randomized dose-response controlled trial, 60 volunteers [5 men and 55 women; aged 49 ± 10 y; BMI: 36 ± 5 kg/m(2) (means ± SDs)] were assigned to consume 1 of the following 4 beverages for 12 wk: 1) low-dose FDS (LD-FDS; 25 g/d); 2) low-dose control (LD-C); 3) high-dose FDS (HD-FDS; 50 g/d); and 4) high-dose control (HD-C). Control beverages were matched for calories and total fiber. Blood draws, anthropometrics, blood pressure, and dietary data were collected at screening (0 wk) and after 12-wk intervention. Dose-response analyses revealed significantly greater decreases in serum total and LDL cholesterol and nuclear magnetic resonance (NMR)-derived small LDL particle concentration in HD-FDS [33 ± 6 mg/dL, 28 ± 7 mg/dL, and 301 ± 78 nmol/L, respectively (means ± SEMs)] vs. LD-FDS (-3 ± 11 mg/dL, -3 ± 9 mg/dL, and -28 ± 124 nmol/L, respectively) over 12 wk (0-12 wk; all P < 0.05). Compared with controls, only the decreases in total and LDL cholesterol in HD-FDS remained significant vs. HD-C (0.7 ± 12 and 1.4 ± 9 mg/dL, respectively) over 12 wk (0-12 wk; all P < 0.05). Both doses of strawberries showed a similar decrease in serum malondialdehyde at 12 wk (LD-FDS: 1.3 ± 0.2 μmol/L; HD-FDS: 1.2 ± 0.1 μmol/L) vs. controls (LD-C: 2.1 ± 0.2 μmol/L; HD-C: 2.3 ± 0.2 μmol/L) (P < 0.05). In general, strawberry intervention did not affect any measures of adiposity, blood pressure, glycemia, and serum concentrations of HDL cholesterol and triglycerides, C-reactive protein, and adhesion molecules

  17. Changes in Serum Cholesterol and Diet in North Karelia and All Finland.

    PubMed

    Vartiainen, Erkki; Laatikainen, Tiina; Tapanainen, Heli; Puska, Pekka

    2016-06-01

    Finland in the 1960s, and especially North Karelia in the eastern part of the country, had the highest cardiovascular mortality in the world. The classical cardiovascular risk factors were all common, but serum cholesterol level was extremely high because of the very high intake of saturated fats, mainly from dairy products. The North Karelia Project was started as a comprehensive preventive program to reduce serum cholesterol levels by reducing the intake of saturated fats and increasing the intake of polyunsaturated fats in the whole population. Cross-sectional population surveys were done in North Karelia and nearby Kuopio province every 5 years starting in 1972. After 1982, surveys were started in 2 other areas. Blood cholesterol was measured from serum samples, and diet was assessed by a questionnaire in all surveys-since 1982 by 3-day food record, since 1997 by 24-hour recall, and since 2002 by 48-hour recall. Between 1972 and 2012, the population in North Karelia reduced serum cholesterol from 6.92 mmol/l to 5.46 mmol/l (21%) in men and from 6.81 mmol/l to 5.37 mmol/l (21%) in women. In men, serum cholesterol level reduced more in North Karelia than in the reference province of Kuopio during the first 5 years from 1972 to 1977. Since that time, changes in serum cholesterol level have been very similar in different parts of the country. Saturated fats were reduced from 20% of energy intake to 12% in 2007 but increased from 2007 to 2012 to 14%. In conclusion, serum cholesterol reduction by dietary changes is feasible on the population level but requires active work and large-scale cooperation between all the meaningful sectors in the society. PMID:27242084

  18. Serum Opacity Factor Enhances HDL-Mediated Cholesterol Efflux, Esterification and Anti Inflammatory Effects

    PubMed Central

    Tchoua, Urbain; Rosales, Corina; Tang, Daming; Gillard, Baiba K.; Vaughan, Ashley; Lin, Hu Yu; Courtney, Harry S.

    2011-01-01

    Serum opacity factor (SOF) is a streptococcal protein that disrupts the structure of human high density lipoproteins (HDL) releasing lipid-free apo A-I while forming a large cholesteryl ester-rich particle and a small neo HDL. Given its low cholesterol and high phospholipid contents, we tested the hypotheses that neo HDL is a better substrate for cholesterol esterification via lecithin:cholesterol acyltransferase (LCAT), better than HDL as an acceptor of THP-1 macrophage cholesterol efflux, and improves reduction of oxidized LDL-induced production of inflammatory markers. We observed that both cholesterol efflux and esterification were improved by recombinant (r)SOF treatment of whole plasma and that the underlying cause of the improved cholesterol esterification in plasma and macrophage cholesterol efflux to rSOF-treated plasma was due to the rSOF-mediated conversion of HDL to neo HDL. Moreover, the reduction of secretion of TNF-α and IL-6 by THP-1 cells by neo HDL was twice that of HDL. Studies in BHK cells overexpressing cholesterol transporters showed that efflux to neo HDL occurred primarily via ABCA1 not ABCG1. Thus, rSOF improves two steps in reverse cholesterol transport with a concomitant reduction in the release of macrophage markers of inflammation. We conclude that rSOF catalyzes a novel reaction that might be developed as a new therapy that prevents or reverses atherosclerosis via improved reverse cholesterol transport. PMID:20972840

  19. Serum albumin acts as a shuttle to enhance cholesterol efflux from cells[S

    PubMed Central

    Sankaranarayanan, Sandhya; de la Llera-Moya, Margarita; Drazul-Schrader, Denise; Phillips, Michael C.; Kellner-Weibel, Ginny; Rothblat, George H.

    2013-01-01

    An important mechanism contributing to cell cholesterol efflux is aqueous transfer in which cholesterol diffuses from cells into the aqueous phase and becomes incorporated into an acceptor particle. Some compounds can enhance diffusion by acting as shuttles transferring cholesterol to cholesterol acceptors, which act as cholesterol sinks. We have examined whether particles in serum can enhance cholesterol efflux by acting as shuttles. This task was accomplished by incubating radiolabeled J774 cells with increasing concentrations of lipoprotein-depleted sera (LPDS) or components present in serum as shuttles and a constant amount of LDL, small unilamellar vesicles, or red blood cells (RBC) as sinks. Synergistic efflux was measured as the difference in fractional efflux in excess of that predicted by the addition of the individual efflux values of sink and shuttle alone. Synergistic efflux was obtained when LPDS was incubated with cells and LDL. When different components of LPDS were used as shuttles, albumin produced synergistic efflux, while apoA-I did not. A synergistic effect was also obtained when RBC was used as the sink and albumin as shuttle. The previously observed negative association of albumin with coronary artery disease might be linked to reduced cholesterol shuttling that would occur when serum albumin levels are low. PMID:23288948

  20. Serum reserve cholesterol binding capacity (SRCBC): the relative importance of different lipoprotein classes.

    PubMed

    Børresen, A L; Berg, K

    1981-01-01

    Findings by several authors have motivated studies in our laboratory on the relationship between HDL and "serum reserve cholesterol binding capacity" (SRCBC). We found that incubation for 25 hours at 37 degrees C provided optimal conditions for uptake and saturation when 14 mg sonicated and pulverized cholesterol was added to 1 ml serum. Upon separation of serum to which 14C labelled cholesterol had been added, into lipoprotein classes, a higher cpm:protein ratio than expected (from the free cholesterol:protein ratio, assuming isotope exchange exclusively) was found in LDL and the HDL fraction. In a second series of experiments, the different lipoprotein classes were separated prior to addition of 14C-cholesterol. The highest capacity for uptake of labelled cholesterol was found in the HDL fraction. The major part of the 14C-cholesterol appeared in the LDL density area when this HDL fraction was subjected to repeated ultracentrifugation. This suggested that the uptake of added cholesterol by HDL had led to the formation of an altered particle with density characteristics similar to those of LDL particles. This was confirmed by the demonstration of a "new" particle which contained apoA-I, apoA-II, and apoE, but no apoB or Lp(a) antigen. Its electrophoretic mobility was similar to that of HDL. Electron microscopy revealed that this particle is larger than normal HDL. The findings suggest that a sub-population of HDL molecules may be responsible for serum binding of added excess cholesterol. PMID:6794547

  1. Soy milk powder supplemented with phytosterol esters reduced serum cholesterol level in hypercholesterolemia independently of lipoprotein E genotype: a random clinical placebo-controlled trial.

    PubMed

    Dong, Shan; Zhang, Ran; Ji, Ya-Cheng; Hao, Jia-Yin; Ma, Wei-Wei; Chen, Xu-Dong; Xiao, Rong; Yu, Huan-Ling

    2016-08-01

    Phytosterols (PSs) are reported to lower the serum total cholesterol and low-density lipoprotein cholesterol concentrations enriched in some fatty foods, such as margarine. However, these high-fat foods are not very suitable for older people. Soy milk is the favorite food for elderly people in China; therefore, we hypothesized that the consumption of soy milk powder supplemented with PSs would decrease the serum cholesterol levels in older Chinese people independent of the genotypes of apolipoprotein E (ApoE). Mild to moderate hyperlipidemic patients (n = 170) were recruited from different communities and treated with placebo soy milk powder or 3.4 g PS esters-enriched soy milk powder (2.0 g/d free PS in 30 g soy milk powder). The fasting serum lipid profiles at the baseline and after 3 and 6 months of intervention were measured. The ApoE genotype was also determined. After 3 months of PS intervention, the serum lipid profile was not changed significantly in either group. The serum total cholesterol, low-density lipoprotein cholesterol, and non- high-density lipoprotein cholesterol levels decreased by 9.3%, 11.4%, and 12.6%, respectively, in the PS group at the end of the intervention (6 months) compared with the control group, whereas the serum high-density lipoprotein cholesterol and triglyceride levels were not affected significantly. In the PS group, both the ApoE3 and ApoE4 carriers had a similar response to PS consumption. These findings suggested that PS-fortified soy milk powder was effective in lowering the serum cholesterol levels in older Chinese volunteers with mild to moderate hypercholesterolemia in both the ApoE3 and ApoE4 carriers. PMID:27440543

  2. Changes during hibernation in different phospholipid and free and esterified cholesterol serum levels in black bears

    USGS Publications Warehouse

    Chauhan, V.; Sheikh, A.; Chauhan, A.; Tsiouris, J.; Malik, M.; Vaughan, M.

    2002-01-01

    During hibernation, fat is known to be the preferred source of energy. A detailed analysis of different phospholipids, as well as free and esterified cholesterol, was conducted to investigate lipid abnormalities during hibernation. The levels of total phospholipids and total cholesterol in the serum of black bears were found to increase significantly in hibernation as compared with the active state. Both free and esterified cholesterol were increased in the hibernating state in comparison with the active state (P < 0.05). The percentage increase during hibernation was more in free cholesterol (57%) than in esterified cholesterol (27%). Analysis of subclasses of serum phospholipids showed that choline containing phospholipids, i.e., sphingomyelin (SPG) (14%) and phosphatidylcholine (PC) (76%), are the major phospholipids in the serum of bear. The minor phospholipids included 8% of phosphatidylserine (PS) + phosphatidylinositol (PI), while phosphatidylethanolamine (PE) was only 2% of the total phospholipids. A comparison of phospholipid subclasses showed that PC, PS + PI and SPG were significantly increased, while PE was significantly decreased (P < 0.05) in the hibernating state as compared with the active state in black bears. These results suggest that the catabolism of phospholipids and cholesterol is decreased during hibernation in black bears, leading to their increased levels in the hibernating state as compared with the active state. In summary, our results indicate that serum cholesterol and phospholipid fractions (except PE) are increased during hibernation in bears. It is proposed that the increase of these lipids may be due to the altered metabolism of lipoproteins that are responsible for the clearance of the lipids. ?? 2002 E??ditions scientifiques et me??dicales Elsevier SAS and Socie??te?? franc??aise de biochimie et biologie mole??culaire. All rights reserved.

  3. Dietary palmitic and oleic acids exert similar effects on serum cholesterol and lipoprotein profiles in normocholesterolemic men and women.

    PubMed

    Ng, T K; Hayes, K C; DeWitt, G F; Jegathesan, M; Satgunasingam, N; Ong, A S; Tan, D

    1992-08-01

    To compare the effects of dietary palmitic acid (16:0) vs oleic acid (18:1) on serum lipids, lipoproteins, and plasma eicosanoids, 33 normocholesterolemic subjects (20 males, 13 females; ages 22-41 years) were challenged with a coconut oil-rich diet for 4 weeks. Subsequently they were assigned to either a palm olein-rich or olive oil-rich diet followed by a dietary crossover during two consecutive 6-week periods. Each test oil served as the sole cooking oil and contributed 23% of dietary energy or two-thirds of the total daily fat intake. Dietary myristic acid (14:0) and lauric acid (12:0) from coconut oil significantly raised all the serum lipid and lipoprotein parameters measured. Subsequent one-to-one exchange of 7% energy between 16:0 (palm olein diet) and 18:1 (olive oil diet) resulted in identical serum total cholesterol (192, 193 mg/dl), low-density lipoprotein cholesterol (LDL-C) (130, 131 mg/dl), high-density lipoprotein cholesterol (HDL-C) (41, 42 mg/dl), and triglyceride (TG) (108, 106 mg/dl) concentrations. Effects attributed to gender included higher HDL in females and higher TG in males associated with the tendency for higher LDL and LDL/HDL ratios in men. However, both sexes were equally responsive to changes in dietary fat saturation. The results indicate that in healthy, normocholesterolemic humans, dietary 16:0 can be exchanged for 18:1 within the range of these fatty acids normally present in typical diets without affecting the serum lipoprotein cholesterol concentration or distribution. In addition, replacement of 12:0 + 14:0 by 16:0 + 18:1, but especially 16:0 or some component of palm olein, appeared to have a beneficial impact on an important index of thrombogenesis, i.e., the thromboxane/prostacyclin ratio in plasma. PMID:1506599

  4. Concord grape juice attenuates platelet aggregation, serum cholesterol and development of atheroma in hypercholesterolemic rabbits.

    PubMed

    Shanmuganayagam, Dhanansayan; Warner, Thomas F; Krueger, Christian G; Reed, Jess D; Folts, John D

    2007-01-01

    Intake of Concord grape juice (CGJ), rich in polyphenolics, inhibits platelet aggregation (PA), a risk factor for cardiovascular disease (CVD), in normocholesterolemic animals and humans. It is unclear whether CGJ can attenuate hypercholesterolemia-enhanced PA. The effects of daily CGJ consumption on hypercholesterolemia-enhanced PA and the development of atherosclerosis were investigated. Two groups of rabbits (Control and Treated; n=10 each) were fed a hypercholesterolemic diet for 48 days. Treated group then received supplemental CGJ (225mL/day) while Control group received supplemental iso-caloric sugar water for 48 days. Collagen-, collagen+epinephrine- and phorbol-12-myristate-13-acetate-induced whole blood PA responses were measured on Days 0, 48 and 96; total serum cholesterol and blood pressure were also measured. The development of aortic atheroma was quantified at the end. Both groups showed significant increases in PA and serum cholesterol at Day 48. However, at Day 96, Treated group showed significantly lower PA and development of atheroma (30.7+/-3.9% lower (p<0.001)) than Control group; Treated group also had significantly lower total serum cholesterol and blood pressure than Control group. In conclusion, daily consumption of CGJ attenuates hypercholesterolemia-enhanced PA, blood pressure, total serum cholesterol and development of atheroma in rabbits. PMID:16780846

  5. Neonatal dietary cholesterol and alleles of cholesterol 7-alpha hydroxylase affect piglet cerebrum weight, cholesterol concentration, and behavior

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This experiment was designed to test the effect of polymorphism in the cholesterol 7-alpha hydroxylase (CYP7) gene locus, and dietary cholesterol (C) on cerebrum C in neonatal pigs fed sow's milk formulas. Thirty-six pigs (18 male and 18 female) genetically selected for high (HG), or low (LG) plasma...

  6. In Ovo injection of betaine affects hepatic cholesterol metabolism through epigenetic gene regulation in newly hatched chicks.

    PubMed

    Hu, Yun; Sun, Qinwei; Li, Xiaoliang; Wang, Min; Cai, Demin; Li, Xi; Zhao, Ruqian

    2015-01-01

    Betaine is reported to regulate hepatic cholesterol metabolism in mammals. Chicken eggs contain considerable amount of betaine, yet it remains unknown whether and how betaine in the egg affects hepatic cholesterol metabolism in chicks. In this study, eggs were injected with betaine at 2.5 mg/egg and the hepatic cholesterol metabolism was investigated in newly hatched chicks. Betaine did not affect body weight or liver weight, but significantly increased the serum concentration (P < 0.05) and the hepatic content (P < 0.01) of cholesterol. Accordingly, the cholesterol biosynthetic enzyme HMGCR was up-regulated (P < 0.05 for both mRNA and protein), while CYP7A1 which converts cholesterol to bile acids was down-regulated (P < 0.05 for mRNA and P = 0.07 for protein). Moreover, hepatic protein content of the sterol-regulatory element binding protein 1 which regulates cholesterol and lipid biosynthesis, and the mRNA abundance of ATP binding cassette sub-family A member 1 (ABCA1) which mediates cholesterol counter transport were significantly (P < 0.05) increased in betaine-treated chicks. Meanwhile, hepatic protein contents of DNA methyltransferases 1 and adenosylhomocysteinase-like 1 were increased (P < 0.05), which was associated with global genomic DNA hypermethylation (P < 0.05) and diminished gene repression mark histone H3 lysine 27 trimethylation (P < 0.05). Furthermore, CpG methylation level on gene promoters was found to be increased (P < 0.05) for CYP7A1 yet decreased (P < 0.05) for ABCA1. These results indicate that in ovo betaine injection regulates hepatic cholesterol metabolism in chicks through epigenetic mechanisms including DNA and histone methylations. PMID:25860502

  7. In Ovo Injection of Betaine Affects Hepatic Cholesterol Metabolism through Epigenetic Gene Regulation in Newly Hatched Chicks

    PubMed Central

    Hu, Yun; Sun, Qinwei; Li, Xiaoliang; Wang, Min; Cai, Demin; Li, Xi; Zhao, Ruqian

    2015-01-01

    Betaine is reported to regulate hepatic cholesterol metabolism in mammals. Chicken eggs contain considerable amount of betaine, yet it remains unknown whether and how betaine in the egg affects hepatic cholesterol metabolism in chicks. In this study, eggs were injected with betaine at 2.5 mg/egg and the hepatic cholesterol metabolism was investigated in newly hatched chicks. Betaine did not affect body weight or liver weight, but significantly increased the serum concentration (P < 0.05) and the hepatic content (P < 0.01) of cholesterol. Accordingly, the cholesterol biosynthetic enzyme HMGCR was up-regulated (P < 0.05 for both mRNA and protein), while CYP7A1 which converts cholesterol to bile acids was down-regulated (P < 0.05 for mRNA and P = 0.07 for protein). Moreover, hepatic protein content of the sterol-regulatory element binding protein 1 which regulates cholesterol and lipid biosynthesis, and the mRNA abundance of ATP binding cassette sub-family A member 1 (ABCA1) which mediates cholesterol counter transport were significantly (P < 0.05) increased in betaine-treated chicks. Meanwhile, hepatic protein contents of DNA methyltransferases 1 and adenosylhomocysteinase-like 1 were increased (P < 0.05), which was associated with global genomic DNA hypermethylation (P < 0.05) and diminished gene repression mark histone H3 lysine 27 trimethylation (P < 0.05). Furthermore, CpG methylation level on gene promoters was found to be increased (P < 0.05) for CYP7A1 yet decreased (P < 0.05) for ABCA1. These results indicate that in ovo betaine injection regulates hepatic cholesterol metabolism in chicks through epigenetic mechanisms including DNA and histone methylations. PMID:25860502

  8. Transition diseases in grazing dairy cows are related to serum cholesterol and other analytes.

    PubMed

    Sepúlveda-Varas, Pilar; Weary, Daniel M; Noro, Mirela; von Keyserlingk, Marina A G

    2015-01-01

    The objectives of this study were to describe the incidence of postpartum disease and to evaluate the association with serum cholesterol concentrations during the first 3 weeks after calving in grazing dairy cows. The association between non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), calcium and postpartum diseases was also evaluated. A total of 307 Holstein dairy cows from 6 commercial grazing herds in Osorno, Chile, were monitored from calving until 21 days in milk. Cases of retained placenta, clinical hypocalcemia and clinical mastitis were recorded by the farmer using established definitions. Twice weekly, cows were evaluated for metritis by the same veterinarian based on vaginal discharge and body temperature. Postpartum blood samples were collected weekly and analyzed for serum concentrations of cholesterol, NEFA, BHBA and calcium. Cows were considered as having subclinical ketosis if BHBA >1.2 mmol/L, and subclinical hypocalcemia if calcium <2.0 mmol/L in any of the 3 weekly samples. Overall, 56% of the cows studied developed at least one clinical or subclinical disease after calving. Incidence of individual diseases was 8.8% for retained placenta, 4.2% for clinical hypocalcemia, 11.7% for clinical mastitis, 41.1% for metritis, 19.9% for subclinical hypocalcemia and 16.6% for subclinical ketosis. Lower postpartum cholesterol in cows was associated with developing severe metritis or having more than one clinical disease after calving. For every 0.4 mmol/L decrease in serum cholesterol cows were nearly twice as likely to be diagnosed with multiple clinical diseases after calving. Higher BHBA concentrations and lower calcium concentrations during week 1 were associated with severe cases of metritis. Low serum calcium concentration during week 1 was also associated with developing more than one clinical disorder after calving. In conclusion, the incidence of postpartum diseases can be high even in grazing herds and lower serum cholesterol

  9. Transition Diseases in Grazing Dairy Cows Are Related to Serum Cholesterol and Other Analytes

    PubMed Central

    2015-01-01

    The objectives of this study were to describe the incidence of postpartum disease and to evaluate the association with serum cholesterol concentrations during the first 3 weeks after calving in grazing dairy cows. The association between non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), calcium and postpartum diseases was also evaluated. A total of 307 Holstein dairy cows from 6 commercial grazing herds in Osorno, Chile, were monitored from calving until 21 days in milk. Cases of retained placenta, clinical hypocalcemia and clinical mastitis were recorded by the farmer using established definitions. Twice weekly, cows were evaluated for metritis by the same veterinarian based on vaginal discharge and body temperature. Postpartum blood samples were collected weekly and analyzed for serum concentrations of cholesterol, NEFA, BHBA and calcium. Cows were considered as having subclinical ketosis if BHBA >1.2 mmol/L, and subclinical hypocalcemia if calcium <2.0 mmol/L in any of the 3 weekly samples. Overall, 56% of the cows studied developed at least one clinical or subclinical disease after calving. Incidence of individual diseases was 8.8% for retained placenta, 4.2% for clinical hypocalcemia, 11.7% for clinical mastitis, 41.1% for metritis, 19.9% for subclinical hypocalcemia and 16.6% for subclinical ketosis. Lower postpartum cholesterol in cows was associated with developing severe metritis or having more than one clinical disease after calving. For every 0.4 mmol/L decrease in serum cholesterol cows were nearly twice as likely to be diagnosed with multiple clinical diseases after calving. Higher BHBA concentrations and lower calcium concentrations during week 1 were associated with severe cases of metritis. Low serum calcium concentration during week 1 was also associated with developing more than one clinical disorder after calving. In conclusion, the incidence of postpartum diseases can be high even in grazing herds and lower serum cholesterol

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  12. Dependence of the effects of dietary cholesterol and experimental conditions on serum lipids in man. III. The effect on serum cholesterol of removal of eggs from the diet of free-living habitually egg-eating people.

    PubMed

    Bronsgeest-Schoute, D C; Hermus, R J; Dallinga-Thie, G M; Hautvast, J G

    1979-11-01

    Forty-four healthy free living volunteers were used to study the effect of the removal of eggs from a habitual egg-rich diet. The subjects, recruited by advertising, normally consumed at least 1 egg per day. During the 3-week experimental period they were not allowed to eat any eggs or products containing large amounts of eggs, except cakes and tarts. Elimination of eggs from a habitual egg-rich diet did result in a small but significant decrease in serum cholesterol levels in all subjects. No correlation could be demonstrated between changes in serum cholesterol levels and the age of the subjects and between changes in serum cholesterol levels and the numbers of eggs eaten per week before the experimental period. A significant negative correlation was found between changes in serum cholesterol levels and the Quételet index for obesity and between changes in serum cholesterol levels and the serum cholesterol levels before the experimental period. The results indicate that a very variable response is present in a human population toward dietary cholesterol. More research seems to be necessary to describe and select the population of hyperresponders, the subjects who are more sensitive to changes in dietary cholesterol, and the hyporesponders. The results moreover indicate that effects of dietary changes in a free-living population are much smaller than can be accomplished in populations under controlled conditions. PMID:495535

  13. Determination of total cholesterol in serum by liquid chromatography-isotope dilution mass spectrometry.

    PubMed

    Kock, R; Delvoux, B; Greiling, H

    1997-10-01

    We have developed a liquid chromatography-isotope dilution mass spectrometry procedure to quantify total cholesterol in serum. A particle-beam interface was used for coupling the liquid chromatograph and the mass spectrometer. After electron impact ionization the ions m/z = 386 and m/z = 389 were used for selective ion monitoring of cholesterol and the internal standard [25,26,27-(13)C]cholesterol. The sample preparation steps required for serum materials are alkaline hydrolysis and an extraction of the cholesterol into the cyclohexane phase. Imprecision for the determination of cholesterol in control materials is typically <1.0%. The deviation from the certified reference values was <0.75% for all control materials tested. A method comparison of the results obtained by this method with those obtained by gas chromatography-isotope dilution mass spectrometry for n = 28 pooled human sera derived from samples analyzed in our routine laboratory did not show differences >2.5%. PMID:9342010

  14. Effect of dietary karaya saponin on serum and egg yolk cholesterol in laying hens.

    PubMed

    Afrose, S; Hossain, M S; Tsujii, H

    2010-12-01

    1. The objective of the study was to investigate the effect of dietary karaya saponin on cholesterol deposition in laying hens. 2. A total of 40 Boris Brown hens were randomly assigned at 20 weeks of age to 4 treatment groups and fed on diets supplemented with 0 (control), 25, 50 or 75 mg/kg karaya saponin for an 8-week experimental period. 3. After 8 weeks of dietary supplementation, karaya-saponin-treated groups had significantly lower serum cholesterol (23·0%) and triglycerides but increased high density lipoproteins cholesterol concentration than controls, irrespective of karaya saponin content in the diet. Egg yolk cholesterol and triglycerides were also significantly reduced by dietary karaya saponin. Hepatic cholesterol and triglycerides were significantly reduced by karaya saponin but bile acids concentration in the faeces and liver were significantly increased by karaya saponin. The concentrations of oleic, linoleic and linolenic acids in the yolk were greater in hens receiving karaya saponin than in controls. Karaya saponin significantly increased egg production, feed efficiency and yolk colour compared with controls. Karaya saponin tended to increase egg weight, feed consumption, Haugh units, albumen weight and yolk index. 4. In conclusion, karaya saponin is a potential agent for reducing yolk cholesterol concentration together with an overall increase of production performance and improvement in egg quality. PMID:21161787

  15. Effect of a multivitamin preparation supplemented with phytosterol on serum lipids and infarct size in rats fed with normal and high cholesterol diet

    PubMed Central

    2013-01-01

    Background Although complex multivitamin products are widely used as dietary supplements to maintain health or as special medical food in certain diseases, the effects of these products were not investigated in hyperlipidemia which is a major risk factor for cardiovascular diseases. Therefore, here we investigated if a preparation developed for human use containing different vitamins, minerals and trace elements enriched with phytosterol (VMTP) affects the severity of experimental hyperlipidemia as well as myocardial ischemia/reperfusion injury. Methods Male Wistar rats were fed a normal or cholesterol-enriched (2% cholesterol + 0.25% cholate) diet for 12 weeks to induce hyperlipidemia. From week 8, rats in both groups were fed with a VMTP preparation or placebo for 4 weeks. Serum triglyceride and cholesterol levels were measured at week 0, 8 and 12. At week 12, hearts were isolated, perfused according to Langendorff and subjected to a 30-min coronary occlusion followed by 120 min reperfusion to measure infarct size. Results At week 8, cholesterol-fed rats showed significantly higher serum cholesterol level as compared to normal animals, however, serum triglyceride level did not change. VMTP treatment significantly decreased serum cholesterol level in the hyperlipidemic group by week 12 without affecting triglyceride levels. However, VMTP did not show beneficial effect on infarct size. The inflammatory marker hs-CRP and the antioxidant uric acid were also not significantly different. Conclusions This is the first demonstration that treatment of hyperlipidemic subjects with a VMTP preparation reduces serum cholesterol, the major risk factor for cardiovascular disease; however, it does not provide cardioprotection. PMID:24063587

  16. Effects of palm and sunflower oils on serum cholesterol and fatty liver in rats.

    PubMed

    Go, Ryeo-Eun; Hwang, Kyung-A; Kim, Ye-Seul; Kim, Seung-Hee; Nam, Ki-Hoan; Choi, Kyung-Chul

    2015-03-01

    Palm oil is a common cooking ingredient used in the commercial food industry as the second largest consumed vegetable oil in the world. Because of its lower cost and highly saturated nature, it usually maintains a solid form at room temperature and is used as a cheap substitute for butter. However, there has been a growing health concern about palm oil because of the link between dietary fats and coronary heart disease. Palm oil contains ∼49% saturated fat, a relatively high concentration compared with other vegetable oils. Consequently, high intakes of saturated fat from palm oil induce a larger increase in plasma concentrations of total cholesterol and low-density lipoproteins. In the present study, we examined the hyperlipidemia of palm oil and the risk of cardiovascular disease (CVD) using a rat model in comparison with sunflower oil with a relatively low level of saturated fat. On in vivo examination using Sprague-Dawley (SD) rats for 22 days, there were no significant differences in serum lipid levels, suggesting that palm oil may not cause hyperlipidemia and elevate CVD risk. However, liver samples obtained from SD rats fed with palm oil showed a lot of large lipid inclusions stained with the Oil Red O working solution, but not much lipid accumulation was observed in rats treated with sunflower oil. In addition, lipid accumulation in the mixed oil group fed the combination of palm and sunflower (1:1) oil was shown to be at an intermediary level between the palm oil group and sunflower oil group. Taken together, these results indicate that palm oil, a highly saturated form of vegetable oil, may induce dysfunction of the liver lipid metabolism before affecting serum lipid levels. On the other hand, sunflower oil, a highly unsaturated vegetable oil, was shown to be well metabolized in liver. PMID:25393932

  17. The Effect of a Three-Month Physical Fitness Program on Serum Free Cholesterol.

    ERIC Educational Resources Information Center

    Montgomery, D. L.; Ismail, A. H.

    This study investigates the effect of a three-month physical fitness program on serum-free cholesterol concentration in four age and fitness adult groups. Twenty-four men were divided into the following groups: (a) young, low-fit; (b) old, low-fit; (c) young, high-fit; and (d) old, high-fit. All subjects had normal resting glucose and triglyceride…

  18. Effect of egg white on serum cholesterol concentration in young women.

    PubMed

    Asato, L; Wang, M F; Chan, Y C; Yeh, S H; Chung, H M; Chung, S Y; Chida, S; Uezato, T; Suzuki, I; Yamagata, N; Kokubu, T; Yamamoto, S

    1996-04-01

    In a previous study we observed favorable effects of egg white on serum lipids in rats and mice. The present study was designed to elucidate these effects in 24 female university students with moderate hypercholesterolemia. About 30% of total protein was supplied with egg white, tofu or cheese. The experiment was conducted for a complete menstruation cycle of each subject. Lipid intake was about 30% of total energy intake. The energy intake of each subject was constant throughout the experiment. Body weight was measured every morning. Daily activity was measured by a pedometer. Blood was withdrawn after an overnight fast on the first, 15th and last days and serum lipids were measured. Body weight was measured every morning. Daily activity was measured by a pedometer. Blood was withdrawn after an overnight fast on the first, 15th and last days and serum lipids were measured. Body weight and daily activity were maintained in all the groups throughout the experiment. The egg white group showed a similar decrease in the total cholesterol (Total-C) concentration but a greater increase of high-density lipoprotein cholesterol (HDL-C) concentration as compared to the tofu group and a greater decrease in Total-C and low-density lipoprotein cholesterol (LDL-C) concentrations and a greater increase in the HDL-C concentration as compared to the cheese group (p < 0.05). The results indicate the favorable effects of egg white in the control of hypercholesterolemia. PMID:8780967

  19. Comparative Study of Tomato and Tomato Paste Supplementation on the Level of Serum Lipids and Lipoproteins Levels in Rats Fed With High Cholesterol

    PubMed Central

    Khayat Nouri, Mir Hadi; Namvaran Abbas Abad, Ali

    2013-01-01

    Background Hypercholesterolemia is one of the risk factors of cardiovascular diseases. Increased blood cholesterol affects general health and increases mortality due to cardiovascular disease. Poor nutrition increases LDL cholesterol and decreases LDL receptor activities in the liver. Scientists have shown that consumption of antioxidants can reduce hypercholesterolemia and proved benefits of fruit and vegetables. Tomato reduces oxidative stress by increasing serum total antioxidant level. Objectives This study compared the tomato and tomato paste supplementation on the level of serum lipids and lipoproteins in rats fed with high cholesterol. Materials and Methods In this study, four male rat groups (10 rats per group) were used. Control group received basal diet, second group received basal diet and 2% cholesterol (Chol), third and fourth groups received basal diet, 2% cholesterol tomato and tomato paste respectively (20 percent of the diet) for a month. Then serum TC, LDL, HDL and TG were measured. Results Results showed that in Chol group, all lipids increased significantly (P < 0.05) except HDL compared to the control group. Tomato and tomato paste supplementation decreased TC, LDL and TG concentration significantly (P < 0.05) compared to Chol group. Tomato paste had the higher effect on lipids decreasing than tomato. Conclusions Decreases of TC, LDL and TG may be related to tomato antioxidant effect. This course in human required more investigations. PMID:24082999

  20. Effects of stent design and serum cholesterol level on the restenosis rate in atherosclerotic rabbits.

    PubMed

    Tominaga, R; Harasaki, H; Sutton, C; Emoto, H; Kambic, H; Hollman, J

    1993-11-01

    We investigated the effect of serum cholesterol level and stent design on the restenosis rate within the stent after balloon angioplasty and stent implantation using atherosclerotic rabbits. Two types of nickel/titanium stents with gaps (open stent) and without gaps (closed stent) between the wire coils were implanted into the aorta of the rabbits 10 weeks after atherosclerosis had been induced using a standard high cholesterol diet and balloon abrasion. Each rabbit had an open stent and a closed stent implanted into the infrarenal abdominal aorta. Between these two stents a control segment of the aorta was treated with angioplasty alone. The animals were divided into two groups according to the diet protocol as follows: in group I (n = 9) a high cholesterol diet was stopped after stent implantation; in group II (n = 10) a high cholesterol diet was maintained after stent implantation. Digital subtraction angiograms were obtained every 4 weeks for up to 24 weeks and the narrowest diameter of the arterial segments within each stent and in the segment between stents was measured. The diameter narrowing within the closed stent was greater in the high cholesterol group compared with the low cholesterol group: 12 weeks (2.57 +/- 0.09 mm in group I vs 2.14 +/- 0.15 mm in group II, mean +/- S.E., p < 0.05); 16 weeks (2.55 +/- 0.09 mm vs 2.14 +/- 0.12 mm, p < 0.05); 20 weeks (2.59 +/- 0.06 mm vs 1.98 +/- 0.12 mm, p < 0.01); and 24 weeks (2.45 +/- 0.11 mm vs 2.01 +/- 0.11 mm, p < 0.05). No significant differences in the narrowest diameter of the arterial segments were observed between high and low cholesterol groups in the angioplasty alone areas or within the open stents. There was a significant difference in the narrowest diameter between stents with versus those without gaps (at 12, 16, and 20 weeks poststenting in group I and at 4, 8, 12, 16, 20, and 24 weeks in group II). Thus the stent with the least metal is correlated with less stenosis and intimal hyperplasia. From

  1. Common and Rare Gene Variants Affecting Plasma LDL Cholesterol

    PubMed Central

    Burnett, John R; Hooper, Amanda J

    2008-01-01

    The plasma level of LDL cholesterol is clinically important and genetically complex. LDL cholesterol levels are in large part determined by the activity of LDL receptors (LDLR) in the liver. Autosomal dominant familial hypercholesterolaemia (FH) – with its high LDL cholesterol levels, xanthomas, and premature atherosclerosis – is caused by mutations in either the LDLR or in APOB – the protein in LDL recognised by the LDLR. A third, rare form – autosomal recessive hypercholesterolaemia – arises from mutations in the gene encoding an adaptor protein involved in the internalisation of the LDLR. A fourth variant of inherited hypercholesterolaemia was recently found to be associated with missense mutations in PCSK9, which encodes a serine protease that degrades LDLR. Whereas the gain-of-function mutations in PCSK9 are rare, a spectrum of more frequent loss-of-function mutations in PCSK9 associated with low LDL cholesterol levels has been identified in selected populations and could protect against coronary heart disease. Heterozygous familial hypobetalipoproteinaemia (FHBL) – with its low LDL cholesterol levels and resistance to atherosclerosis – is caused by mutations in APOB. In contrast to other inherited forms of severe hypocholesterolaemia such as abetalipoproteinaemia - caused by mutations in MTP - and homozygous FHBL, a deficiency of PCSK9 appears to be benign. Rare variants of NPC1L1, the gene encoding the putative intestinal cholesterol receptor, have shown more modest effects on plasma LDL cholesterol than PCSK9 variants, similar in magnitude to the effect of common APOE variants. Taken together, these findings indicate that heritable variation in plasma LDL cholesterol is conferred by sequence variation in various loci, with a small number of common and multiple rare gene variants contributing to the phenotype. PMID:18566665

  2. Effects of Pyrroloquinoline Quinone Disodium Salt Intake on the Serum Cholesterol Levels of Healthy Japanese Adults.

    PubMed

    Nakano, Masahiko; Kawasaki, Yuuki; Suzuki, Naoko; Takara, Tsuyoshi

    2015-01-01

    Pyrroloquinoline quinone (PQQ) is a water-soluble quinone compound that has a strong anti-oxidant capacity. A previous study in rats fed a PQQ-depleted diet showed that elevated levels of serum triglyceride (TG) decreased after PQQ supplementation. However, there is only one study reporting the effects of PQQ on serum lipid levels, such as those of TG and cholesterol, in humans. In this study, the effects of PQQ disodium salt (BioPQQ™) on serum TG and cholesterol levels in humans after 6 and 12 wk of treatment at an oral dosage of 20 mg/d were examined. This trial was conducted according to a randomized, placebo-controlled, double-blinded protocol. A total of 29 healthy Japanese adults, ranging from 40 to 57 y old, with normal to moderately high TG levels (110-300 mg/dL) as measured by a recent blood examination, were included in this study. In eleven volunteers out of 29, serum low-density lipoprotein cholesterol (LDL-chol) levels at baseline were high (≥140 mg/dL). After 12 wk, the mean serum TG levels had not changed; however, a marginally significant decrease in the mean LDL-chol (from 136.1 to 127.0 mg/dL) was observed in the PQQ group. In the stratification analysis of the high LDL-chol subgroup (baseline LDL-chol level ≥140 mg/dL), the mean LDL-chol levels decreased significantly from the baseline values in the PQQ group compared to the placebo group. Our study findings suggest that PQQ suppressed the LDL-chol level, which is an important finding, because a high level of this lipid is a risk factor for various lifestyle-related diseases. PMID:26226960

  3. The Affinity of Cholesterol for Different Phospholipids Affects Lateral Segregation in Bilayers.

    PubMed

    Engberg, Oskar; Hautala, Victor; Yasuda, Tomokazu; Dehio, Henrike; Murata, Michio; Slotte, J Peter; Nyholm, Thomas K M

    2016-08-01

    Saturated and unsaturated phospholipids (PLs) can segregate into lateral domains. The preference of cholesterol for saturated acyl chains over monounsaturated, and especially polyunsaturated ones, may also affect lateral segregation. Here we have studied how cholesterol influenced the lateral segregation of saturated and unsaturated PLs, for which cholesterol had a varying degree of affinity. The fluorescence lifetime of trans-parinaric acid reported the formation of ordered domains (gel or liquid-ordered (lo)) in bilayers composed of different unsaturated phosphatidylcholines, and dipalmitoyl-phosphatidylcholine or n-palmitoyl-sphingomyelin, in the presence or absence of cholesterol. We observed that cholesterol facilitated lateral segregations and the degree of facilitation correlated with the relative affinity of cholesterol for the different PLs in the bilayers. Differential scanning calorimetry and (2)H nuclear magnetic resonance showed that cholesterol increased the thermostability of both the gel and lo-domains. Increased number of double bonds in the unsaturated PL increased the order in the lo-domains, likely by enriching the ordered domains in saturated lipids and cholesterol. This supported the conclusions from the trans-parinaric acid experiments, and offers insight into how cholesterol facilitated lateral segregation. In conclusion, the relative affinity of cholesterol for different PLs appears to be an important determinant for the formation of ordered domains. Our data suggests that knowledge of the affinity of cholesterol for the different PLs in a bilayer allows prediction of the degree to which the sterol promotes lo-domain formation. PMID:27508438

  4. Micellar lipid composition profoundly affects LXR-dependent cholesterol transport across CaCo2 cells.

    PubMed

    Petruzzelli, Michele; Groen, Albert K; van Erpecum, Karel J; Vrins, Carlos; van der Velde, Astrid E; Portincasa, Piero; Palasciano, Giuseppe; van Berge Henegouwen, Gerard P; Lo Sasso, Giuseppe; Morgano, Annalisa; Moschetta, Antonio

    2009-04-17

    Intraluminal phospholipids affect micellar solubilization and absorption of cholesterol. We here study cholesterol transport from taurocholate-phospholipid-cholesterol micelles to CaCo2 cells, and associated effects on ABC-A1 mediated cholesterol efflux. Micellar incorporation of egg-yolk-phosphatidylcholine markedly increased apical retention of the sterol with decreased expression of ABC-A1, an effect that is prevented by synthetic liver X receptor (LXR) or retinoid X receptor (RXR) agonists. On the other hand, incorporation of lyso-phosphatidylcholine (LysoPC) increased ABC-A1-HDL-dependent basolateral cholesterol efflux, an effect that is abated when LXR is silenced. Thus, the modulation of cholesterol metabolism via intraluminal phospholipids is related to the activity of the oxysterol nuclear receptor LXR. PMID:19303409

  5. Reference Ranges for Serum Total Cholesterol, HDL-Cholesterol, LDL-Cholesterol, and VLDL-Cholesterol and Triglycerides in Healthy Iranian Ahvaz Population.

    PubMed

    Jalali, Mohammad Taha; Honomaror, Abdolhosain Mosavi; Rekabi, Abdolkarim; Latifi, Mahmod

    2013-07-01

    Cardiovascular diseases (CVD) are recognized as major mortality causes and imposes tremendously heavy socio-economic burden worldwide. A vast variety of risk factors have been introduced in the literature known to enhance the incidence of CVD, such as hyperlipidemia. Therefore in order to make an accurate clinical decision it is essential to have appropriate reference ranges for lipids and lipoprotein particles in a particular population. Healthy female (n = 601) and male (n = 617) cases were randomly selected according to certain exclusion criteria from individuals visiting the major University hospital clinics situated in different part of Ahvaz city, Iran, from June 2010 to December 2010. Fasting blood samples (10 ml) were collected and analyzed for total cholesterol, total triglyceride and HDL-C employing enzymatic assays of CHOD-PAP, GPO-PAP and homogenous methods respectively. The samples were obtained such to include the ethnic populations of Persian, Arab. Lore leaving in this city. The data were analyzed statistically by SPSS-18 software. The obtained results were analyzed then age ethnic-wise and reference ranges (mean ± 1SD) were calculated. Remarkable differences between the obtained results for our population with other nations were seen. Also ethnic difference for HDL-C among our cases was noted. The observed significant differences among different nations and ethnicities emphasizes the need for nation-specific, local reference ranges for lipids and lipoproteins particles, to be established. PMID:24426224

  6. Body Fatness and Risk for Elevated Blood Pressure, Total Cholesterol, and Serum Lipoprotein Ratios in Children and Adolescents.

    ERIC Educational Resources Information Center

    Williams, Daniel P.; And Others

    1992-01-01

    Examines the relationship between body fat percent and risk for elevated blood pressure, serum total cholesterol, and serum lipoprotein ratios in 1,230 African-American and 2,090 white 5-18 year olds (1,667 males and 1,653 females). Results support body fatness standards in children and adolescents as cardiovascular risk factors. (SLD)

  7. Gene Transfection in High Serum Levels: Case Studies with New Cholesterol Based Cationic Gemini Lipids

    PubMed Central

    Misra, Santosh K.; Biswas, Joydeep; Kondaiah, Paturu; Bhattacharya, Santanu

    2013-01-01

    Background Six new cationic gemini lipids based on cholesterol possessing different positional combinations of hydroxyethyl (-CH2CH2OH) and oligo-oxyethylene -(CH2CH2O)n- moieties were synthesized. For comparison the corresponding monomeric lipid was also prepared. Each new cationic lipid was found to form stable, clear suspensions in aqueous media. Methodology/Principal Findings To understand the nature of the individual lipid aggregates, we have studied the aggregation properties using transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential measurements and X-ray diffraction (XRD). We studied the lipid/DNA complex (lipoplex) formation and the release of the DNA from such lipoplexes using ethidium bromide. These gemini lipids in presence of a helper lipid, 1, 2-dioleoyl phophatidyl ethanol amine (DOPE) showed significant enhancements in the gene transfection compared to several commercially available transfection agents. Cholesterol based gemini having -CH2-CH2-OH groups at the head and one oxyethylene spacer was found to be the most effective lipid, which showed transfection activity even in presence of high serum levels (50%) greater than Effectene, one of the potent commercially available transfecting agents. Most of these geminis protected plasmid DNA remarkably against DNase I in serum, although the degree of stability was found to vary with their structural features. Conclusions/Significance -OH groups present on the cationic headgroups in combination with oxyethylene linkers on cholesterol based geminis, gave an optimized combination of new genera of gemini lipids possessing high transfection efficiency even in presence of very high percentage of serum. This property makes them preferential transfection reagents for possible in vivo studies. PMID:23861884

  8. Association of lecithin-cholesterol acyltransferase activity measured as a serum cholesterol esterification rate and low-density lipoprotein heterogeneity with cardiovascular risk: a cross-sectional study.

    PubMed

    Tani, Shigemasa; Takahashi, Atsuhiko; Nagao, Ken; Hirayama, Atsushi

    2016-06-01

    The cholesterol-esterifying enzyme, lecithin-cholesterol acyltransferase (LCAT), is believed to play a key role in reverse cholesterol transport. However, recent investigations have demonstrated that higher LCAT activity levels increase the formation of triglyceride (TG)-rich lipoproteins (TRLs) and atherogenesis. We hypothesized that higher LCAT activity measured as a serum cholesterol esterification rate by the endogenous substrate method might increase the formation of TRLs and thereby alter low-density lipoprotein (LDL) heterogeneity. The estimated LDL particle size [relative LDL migration (LDL-Rm)] was measured by polyacrylamide gel electrophoresis with the LipoPhor system (Joko, Tokyo, Japan) in 538 consecutive patients with at least risk factor for atherosclerosis. Multivariate regression analysis after adjustments for traditional risk factors identified elevated TRL-related marker (TG, remnant-like particle cholesterol, apolipoprotein C-II, and apolipoprotein C-III) levels as independent predictors of smaller-sized LDL particle size, both in the overall subject population and in the subset of patients with serum LDL cholesterol levels of <100 mg/dL. Area under the receiver operating characteristic curve of the LCAT activity (0.79; sensitivity 60 %; specificity 84.8 %) was observed for the evaluation of the indicators of an LDL-Rm value of ≥0.40, which suggests the presence of large amounts of small-dense LDL. The results lend support to the hypothesis that increased LCAT activity may be associated with increased formation of TRLs, leading to a reduction in LDL particle size. Therefore, to reduce the risk of atherosclerotic cardiovascular disease, it may be of importance to pay attention not only to a quantitative change in the serum LDL-C, but also to the LCAT activity which is possibly associated with LDL heterogeneity. PMID:25894629

  9. Enterostatin deficiency increases serum cholesterol but does not influence growth and food intake in mice.

    PubMed

    Miller, Rita; D'Agostino, Dymphna; Erlanson-Albertsson, Charlotte; Lowe, Mark E

    2009-10-01

    A pentapeptide released from procolipase, enterostatin, selectively attenuates dietary fat intake when administered peripherally or centrally. Enterostatin may act through the afferent vagus nerve and in the hypothalamus and amygdala, primarily in the central nucleus of the amygdala. To investigate the physiological role of endogenous enterostatin, we created an enterostatin-deficient, colipase-sufficient (Ent(-/-)) mouse. Ent(-/-) mice are viable, normally active, and fertile. They exhibit normal growth on low-fat and high-fat diets. Furthermore, Ent(-/-) mice develop diet-induced obesity, as do Ent(+/+) mice, and have normal responses to a two-macronutrient choice diet and to a switch from a high-fat to a low-fat diet. Levels of total serum (P = 0.004) and non-HDL (P cholesterol were higher and levels of HDL cholesterol (P = 0.01) were lower in Ent(-/-) than in wild-type mice. To determine whether enterostatin contributed to the decreased survival or whether colipase deficiency was the sole contributor, we administered enterostatin to procolipase-deficient (Clps(-/-)) mouse pups. Enterostatin significantly improved survival (P cholesterol metabolism. PMID:19622781

  10. Association of dietary fiber intake with serum total cholesterol and low density lipoprotein cholesterol levels in Urban Asian-Indian adults with type 2 diabetes

    PubMed Central

    Narayan, Shreya; Lakshmipriya, Nagarajan; Vaidya, Ruchi; Bai, Mookambika Ramya; Sudha, Vasudevan; Krishnaswamy, Kamala; Unnikrishnan, Ranjit; Anjana, Ranjit Mohan; Mohan, Viswanathan

    2014-01-01

    Context: There is little data correlating dietary fibre (DF) intake and cardiovascular risk in Asian Indians with diabetes. Aim: To assess the DF intake and its association with lipid profile (total serum cholesterol and low density lipoprotein [LDL] - cholesterol levels) in urban Asian Indians with diabetes. Subjects and Methods: Dietary assessment using validated Food Frequency Questionnaire was conducted in 1191 free-living adults with known diabetes in the Chennai Urban Rural Epidemiology Study. Subjects taking medication for dyslipidemia, and those with cardiovascular disease and implausible energy intake (n = 262) were excluded, leaving 929 participants. Anthropometric and relevant biochemical parameters were measured using standardized techniques. Results: Diabetic individuals who consumed DF < median intake (29 g/day) had a higher prevalence of hypercholesterolemia (49.5% vs. 40.1% [P = 0.01]) and higher LDL cholesterol (46.2% vs. 35.5% [P = 0.001]) than those in the > median intake of DF group. The risk of hypercholesterolemia (odds ratio [OR] =1.38 [95% confidence interval [CI]: 1.02–1.85], P = 0.04), and high LDL cholesterol (OR: 1.43 [95% CI: 1.06–1.94], P = 0.02) was higher among those whose DF intake was less than the median. Serum triglycerides and high density lipoprotein cholesterol were not associated with DF intake. The main sources of DF were vegetables and legumes. Conclusion: In urban Asian Indians with diabetes, lower DF intake is positively related to total cholesterol and LDL cholesterol levels. PMID:25285277

  11. Serum cholesterol levels in middle-aged euthyroid subjects with positive thyroid peroxidase antibodies

    PubMed Central

    Kang, Dongmei; Yin, Quhua; Yan, Xiaoli; Song, Huaidong; Gao, Guanqi; Liang, Jun; Zhao, Jiajun

    2015-01-01

    Objective: This study was designed to investigate serum cholesterol levels in middle-aged euthyroid subjects with positive thyroid peroxidase antibodies (TPOAbs). Methods: We screened 1607 euthyroid subjects aged 35-65 years old. All the subjects were divided into 2 groups (i.e., TPOAb-positive group, n=205; TPOAb-negative group, n=1402) according to the level of TPOAb. The subjects were then subgrouped according to serum thyroid stimulating hormone (TSH) levels; those with a TSH level of 0.3-0.99 mIU/L, 1.0-1.89 mIU/L, and 1.9-4.80 mIU/L were classified into the low-normal, mid-range, and high-normal TSH subgroups, respectively). Each TSH group further subdivided into TPOAb-positive and TPOAb-negative subgroup. Data regarding the subjects’ height, body weight, blood pressure, and levels of serum TSH, TPOAb, fasting plasma glucose, total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) were collected. Results: Compared with TPOAb-negative subjects, TPOAb-positive patients had higher levels of TSH, TC, and HDL-C (P=0.001, P=0.012, and P=0.049 respectively) with a tendency for increased LDL-C levels (P=0.053). In the low-normal TSH subgroup, subjects with and without TPOAb had similar levels of TSH, TC, HDL-C, and LDL-C (P>0.05). In mid-range TSH subgroup, TPOAb-positive patients had higher HDL-C levels compared to TPOAb-negative subjects (P=0.008) and a tendency for increased TC levels (P=0.121). In the high-normal TSH subgroup, TPOAb-positive patients had higher TSH and TC levels compared to TPOAb-negative subjects (P<0.001 and P=0.046 respectively). Conclusions: High TPOAb levels above the normal range appears in euthyroid population, dyslipidemia have begun. PMID:26885115

  12. Serum cholesterol reduction efficacy of biscuits with added plant stanol ester.

    PubMed

    Kriengsinyos, Wantanee; Wangtong, Ajima; Komindr, Surat

    2015-01-01

    This study's aim was to test the low-density lipoprotein cholesterol- (LDL-c-) lowering efficacy of biscuits containing 2 g of plant stanols, which corresponded to 3.4 g of plant stanol esters. The biscuit is a new food format that can be consumed as a snack. In a double-blind, placebo-controlled parallel design study, 119 mildly to moderately hypercholesterolemic volunteers were randomized to plant stanol or control groups. Subjects were comparable in age, gender, lipid profiles, and body mass index. They consumed a control biscuit once a day for a two-week period, followed by a four-week intervention period that either had a plant stanol ester biscuit or a control. During the habitual diet, one biscuit per day was consumed at any time that subjects wished. Serum lipid profiles were measured at the first day of run-in, at baseline, and at the study's end. Compared to the control, the total cholesterol (TC), LDL-c, and the LDL-to-high-density lipoprotein (LDL/HDL) ratio had serum reductions of 4.9%, 6.1%, and 4.3%, respectively, and were observed after 4 weeks of biscuit consumption with added plant stanols (P < 0.05). A significantly higher reduction in LDL-c (8.9%) and LDL/HDL ratio (11.4%) was measured in those taking a plant stanol biscuit with a meal compared to those who consumed a plant stanol biscuit without other food. In conclusion, incorporating plant stanols into a biscuit is an attractive, convenient, and acceptable way to modestly lower elevated cholesterol concentrations. For optimal efficacy, biscuits should be consumed with a meal as part of a healthy diet. PMID:25861469

  13. Serum Cholesterol Reduction Efficacy of Biscuits with Added Plant Stanol Ester

    PubMed Central

    Kriengsinyos, Wantanee; Wangtong, Ajima; Komindr, Surat

    2015-01-01

    This study's aim was to test the low-density lipoprotein cholesterol- (LDL-c-) lowering efficacy of biscuits containing 2 g of plant stanols, which corresponded to 3.4 g of plant stanol esters. The biscuit is a new food format that can be consumed as a snack. In a double-blind, placebo-controlled parallel design study, 119 mildly to moderately hypercholesterolemic volunteers were randomized to plant stanol or control groups. Subjects were comparable in age, gender, lipid profiles, and body mass index. They consumed a control biscuit once a day for a two-week period, followed by a four-week intervention period that either had a plant stanol ester biscuit or a control. During the habitual diet, one biscuit per day was consumed at any time that subjects wished. Serum lipid profiles were measured at the first day of run-in, at baseline, and at the study's end. Compared to the control, the total cholesterol (TC), LDL-c, and the LDL-to-high-density lipoprotein (LDL/HDL) ratio had serum reductions of 4.9%, 6.1%, and 4.3%, respectively, and were observed after 4 weeks of biscuit consumption with added plant stanols (P < 0.05). A significantly higher reduction in LDL-c (8.9%) and LDL/HDL ratio (11.4%) was measured in those taking a plant stanol biscuit with a meal compared to those who consumed a plant stanol biscuit without other food. In conclusion, incorporating plant stanols into a biscuit is an attractive, convenient, and acceptable way to modestly lower elevated cholesterol concentrations. For optimal efficacy, biscuits should be consumed with a meal as part of a healthy diet. PMID:25861469

  14. Body mass index, serum total cholesterol, and risk of gastric high-grade dysplasia

    PubMed Central

    Huang, Ya-Kai; Kang, Wei-Ming; Ma, Zhi-Qiang; Liu, Yu-Qin; Zhou, Li; Yu, Jian-Chun

    2016-01-01

    Abstract Obesity is related to an increased risk of gastric cardia cancer. However, the influences of excess body weight and serum total cholesterol on the risk of gastric high-grade dysplasia have not been fully characterized. A case–control study was conducted to explore the relationships between body mass index (BMI), serum total cholesterol level, and the risk of gastric high-grade dysplasia in Chinese adults. A total of 893 consecutive patients with gastric high-grade dysplasia (537 men and 356 women) and 902 controls (543 men and 359 women) were enrolled from January 2000 to October 2015. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated, and a multivariate analysis was conducted. After adjusting for age, alcohol consumption, smoking status, family history of gastric cancer or esophageal cancer, and serum total cholesterol level, a BMI ranging from 27.5 to 29.9 was significantly related to an increased risk of gastric high-grade dysplasia in both men (adjusted OR = 1.87, 95% CI = 1.24–2.81) and women (adjusted OR = 2.72, 95% CI = 1.44–5.16). The 2 highest BMI categories (27.5–29.9 and ≥30.0) were identified as risk factors for gastric cardia high-grade dysplasia in both men (BMI = 27.5–29.9: adjusted OR = 1.78, 95% CI = 1.02–3.10; BMI ≥ 30.0: adjusted OR = 2.54, 95% CI = 1.27–5.08) and women (BMI = 27.5–29.9: adjusted OR = 2.88, 95% CI = 1.27–6.55; BMI ≥ 30.0: adjusted OR = 2.77, 95% CI = 1.36–5.64), whereas only a BMI ranging from 27.5 to 29.9 was a risk factor for gastric noncardia high-grade dysplasia in both men (adjusted OR = 1.98, 95% CI = 1.25–3.14) and women (adjusted OR = 2.88, 95% CI = 1.43–5.81). In addition, higher serum total cholesterol was associated with an increased risk of gastric noncardia high-grade dysplasia (adjusted OR = 1.83, 95% CI = 1.25–2.69) in women. Increased BMI was associated with an increased risk

  15. Luteolin and Quercetin Affect the Cholesterol Absorption Mediated by Epithelial Cholesterol Transporter Niemann–Pick C1-Like 1 in Caco-2 Cells and Rats

    PubMed Central

    Nekohashi, Mari; Ogawa, Mana; Ogihara, Takuo; Nakazawa, Kyoko; Kato, Hisanori; Misaka, Takumi; Abe, Keiko; Kobayashi, Shoko

    2014-01-01

    Niemann–Pick C1-Like 1 (NPC1L1) mediates cholesterol absorption, and ezetimibe is a potent NPC1L1 inhibitor applicable for medication of hypercholesterolemia. Epidemiological studies demonstrated that consumption of polyphenols correlates with a decreased risk for atherosclerosis due to their antioxidant effect. This activity can hardly be attributable to the antioxidant activity only, and we hypothesized that polyphenols inhibit intestinal transport of cholesterol. We elucidated the kinetic parameters of intestinal cholesterol absorption, screened several polyphenols for their ability to specifically inhibit intestinal cholesterol absorption, and determined the inhibitory effects of selected flavonoids in vitro and in vivo. The concentration-dependent uptake of cholesterol by Caco-2 cells obeyed a monophasic saturation process. This indicates the involvement of an active-passive transport, i.e., NPC1L1. Parameters of cholesterol uptake by Caco-2 cells were as follows: Jmax, Kt, and Kd were 6.89±2.96 19.03±11.58 µM, and 0.11±0.02 pmol/min/mg protein, respectively. Luteolin and quercetin inhibited cholesterol absorption by Caco-2 cells and human embryonic kidney 293T cells expressing NPC1L1. When preincubated Caco-2 cells with luteolin and quercetin before the assay, cholesterol uptake significantly decreased. The inhibitory effects of these flavonoids were maintained for up to 120 min. The level of inhibition and irreversible effects were similar to that of ezetimibe. Serum cholesterol levels significantly decreased more in rats fed both cholesterol and luteolin (or quercetin), than in those observed in the cholesterol feeding group. As quercetin induced a significant decrease in the levels of NPC1L1 mRNA in Caco-2 cells, the in vivo inhibitory effect may be due to the expression of NPC1L1. These results suggest that luteolin and quercetin reduce high blood cholesterol levels by specifically inhibiting intestinal cholesterol absorption mediated by NPC1L1

  16. [Medical and social medicine correlates of serum cholesterol value during and after inpatient cardiologic rehabilitation--a prospective study].

    PubMed

    Keck, M; Budde, H G

    1999-08-01

    The connection between changes in the serum cholesterol value during and after in-patient cardiological rehabilitation on the one hand and medical and sociomedical variables on the other is investigated. In 162 male and female patients up to 60 years of age undergoing inpatient cardiological rehabilitation under the pension insurance scheme for workers, a significant decrease of serum cholesterol values could be observed between the beginning and the end of cardiological rehabilitation of 24.5 mg% (10.6%), with a subsequent increase of 12.5 mg% (6%) seven months later. Independent of a possible medical antilipemic therapy the group of patients with a positive occupational perspective was found to have better controlled serum cholesterol values than pensioners or those patients with a negative occupational perspective such as unemployment or dismissal. It can be assumed that those patients having a positive occupational perspective are more likely to follow dietetic and/or medical therapeutic regimes. PMID:10507094

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

    PubMed

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

    2012-10-01

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

  18. Exposure to Polymers Reverses Inhibition of Pulmonary Surfactant by Serum, Meconium, or Cholesterol in the Captive Bubble Surfactometer

    PubMed Central

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

    2012-01-01

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

  19. Relation of serum cholesterol, lipid, serotonin and tryptophan levels to severity of depression and to suicide attempts.

    PubMed Central

    Almeida-Montes, L G; Valles-Sanchez, V; Moreno-Aguilar, J; Chavez-Balderas, R A; García-Marín, J A; Cortés Sotres, J F; Hheinze-Martin, G

    2000-01-01

    OBJECTIVE: To determine if there is a relation to low serum cholesterol, lipoprotein, serotonin or tryptophan levels in patients with depression who have recently attempted suicide. DESIGN: Biochemical and behavioural study. SETTING: Inpatient and outpatient treatment at the Instituto Mexicano de Psiquiatría. PARTICIPANTS: Thirty-three patients with a diagnosis of major depressive episode. Eighteen of these patients had attempted suicide in the month before the start of the study; 15 patients had never attempted suicide. OUTCOME MEASURES: Serum levels of total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, serotonin (5-HT) and tryptophan. Scores on Hamilton Depression Rating Scale, Carroll Depression Rating Scale, Beck Hopelessness Scale and Beck Suicide Attempt Severity Scale. RESULTS: There were no significant differences between patients who had attempted suicide and those who had not in terms of serum cholesterol, HDL, LDL and triglyceride levels. Serum levels of 5-HT and tryptophan were significantly lower in patients with depression who had a recent suicide attempt than in those patients who had never attempted suicide. A comparison of patients not taking antidepressant medication found serum 5-HT levels to be more than 3 times lower in those patients with a recent suicide attempt than in patients with no history of suicide attempt. CONCLUSIONS: The study found no difference in lipid profiles between patients who had attempted suicide and those who had not. Low serum levels of 5-HT may increase the risk of suicide attempt in patients who are depressed. PMID:11022402

  20. CYP2E1-dependent elevation of serum cholesterol, triglycerides, and hepatic bile acids by isoniazid

    SciTech Connect

    Cheng, Jie; Krausz, Kristopher W.; Li, Feng; Ma, Xiaochao; Gonzalez, Frank J.

    2013-01-15

    Isoniazid is the first-line medication in the prevention and treatment of tuberculosis. Isoniazid is known to have a biphasic effect on the inhibition–induction of CYP2E1 and is also considered to be involved in isoniazid-induced hepatotoxicity. However, the full extent and mechanism of involvement of CYP2E1 in isoniazid-induced hepatotoxicity remain to be thoroughly investigated. In the current study, isoniazid was administered to wild-type and Cyp2e1-null mice to investigate the potential toxicity of isoniazid in vivo. The results revealed that isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice, but produced elevated serum cholesterol and triglycerides, and hepatic bile acids in wild-type mice, as well as decreased abundance of free fatty acids in wild-type mice and not in Cyp2e1-null mice. Metabolomic analysis demonstrated that production of isoniazid metabolites was elevated in wild-type mice along with a higher abundance of bile acids, bile acid metabolites, carnitine and carnitine derivatives; these were not observed in Cyp2e1-null mice. In addition, the enzymes responsible for bile acid synthesis were decreased and proteins involved in bile acid transport were significantly increased in wild-type mice. Lastly, treatment of targeted isoniazid metabolites to wild-type mice led to similar changes in cholesterol, triglycerides and free fatty acids. These findings suggest that while CYP2E1 is not involved in isoniazid-induced hepatotoxicity, while an isoniazid metabolite might play a role in isoniazid-induced cholestasis through enhancement of bile acid accumulation and mitochondria β-oxidation. -- Highlights: ► Isoniazid metabolites were elevated only in wild-type mice. ► Isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice. ► Isoniazid elevated serum cholesterol and triglycerides, and hepatic bile acids. ► Bile acid transporters were significantly decreased in isoniazid-treated mice.

  1. Curcumin Supplementation Decreases Intestinal Adiposity Accumulation, Serum Cholesterol Alterations, and Oxidative Stress in Ovariectomized Rats

    PubMed Central

    Morrone, Maurilio da Silva; Schnorr, Carlos Eduardo; Behr, Guilherme Antônio; Gasparotto, Juciano; Bortolin, Rafael Calixto; da Boit Martinello, Katia; Saldanha Henkin, Bernardo; Rabello, Thallita Kelly; Zanotto-Filho, Alfeu; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca

    2016-01-01

    The aim of this study was to investigate the potential of curcumin oral supplementation (50 and 100 mg/Kg/day, for 30 days) in circumventing menopause-associated oxidative stress and lipid profile dysfunctions in a rat ovariectomy (OVX) model. Female Wistar rats were operated and randomly divided into either sham-operated or OVX groups. Sham-operated group (n = 8) and one OVX group (n = 11) were treated with vehicle (refined olive oil), and the other two OVX groups received curcumin at 50 or 100 mg/Kg/day doses (n = 8/group). OVX vehicle-treated animals presented a higher deposition of intestinal adipose tissue as well as increased serum levels of IL-6, LDL, and total cholesterol when compared to sham-operated rats. In addition, several oxidative stress markers in serum, blood, and liver (such as TBARS, carbonyl, reduced-sulphydryl, and nonenzymatic antioxidant defenses) were altered toward a prooxidant status by OVX. Interestingly, curcumin supplementation attenuated most of these parameters to sham comparable values. Thus, the herein presented results show that curcumin may be useful to ameliorate lipid metabolism alterations and oxidative damage associated with hormone deprivation in menopause. PMID:26640615

  2. Cholesterol derived cationic lipids as potential non-viral gene delivery vectors and their serum compatibility.

    PubMed

    Ju, Jia; Huan, Meng-Lei; Wan, Ning; Hou, Yi-Lin; Ma, Xi-Xi; Jia, Yi-Yang; Li, Chen; Zhou, Si-Yuan; Zhang, Bang-Le

    2016-05-15

    Cholesterol derivatives M1-M6 as synthetic cationic lipids were designed and the biological evaluation of the cationic liposomes based on them as non-viral gene delivery vectors were described. Plasmid pEGFP-N1, used as model gene, was transferred into 293T cells by cationic liposomes formed with M1-M6 and transfection efficiency and GFP expression were tested. Cationic liposomes prepared with cationic lipids M1-M6 exhibited good transfection activity, and the transfection activity was parallel (M2 and M4) or superior (M1 and M6) to that of DC-Chol derived from the same backbone. Among them, the transfection efficiency of cationic lipid M6 was parallel to that of the commercially available Lipofectamine2000. The optimal formulation of M1 and M6 were found to be at a mol ratio of 1:0.5 for cationic lipid/DOPE, and at a N/P charge mol ratio of 3:1 for liposome/DNA. Under optimized conditions, the efficiency of M1 and M6 is greater than that of all the tested commercial liposomes DC-Chol and Lipofectamine2000, even in the presence of serum. The results indicated that M1 and M6 exhibited low cytotoxicity, good serum compatibility and efficient transfection performance, having the potential of being excellent non-viral vectors for gene delivery. PMID:27072908

  3. The clinical significance of preoperative serum cholesterol and high-density lipoprotein-cholesterol levels in hepatocellular carcinoma

    PubMed Central

    Jiang, Shan-Shan; Weng, De-Sheng; Jiang, Long; Zhang, Yao-Jun; Pan, Ke; Pan, Qiu-Zhong; Chen, Chang-Long; Zhao, Jing-Jing; Zhang, Xiao-Fei; Zhang, Hong-Xia; Tang, Yan; Zhou, Zi-Qi; Chen, Min-Shan; Xia, Jian-Chuan

    2016-01-01

    Purpose: To evaluate the prognostic role of the preoperative plasma lipid profile, including low-density lipoprotein -cholesterol [LDL-C], high-density lipoprotein-cholesterol [HDL-C], cholesterol, and triglycerides, in hepatocellular carcinoma patients undergoing radical resection. Methods: Clinical data, including the preoperative plasma profile levels, were retrospectively collected and reviewed in 1411 hepatocellular carcinoma patients, who underwent operation between 2001 and 2010. Kaplan-Meier method and the Cox proportional hazards regression model were used in analyzing the DFS and OS. Results: We found that HDL-C ≤ 0.88 mmol/L and cholesterol ≤ 4.420 mmol/L were preoperative risk factors of disease-free survival (DFS) and overall survival (OS). A decreased CHO level was significantly associated with decreased OS (HR, 0.800; 95% CI, (0.691-0.926), P =0.003) and decreased DFS (HR, 0.844; 95% CI, 0.737-0.966, P=0.012). Additionally, an increased HDL-C level was shown significant association with increased OS (HR, 0.679; 95% CI, 0.570-0.808, P<0.01) and DFS (HR, 2.085; 95% CI, 1.271- 3.422, P = 0.002). In the univariate and multivariate analyses involving OS and DFS, no significant relativity were observed between the LDL-C and TG groups. Conclusions: Decreased levels of CHO and HDL might predict worse outcomes both DFS and OS for hepatocellular carcinoma patients. PMID:27076843

  4. The efficacy of vitamin C supplementation on reducing total serum cholesterol in human subjects: a review and analysis of 51 experimental trials

    PubMed Central

    McRae, Marc P.

    2006-01-01

    Abstract Objective Observational studies in humans have shown an inverse relationship between plasma vitamin C concentration and total serum cholesterol. However, experimental studies have shown inconsistent results regarding the ability of vitamin C to reduce total serum cholesterol. Methods Published reports of trials studying the effects of vitamin C on serum lipids were identified by a search of Medline from 1966 to 2004. Data from 51 experimental studies comprising of 1666 pooled subjects were selected for analysis. Results A very strong negative association was observed between baseline total serum cholesterol and the percent change in cholesterol (r = −0.585, p<0.001). When subjects were divided into 4 groups based on their baseline total serum cholesterol levels, the following weighted mean percent changes in cholesterol from baseline were observed: normal cholesterol (<199mg/dl): 0.91±6.8% (n=508); borderline high cholesterol (200–239mg/dl): 3.90±5.78% (n=605); high cholesterol (240–279mg/dl): 11.40±7.96% (n=300); severe cholesterol (>280mg/dl): 14.30±8.36% (n=253). A significant inverse relationship was found between the baseline plasma vitamin C concentrations and mean percent change in total cholesterol from baseline (r = −0.500, p<0.005). It was also observed that the high and severe baseline cholesterol groups possessed lower baseline plasma vitamin C concentrations than those in the normal cholesterol groups (0.79 and 0.55 versus 1.24 mg/dl respectively). Conclusion This finding strengthens the hypothesis that the cholesterol lowering and cardio-protective benefit of vitamin C supplementation may be in its ability to elevate plasma vitamin C concentrations in those patients who initially possess lower than normal vitamin C plasma concentrations. PMID:19674666

  5. The LXR ligand GW3965 inhibits Newcastle disease virus infection by affecting cholesterol homeostasis.

    PubMed

    Sheng, Xiang-Xiang; Sun, Ying-Jie; Zhan, Yuan; Qu, Yu-Rong; Wang, Hua-Xia; Luo, Miao; Liao, Ying; Qiu, Xu-Sheng; Ding, Chan; Fan, Hong-Jie; Mao, Xiang

    2016-09-01

    Newcastle disease (ND) is a contagious disease that affects most species of birds. Its causative pathogen, Newcastle disease virus (NDV), also exhibits considerable oncolytic activity against mammalian cancers. A better understanding of the pathogenesis of NDV will help us design efficient vaccines and novel anticancer strategies. GW3965, a widely used synthetic ligand of liver X receptor (LXR), induces the expression of LXRs and its downstream genes, including ATP-binding cassette transporter A1 (ABCA1). ABCA1 regulates cellular cholesterol homeostasis. Here, we found that GW3965 inhibited NDV infection in DF-1 cells. It also inhibited NF-κB activation and reduced the upregulation of proinflammatory cytokines induced by the infection. Further studies showed that GW3965 exerted its inhibitory effects on virus entry and replication. NDV infection increased the mRNA levels of several lipogenic genes but decreased the ABCA1 mRNA level. Overexpression of ABCA1 inhibited NDV infection and reduced the cholesterol content in DF-1 cells, but when the cholesterol was replenished, NDV infection was restored. GW3965 treatment prevented cholesterol accumulation in the perinuclear area of the infected cells. In summary, our studies suggest that GW3965 inhibits NDV infection, probably by affecting cholesterol homeostasis. PMID:27357231

  6. Serum Cholesterol Levels in College Students: Opportunities for Education and Intervention.

    ERIC Educational Resources Information Center

    Sparling, Phillip B.; Snow, Teresa K.; Beavers, Bill D.

    1999-01-01

    Analyzed lipid profiles in 1,088 college students at a university where lipid profiles were available to students in selected health/wellness courses. Mean total cholesterol levels were similar for men and women, but men had significantly lower high-density lipoprotein cholesterol and higher low-density lipoprotein cholesterol than women. About 11…

  7. Exploring the Factors That Affect Blood Cholesterol and Heart Disease Risk: Is Dietary Cholesterol as Bad for You as History Leads Us to Believe?12

    PubMed Central

    Kanter, Mitchell M.; Kris-Etherton, Penny M.; Fernandez, Maria Luz; Vickers, Kasey C.; Katz, David L.

    2012-01-01

    This paper summarizes presentations given at the 2011 Experimental Biology meetings about the latest research and a paleoanthropological perspective pertaining to the relationship between dietary cholesterol intake and cardiovascular disease risk. For much of the past 50 years, a great deal of the scientific literature regarding dietary fat and cholesterol intake has indicated a strong positive correlation with heart disease. In recent years, however, there have been a number of epidemiological studies that did not support a relationship between cholesterol intake and cardiovascular disease. Further, a number of recent clinical trials that looked at the effects of long-term egg consumption (as a vehicle for dietary cholesterol) reported no negative impact on various indices of cardiovascular health and disease. Coupled with data indicating that the impact of lowering dietary cholesterol intake on serum LDL levels is small compared with other dietary and lifestyle factors, there is a need to consider how otherwise healthy foods can be incorporated in the diet to meet current dietary cholesterol recommendations. Because eggs are a healthful food, it is particularly important that sensible strategies be recommended for inclusions of eggs in a healthy diet. PMID:22983850

  8. Exploring the factors that affect blood cholesterol and heart disease risk: is dietary cholesterol as bad for you as history leads us to believe?

    PubMed

    Kanter, Mitchell M; Kris-Etherton, Penny M; Fernandez, Maria Luz; Vickers, Kasey C; Katz, David L

    2012-01-01

    This paper summarizes presentations given at the 2011 Experimental Biology meetings about the latest research and a paleoanthropological perspective pertaining to the relationship between dietary cholesterol intake and cardiovascular disease risk. For much of the past 50 years, a great deal of the scientific literature regarding dietary fat and cholesterol intake has indicated a strong positive correlation with heart disease. In recent years, however, there have been a number of epidemiological studies that did not support a relationship between cholesterol intake and cardiovascular disease. Further, a number of recent clinical trials that looked at the effects of long-term egg consumption (as a vehicle for dietary cholesterol) reported no negative impact on various indices of cardiovascular health and disease. Coupled with data indicating that the impact of lowering dietary cholesterol intake on serum LDL levels is small compared with other dietary and lifestyle factors, there is a need to consider how otherwise healthy foods can be incorporated in the diet to meet current dietary cholesterol recommendations. Because eggs are a healthful food, it is particularly important that sensible strategies be recommended for inclusions of eggs in a healthy diet. PMID:22983850

  9. Joint analyses model for total cholesterol and triglyceride in human serum with near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Yao, Lijun; Lyu, Ning; Chen, Jiemei; Pan, Tao; Yu, Jing

    2016-04-01

    The development of a small, dedicated near-infrared (NIR) spectrometer has promising potential applications, such as for joint analyses of total cholesterol (TC) and triglyceride (TG) in human serum for preventing and treating hyperlipidemia of a large population. The appropriate wavelength selection is a key technology for developing such a spectrometer. For this reason, a novel wavelength selection method, named the equidistant combination partial least squares (EC-PLS), was applied to the wavelength selection for the NIR analyses of TC and TG in human serum. A rigorous process based on the various divisions of calibration and prediction sets was performed to achieve modeling optimization with stability. By applying EC-PLS, a model set was developed, which consists of various models that were equivalent to the optimal model. The joint analyses model of the two indicators was further selected with only 50 wavelengths. The random validation samples excluded from the modeling process were used to validate the selected model. The root-mean-square errors, correlation coefficients and ratio of performance to deviation for the prediction were 0.197 mmol L- 1, 0.985 and 5.6 for TC, and 0.101 mmol L- 1, 0.992 and 8.0 for TG, respectively. The sensitivity and specificity for hyperlipidemia were 96.2% and 98.0%. These findings indicate high prediction accuracy and low model complexity. The proposed wavelength selection provided valuable references for the designing of a small, dedicated spectrometer for hyperlipidemia. The methodological framework and optimization algorithm are universal, such that they can be applied to other fields.

  10. Joint analyses model for total cholesterol and triglyceride in human serum with near-infrared spectroscopy.

    PubMed

    Yao, Lijun; Lyu, Ning; Chen, Jiemei; Pan, Tao; Yu, Jing

    2016-04-15

    The development of a small, dedicated near-infrared (NIR) spectrometer has promising potential applications, such as for joint analyses of total cholesterol (TC) and triglyceride (TG) in human serum for preventing and treating hyperlipidemia of a large population. The appropriate wavelength selection is a key technology for developing such a spectrometer. For this reason, a novel wavelength selection method, named the equidistant combination partial least squares (EC-PLS), was applied to the wavelength selection for the NIR analyses of TC and TG in human serum. A rigorous process based on the various divisions of calibration and prediction sets was performed to achieve modeling optimization with stability. By applying EC-PLS, a model set was developed, which consists of various models that were equivalent to the optimal model. The joint analyses model of the two indicators was further selected with only 50 wavelengths. The random validation samples excluded from the modeling process were used to validate the selected model. The root-mean-square errors, correlation coefficients and ratio of performance to deviation for the prediction were 0.197mmolL(-1), 0.985 and 5.6 for TC, and 0.101mmolL(-1), 0.992 and 8.0 for TG, respectively. The sensitivity and specificity for hyperlipidemia were 96.2% and 98.0%. These findings indicate high prediction accuracy and low model complexity. The proposed wavelength selection provided valuable references for the designing of a small, dedicated spectrometer for hyperlipidemia. The methodological framework and optimization algorithm are universal, such that they can be applied to other fields. PMID:26827178

  11. First missense mutation outside of SERAC1 lipase domain affecting intracellular cholesterol trafficking.

    PubMed

    Rodríguez-García, María Elena; Martín-Hernández, Elena; de Aragón, Ana Martínez; García-Silva, María Teresa; Quijada-Fraile, Pilar; Arenas, Joaquín; Martín, Miguel A; Martínez-Azorín, Francisco

    2016-01-01

    We report the clinical and genetic findings in a Spanish boy who presented MEGDEL syndrome, a very rare inborn error of metabolism. Whole-exome sequencing uncovered a new homozygous mutation in the serine active site containing 1 (SERAC1) gene, which is essential for both mitochondrial function and intracellular cholesterol trafficking. Functional studies in patient fibroblasts showed that p.D224G mutation affects the intracellular cholesterol trafficking. Only three missense mutations in this gene have been described before, being p.D224G the first missense mutation outside of the SERAC1 serine-lipase domain. Therefore, we conclude that the defect in cholesterol trafficking is not limited to alterations in this specific part of the protein. PMID:26445863

  12. Serum uric acid and low-density lipoprotein cholesterol levels are independent predictors of coronary artery disease in Asian Indian patients with type 2 diabetes mellitus

    PubMed Central

    Jayashankar, C. A.; Andrews, Henley Punnen; Vijayasarathi; Pinnelli, Venkata BharatKumar; Shashidharan, Basappaji; Nithin Kumar, H. N.; Vemulapalli, Swaapnika

    2016-01-01

    Aim: We aimed to identify the predictors of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (type 2 DM). Methods: About fifty Asian Indian patients with type 2 DM patients aged >40 years and fifty sex- and age-matched nondiabetic controls were enrolled for this study. Following complete medical history and baseline clinical data, laboratory investigations were performed to assess fasting and postprandial plasma glucose levels, lipid profile, blood urea, serum creatinine, and serum uric acid levels. Results: Body mass index (BMI), waist-to-hip ratio, serum uric acid, serum total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, very LDL cholesterol were significantly higher among diabetic patients compared to controls. On univariate analysis, serum LDL cholesterol (odds ratio [OR]: 29.67, P < 0.001), serum uric acid (OR: 25.65, P < 0.001), low high-density lipoprotein (HDL) cholesterol (OR: 21.12, P < 0.001), hypertension (OR: 17.06, P < 0.001), family history of cardiovascular disease (CVD) (OR: 9.43, P = 0.002), and duration of diabetes (OR: 4.65, P = 0.03) were identified as predictors of CVD among diabetic patients. On multivariate regression, only LDL cholesterol (OR: 1.51, P = 0.002) and serum uric acid (OR: 1.21, P = 0.01) were the independent predictors of CAD among diabetic patients. Significant positive correlation of serum uric acid with duration of diabetes (r = 0.38, P = 0.006), BMI (r = 0.35, P = 0.01), triglycerides (r = 0.356, P = 0.01), LDL cholesterol (r = 0.38, P = 0.007), HDL cholesterol (r = −0.514, P < 0.001), and hypertension (r = 0.524, P < 0.001) was observed. Conclusion: Serum LDL cholesterol and hyperuricemia may serve as independent predictors of CAD among Asian Indian subjects with type 2 DM. PMID:27433067

  13. Blueberry polyphenol-enriched soybean flour reduces hyperglycemia, body weight gain and serum cholesterol in mice

    PubMed Central

    Roopchand, Diana E.; Kuhn, Peter; Rojo, Leonel E.; Lila, Mary Ann; Raskin, Ilya

    2013-01-01

    Defatted soybean flour (DSF) can sorb and concentrate blueberry anthocyanins and other polyphenols, but not sugars. In this study blueberry polyphenol-enriched DSF (BB-DSF) or DSF were incorporated into very high fat diet (VHFD) formulations and provided ad libitum to obese and hyperglycemic C57BL/6 mice for 13 weeks to investigate anti-diabetic effects. Compared to the VHFD containing DSF, the diet supplemented with BB-DSF reduced weight gain by 5.6%, improved glucose tolerance, and lowered fasting blood glucose levels in mice within 7 weeks of intervention. Serum cholesterol of mice consuming the BB-DSF-supplemented diet was 13.2% lower than mice on the diet containing DSF. Compounds were eluted from DSF and BB-DSF for in vitro assays of glucose production and uptake. Compared to untreated control, doses of BB-DSF eluate containing 0.05 – 10 μg/μL of blueberry anthocyanins significantly reduced glucose production by 24% - 74% in H4IIE rat hepatocytes, but did not increase glucose uptake in L6 myotubes. The results indicate that delivery of blueberry polyphenols stabilized in a high-protein food matrix may be useful for the dietary management of pre-diabetes and/or diabetes. PMID:23220243

  14. THE RELATIONSHIP BETWEEN SERUM CHOLESTEROL AND VERBAL MEMORY MAY BE INFLUENCED BY BODY MASS INDEX (BMI) IN YOUNG HEALTHY WOMEN.

    PubMed

    Darnai, Gergely; Plózer, Enikő; Altbácker, Anna; Perlaki, Gábor; Orsi, Gergely; Kőszegi, Tamás; Nagy, Szilvia Anett; Lucza, Tivadar; Kovács, Norbert; Janszky, József; Zsófia, Clemens

    2016-03-30

    The objective of this study was to examine the relationship between verbal memory and total cholesterol (TC) levels related to body mass index (BMI) in healthy young women. Verbal memory was assessed using the Rey Auditory-Verbal Learning Test (RAVLT) while total serum cholesterol was measured by enzymatic colorimetric test. In order to analyze the potential significance of BMI subjects were divided into three groups according to their calculated BMI percentile values. No significant correlation was found when assessing the group as a whole. However a remarkable pattern of correlation emerged when assessing the BMI groups separately: a close-to-significant positive correlation was found for total learning score and TC in the low BMI group, no correlation emerged in the medium BMI group while a strong inverse correlation was found in the high BMI group. These findings indicate that the relationship between verbal memory and serum TC level is also influenced by BMI. PMID:27468607

  15. Quantitative assessment of aortic atherosclerosis in APOE*3 Leiden transgenic mice and its relationship to serum cholesterol exposure.

    PubMed

    Groot, P H; van Vlijmen, B J; Benson, G M; Hofker, M H; Schiffelers, R; Vidgeon-Hart, M; Havekes, L M

    1996-08-01

    Transgenic mice overexpressing the human dysfunctional apolipoprotein E variant, APOE*3 Leiden, develop hyperlipidemia and are highly susceptible to diet-induced atherosclerosis. In the present study, we investigated the effects of diet composition and feeding period on serum cholesterol exposure and the amount of atherosclerosis in the aortic sinus in these mice, using quantitative image analysis. On each of the three diets tested--a low-fat diet, a high-saturated-fat/cholesterol diet, and a high saturated-fat/high-cholesterol/0.5%-cholate diet--transgenic animals showed a marked hyperlipidemia compared with nontransgenic littermates. Measurement of the atherosclerotic lesion areas in cross sections of the aortic sinus in animals exposed to these three diets for up to 6 months showed a 5 to 10 times greater lesion area in transgenic mice compared with nontransgenic controls. Highly significant positive correlations were found between the log-transformed data on lesion area and serum cholesterol exposure (r = .82 to .85 for the 1-, 2-, and 3-month treatment groups), indicating that the hyperlipidemia is likely to be a major determinant in lesion formation. On the basis of these findings, we suggest that the APOE*3 Leiden mouse represents a promising model for intervention studies with hypolipidemic and antiatherosclerotic drugs. PMID:8696955

  16. Alcohol Dehydrogenase-1B (rs1229984) and Aldehyde Dehydrogenase-2 (rs671) Genotypes Are Strong Determinants of the Serum Triglyceride and Cholesterol Levels of Japanese Alcoholic Men

    PubMed Central

    Yokoyama, Akira; Yokoyama, Tetsuji; Matsui, Toshifumi; Mizukami, Takeshi; Kimura, Mitsuru; Matsushita, Sachio; Higuchi, Susumu; Maruyama, Katsuya

    2015-01-01

    Background Elevated serum triglyceride (TG) and high-density-lipoprotein cholesterol (HDL-C) levels are common in drinkers. The fast-metabolizing alcohol dehydrogenase-1B encoded by the ADH1B*2 allele (vs. ADH1B*1/*1 genotype) and inactive aldehyde dehydrogenase-2 encoded by the ALDH2*2 allele (vs. ALDH2*1/*1 genotype) modify ethanol metabolism and are prevalent (≈90% and ≈40%, respectively) in East Asians. We attempted to evaluate the associations between the ADH1B and ALDH2 genotypes and lipid levels in alcoholics. Methods The population consisted of 1806 Japanese alcoholic men (≥40 years) who had undergone ADH1B and ALDH2 genotyping and whose serum TG, total cholesterol, and HDL-C levels in the fasting state had been measured within 3 days after admission. Results High serum levels of TG (≥150 mg/dl), HDL-C (>80 mg/dl), and low-density-lipoprotein cholesterol (LDL-C calculated by the Friedewald formula ≥140 mg/dl) were observed in 24.3%, 16.8%, and 15.6%, respectively, of the subjects. Diabetes, cirrhosis, smoking, and body mass index (BMI) affected the serum lipid levels. Multivariate analysis revealed that the presence of the ADH1B*2 allele and the active ALDH2*1/*1 genotype increased the odds ratio (OR; 95% confidence interval) for a high TG level (2.22 [1.67–2.94] and 1.39 [0.99–1.96], respectively), and decreased the OR for a high HDL-C level (0.37 [0.28–0.49] and 0.51 [0.37–0.69], respectively). The presence of the ADH1B*2 allele decreased the OR for a high LDL-C level (0.60 [0.45–0.80]). The ADH1B*2 plus ALDH2*1/*1 combination yielded the highest ORs for high TG levels and lowest OR for a high HDL-C level. The genotype effects were more prominent in relation to the higher levels of TG (≥220 mg/dl) and HDL-C (≥100 mg/dl). Conclusions The fast-metabolizing ADH1B and active ALDH2, and especially a combination of the two were strongly associated with higher serum TG levels and lower serum HDL-C levels of alcoholics. The fast

  17. Furin-cleaved Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Is Active and Modulates Low Density Lipoprotein Receptor and Serum Cholesterol Levels

    PubMed Central

    Lipari, Michael T.; Li, Wei; Moran, Paul; Kong-Beltran, Monica; Sai, Tao; Lai, Joyce; Lin, S. Jack; Kolumam, Ganesh; Zavala-Solorio, Jose; Izrael-Tomasevic, Anita; Arnott, David; Wang, Jianyong; Peterson, Andrew S.; Kirchhofer, Daniel

    2012-01-01

    Proprotein convertase subtilisin/kexin 9 (PCSK9) regulates plasma LDL cholesterol levels by regulating the degradation of LDL receptors. Another proprotein convertase, furin, cleaves PCSK9 at Arg218-Gln219 in the surface-exposed “218 loop.” This cleaved form circulates in blood along with the intact form, albeit at lower concentrations. To gain a better understanding of how cleavage affects PCSK9 function, we produced recombinant furin-cleaved PCSK9 using antibody Ab-3D5, which binds the intact but not the cleaved 218 loop. Using Ab-3D5, we also produced highly purified hepsin-cleaved PCSK9. Hepsin cleaves PCSK9 at Arg218-Gln219 more efficiently than furin but also cleaves at Arg215-Phe216. Further analysis by size exclusion chromatography and mass spectrometry indicated that furin and hepsin produced an internal cleavage in the 218 loop without the loss of the N-terminal segment (Ser153–Arg218), which remained attached to the catalytic domain. Both furin- and hepsin-cleaved PCSK9 bound to LDL receptor with only 2-fold reduced affinity compared with intact PCSK9. Moreover, they reduced LDL receptor levels in HepG2 cells and in mouse liver with only moderately lower activity than intact PCSK9, consistent with the binding data. Single injection into mice of furin-cleaved PCSK9 resulted in significantly increased serum cholesterol levels, approaching the increase by intact PCSK9. These findings indicate that circulating furin-cleaved PCSK9 is able to regulate LDL receptor and serum cholesterol levels, although somewhat less efficiently than intact PCSK9. Therapeutic anti-PCSK9 approaches that neutralize both forms should be the most effective in preserving LDL receptors and in lowering plasma LDL cholesterol. PMID:23135270

  18. Dose-dependent suppression of serum cholesterol by tocotrienol-rich fraction (TRF25) of rice bran in hypercholesterolemic humans.

    PubMed

    Qureshi, Asaf A; Sami, Saeed A; Salser, Winston A; Khan, Farooq A

    2002-03-01

    Tocotrienols are effective in lowering serum total and LDL-cholesterol levels by inhibiting the hepatic enzymic activity of beta-hydroxy-beta-methylglutaryl coenzymeA (HMG-CoA) reductase through the post-transcriptional mechanism. alpha-Tocopherol, however, has an opposite effect (induces) on this enzyme activity. Since tocotrienols are also converted to tocopherols in vivo, it is necessary not to exceed a certain dose, as this would be counter-productive. The present study demonstrates the effects of various doses of a tocotrienol-rich fraction (TRF25) of stabilized and heated rice bran in hypercholesterolemic human subjects on serum lipid parameters. Ninety (18/group) hypercholesterolemic human subjects participated in this study, which comprised three phases of 35 days each. The subjects were initially placed on the American Heart Association (AHA) Step-1 diet and the effects noted. They were then administered 25, 50, 100, and 200 mg/day of TRF25 while on the restricted (AHA) diet. The results show that a dose of 100 mg/day of TRF25 produce maximum decreases of 20, 25, 14 (P<0.05) and 12%, respectively, in serum total cholesterol, LDL-cholesterol, apolipoprotein B and triglycerides compared with the baseline values, suggesting that a dose of 100 mg/day TRF25 plus AHA Step-1 diet may be the optimal dose for controlling the risk of coronary heart disease in hypercholesterolemic human subjects. PMID:11882333

  19. Supplementation of broccoli or Bifidobacterium longum-fermented broccoli suppresses serum lipid peroxidation and osteoclast differentiation on alveolar bone surface in rats fed a high-cholesterol diet.

    PubMed

    Tomofuji, Takaaki; Ekuni, Daisuke; Azuma, Tetsuji; Irie, Koichiro; Endo, Yasumasa; Yamamoto, Tatsuo; Ishikado, Atsushi; Sato, Takehiko; Harada, Kayo; Suido, Hirohisa; Morita, Manabu

    2012-04-01

    High-cholesterol diet enhances osteoclastic activity on alveolar bone by increasing serum lipid peroxidation. We hypothesized that supplementation with dietary antioxidants, such as found in broccoli and its fermented products, might suppress increases in serum lipid peroxidation, contributing to the inhibition of osteoclastic activity after high-cholesterol diet intake. The purpose of the present study was to investigate the effects of broccoli and fermented broccoli consumption on serum lipid peroxidation and osteoclast differentiation in alveolar bone of rats fed a high-cholesterol diet. In this 12-week study, rats were divided into 4 groups (n = 6/group): a control group (fed regular diet) and 3 experimental groups (fed a high-cholesterol [1% wt/wt] diet, or a high-cholesterol diet supplemented with either broccoli powder [5% wt/wt] or Bifidobacterium longum-fermented broccoli powder [5% wt/wt]). Serum hexanoyl-lysine (HEL) levels were measured as a parameter of lipid peroxidation. The number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts in alveolar bone was enumerated to evaluate osteoclast differentiation. When compared with regular diet, the high-cholesterol diet increased serum HEL levels and resulted in a higher number of TRAP-positive osteoclasts at 12 weeks. The high-cholesterol diet supplemented with broccoli or B. longum-fermented broccoli showed lower levels of serum HEL and fewer TRAP-positive osteoclasts than the high-cholesterol diet at 12 weeks. In conclusion, consumption of broccoli, or its fermented product, inhibited the effects of a high-cholesterol diet on osteoclast differentiation in rat alveolar bone by suppressing serum lipid peroxidation. PMID:22575044

  20. Correlation between pretreatment serum LDL-cholesterol levels and prognosis in nasopharyngeal carcinoma patients

    PubMed Central

    Tang, Qiu; Hu, Qiao-Ying; Piao, Yong-feng; Hua, Yong-Hong

    2016-01-01

    Purpose To investigate the correlations between long-term survival outcomes in patients with nasopharyngeal carcinoma (NPC) and pretreatment serum low-density lipoprotein cholesterol (LDL-C) levels. Patients and methods Between January 2008 and December 2011, 935 patients with newly diagnosed NPC who were treated with intensity-modulated radiation therapy were included in this retrospective clinical analysis. Patients were divided into two groups based on pretreatment LDL-C levels: normal LDL-C (≤3.64 mmol/L; n=816) and elevated LDL-C (>3.64 mmol/L; n=119). Associations between pretreatment LDL-C levels and treatment outcome were analyzed by univariate and multivariate analyses. Results The overall patient follow-up rate was 95.1%, and 726 patients received more than 5 years of follow-up. Five-year overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS) rates of the entire patient population were 87.1%, 91.1%, and 87.2%, respectively. Rates of 5-year OS, LC, and DMFS for the elevated versus normal LDL-C groups were 77.0% vs 89.1% (P<0.001), 85.8% vs 91.9% (P=0.041), and 81.1% vs 88.1% (P=0.038), respectively. Compared with normal LDL-C levels, elevated LDL-C levels were identified as an independent prognostic factor of a poorer OS (hazard ratio [HR] =2.171; 95% confidence interval [CI] =1.424–3.309), LC rate (HR =1.762; 95% CI =1.021–3.942), and DMFS (HR =1.594; 95% CI =1.003–2.532). Conclusion This study found that elevated pretreatment LDL-C levels are negative prognostic indicators of NPC. Elevated LDL-C levels may be useful indicators of locoregional control and distant metastasis in NPC patients. PMID:27217776

  1. Role of Serum Cholesterol and Statin Use in the Risk of Prostate Cancer Detection and Tumor Aggressiveness

    PubMed Central

    Morote, Juan; Celma, Anna; Planas, Jacques; Placer, José; de Torres, Inés; Olivan, Mireia; Carles, Juan; Reventós, Jaume; Doll, Andreas

    2014-01-01

    The aim of this study was to analyze the relationship between statin use along with serum cholesterol levels and prostate cancer (PCa) detection and aggressiveness. Statin users of three years or more and serum cholesterol levels (SC) were assessed in 2408 men scheduled for prostate biopsy. SC was classified as normal (NSC: <200 mg/dL) or high (HSC: >200 mg/dL). High-grade PCa (HGPCa) was considered if the Gleason score was greater than 7. Statin users comprised 30.9% of those studied. The PCa detection rate was 31.2% of men on statins and 37% of non-statin users (p < 0.006). The PCa detection rate was 26.3% in men with NSC and 40.6% in those with HSC (p < 0.001). In the subset of NSC men, the PCa rate was 26.5% for statin users and 26.2% for non-users (p = 0.939), while in men with HSC, the PCa rate was 36.4% for statin users and 42.0% for non-statin users (p = 0.063). The HGPCa rate was 41.8% for statin users and 32.5% for non-users (p = 0.012). NSC men had a 53.8% rate of HGPCa, while the rate was only 27.6% in HSC men (p < 0.001). NSC men on statins had an HGPCa rate of 70.2%, while non-statin users had a rate of 41.2% (p < 0.001). The HGPCa rate for HSC men on statins was 18.8%, while the rate was 30.0% (p = 0.011) for non-users. Logistic regression analysis suggested that serum cholesterol levels could serve as an independent predictor of PCa risk, OR 1.87 (95% CI 1.56–2.24) and HGPCa risk, OR 0.31 (95% CI 0.23–0.44), while statin usage could not. Statin treatment may prevent PCa detection through serum cholesterol-mediated mechanisms. A disturbing increase in the HGPCa rate was observed in statin users who normalized their serum cholesterol. PMID:25101846

  2. CNT loading into cationic cholesterol suspensions show improved DNA binding and serum stability and ability to internalize into cancer cells

    NASA Astrophysics Data System (ADS)

    Chhikara, Bhupender S.; Misra, Santosh K.; Bhattacharya, Santanu

    2012-02-01

    Methods which disperse single-walled carbon nanotubes (SWNTs) in water as ‘debundled’, while maintaining their unique physical properties are highly useful. We present here a family of cationic cholesterol compounds (Chol+) {Cholest-5en-3β-oxyethyl pyridinium bromide (Chol-PB+), Cholest-5en-3β-oxyethyl N-methyl pyrrolidinium bromide (Chol-MPB+), Cholest-5en-3β-oxyethyl N-methyl morpholinium bromide (Chol-MMB+) and Cholest-5en-3β-oxyethyl diazabicyclo octanium bromide (Chol-DOB+)}. Each of these could be easily dispersed in water. The resulting cationic cholesterol (Chol+) suspensions solubilized single-walled carbon nanotubes (SWCNTs) by the non-specific physical adsorption of Chol+ to form stable, transparent, dark aqueous suspensions at room temperature. Electron microscopy reveals the existence of highly segregated CNTs in these samples. Zeta potential measurements showed an increase in potential of cationic cholesterol aggregates on addition of CNTs. The CNT-Chol+ suspensions were capable of forming stable complexes with genes (DNA) efficiently. The release of double-helical DNA from such CNT-Chol+ complexes could be induced upon the addition of anionic micellar solution of SDS. Furthermore, the CNT-based DNA complexes containing cationic cholesterol aggregates showed higher stability in fetal bovine serum media at physiological conditions. Confocal studies confirm that CNT-Chol+ formulations adhere to HeLa cell surfaces and get internalized more efficiently than the cationic cholesterol suspensions alone (devoid of any CNTs). These cationic cholesterol-CNT suspensions therefore appear to be a promising system for further use in biological applications.

  3. Glycated human serum albumin isolated from poorly controlled diabetic patients impairs cholesterol efflux from macrophages: an investigation by mass spectrometry.

    PubMed

    Traldi, Pietro; Castilho, Gabriela; Sartori, Camila H; Machado-Lima, Adriana; Nakandakare, Edna R; Corrêa-Giannella, Maria Lucia C; Roverso, Marco; Porcu, Simona; Lapolla, Annunziata; Passarelli, Marisa

    2015-01-01

    Advanced glycation end-products impair ABCA-1-mediated cholesterol efflux by eliciting inflammation, the generation of reactive oxygen species and endoplasmatic reticulum (ER) stress. The glycation level of human serum albumin (HSA) from type 1 and type 2 diabetic patients was determined by matrix assisted laser desorption/ionization (MALDI) mass spectrometry and related to possible impairment of ER function and cellular cholesterol efflux. Comparison of the MALDI spectra from healthy and diabetic subjects allowed us to determine an increased HSA mean mass of 1297 Da for type 1 and 890 Da for type 2. These values reflect a mean condensation of at least 8 glucose units and 5 glucose units, respectively. Mouse peritoneal macrophages were treated with HSA from control, type 1 and type 2 diabetic subjects in order to measure the expression of Grp78, Grp94, protein disulfide isomerase (PDI), calreticulin (CRT) and ABCA-1. (14)C-cholesterol overloaded-J774 macrophages were treated with HSA from control and diabetic subjects and further incubated with apo A-1 to determine the cholesterol efflux. Combined analyses comprising HSA from type 1 and type 2 diabetic patients were performed in cellular functional assays. In macrophages, PDI expression increased 89% and CRT 3.4 times in comparison to HSA from the control subjects. ABCA-1 protein level and apo A-I mediated cholesterol efflux were, respectively, 50% and 60% reduced in macrophages exposed to HSA from type 1 and type 2 diabetic patients when compared to that exposed to HSA from control subjects. We provide evidence that the level of glycation that occurs in albumin in vivo damages the ER function related to the impairment in macrophage reverse cholesterol transport and so contributes to atherosclerosis in diabetes. PMID:26307703

  4. Effect of bovine serum albumin on the structure and properties of Langmuir Blodgett films based phosphocholine and cholesterol

    NASA Astrophysics Data System (ADS)

    Dubatovka, K. I.; Zhavnerko, G. K.; Agabekov, V. E.

    2014-02-01

    Mono- and bilayer Langmuir-Blodgett films based on phosphocholine and cholesterol and prepared by horizontal and vertical deposition are investigated by atomic force microscopy. It was found that bovine serum albumin (BSA) included at the stage of film formation. At the same time, isolation has a considerable effect on their structure. It was shown that the globular formation of nanostructures with heights of 4-7 nm occurs as a result of transferring lipids to a hydrophobic surface from a subphase containing BSA, indicating the reorganization of monolayers during protein isolation and inclusion in its composition.

  5. Is higher serum cholesterol associated with altered tendon structure or tendon pain? A systematic review

    PubMed Central

    Tilley, Benjamin J; Cook, Jill L; Docking, Sean I; Gaida, James E

    2015-01-01

    Background Tendon pain occurs in individuals with extreme cholesterol levels (familial hypercholesterolaemia). It is unclear whether the association with tendon pain is strong with less extreme elevations of cholesterol. Objective To determine whether lipid levels are associated with abnormal tendon structure or the presence of tendon pain. Methods We conducted a systematic review and meta-analysis. Relevant articles were found through an electronic search of 6 medical databases—MEDLINE, Cochrane, AMED, EMBASE, Web of Science and Scopus. We included all case–control or cross-sectional studies with data describing (1) lipid levels or use of lipid-lowering drugs and (2) tendon structure or tendon pain. Results 17 studies (2612 participants) were eligible for inclusion in the review. People with altered tendon structure or tendon pain had significantly higher total cholesterol, low-density lipoprotein cholesterol and triglycerides, as well as lower high-density lipoprotein cholesterol; with mean difference values of 0.66, 1.00, 0.33, and −0.19 mmol/L, respectively. Conclusions The results of this review indicate that a relationship exists between an individual’s lipid profile and tendon health. However, further longitudinal studies are required to determine whether a cause and effect relationship exists between tendon structure and lipid levels. This could lead to advancement in the understanding of the pathoaetiology and thus treatment of tendinopathy. PMID:26474596

  6. Cohort study of serum total cholesterol and in-hospital incidence of infectious diseases.

    PubMed Central

    Iribarren, C.; Jacobs, D. R.; Sidney, S.; Claxton, A. J.; Feingold, K. R.

    1998-01-01

    A multiethnic cohort of adult members of the Kaiser Permanente Medical Care Program (55300 men and 65271 women) was followed for 15 years (1979-93) to assess the association between total cholesterol and risk of infections (other than respiratory and HIV) diagnosed in the in-patient setting. Using multivariate Cox regression, total cholesterol was inversely and significantly related to urinary tract, venereal, musculo-skeletal, and all infections among men; and to urinary tract, all genito-urinary, septicaemia or bacteraemia, miscellaneous viral site unspecified, and all infections among women. The reduction of risk of all infections associated with a 1 S.D. increase in total cholesterol was 8% in both men (95% CI, 4-12 %) and women (95% CI, 5-11%). For urinary tract infections among men, as for septicaemia or bacteraemia and nervous system infections among women, the risk relation was restricted to persons aged 55-89 years. Nervous system infections were positively related to total cholesterol among women aged 25-54. In both genders, the significant inverse association with all infections persisted after excluding the first 5 years of follow-up. Collectively, these data are suggestive of an inverse association, although not entirely consistent, between total cholesterol and incidence of infections either requiring hospitalization or acquired in the hospital. Further research is needed to elucidate whether these associations are biologically plausible or represent uncontrolled confounding by unmeasured risk factors. PMID:9825784

  7. Serum concentrations of cholesterol, apolipoprotein A-I, and apolipoprotein B in a total of 1 694 meat-eaters, fish-eaters, vegetarians, and vegans

    PubMed Central

    Bradbury, Kathryn E; Crowe, Francesca L; Appleby, Paul N; Schmidt, Julie A; Travis, Ruth C; Key, Timothy J

    2013-01-01

    BACKGROUND The objective of this study was to describe serum lipid concentrations, including apolipoproteins A-I and B, in different diet groups. METHODS A cross-sectional analysis of a sample of 424 meat-eaters, 425 fish-eaters, 423 vegetarians, and 422 vegans, matched on sex and age, from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Oxford cohort. Serum concentrations of total, and HDL cholesterol, as well as apolipoproteins A-I and B were measured, and serum non-HDL cholesterol was calculated. RESULTS Vegans had the lowest BMI, and the highest and lowest intakes of polyunsaturated and saturated fat, respectively. After adjustment for age, alcohol and physical activity, compared to meat-eaters, fish-eaters and vegetarians, serum concentrations of total and non-HDL cholesterol, and apolipoprotein B were significantly lower in vegans. Serum apolipoprotein A-I concentrations did not differ between the diet groups. In males, the mean serum total cholesterol concentration was 0.87 nmol/L lower in vegans than in meat-eaters; after further adjustment for BMI this difference was 0.76 nmol/L. In females, the difference in total cholesterol between these two groups was 0.60 nmol/L, and after further adjustment for BMI was 0.55 nmol/L. CONCLUSIONS In this study, which included a large number of vegans, serum total cholesterol and apolipoprotein B concentrations were lower in vegans compared to meat-eaters, fish-eaters and vegetarians. A small proportion of the observed differences in serum lipid concentrations was explained by differences in BMI, but a large proportion is most likely due to diet. PMID:24346473

  8. CHLORINATION, WATER HARDNESS, AND SERUM CHOLESTEROL IN FORTY-SIX WISCONSIN COMMUNITIES

    EPA Science Inventory

    The Wisconsin Heart Health Research Program measured serum lipids and other clinical parameters among residents of forty-six neighboring small communities in central Wisconsin. he purpose of the study was to determine whether distribution of serum lipids, blood pressure or thyroi...

  9. Genome scan linkage analysis identifies quantitative trait loci affecting serum clinical-chemical traits in Korean native chicken.

    PubMed

    Seo, Dong-Won; Park, Hee-Bok; Jin, Shil; Cahyadi, Muhammad; Choi, Nuri; Heo, Kang-Nyeong; Jo, Cheorun; Lee, Jun-Heon

    2016-07-01

    Alterations in robustness- and health-related traits lead to physiological changes, such as changes in the serum clinical chemical parameters in individuals. Therefore, clinical-chemical traits can be used as biomarkers to examine the health status of chickens. The aim of the present study was to detect the quantitative trait loci (QTLs) influencing eight clinical-chemical traits (glucose, total protein, creatinine, high-density lipoprotein cholesterol, total cholesterol, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and α-amylase) in an F1 nuclear families comprising 83 F0 founders and 585 F1 progeny of Korean native chickens. Genotypic data on 135 DNA markers representing 26 autosomes have been generated for this resource pedigree. The total length of the map was 2729.4 cM. We used a multipoint variance component linkage approach to identify QTLs for the traits. A significant QTL affecting serum α-amylase levels was identified on chicken chromosome (GGA) 7 [logarithm of odds (LOD) = 3.02, P value = 1.92 × 10(-4)]. Additionally, we detected several suggestive linkage signals for the levels of total cholesterol, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and creatinine on GGA 4, 12, 13, and 15. In this study, serum α-amylase levels related significant QTL was mapped on GGA7 and cholesterol, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and creatinine traits related suggestive QTLs were detected on GGA4, 12, 13 and 15, respectively. Further verification and fine mapping of these identified QTLs can provide valuable information for understanding the variations of clinical chemical trait in chickens. PMID:27188424

  10. Simvastatin Treatment Does Not Affect Serum Vitamin D Concentrations in Patients with Dyslipidemia: A Randomized Double-blind Placebo-controlled Cross-over Trial

    PubMed Central

    Mazidi, Mohsen; Rokni, Haleh; Sahebkar, Amir Hossein; Mohammadi, Akram; Ghayour-Mobarhan, Majid; Ferns, Gordon A.

    2016-01-01

    Background: Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) are antihyperlipidemic drugs with an established efficacy in stabilizing atherosclerotic plaques and preventing atherogenesis and reducing cardiovascular events. The purpose of this study was to determine the effect of simvastatin on serum Vitamin D status in dyslipidemic patients as Vitamin D status has an impact on monocyte/macrophage function and may also contribute to cardiovascular risk. Methods: Selected individuals (n = 102) were treated with simvastatin (40 mg/day), or matching placebo in a randomized, double-blind, placebo-controlled, crossover trial. Each treatment period (with simvastatin or placebo) lasted for 30 days and was separated by a 2-week washout phase. Serum Vitamin D concentration was assessed pre- and post-treatment. Results: Seventy-seven completed the trial, noncompliance with the study protocol and drug intolerance or relocation were the causes for drop-out. No significant carry-over effect was observed for the assessed parameters. There was a reduction in the serum levels of low-density lipoprotein cholesterol (P < 0.001), total cholesterol (P < 0.001), and triglycerides (P < 0.05). Nevertheless, simvastatin therapy did not significantly affect serum level of high-density lipoprotein cholesterol and Vitamin D level (P > 0.05). Conclusions: Short-term treatment with simvastatin (40 mg/day) does not have a significant affect on serum levels of Vitamin D. PMID:27330686

  11. Streptococcal serum opacity factor promotes cholesterol ester metabolism and bile acid secretion in vitro and in vivo.

    PubMed

    Gillard, Baiba K; Rodriguez, Perla J; Fields, David W; Raya, Joe L; Lagor, William R; Rosales, Corina; Courtney, Harry S; Gotto, Antonio M; Pownall, Henry J

    2016-03-01

    Plasma high density lipoprotein-cholesterol (HDL-C) concentrations negatively correlate with atherosclerotic cardiovascular disease. HDL is thought to have several atheroprotective functions, which are likely distinct from the epidemiological inverse relationship between HDL-C levels and risk. Specifically, strategies that reduce HDL-C while promoting reverse cholesterol transport (RCT) may have therapeutic value. The major product of the serum opacity factor (SOF) reaction versus HDL is a cholesteryl ester (CE)-rich microemulsion (CERM), which contains apo E and the CE of ~400,000 HDL particles. Huh7 hepatocytes take up CE faster when delivered as CERM than as HDL, in part via the LDL-receptor (LDLR). Here we compared the final RCT step, hepatic uptake and subsequent intracellular processing to cholesterol and bile salts for radiolabeled HDL-, CERM- and LDL-CE by Huh7 cells and in vivo in C57BL/6J mice. In Huh7 cells, uptake from LDL was greater than from CERM (2-4X) and HDL (5-10X). Halftimes for [(14)C]CE hydrolysis were 3.0±0.2, 4.4±0.6 and 5.4±0.7h respectively for HDL, CERM and LDL-CE. The fraction of sterols secreted as bile acids was ~50% by 8h for all three particles. HDL, CERM and LDL-CE metabolism in mice showed efficient plasma clearance of CERM-CE, liver uptake and metabolism, and secretion as bile acids into the gall bladder. This work supports the therapeutic potential of the SOF reaction, which diverts HDL-CE to the LDLR, thereby increasing hepatic CE uptake, and sterol disposal as bile acids. PMID:26709142

  12. Wild rice ( Zizania latifolia (Griseb) Turcz) improves the serum lipid profile and antioxidant status of rats fed with a high fat/cholesterol diet.

    PubMed

    Zhang, Hong; Cao, Pei; Agellon, Luis B; Zhai, Cheng-Kai

    2009-12-01

    The diet consumed by urban residents in modern China has become rich in saturated fats and cholesterol. In addition, the diet is high in carbohydrates from white rice and processed wheat starch. The aim of the present study was to determine the effects of replacing white rice and processed wheat starch with wild rice (WR) as the chief source of dietary carbohydrates. Rats fed with the diet patterned after the diet consumed by city residents of modern China showed elevated serum lipid levels comparable with rats consuming a high fat/cholesterol diet known to induce hyperlipidaemia in this species. Meanwhile, rats consuming the city diet with WR as the carbohydrate source suppressed the increase in serum TAG and total cholesterol, and the decrease in HDL cholesterol level. In addition, the rats fed the WR diet suppressed the build-up of oxidative stress by improving antioxidant capacity, increasing superoxide dismutase activity and reducing malondialdehyde concentration, both in the serum and liver. These findings illustrate that WR is effective in suppressing hyperlipidaemia and oxidative stress in rats even when the diet consumed is high in fat and cholesterol. PMID:19631021

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  14. Comparison of the frequency and level of serum total cholesterol >300 mg/dL in patients at the same Texas hospital in a single month in 1993 and in 2013

    PubMed Central

    Ko, Jong Mi; Benavides, Raul

    2014-01-01

    The clinical pathology laboratory database of a large tertiary hospital in Dallas, Texas, was searched for patients having a serum total cholesterol > 300 mg in a single month in 1993 and in 2013. In September 1993, 63 patients had a serum total cholesterol > 300 mg/dL (range 302–1515 [mean 431, median 349]), and in September 2013, 12 patients had serum total cholesterol levels > 300 mg/dL (range 303–442 [mean 334, median 316.5]), an 81% decline in the numbers of patients and a 23% decline in the average total cholesterol levels during the 20-year period. PMID:24688188

  15. The non-psychoactive plant cannabinoid, cannabidiol affects cholesterol metabolism-related genes in microglial cells.

    PubMed

    Rimmerman, Neta; Juknat, Ana; Kozela, Ewa; Levy, Rivka; Bradshaw, Heather B; Vogel, Zvi

    2011-08-01

    Cannabidiol (CBD) is a non-psychoactive plant cannabinoid that is clinically used in a 1:1 mixture with the psychoactive cannabinoid Δ(9)-tetrahydrocannabinol (THC) for the treatment of neuropathic pain and spasticity in multiple sclerosis. Our group previously reported that CBD exerts anti-inflammatory effects on microglial cells. In addition, we found that CBD treatment increases the accumulation of the endocannabinoid N-arachidonoyl ethanolamine (AEA), thus enhancing endocannabinoid signaling. Here we proceeded to investigate the effects of CBD on the modulation of lipid-related genes in microglial cells. Cell viability was tested using FACS analysis, AEA levels were measured using LC/MS/MS, gene array analysis was validated with real-time qPCR, and cytokine release was measured using ELISA. We report that CBD significantly upregulated the mRNAs of the enzymes sterol-O-acyl transferase (Soat2), which synthesizes cholesteryl esters, and of sterol 27-hydroxylase (Cyp27a1). In addition, CBD increased the mRNA of the lipid droplet-associated protein, perilipin2 (Plin2). Moreover, we found that pretreatment of the cells with the cholesterol chelating agent, methyl-β-cyclodextrin (MBCD), reversed the CBD-induced increase in Soat2 mRNA but not in Plin2 mRNA. Incubation with AEA increased the level of Plin2, but not of Soat2 mRNA. Furthermore, MBCD treatment did not affect the reduction by CBD of the LPS-induced release of the proinflammatory cytokine IL-1β. CBD treatment modulates cholesterol homeostasis in microglial cells, and pretreatment with MBCD reverses this effect without interfering with CBD's anti-inflammatory effects. The effects of the CBD-induced increase in AEA accumulation on lipid-gene expression are discussed. PMID:21533611

  16. Influence of thermally-oxidized vegetable oils and animal fats on growth performance, liver gene expression, and liver and serum cholesterol and triglycerides in young pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To evaluate the effect of feeding thermally-oxidized vegetable oils and animal fats on growth performance, liver gene expression, and liver and serum fatty acid and cholesterol concentration in young pigs, 102 barrows (6.67 ± 0.03 kg BW) were divided into 3 groups and randomly assigned to dietary tr...

  17. Modification of Cellular Cholesterol Content Affects Traction Force, Adhesion and Cell Spreading

    PubMed Central

    Norman, Leann L.; Oetama, Ratna J.; Dembo, Micah; Byfield, F.; Hammer, Daniel A.; Levitan, Irena; Aranda-Espinoza, Helim

    2011-01-01

    Cellular cholesterol is a critical component of the plasma membrane, and plays a key role in determining the physical properties of the lipid bilayer, such as elasticity, viscosity, and permeability. Surprisingly, it has been shown that cholesterol depletion increases cell stiffness, not due to plasma membrane stiffening, but rather, due to the interaction between the actin cytoskeleton and the plasma membrane. This indicates that traction stresses of the acto-myosin complex likely increase during cholesterol depletion. Here we use force traction microscopy to quantify the forces individual cells are exerting on the substrate, and total internal reflection fluorescence microscopy as well as interference reflection microscopy to observe cell–substrate adhesion and spreading. We show that single cells depleted of cholesterol produce larger traction forces and have large focal adhesions compared to untreated or cholesterol-enriched cells. Cholesterol depletion also causes a decrease in adhesion area for both single cells and monolayers. Spreading experiments illustrate a decrease in spreading area for cholesterol-depleted cells, and no effect on cholesterol-enriched cells. These results demonstrate that cholesterol plays an important role in controlling and regulating the cell–substrate interactions through the actin–plasma membrane complex, cell–cell adhesion, and spreading. PMID:21461187

  18. A dual enzymatic-biosensor for simultaneous determination of glucose and cholesterol in serum and peritoneal macrophages of diabetic mice: evaluation of the diabetes-accelerated atherosclerosis risk.

    PubMed

    Huang, Qilin; An, Yarui; Tang, Linlin; Jiang, Xiaoli; Chen, Hua; Bi, Wenji; Wang, Zhongchuan; Zhang, Wen

    2011-11-30

    In this paper, a novel dual enzymatic-biosensor is described for simultaneous determination of glucose and cholesterol in serum and peritoneal macrophages (PMs) of diabetic mice to evaluate the risk of diabetes-accelerated atherosclerosis. The biosensor was constructed by a three-step method. First, a poly-thionine (PTH) film was assembled on the surface of glassy carbon electrode by cyclic voltammetric electropolymerization of thionine, which serves as an electron transfer mediator (ETM). Second, gold nanoparticles (GNPs) were covered on the surface of PTH facilitating the electron transfer between glucose oxidase (GOx), cholesterol oxidase (ChOx) and electrode. Finally, the enzymes, GOx, cholesterol esterase (ChE), and ChOx, were covalently attached to the PTH layer through a chitosan (CH) linker. The PTH coupled with GNPs provides good selectivity, high sensitivity and little crosstalk for the dual enzymatic-biosensor. The developed biosensor had good electrocatalytic activity toward the oxidations of glucose and cholesterol, exhibiting a linear range from 0.008 mM to 6.0 mM for glucose with a detection limit of 2.0 μM, and a linear range from 0.002 mM to 1.0 mM for cholesterol with a detection limit of 0.6 μM. The results of the diabetic mice demonstrated that the cholesterol level did not change obviously with the increase of glucose level in serum, while the cholesterol level was induced with the increase of the glucose level in PMs. Previous studies have shown that the large accumulation of cholesterol in macrophage could lead to macrophage foam cell formation, which is the hallmark of early atherosclerosis. This study provides useful further evidences for the development of diabetes-accelerated atherosclerosis. PMID:22027130

  19. Association between total serum cholesterol and depression, aggression, and suicidal ideations in war veterans with posttraumatic stress disorder: a cross-sectional study

    PubMed Central

    Vilibić, Maja; Jukić, Vlado; Pandžić-Sakoman, Mirna; Bilić, Petar; Milošević, Milan

    2014-01-01

    Aim To investigate the relationship between total serum cholesterol and levels of depression, aggression, and suicidal ideations in war veterans with posttraumatic stress disorder (PTSD) without psychiatric comorbidity. Methods A total of 203 male PTSD outpatients were assessed for the presence of depression, aggression, and suicidality using the 17-item Hamilton Depression Rating Scale (HAM-D17), Corrigan Agitated Behavior Scale (CABS), and Scale for Suicide Ideation (SSI), respectively, followed by plasma lipid parameters determination (total cholesterol, high density lipoprotein [HDL]-cholesterol, low density lipoprotein [LDL]-cholesterol, and triglycerides). PTSD severity was assessed using the Clinician-Administered PTSD Scale for DSM-IV, Current and Lifetime Diagnostic Version (CAPS-DX) and the Clinical Global Impressions of Severity Scale (CGI-S), before which Mini-International Neuropsychiatric Interview (MINI) was administered to exclude psychiatric comorbidity and premorbidity. Results After adjustments for PTSD severity, age, body mass index, marital status, educational level, employment status, use of particular antidepressants, and other lipid parameters (LDL- and HDL- cholesterol and triglycerides), higher total cholesterol was significantly associated with lower odds for having higher suicidal ideation (SSI≥20) (odds ratio [OR] 0.09; 95% confidence interval [CI] 0.03-0.23], clinically significant aggression (CABS≥22) (OR 0.28; 95% CI 0.14-0.59), and at least moderate depressive symptoms (HAM-D17≥17) (OR 0.20; 95% CI 0.08-0.48). Association of total cholesterol and HAM-D17 scores was significantly moderated by the severity of PTSD symptoms (P < 0.001). Conclusion Our results indicate that higher total serum cholesterol is associated with lower scores on HAM-D17, CABS, and SSI in patients with chronic PTSD. PMID:25358885

  20. The importance of low serum levels of high-density lipoprotein cholesterol (HDL-C) as a cardiovascular risk factor.

    PubMed

    Espinosa-Larrañaga, Francisco; Vejar-Jalaf, Margarita; Medina-Santillán, Roberto

    2005-10-01

    In order to discuss and establish a joint position on the treatment of low serum levels of high-density lipoprotein cholesterol (HDL-C), a group of experts involved in the care of people with dyslipidaemia and at risk of cardiovascular disease met in Miami, Florida, U.S., on 5th and 6th March 2005. The experts came from the Latin American countries Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Mexico and Venezuela and had at least five years of experience in the care of patients with dyslipidaemia and low HDL-C. The main objective of the meeting was to discuss and propose a treatment for low serum HDL-C levels as a cardiovascular risk factor in patients and to create a group of useful recommendations in this regard, applicable to the daily clinical practice of physicians dealing with patients with dyslipidaemia and cardiovascular disease. This document describes the methodology developed to obtain these recommendations and presents the results of this academic meeting. PMID:16342610

  1. The Level of Serum Cholesterol is Negatively Associated with Lean Body Mass in Korean non-Diabetic Cancer Patients

    PubMed Central

    2016-01-01

    Due to poor nutrition and abnormal energy metabolism, cancer patients typically experience the loss of muscle mass. Although the diabetic conditions or dyslipidemia have been reported as a causal link of cancer but the consequence of such conditions in relation to gain or loss of skeletal muscle mass in cancer patients has not been well documented. The purpose of this study was to investigate the relationship of lean body mass and systemic parameters related to lipid metabolism in non-diabetic cancer patients using data from the Korean National Health and Nutrition Examination Survey (KNHANES) 2008-2011. As results the level of serum total cholesterol (total-C) was negatively associated with both total lean body mass and appendicular lean body mass in cancer patients after adjustment for sex, physical activity, energy intake and comorbidity. The associations between consumption of dietary factors (energy, carbohydrate, protein and fat) and lean body mass were disappeared after adjusting comorbidities of cancer patients. Multivariate-adjusted linear regression analysis by quartiles of serum total-C showed that higher quartile group of total-C had significantly lower percent of lean body mass than reference group in cancer patients. The data indicate that serum lipid status can be the potential estimate of loss of skeletal muscle mass in cancer patients and be referenced in nutrition care of cancer patients under the onset of cachexia or parenteral/enteral nutrition. This data need to be confirmed with large pool of subjects and should be specified by stage of cancer or the site of cancer in future studies. PMID:27152302

  2. The Level of Serum Cholesterol is Negatively Associated with Lean Body Mass in Korean non-Diabetic Cancer Patients.

    PubMed

    Han, Ji Eun; Lee, Jun Yeup; Bu, So Young

    2016-04-01

    Due to poor nutrition and abnormal energy metabolism, cancer patients typically experience the loss of muscle mass. Although the diabetic conditions or dyslipidemia have been reported as a causal link of cancer but the consequence of such conditions in relation to gain or loss of skeletal muscle mass in cancer patients has not been well documented. The purpose of this study was to investigate the relationship of lean body mass and systemic parameters related to lipid metabolism in non-diabetic cancer patients using data from the Korean National Health and Nutrition Examination Survey (KNHANES) 2008-2011. As results the level of serum total cholesterol (total-C) was negatively associated with both total lean body mass and appendicular lean body mass in cancer patients after adjustment for sex, physical activity, energy intake and comorbidity. The associations between consumption of dietary factors (energy, carbohydrate, protein and fat) and lean body mass were disappeared after adjusting comorbidities of cancer patients. Multivariate-adjusted linear regression analysis by quartiles of serum total-C showed that higher quartile group of total-C had significantly lower percent of lean body mass than reference group in cancer patients. The data indicate that serum lipid status can be the potential estimate of loss of skeletal muscle mass in cancer patients and be referenced in nutrition care of cancer patients under the onset of cachexia or parenteral/enteral nutrition. This data need to be confirmed with large pool of subjects and should be specified by stage of cancer or the site of cancer in future studies. PMID:27152302

  3. Dietary supplementation with cholesterol and docosahexaenoic acid affects concentrations of amino acids in tissues of young pigs

    PubMed Central

    Li, Peng; Kim, Sung Woo; Li, Xilong; Datta, Sujay; Pond, Wilson G.

    2013-01-01

    Cholesterol and docosahexaenoic acid (DHA) are important nutrients for neural development of infants. However, little is known about the effect of cholesterol or DHA on concentrations of amino acids (AA) in neonatal tissues. This study was conducted with the piglet (an established model for studying human infant nutrition) to test the hypothesis that dietary supplementation with the lipids may modulate AA availability in tissues. Sixteen newborn pigs were nursed by sows for 24 h and then assigned to one of four treatment groups, representing supplementation with 0.0% (control), 0.2% cholesterol, 0.2% DHA, or cholesterol plus DHA to the basal milk-formula. All piglets were euthanized at 49 days of age. In brain, cholesterol supplementation reduced (P < 0.05) concentrations of glutamate, serine, glutamine, threonine, β-alanine, alanine, methionine, isoleucine, leucine, and γ-aminobutyrate but increased (P < 0.05) concentrations of glycine and lysine, whereas DHA supplementation similarly affected (P < 0.05) concentrations of the same AA (except for isoleucine and lysine) and taurine. In addition, concentrations of most AA in liver, muscle and plasma were substantially altered by dietary supplementation of cholesterol and DHA in a tissue-dependent manner. Further, DHA reduced concentrations of carnosine in skeletal muscle, as well as ammonia in both plasma and brain. The results reveal that cholesterol and DHA can regulate AA metabolism and availability in various tissues of piglets. These novel findings have important implications for designing the next generation of infant formula to optimize neonatal growth and development. PMID:18972185

  4. Streptococcal serum opacity factor increases the rate of hepatocyte uptake of human plasma high-density lipoprotein cholesterol.

    PubMed

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

    2010-11-16

    Serum opacity factor (SOF), a virulence determinant of Streptococcus pyogenes, converts plasma high-density lipoproteins (HDL) to three distinct species: lipid-free apolipoprotein (apo) A-I, neo HDL, a small discoidal HDL-like particle, and a large cholesteryl ester-rich microemulsion (CERM) that contains the cholesterol esters (CE) of up to ∼400000 HDL particles and apo E as its major protein. Similar SOF reaction products are obtained with HDL, total plasma lipoproteins, and whole plasma. We hypothesized that hepatic uptake of CERM-CE via multiple apo E-dependent receptors would be faster than that of HDL-CE. We tested our hypothesis using human hepatoma cells and lipoprotein receptor-specific Chinese hamster ovary (CHO) cells. The uptake of [(3)H]CE by HepG2 and Huh7 cells from HDL after SOF treatment, which transfers >90% of HDL-CE to CERM, was 2.4 and 4.5 times faster, respectively, than from control HDL. CERM-[(3)H]CE uptake was inhibited by LDL and HDL, suggestive of uptake by both the LDL receptor (LDL-R) and scavenger receptor class B type I (SR-BI). Studies in CHO cells specifically expressing LDL-R and SR-BI confirmed CERM-[(3)H]CE uptake by both receptors. RAP and heparin inhibit CERM-[(3)H]CE but not HDL-[(3)H]CE uptake, thereby implicating LRP-1 and cell surface proteoglycans in this process. These data demonstrate that SOF treatment of HDL increases the rate of CE uptake via multiple hepatic apo E receptors. In so doing, SOF might increase the level of hepatic disposal of plasma cholesterol in a way that is therapeutically useful. PMID:20879789

  5. Fabrication and Optimization of ChE/ChO/HRP-AuNPs/c-MWCNTs Based Silver Electrode for Determining Total Cholesterol in Serum.

    PubMed

    Lata, Kusum; Dhull, Vikas; Hooda, Vikas

    2016-01-01

    The developed method used three enzymes comprised of cholesterol esterase, cholesterol oxidase, and peroxidase for fabrication of amperometric biosensor in order to determine total cholesterol in serum samples. Gold nanoparticles (AuNPs) and carboxylated multiwall carbon nanotubes (cMWCNTs) were used to design core of working electrode, having covalently immobilized ChO, ChE, and HRP. Polyacrylamide layer was finally coated on working electrode in order to prevent enzyme leaching. Chemically synthesised Au nanoparticles were subjected to transmission electron microscopy (TEM) for analysing the shape and size of the particles. Working electrode was subjected to FTIR and XRD. The combined action of AuNP and c-MWCNT showed enhancement in electrocatalytic activity at a very low potential of 0.27 V. The pH 7, temperature 40°C, and response time of 20 seconds, respectively, were observed. The biosensor shows a broad linear range from 0.5 mg/dL to 250 mg/dL (0.01 mM-5.83 mM) with minimum detection limit being 0.5 mg/dL (0.01 mM). The biosensor showed reusability of more than 45 times and was stable for 60 days. The biosensor was successfully tested for determining total cholesterol in serum samples amperometrically with no significant interference by serum components. PMID:26885393

  6. Fabrication and Optimization of ChE/ChO/HRP-AuNPs/c-MWCNTs Based Silver Electrode for Determining Total Cholesterol in Serum

    PubMed Central

    Lata, Kusum; Dhull, Vikas

    2016-01-01

    The developed method used three enzymes comprised of cholesterol esterase, cholesterol oxidase, and peroxidase for fabrication of amperometric biosensor in order to determine total cholesterol in serum samples. Gold nanoparticles (AuNPs) and carboxylated multiwall carbon nanotubes (cMWCNTs) were used to design core of working electrode, having covalently immobilized ChO, ChE, and HRP. Polyacrylamide layer was finally coated on working electrode in order to prevent enzyme leaching. Chemically synthesised Au nanoparticles were subjected to transmission electron microscopy (TEM) for analysing the shape and size of the particles. Working electrode was subjected to FTIR and XRD. The combined action of AuNP and c-MWCNT showed enhancement in electrocatalytic activity at a very low potential of 0.27 V. The pH 7, temperature 40°C, and response time of 20 seconds, respectively, were observed. The biosensor shows a broad linear range from 0.5 mg/dL to 250 mg/dL (0.01 mM–5.83 mM) with minimum detection limit being 0.5 mg/dL (0.01 mM). The biosensor showed reusability of more than 45 times and was stable for 60 days. The biosensor was successfully tested for determining total cholesterol in serum samples amperometrically with no significant interference by serum components. PMID:26885393

  7. Food products containing free tall oil-based phytosterols and oat beta-glucan lower serum total and LDL cholesterol in hypercholesterolemic adults.

    PubMed

    Maki, Kevin C; Shinnick, Fred; Seeley, Marlyn A; Veith, Patricia E; Quinn, Laura C; Hallissey, Pamela J; Temer, Arlene; Davidson, Michael H

    2003-03-01

    This randomized, double-blind, controlled trial evaluated the influence of low fat, low saturated fat food products that contained free tall oil-based phytosterols (TOP) and oat beta-glucan (from whole oats and bran concentrate) on serum lipid concentrations in adults with mild-to-moderate hypercholesterolemia. After a 5-wk National Cholesterol Education Program Step I diet lead-in period, 112 subjects incorporated one of two treatments into their diets for 6 wk: food products (cereal, snack bar and beverage) that provided 1.8 g TOP and 2.8 g beta-glucan/d and contained < or =3.0 g total fat and < or =1.0 g saturated fat (TOP/beta-glucan treatment) or similar control foods. The serum LDL cholesterol response from baseline to the end of study was significantly larger in the TOP/beta-glucan treated group than in the control group, in which there was no change (-3.7 vs. 0.4%; P = 0.013). Likewise, total cholesterol decreased in the TOP/beta-glucan treatment group and did not change significantly in the controls (-2.3 vs. 0.8%; P = 0.043). Serum HDL cholesterol and triglyceride responses did not differ between the groups. The results of this trial suggest that consumption of a group of low fat, TOP and beta-glucan- containing foods is a useful adjunct in the dietary management of hypercholesterolemia. PMID:12612157

  8. Cytolethal Distending Toxin Family Members Are Differentially Affected by Alterations in Host Glycans and Membrane Cholesterol*

    PubMed Central

    Eshraghi, Aria; Maldonado-Arocho, Francisco J.; Gargi, Amandeep; Cardwell, Marissa M.; Prouty, Michael G.; Blanke, Steven R.; Bradley, Kenneth A.

    2010-01-01

    Cytolethal distending toxins (CDTs) are tripartite protein exotoxins produced by a diverse group of pathogenic Gram-negative bacteria. Based on their ability to induce DNA damage, cell cycle arrest, and apoptosis of cultured cells, CDTs are proposed to enhance virulence by blocking cellular division and/or directly killing epithelial and immune cells. Despite the widespread distribution of CDTs among several important human pathogens, our understanding of how these toxins interact with host cells is limited. Here we demonstrate that CDTs from Haemophilus ducreyi, Aggregatibacter actinomycetemcomitans, Escherichia coli, and Campylobacter jejuni differ in their abilities to intoxicate host cells with defined defects in host factors previously implicated in CDT binding, including glycoproteins, and glycosphingolipids. The absence of cell surface sialic acid sensitized cells to intoxication by three of the four CDTs tested. Surprisingly, fucosylated N-linked glycans and glycolipids, previously implicated in CDT-host interactions, were not required for intoxication by any of the CDTs tested. Finally, altering host-cellular cholesterol, also previously implicated in CDT binding, affected intoxication by only a subset of CDTs tested. The findings presented here provide insight into the molecular and cellular basis of CDT-host interactions. PMID:20385557

  9. Cholesterol level affects surface charge of lipid membranes in saline solution

    PubMed Central

    Magarkar, Aniket; Dhawan, Vivek; Kallinteri, Paraskevi; Viitala, Tapani; Elmowafy, Mohammed; Róg, Tomasz; Bunker, Alex

    2014-01-01

    Cholesterol is an important component of all biological membranes as well as drug delivery liposomes. We show here that increasing the level of cholesterol in a phospholipid membrane decreases surface charge in the physiological environment. Through molecular dynamics simulation we have shown that increasing the level of cholesterol decreases Na+ ion binding. Complementary experimental ζ – potential measurements have shown a decreased ζ – potential with increasing cholesterol content, indicative of reduced surface charge. Both experiments and simulations have been carried out on both saturated 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and monounsaturated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membranes. This result is particularly important because membrane surface charge plays an important role in the interactions of biomembranes with peripheral membrane proteins and drug delivery liposomes with the immune system. PMID:24845659

  10. Contrast Ultrasound Imaging Does Not Affect Heat Shock Protein 70 Expression in Cholesterol-Fed Rabbit Aorta

    PubMed Central

    Smith, Brendon W.; Simpson, Douglas G.; Miller, Rita J.; Erdman, John W.; O’Brien, William D.

    2015-01-01

    Objectives Diagnostic ultrasound imaging is enhanced by the use of circulating microbubble contrast agents (UCAs), but the interactions between ultrasound, UCAs, and vascular tissue are not fully understood. We hypothesized that ultrasound with a UCA would stress the vascular tissue and increase levels of heat shock protein 70 (Hsp70), a cellular stress protein. Methods Male New Zealand White rabbits (n = 32) were fed a standard chow diet (n = 4) or a 1% cholesterol, 10% fat, and 0.11% magnesium diet (n = 28). At 21 days, 24 rabbits on the cholesterol diet were either exposed to ultrasound (3.2-MHz f/3 transducer; 2.1 MPa; mechanical index, 1.17; 10 Hz pulse repetition frequency; 1.6 micro -seconds pulse duration; 2 minutes exposure duration at 4 sites along the aorta) with the UCA Definity (1× concentration, 1 mL/min; Lantheus Medical Imaging, North Billerica, MA) or sham exposed with a saline vehicle injection (n = 12 per group). Four rabbits on the cholesterol diet and 4 on the chow diet served as cage controls and were not exposed to ultrasound or restrained for blood sample collection. Animals were euthanized 24 hours after exposure, and aortas were quickly isolated and frozen in liquid nitrogen. Aorta lysates from the area of ultrasound exposure were analyzed for Hsp70 level by Western blot. Blood plasma was analyzed for cholesterol, Hsp70, and von Willebrand factor, a marker of endothelial function. Results Plasma total cholesterol levels increased to an average of 705 mg/dL. Ultrasound did not affect plasma von Willebrand factor, plasma Hsp70, or aorta Hsp70. Restraint increased Hsp70 (P < .001, analysis of variance). Conclusions Restraint, but not ultrasound with the UCA or cholesterol feeding, significantly increased Hsp70. PMID:26112623

  11. LXR driven induction of HDL-cholesterol is independent of intestinal cholesterol absorption and ABCA1 protein expression.

    PubMed

    Kannisto, Kristina; Gåfvels, Mats; Jiang, Zhao-Yan; Slätis, Katharina; Hu, Xiaoli; Jorns, Carl; Steffensen, Knut R; Eggertsen, Gösta

    2014-01-01

    We investigated whether: (1) liver X receptor (LXR)-driven induction of high-density lipoprotein cholesterol (HDL-C) and other LXR-mediated effects on cholesterol metabolism depend on intestinal cholesterol absorption; and (2) combined treatment with the LXR agonist GW3965 and the cholesterol absorption inhibitor ezetimibe results in synergistic effects on cholesterol metabolism that could be beneficial for treatment of atherosclerosis. Mice were fed 0.2 % cholesterol and treated with GW3965+ezetimibe, GW3965 or ezetimibe. GW3965+ezetimibe treatment elevated serum HDL-C and Apolipoprotein (Apo) AI, effectively reduced the intestinal cholesterol absorption and increased the excretion of faecal neutral sterols. No changes in intestinal ATP-binding cassette (ABC) A1 or ABCG5 protein expression were observed, despite increased mRNA expression, while hepatic ABCA1 was slightly reduced. The combined treatment caused a pronounced down-regulation of intestinal Niemann-Pick C1-like 1 (NPC1L1) and reduced hepatic and intestinal cholesterol levels. GW3965 did not affect the intestinal cholesterol absorption, but increased serum HDL-C and ApoAI levels. GW3965 also increased Apoa1 mRNA levels in primary mouse hepatocytes and HEPA1-6 cells. Ezetimibe reduced the intestinal cholesterol absorption, ABCA1 and ABCG5, but did not affect the serum HDL-C or ApoAI levels. Thus, the LXR-driven induction of HDL-C and ApoAI was independent of the intestinal cholesterol absorption and increased expression of intestinal or hepatic ABCA1 was not required. Inhibited influx of cholesterol via NPC1L1 and/or low levels of intracellular cholesterol prevented post-transcriptional expression of intestinal ABCA1 and ABCG5, despite increased mRNA levels. Combined LXR activation and blocked intestinal cholesterol absorption induced effective faecal elimination of cholesterol. PMID:24163219

  12. Effects of Physical Examination and Diet Consultation on Serum Cholesterol and Health-behavior in the Korean Pilots Employed in Commercial Airline

    PubMed Central

    CHOI, Yun Young; KIM, Ki Youn

    2013-01-01

    An objective of this study is to search how physical examination and diet consultation can influence those risk factors of cardiovascular disease. The subjects were 326 pilots of the “B” airline company in Korea whose total cholesterol values were over 220 mg/dl on their regular physical examinations from April 2006 to December 2008. They were divided into two groups, one who had diet consultation (an intervention group) and a control group. The physical examination components used to each group were body mass index (BMI), total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL) and triglyceride (TG). The behavioral, anthropometric and biomedical measurements were collected at each visit. This study compares and investigates the changes of serum cholesterol and also the health-behavior at each physical examination. Within the intervention group significant improvements were observed for total cholesterol, BMI (body mass index) and HDL (high density lipoprotein). The normalizing rates for cholesterol level to decrease down to lower than 200 mg/dl were 17.7% in intervention group and 8.7% in control group, which is statistically significantly higher among the intervention group. The odds ratio of diet consultation was 2.80 (95% CI=1.35–5.79), which indicates that it is a significantly contributing factor to normalize the serum cholesterol value down to lower than 200 mg/dl. Based on result, it is recommended to have regular physical examination and intensive management with diet and exercise consultation. PMID:24131872

  13. Similar Reduction of Cholesterol-Adjusted Vitamin E Serum Levels in Simple Steatosis and Non-Alcoholic Steatohepatitis

    PubMed Central

    Pastori, Daniele; Baratta, Francesco; Carnevale, Roberto; Cangemi, Roberto; Del Ben, Maria; Bucci, Tommaso; Polimeni, Licia; Labbadia, Giancarlo; Nocella, Cristina; Scardella, Laura; Pani, Arianna; Pignatelli, Pasquale; Violi, Francesco; Angelico, Francesco

    2015-01-01

    Objectives: Reduced vitamin E levels have been reported in patients with non-alcoholic steatohepatitis (NASH), but no conclusive data on patients with simple steatosis (SS) are available. Aim of this study was to investigate the association between serum vitamin E levels and SS. Methods: A cohort of 312 patients with cardio-metabolic risk factors was screened for liver steatosis by ultrasonography (US). We reasonably classified as SS patients with US-fatty liver, normal liver function tests (LFTs) and with Cytokeratin 18 <246 mIU/ml. Liver biopsy was performed in 41 patients with US-fatty liver and persistent elevation of LFTs (>6 months). Serum cholesterol-adjusted vitamin E (Vit E/chol) levels were measured. Results: Mean age was 53.9±12.5 years and 38.4% were women. Non-alcoholic fatty liver disease (NAFLD) was detected at US in 244 patients; of those 39 had biopsy-proven NASH and 2 borderline NASH. Vit E/chol was reduced in both SS (3.4±2.0, P<0.001), and NASH (3.5±2.1, P=0.006) compared with non-NAFLD patients (4.8±2.0 μmol/mmol chol). No difference was found between SS and NASH (P=0.785). After excluding patients with NASH, a multivariable logistic regression analysis found that Vit E/chol (odds ratio (OR): 0.716, 95% confidence interval (CI) 0.602–0.851, P<0.001), alanine aminotransferase (ALT, OR: 1.093, 95% CI 1.029–1.161, P=0.004), body mass index (OR: 1.162, 95% CI 1.055–1.279, P=0.002) and metabolic syndrome (OR: 5.725, 95% CI 2.247–14.591, P<0.001) were factors independently associated with the presence of SS. Conclusions: Reduced vitamin E serum levels are associated with SS, with a similar reduction between patients with SS and NASH, compared with non-NAFLD patients. Our findings suggest that the potential benefit of vitamin E supplementation should be investigated also in patients with SS. PMID:26426796

  14. Plant sterol consumption frequency affects plasma lipid levels and cholesterol kinetics in humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background/Objectives: To compare the efficacy of single versus multiple doses of plant sterols on circulating lipid level and cholesterol trafficking. Subjects/Methods: A randomized, placebo-controlled, three-phase (6 days/phase) crossover, supervised feeding trial was conducted in 19 subjects. Sub...

  15. Timing of Levothyroxine Administration Affects Serum Thyrotropin Concentration

    PubMed Central

    Bach-Huynh, Thien-Giang; Nayak, Bindu; Loh, Jennifer; Soldin, Steven; Jonklaas, Jacqueline

    2009-01-01

    Context: Patients treated with levothyroxine typically ingest it in a fasting state to prevent food impairing its absorption. The serum thyrotropin concentration is the therapeutic index of levothyroxine action. Objective: The study objective was to determine the effect of the timing of levothyroxine administration in relationship to food on serum thyrotropin levels. Design: Participants were randomized to one of six sequences, each consisting of three 8-wk regimens in a three-period crossover design. These regimens were in a fasting state, at bedtime, and with breakfast. The concentrations of TSH, free T4, and total T3 during each of the three timing regimens were documented. The primary outcome was the difference between serum TSH concentrations under fasting conditions compared with concentrations during the other 8-wk regimens. Setting: The study was conducted in an academic medical center. Participants: Study participants were receiving levothyroxine for treatment of hypothyroidism or thyroid cancer. Results: Sixty-five patients completed the study. The mean thyrotropin concentration was 1.06 ± 1.23 mIU/liter when levothyroxine was administered in the fasting state. When levothyroxine was taken with breakfast, the serum thyrotropin concentration was significantly higher (2.93 ± 3.29 mIU/liter). When levothyroxine was taken at bedtime, the serum TSH concentration was also significantly higher (2.19 ± 2.66 mIU/liter). Conclusion: Nonfasting regimens of levothyroxine administration are associated with higher and more variable serum TSH concentrations. If a specific serum TSH goal is desired, thereby avoiding iatrogenic subclinical thyroid disease, then fasting ingestion of levothyroxine ensures that TSH concentrations remain within the narrowest target range. PMID:19584184

  16. Growth hormone (GH) replacement decreases serum total and LDL-cholesterol in hypopituitary patients on maintenance HMG CoA reductase inhibitor (statin) therapy

    PubMed Central

    Monson, John P; Jönsson, Peter; Koltowska-Häggström, Maria; Kourides, Ione

    2007-01-01

    Objective Adult onset GH deficiency (GHD) is characterized by abnormalities of serum lipoprotein profiles and GH replacement results in favourable alterations in serum total and low density lipoprotein (LDL)-cholesterol. Preliminary evidence has indicated that the effect of GH replacement in this respect may be additive to that of HMG CoA reductase inhibitor (statin) therapy. We have examined this possibility during prospective follow-up of adult onset hypopituitary patients enrolled in KIMS (Pfizer International Metabolic Database), a pharmacoepidemiological study of GH replacement in adult hypopituitary patients. Design Lipoprotein profiles were measured centrally at baseline and after 12 months GH replacement therapy. Patients Sixty-one hypopituitary patients (30 male, 31 female) on maintenance statin therapy (mean 2·5 ± 2·7 SD years before GH) (statin group – SG) and 1247 (608 male, 639 female) patients not on hypolipidaemic therapy (nonstatin group – NSG) were studied. All patients were naïve or had not received GH replacement during the 6 months prior to study. Patients who developed diabetes mellitus during the first year of GH therapy or in the subsequent year and those with childhood onset GHD were excluded from this analysis. An established diagnosis of diabetes mellitus was present in 18% SG and 4·4% NSG at baseline. Measurements Serum concentrations of total, high density lipoprotein (HDL)-cholesterol, triglycerides and IGF-I were measured centrally in all patients and LDL-cholesterol was estimated using Friedewald's formula. Results The relative frequency of various statin use was simvastatin 52% (15·8 ± 8·1 mg, mean ± SD), atorvastatin 30% (14·4 ± 7·8 mg), pravastatin 9·8% (31·6 mg ± 13·9 mg), lovastatin 6·6% (17·5 ± 5 mg) and fluvastatin 1·6% (40 mg). Baseline serum total and LDL-cholesterol (mean ± SD) were 5·2 ± 1·4 and 3·1 ± 1·3 mmol/l in SG and 5·8 ± 1·2 and 3·7 ± 1·0 mmol/l in NSG, respectively (P < 0·0001

  17. Increased serum triglyceride clearance and elevated high-density lipoprotein 2 and 3 cholesterol during treatment of primary hypertriglyceridemia with bezafibrate☆

    PubMed Central

    Sakuma, Nagahiko; Ikeuchi, Reiko; Hibino, Takeshi; Yoshida, Takayuki; Mukai, Seiji; Akita, Sachie; Yajima, Kazuhiro; Miyabe, Hiromichi; Goto, Toshihiko; Takada, Norio; Ohte, Nobuyuki; Kunimatu, Mitoshi; Kimura, Genjiro

    2003-01-01

    Background Hypertriglyceridemia accompanied by low levels of high-density lipoprotein cholesterol (HDL-C) is a risk factor for coronary artery disease. High-density lipoprotein 2 (HDL2) and 3 (HDL3) are believed to suppress the progress of atherosclerosis through reverse cholesterol transport. As a result, peripheral tissues can be protected against excessive accumulation of cholesterol. Although bezafibrate is known to accelerate the increase of HDL-C, results are not standardized regarding increases of HDL3 and HDL2 subfractions. Objective This study assessed the effects of bezafibrate on serum triglyceride (TG) fractional clearance rate (K2) and HDL2 and HDL3 cholesterol (HDL2-C and HDL3-C, respectively) levels in patients with primary hypertriglyceridemia (serum TG ≥150 mg/dL). Methods Outpatients with primary hypertriglyceridemia were enrolled in this 8-week study conducted at the Third Department of Internal Medicine, Nagoya City University Hospital (Nagoya, Japan). Oral bezafibrate was administered at a dose of 400 mg/d (200-mg tablet BID, morning and evening) for 8 weeks. After 8 weeks, serum levels of total cholesterol (TC), TG, HDL-C, HDL2-C, and HDL3-C were measured. A fat emulsion tolerance test to assess K2 and measurements of plasma lipoprotein lipase (LPL) mass, LPL activity, and hepatic triglyceride lipase (HTGL) activity in postheparin plasma were performed before bezafibrate administration and after the course of treatment. Results Sixteen patients (10 men, 6 women; mean [SD] age, 54 [12] years [range, 30–69 years]; mean [SD] body mass index, 23 [2] kg/m2) entered the study. The following findings were observed in male and female patients after 8 weeks of treatment. A statistically significant reduction was observed in mean serum TG level (P<0.01). Significant increases were seen in HDL-C, HDL2-C, and HDL3-C (all P<0.01), K2 (P<0.01), and in plasma LPL mass (P<0.01) and LPL activity (P<0.05). TC level and HTGL activity did not change

  18. Evidence for several independent genetic variants affecting lipoprotein (a) cholesterol levels

    PubMed Central

    Lu, Wensheng; Cheng, Yu-Ching; Chen, Keping; Wang, Hong; Gerhard, Glenn S.; Still, Christopher D.; Chu, Xin; Yang, Rongze; Parihar, Ankita; O'Connell, Jeffrey R.; Pollin, Toni I.; Angles-Cano, Eduardo; Quon, Michael J.; Mitchell, Braxton D.; Shuldiner, Alan R.; Fu, Mao

    2015-01-01

    Lipoprotein (a) [Lp(a)] is an independent risk factor for atherosclerosis-related events that is under strong genetic control (heritability = 0.68–0.98). However, causal mutations and functional validation of biological pathways modulating Lp(a) metabolism are lacking. We performed a genome-wide association scan to identify genetic variants associated with Lp(a)-cholesterol levels in the Old Order Amish. We confirmed a previously known locus on chromosome 6q25-26 and found Lp(a) levels also to be significantly associated with a SNP near the APOA5–APOA4–APOC3–APOA1 gene cluster on chromosome 11q23 linked in the Amish to the APOC3 R19X null mutation. On 6q locus, we detected associations of Lp(a)-cholesterol with 118 common variants (P = 5 × 10−8 to 3.91 × 10−19) spanning a ∼5.3 Mb region that included the LPA gene. To further elucidate variation within LPA, we sequenced LPA and identified two variants most strongly associated with Lp(a)-cholesterol, rs3798220 (P = 1.07 × 10−14) and rs10455872 (P = 1.85 × 10−12). We also measured copy numbers of kringle IV-2 (KIV-2) in LPA using qPCR. KIV-2 numbers were significantly associated with Lp(a)-cholesterol (P = 2.28 × 10−9). Conditional analyses revealed that rs3798220 and rs10455872 were associated with Lp(a)-cholesterol levels independent of each other and KIV-2 copy number. Furthermore, we determined for the first time that levels of LPA mRNA were higher in the carriers than non-carriers of rs10455872 (P = 0.0001) and were not different between carriers and non-carriers of rs3798220. Protein levels of apo(a) were higher in the carriers than non-carriers of both rs10455872 and rs3798220. In summary, we identified multiple independent genetic determinants for Lp(a)-cholesterol. These findings provide new insights into Lp(a) regulation. PMID:25575512

  19. Dietary freshwater clam (Corbicula fluminea) extract suppresses accumulation of hepatic lipids and increases in serum cholesterol and aminotransferase activities induced by dietary chloretone in rats.

    PubMed

    Chijimatsu, Takeshi; Umeki, Miki; Kobayashi, Satoru; Kataoka, Yutaro; Yamada, Koji; Oda, Hiroaki; Mochizuki, Satoshi

    2015-01-01

    We investigated the ameliorative effect of freshwater clam extract (FCE) on fatty liver, hypercholesterolemia, and liver injury in rats exposed to chloretone. Furthermore, we examined the effects of major FCE components (fat and protein fractions) to determine the active components in FCE. Chloretone increased serum aminotransferase activities and led to hepatic lipid accumulation. Serum aminotransferase activities and hepatic lipid content were lower in rats fed total FCE or fat/protein fractions of FCE. Expression of fatty acid synthase and fatty acid desaturase genes was upregulated by chloretone. Total FCE and fat/protein fractions of FCE suppressed the increase in gene expression involved in fatty acid synthesis. Serum cholesterol levels increased twofold upon chloretone exposure. Total FCE or fat/protein fractions of FCE showed hypocholesterolemic effects in rats with hypercholesterolemia induced by chloretone. These suggest that FCE contains at least two active components against fatty liver, hypercholesterolemia, and liver injury in rats exposed to chloretone. PMID:25704646

  20. Supplemental barley protein and casein similarly affect serum lipids in hypercholesterolemic women and men.

    PubMed

    Jenkins, David J A; Srichaikul, Korbua; Wong, Julia M W; Kendall, Cyril W C; Bashyam, Balachandran; Vidgen, Edward; Lamarche, Benoicirct; Rao, A Venketeshwer; Jones, Peter J H; Josse, Robert G; Jackson, Chung-Ja C; Ng, Vivian; Leong, Tracy; Leiter, Lawrence A

    2010-09-01

    High-protein diets have been advocated for weight loss and the treatment of diabetes. Yet animal protein sources are often high in saturated fat and cholesterol. Vegetable protein sources, by contrast, are low in saturated fat and without associated cholesterol. We have therefore assessed the effect on serum lipids of raising the protein intake by 5% using a cereal protein, barley protein, as part of a standard therapeutic diet. Twenty-three hypercholesterolemic men and postmenopausal women completed a randomized crossover study comparing a bread enriched with either barley protein or calcium caseinate [30 g protein, 8374 kJ (2000 kcal)] taken separately as two 1-mo treatment phases with a minimum 2-wk washout. Body weight and diet history were collected weekly during each treatment. Fasting blood samples were obtained at wk 0, 2, and 4. Palatability, satiety, and compliance were similar for both the barley protein- and casein-enriched breads, with no differences between the treatments in effects on serum LDL cholesterol or C-reactive protein, measures of oxidative stress, or blood pressure. Nevertheless, because no adverse effects were observed on cardiovascular risk factors, barley protein remains an additional option for raising the protein content of the diet. PMID:20668250

  1. Uric acid or 1-methyl uric acid in the urinary bladder increases serum glucose, insulin, true triglyceride, and total cholesterol levels in Wistar rats.

    PubMed

    Balasubramanian, T

    2003-10-01

    In animals deprived of food for a long period, a drop in the fat mass below 5% of the total body mass results in an increase in blood glucocorticoids and uric acid levels, followed by foraging activity. Since the glucocorticoids increase the uric acid excretion, an increase in the level of uric acid in the bladder urine could be the signal for this feeding behaviour and subsequent fat storage. Accumulation of fat is associated with hyperglycaemia, hyperinsulinaemia, hyperlipidaemia, and hypercholesterolaemia as seen in the metabolic syndrome or hibernation. It is hypothesized that uric acid or its structurally related compound, 1-methyl uric acid (one of the metabolites of the methyl xanthines namely caffeine, theophylline, and theobromine present in coffee, tea, cocoa, and some drugs), can act on the urinary bladder mucosa and increases the blood glucose, insulin, triglyceride, and cholesterol levels. In rats, perfusion of the urinary bladder with saturated aqueous solution of uric acid or 1-methyl uric acid results in a significant increase in the serum levels of glucose, insulin, true triglyceride, and total cholesterol in comparison with perfusion of the bladder with distilled water at 20, 40, and 80 min. The uric acid or the 1-methyl uric acid acts on the urinary bladder mucosa and increases the serum glucose, insulin, true triglyceride, and total cholesterol levels. PMID:15241498

  2. A new cholesterol derivative suitable for transfecting certain type of cells in the presence of 10% serum.

    PubMed

    Sochanik, A; Kaida, I; Mitrus, I; Rajca, A; Szala, S

    2000-04-01

    We developed a new cationic lipid suitable for use as a DNA carrier in the presence of 10% sera. The novel compound (abbreviated as Arg-Chol) contains cholesterol and a dipeptide consisting of glycine and sterically protected arginine. The efficiency of reporter gene transfection using liposomes based on this new reagent was compared with that of liposomes made with other cationic derivatives of cholesterol. Lipoplexes formulated with the newly synthesized lipid mediate in vitro transfection of B16(F10) murine melanoma cells in the presence of 10% sera more efficiently than in other cell lines and compared with other cholesterol derivatives studied. PMID:10811467

  3. Alkaline sphingomyelinase (NPP7) promotes cholesterol absorption by affecting sphingomyelin levels in the gut: A study with NPP7 knockout mice.

    PubMed

    Zhang, Ping; Chen, Ying; Cheng, Yajun; Hertervig, Erik; Ohlsson, Lena; Nilsson, Ake; Duan, Rui-Dong

    2014-05-15

    We previously showed that dietary sphingomyelin (SM) inhibited cholesterol absorption in animals. The key enzyme hydrolyzing SM in the gut is alkaline sphingomyelinase (alk-SMase, nucleotide pyrophosphatase/phosphodiesterase 7). Here using the fecal dual-isotope ratio method we compared cholesterol absorption in the wild-type (WT) and alk-SMase knockout (KO) mice. The animals were fed an emulsion containing [(14)C]cholesterol and [(3)H]sitosterol. The radioactivities in the lipids of the fecal samples collected 4, 8, and 24 h thereafter were determined, and the ratio of (14)C/(3)H was calculated. We found that the fecal [(14)C]cholesterol recovery in the KO mice was significantly higher than in the WT mice. A maximal 92% increase occurred 8 h after feeding. Recovery of [(3)H]sitosterol did not differ between the two groups. Accordingly, the (14)C-to-(3)H ratio of fecal lipids was 133% higher at 8 h and 75% higher at 24 h in the KO than in the WT mice. Decreased [(14)C]cholesterol was also found in the serum of the KO mice 4 h after feeding. Supplement of SM in the emulsion reduced the differences in fecal [(14)C]cholesterol recovery between the WT and KO mice because of a greater increase of [(14)C]cholesterol recovery in the WT mice. Without treatment, the KO mice had significantly higher SM levels in the intestinal content and feces, but not in the intestinal mucosa or serum. The expression of Niemann-Pick C1 like 1 protein in the small intestine was not changed. In conclusion, alk-SMase is a physiological factor promoting cholesterol absorption by reducing SM levels in the intestinal lumen. PMID:24650549

  4. Polymorphism of rs1044925 in the acyl-CoA:cholesterol acyltransferase-1 gene and serum lipid levels in the Guangxi Bai Ku Yao and Han populations

    PubMed Central

    2010-01-01

    Background The association of rs1044925 polymorphism in the acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) gene and serum lipid profiles is not well known in different ethnic groups. Bai Ku Yao is a special subgroup of the Yao minority in China. The present study was carried out to clarify the association of rs1044925 polymorphism in the ACAT-1 gene and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations. Methods A total of 626 subjects of Bai Ku Yao and 624 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples. Genotyping of rs1044925 polymorphism in the ACAT-1 gene was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Results The levels of serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) AI and ApoB were lower in Bai Ku Yao than in Han (P < 0.01 for all). The frequency of A and C alleles was 79.0% and 21.0% in Bai Ku Yao, and 87.3% and 12.7% in Han (P < 0.001); respectively. The frequency of AA, AC and CC genotypes was 63.2%, 31.4% and 5.2% in Bai Ku Yao, and 75.6%, 23.2% and 1.1% in Han (P < 0.001); respectively. The levels of TC, LDL-C and ApoB in Bai Ku Yao but not in Han were different between the AA and AC/CC genotypes in females but not in males (P < 0.05 for all). The C allele carriers had lower serum TC, LDL-C and ApoB levels as compared with the C allele noncarriers. The levels of TC, LDL-C and ApoB in Bai Ku Yao but not in Han were correlated with genotypes in females but not in males (P < 0.05 for all). Serum lipid parameters were also correlated with sex, age, body mass index, alcohol consumption, and blood pressure in both ethnic groups (P < 0.05-0.001). Conclusions These results suggest that the polymorphism of rs1044925 in the ACAT-1 gene is mainly associated with female serum TC, LDL-C and

  5. Vitamin D Status Affects Serum Metabolomic Profiles in Pregnant Adolescents.

    PubMed

    Finkelstein, Julia L; Pressman, Eva K; Cooper, Elizabeth M; Kent, Tera R; Bar, Haim Y; O'Brien, Kimberly O

    2015-06-01

    Vitamin D is linked to a number of adverse pregnancy outcomes through largely unknown mechanisms. This study was conducted to examine the role of vitamin D status in metabolomic profiles in a group of 30 pregnant, African American adolescents (17.1 ± 1.1 years) at midgestation (26.8 ± 2.8 weeks), in 15 adolescents with 25-hydroxy vitamin D (25(OH)D) ≥20 ng/mL, and in 15 teens with 25(OH)D <20 ng/mL. Serum metabolomic profiles were examined using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry. A novel hierarchical mixture model was used to evaluate differences in metabolite profiles between low and high groups. A total of 326 compounds were identified and included in subsequent statistical analyses. Eleven metabolites had significantly different means between the 2 vitamin D groups, after correcting for multiple hypothesis testing: pyridoxate, bilirubin, xylose, and cholate were higher, and leukotrienes, 1,2-propanediol, azelate, undecanedioate, sebacate, inflammation associated complement component 3 peptide (HWESASXX), and piperine were lower in serum from adolescents with 25(OH)D ≥20 ng/mL. Lower maternal vitamin D status at midgestation impacted serum metabolic profiles in pregnant adolescents. PMID:25367051

  6. Variation in the Phosphoinositide 3-Kinase Gamma Gene Affects Plasma HDL-Cholesterol without Modification of Metabolic or Inflammatory Markers

    PubMed Central

    Kächele, Martin; Hennige, Anita M.; Machann, Jürgen; Hieronimus, Anja; Lamprinou, Apostolia; Machicao, Fausto; Schick, Fritz; Fritsche, Andreas; Stefan, Norbert; Nürnberg, Bernd; Häring, Hans-Ulrich; Staiger, Harald

    2015-01-01

    Objective Phosphoinositide 3-kinase γ (PI3Kγ) is a G-protein-coupled receptor-activated lipid kinase mainly expressed in leukocytes and cells of the cardiovascular system. PI3Kγ plays an important signaling role in inflammatory processes. Since subclinical inflammation is a hallmark of atherosclerosis, obesity-related insulin resistance, and pancreatic β-cell failure, we asked whether common genetic variation in the PI3Kγ gene (PIK3CG) contributes to body fat content/distribution, serum adipokine/cytokine concentrations, alterations in plasma lipid profiles, insulin sensitivity, insulin release, and glucose homeostasis. Study Design Using a tagging single nucleotide polymorphism (SNP) approach, we analyzed genotype-phenotype associations in 2,068 German subjects genotyped for 10 PIK3CG SNPs and characterized by oral glucose tolerance tests. In subgroups, data from hyperinsulinaemic-euglycaemic clamps, magnetic resonance spectroscopy of the liver, whole-body magnetic resonance imaging, and intravenous glucose tolerance tests were available, and peripheral blood mononuclear cells (PBMCs) were used for gene expression analysis. Results After appropriate adjustment, none of the PIK3CG tagging SNPs was significantly associated with body fat content/distribution, adipokine/cytokine concentrations, insulin sensitivity, insulin secretion, or blood glucose concentrations (p>0.0127, all; Bonferroni-corrected α-level: 0.0051). However, six non-linked SNPs displayed at least nominal associations with plasma HDL-cholesterol concentrations, two of them (rs4288294 and rs116697954) reaching the level of study-wide significance (p = 0.0003 and p = 0.0004, respectively). More precisely, rs4288294 and rs116697954 influenced HDL2-, but not HDL3-, cholesterol. With respect to the SNPs’ in vivo functionality, rs4288294 was significantly associated with PIK3CG mRNA expression in PBMCs. Conclusions We could demonstrate that common genetic variation in the PIK3CG locus, possibly

  7. High-dose atorvastatin causes a rapid sustained increase in human serum PCSK9 and disrupts its correlation with LDL cholesterol.

    PubMed

    Welder, Greg; Zineh, Issam; Pacanowski, Michael A; Troutt, Jason S; Cao, Guoqing; Konrad, Robert J

    2010-09-01

    Proprotein convertase subtilisin kexin type 9 (PCSK9) is a key regulator of serum LDL-cholesterol (LDL-C) levels. PCSK9 is secreted by the liver into the plasma and binds the hepatic LDL receptor (LDLR), causing its subsequent degradation. We first demonstrated that a moderate dose of atorvastatin (40 mg) increases PCSK9 serum levels, suggesting why increasing statin doses may have diminished efficacy with regard to further LDL-C lowering. Since that initial observation, at least two other groups have reported statin-induced PCSK9 increases. To date, no analysis of the effect of high-dose atorvastatin (80 mg) on PCSK9 over time has been conducted. Therefore, we studied the time course of atorvastatin (80 mg) in human subjects. We measured PCSK9 and lipid levels during a 2-week lead-in baseline period and every 4 weeks thereafter for 16 weeks. We observed that atorvastatin (80 mg) caused a rapid 47% increase in serum PCSK9 at 4 weeks that was sustained throughout 16 weeks of dosing. Importantly, while PCSK9 levels were highly correlated with total cholesterol (TC), LDL-C, and triglyceride (TG) levels at baseline, atorvastatin (80 mg) completely abolished all of these correlations. Together, these results further suggest an explanation for why increasing doses of statins fail to achieve proportional LDL-C lowering. PMID:20525997

  8. Mechanisms of cholesterol-lowering effects of dietary insoluble fibres: relationships with intestinal and hepatic cholesterol parameters.

    PubMed

    van Bennekum, Ariëtte M; Nguyen, David V; Schulthess, Georg; Hauser, Helmut; Phillips, Michael C

    2005-09-01

    Fibres with a range of abilities to perturb cholesterol homeostasis were used to investigate how the serum cholesterol-lowering effects of insoluble dietary fibres are related to parameters of intestinal cholesterol absorption and hepatic cholesterol homeostasis in mice. Cholestyramine, chitosan and cellulose were used as examples of fibres with high, intermediate and low bile acid-binding capacities, respectively. The serum cholesterol levels in a control group of mice fed a high fat/high cholesterol (HFHC) diet for 3 weeks increased about 2-fold to 4.3 mm and inclusion of any of these fibres at 7.5 % of the diet prevented this increase from occurring. In addition, the amount of cholesterol accumulated in hepatic stores due to the HFHC diet was reduced by treatment with these fibres. The three kinds of fibres showed similar hypocholesterolaemic activity; however, cholesterol depletion of liver tissue was greatest with cholestyramine. The mechanisms underlying the cholesterol-lowering effect of cholestyramine were (1) decreased cholesterol (food) intake, (2) decreased cholesterol absorption efficiency, and (3) increased faecal bile acid and cholesterol excretion. The latter effects can be attributed to the high bile acid-binding capacity of cholestyramine. In contrast, incorporation of chitosan or cellulose in the diet reduced cholesterol (food) intake, but did not affect either intestinal cholesterol absorption or faecal sterol output. The present study provides strong evidence that above all satiation and satiety effects underlie the cholesterol-lowering properties of insoluble dietary fibres with moderate or low bile acid-binding capabilities. PMID:16176602

  9. Inhibition of protein kinase C affects on mode of synaptic vesicle exocytosis due to cholesterol depletion.

    PubMed

    Petrov, Alexey M; Zakyrjanova, Guzalija F; Yakovleva, Anastasia A; Zefirov, Andrei L

    2015-01-01

    Previous studies demonstrated that depletion of membrane cholesterol by 10mM methyl-beta-cyclodextrin (MCD) results in increased spontaneous exocytosis at both peripheral and central synapses. Here, we investigated the role of protein kinase C in the enhancement of spontaneous exocytosis at frog motor nerve terminals after cholesterol depletion using electrophysiological and optical methods. Inhibition of the protein kinase C by myristoylated peptide and chelerythrine chloride prevented MCD-induced increases in FM1-43 unloading, whereas the frequency of spontaneous postsynaptic events remained enhanced. The increase in FM1-43 unloading still could be observed if sulforhodamine 101 (the water soluble FM1-43 quencher that can pass through the fusion pore) was added to the extracellular solution. This suggests a possibility that exocytosis of synaptic vesicles under these conditions could occur through the kiss-and-run mechanism with the formation of a transient fusion pore. Inhibition of phospholipase C did not lead to similar change in MCD-induced exocytosis. PMID:25446113

  10. Inhibition of protein kinase C affects on mode of synaptic vesicle exocytosis due to cholesterol depletion

    SciTech Connect

    Petrov, Alexey M. Zakyrjanova, Guzalija F. Yakovleva, Anastasia A. Zefirov, Andrei L.

    2015-01-02

    Highlights: • We examine the involvement of PKC in MCD induced synaptic vesicle exocytosis. • PKC inhibitor does not decrease the effect MCD on MEPP frequency. • PKC inhibitor prevents MCD induced FM1-43 unloading. • PKC activation may switch MCD induced exocytosis from kiss-and-run to a full mode. • Inhibition of phospholipase C does not lead to similar change in exocytosis. - Abstract: Previous studies demonstrated that depletion of membrane cholesterol by 10 mM methyl-beta-cyclodextrin (MCD) results in increased spontaneous exocytosis at both peripheral and central synapses. Here, we investigated the role of protein kinase C in the enhancement of spontaneous exocytosis at frog motor nerve terminals after cholesterol depletion using electrophysiological and optical methods. Inhibition of the protein kinase C by myristoylated peptide and chelerythrine chloride prevented MCD-induced increases in FM1-43 unloading, whereas the frequency of spontaneous postsynaptic events remained enhanced. The increase in FM1-43 unloading still could be observed if sulforhodamine 101 (the water soluble FM1-43 quencher that can pass through the fusion pore) was added to the extracellular solution. This suggests a possibility that exocytosis of synaptic vesicles under these conditions could occur through the kiss-and-run mechanism with the formation of a transient fusion pore. Inhibition of phospholipase C did not lead to similar change in MCD-induced exocytosis.

  11. Distinguishing disease effects from environmental effects in a mountain ungulate: seasonal variation in body weight, hematology, and serum chemistry among Iberian ibex (Capra pyrenaica) affected by sarcoptic mange.

    PubMed

    Pérez, Jesús M; Serrano, Emmanuel; Soriguer, Ramón C; González, Francisco J; Sarasa, Mathieu; Granados, José E; Cano-Manuel, Francisco J; Cuenca, Rafaela; Fandos, Paulino

    2015-01-01

    Our study focuses on the Iberian ibex (Capra pyrenaica) from the Sierra Nevada Natural Space (southern Spain), where sarcoptic mange is an endemic disease and animals are affected by a highly seasonal environment. Our aim was to distinguish between disease and environmental influences on seasonal variation in body weight, hematology, and serum biochemistry in Iberian ibex. We sampled 136 chemically immobilized male ibexes. The single effect of mange influenced hemoglobin, hematocrit, mean corpuscular volume, leukocytes, band neutrophils, monocytes, cholesterol, urea, creatine, and aspartate aminotransferase. Both mange and the period of the year also affected values of mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, neutrophils, glucose, and serum proteins. Scabietic animals showed a marked reduction in body weight (21.4 kg on average), which was more pronounced in winter. These results reveal that 1) infested animals are anemic, 2) secondary infections likely occur, and 3) sarcoptic mange is catabolic. PMID:25380360

  12. Effects of dietary supplementation of emulsifier and carbohydrase on the growth performance, serum cholesterol and breast meat fatty acids profile of broiler chickens.

    PubMed

    Wang, Jian Ping; Zhang, Zheng Fan; Yan, Lei; Kim, In Ho

    2016-02-01

    A total of 540 2-day-old male Ross 308 broilers were used in a 35-day experiment and were randomly divided into five treatments: (i) NC (low energy); (ii) PC (high energy diet); (iii) P1 (NC + 0.1% carbohydrases); (iv) P2 (NC + 0.05% emulsifier); and (v) P3 (NC + 0.1% carbohydrases + 0.05% emulsifier). From days 0 to 21, body weight gain in PC and P3 treatments increased (P < 0.05) compared with NC treatment. The chicks fed PC, P1, P2 and P3 improved (P < 0.05) feed conversion ratio compared with the NC treatment throughout the whole experiment. Abdominal fat weight was heavier (P < 0.05) in PC, P2 and P3 treatments than in NC and P1 treatments. On day 35, serum total cholesterol and low density lipoprotein cholesterol concentration were higher (P < 0.05) and high-density lipoprotein cholesterol was lower (P < 0.05) in NC and P2 treatments than in PC, P1 and P3 treatments. The concentration of oleic acid, linoleic acid and total unsaturated fatty acids were highest (P < 0.05) in PC than in the other treatments. In conclusion, the results indicate that low energy density diet had lower growth performance, while the inclusion of emulsifier and carbohydrases in low energy diets can partially improve growth performance. PMID:26278708

  13. Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomised, single-blind, placebo-controlled, phase 1 trial

    PubMed Central

    Fitzgerald, Kevin; Frank-Kamenetsky, Maria; Shulga-Morskaya, Svetlana; Liebow, Abigail; Bettencourt, Brian R; Sutherland, Jessica E; Hutabarat, Renta M; Clausen, Valerie A; Karsten, Verena; Cehelsky, Jeffrey; Nochur, Saraswathy V; Kotelianski, Victor; Horton, Jay; Mant, Timothy; Chiesa, Joseph; Ritter, James; Munisamy, Malathy; Vaishnaw, Akshay K; Gollob, Jared A; Simon, Amy

    2015-01-01

    Summary Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to LDL receptors, leading to their degradation. Genetics studies have shown that loss-of-function mutations in PCSK9 result in reduced plasma LDL cholesterol and decreased risk of coronary heart disease. We aimed to investigate the safety and efficacy of ALN-PCS, a small interfering RNA that inhibits PCSK9 synthesis, in healthy volunteers with raised cholesterol who were not on lipid-lowering treatment. Methods We did a randomised, single-blind, placebo-controlled, phase 1 dose-escalation study in healthy adult volunteers with serum LDL cholesterol of 3·00 mmol/L or higher. Participants were randomly assigned in a 3:1 ratio by computer algorithm to receive one dose of intravenous ALN-PCS (with doses ranging from 0·015 to 0·400 mg/kg) or placebo. The primary endpoint was safety and tolerability of ALN-PCS. Secondary endpoints were the pharmacokinetic characteristics of ALN-PCS and its pharmacodynamic effects on PCSK9 and LDL cholesterol. Study participants were masked to treatment assignment. Analysis was per protocol and we used ANCOVA to analyse pharmacodynamic endpoint data. This trial is registered with ClinicalTrials.gov, number NCT01437059. Findings Of 32 participants, 24 were randomly allocated to receive a single dose of ALN-PCS (0·015 mg/kg [n=3], 0·045 mg/kg [n=3], 0·090 mg/kg [n=3], 0·150 mg/kg [n=3], 0·250 mg/kg [n=6], or 0·400 mg/kg [n=6]) and eight to placebo. The proportions of patients affected by treatment-emergent adverse events were similar in the ALN-PCS and placebo groups (19 [79%] vs seven [88%]). ALN-PCS was rapidly distributed, with peak concentration and area under the curve (0 to last measurement) increasing in a roughly dose-proportional way across the dose range tested. In the group given 0·400 mg/kg of ALN-PCS, treatment resulted in a mean 70% reduction in circulating PCSK9 plasma protein (p<0·0001) and a mean 40% reduction in LDL cholesterol from

  14. Trend in prevalence of uncontrolled total serum cholesterol for cardio-cerebro-vascular disease in a mediterranean area, 1988/89-2008/09

    PubMed Central

    Capuano, Vincenzo; Lamaida, Norman; Capuano, Ernesto; Borrelli, Maria Immacolata; Capuano, Rocco; Notari, Elisabetta; Iannone, Anna Grazia; Marchese, Federica; Sonderegger, Matteo; Capuano, Eduardo

    2013-01-01

    AIM: To examine trends of uncontrolled total serum cholesterol, treatment and control in a Mediterranean region (Campania). METHODS: We considered and compared the data collected as part of “Montecorvino Rovella Project” 1988-1989 and cross-sectional data from the two phases of the “VIP Project-Valle dell’Irno Prevenzione”: 1998-1999 (1st phase) and 2008-2009 (2nd phase), in the 35-74-year-old-population. RESULTS: Data show a reduction of mean cholesterolemia in the last twenty years of 7.3 mg/dL for men and unchanged values for women. In the three surveys the mean values for serum cholesterol are in men: 205.2 ± 47.1 mg/dL (1988/89), 200 ± 38.9 mg/dL (1998/99) and 197.9 ± 40.2 mg/dL (2008/09); in the women: 203.1 ± 42.5 mg/dL (1988/89), 198.9 ± 37.9 mg/dL (1998/99) and 203.3 ± 39.3 mg/dL (2008/09). Prevalence of uncontrolled high cholesterol ≥ 240 mg/dL for men decreased from 20.8% (1988/89) to 14.3% (1998/99) and 13.9% (2008/9), P = 0.002; for women the values decreased from 19.9% (1988/89), to 18.2% (1998/99) and 18.1% (2008/09), P = 0.007. Is statistically increased the number of patients treated and those treated to target. CONCLUSION: Encouraging increases in awareness, treatment, and control of hypercholesterolemia occurred from 1988 through 2008. Nevertheless, control of hypercholesterolemia remains poor. PMID:24340140

  15. Body mass index, serum total cholesterol, and risk of gastric high-grade dysplasia: A case-control study among Chinese adults.

    PubMed

    Huang, Ya-Kai; Kang, Wei-Ming; Ma, Zhi-Qiang; Liu, Yu-Qin; Zhou, Li; Yu, Jian-Chun

    2016-08-01

    Obesity is related to an increased risk of gastric cardia cancer. However, the influences of excess body weight and serum total cholesterol on the risk of gastric high-grade dysplasia have not been fully characterized.A case-control study was conducted to explore the relationships between body mass index (BMI), serum total cholesterol level, and the risk of gastric high-grade dysplasia in Chinese adults. A total of 893 consecutive patients with gastric high-grade dysplasia (537 men and 356 women) and 902 controls (543 men and 359 women) were enrolled from January 2000 to October 2015. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated, and a multivariate analysis was conducted.After adjusting for age, alcohol consumption, smoking status, family history of gastric cancer or esophageal cancer, and serum total cholesterol level, a BMI ranging from 27.5 to 29.9 was significantly related to an increased risk of gastric high-grade dysplasia in both men (adjusted OR = 1.87, 95% CI = 1.24-2.81) and women (adjusted OR = 2.72, 95% CI = 1.44-5.16). The 2 highest BMI categories (27.5-29.9 and ≥30.0) were identified as risk factors for gastric cardia high-grade dysplasia in both men (BMI = 27.5-29.9: adjusted OR = 1.78, 95% CI = 1.02-3.10; BMI ≥ 30.0: adjusted OR = 2.54, 95% CI = 1.27-5.08) and women (BMI = 27.5-29.9: adjusted OR = 2.88, 95% CI = 1.27-6.55; BMI ≥ 30.0: adjusted OR = 2.77, 95% CI = 1.36-5.64), whereas only a BMI ranging from 27.5 to 29.9 was a risk factor for gastric noncardia high-grade dysplasia in both men (adjusted OR = 1.98, 95% CI = 1.25-3.14) and women (adjusted OR = 2.88, 95% CI = 1.43-5.81). In addition, higher serum total cholesterol was associated with an increased risk of gastric noncardia high-grade dysplasia (adjusted OR = 1.83, 95% CI = 1.25-2.69) in women.Increased BMI was associated with an increased risk of gastric high-grade dysplasia in

  16. Vitamin C may have similar beneficial effects to Gemfibrozil on serum high-density lipoprotein-cholesterol in type 2 diabetic patients

    PubMed Central

    Siavash, Mansour; Amini, Masoud

    2014-01-01

    Objective: Type 2 diabetes mellitus (DM-T2) is commonly associated with increased triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and low high-density lipoprotein cholesterol (HDL-C) levels. Fibrates like gemfibrozil are frequently used in diabetic patients to decrease TG and increase HDL-C levels. We compared the efficacy of Vitamin C, an antioxidant vitamin, with gemfibrozil on serum HDL-C in diabetic patients. Methods: Type 2 diabetic patients, referred to our out-patient clinic were randomly divided into three groups. After 1 month of lifestyle and diet modifications, groups A, B, and C were prescribed 1000 mg Vitamin C, 600 mg gemfibrozil and combination of both, respectively. Before the study initiation and after 6th week of drug prescription, the blood samples were taken and analyzed for total cholesterol (Total-C), HDL-C, TG, fasting blood sugar (FBS), and hemoglobin A1c (HbA1c) levels. Findings: Sixty-seven patients entered, and 50 patients (18 male, 32 female) finished the study. Overall, serum HDL-C increased significantly from 39.8 to 45.2 mg/dL in the participants (P = 0.001). HDL-C increased 6.3, 4.4 and 5.0 mg/dL in groups A, B and C, respectively (related significances were 0.017, 0.022 and 0.033, respectively). Significant decrease of serum TG and Total-C occurred in gemfibrozil and combination groups, but not in Vitamin C group. Changes in serum HDL-C between three groups were not significant (P = 0.963). We found a significant decrease in TG and Total-C in the groups B and C (P < 0.05), but no significant changes of TG, Total-C, LDL-C, FBS and HbA1c in group A (P > 0.05). Conclusion: The results demonstrated that Vitamin C may have beneficial effects on HDL-C in diabetic patients without significant effects on plasma glucose or other lipid parameters; however, its role for the treatment of low HDL-C patients should be evaluated in larger studies. PMID:25328896

  17. What's Cholesterol?

    MedlinePlus

    ... 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" ...

  18. Znf202 Affects High Density Lipoprotein Cholesterol Levels and Promotes Hepatosteatosis in Hyperlipidemic Mice

    PubMed Central

    Vrins, Carlos L. J.; Out, Ruud; van Santbrink, Peter; van der Zee, André; Mahmoudi, Tokameh; Groenendijk, Martine; Havekes, Louis M.; van Berkel, Theo J. C.; van Dijk, Ko Willems; Biessen, Erik A. L.

    2013-01-01

    Background The zinc finger protein Znf202 is a transcriptional suppressor of lipid related genes and has been linked to hypoalphalipoproteinemia. A functional role of Znf202 in lipid metabolism in vivo still remains to be established. Methodology and Principal Findings We generated mouse Znf202 expression vectors, the functionality of which was established in several in vitro systems. Next, effects of adenoviral znf202 overexpression in vivo were determined in normo- as well as hyperlipidemic mouse models. Znf202 overexpression in mouse hepatoma cells mhAT3F2 resulted in downregulation of members of the Apoe/c1/c2 and Apoa1/c3/a4 gene cluster. The repressive activity of Znf202 was firmly confirmed in an apoE reporter assay and Znf202 responsive elements within the ApoE promoter were identified. Adenoviral Znf202 transfer to Ldlr−/− mice resulted in downregulation of apoe, apoc1, apoa1, and apoc3 within 24 h after gene transfer. Interestingly, key genes in bile flux (abcg5/8 and bsep) and in bile acid synthesis (cyp7a1) were also downregulated. At 5 days post-infection, the expression of the aforementioned genes was normalized, but mice had developed severe hepatosteatosis accompanied by hypercholesterolemia and hypoalphalipoproteinemia. A much milder phenotype was observed in wildtype mice after 5 days of hepatic Znf202 overexpression. Interestingly and similar to Ldl−/− mice, HDL-cholesterol levels in wildtype mice were lowered after hepatic Znf202 overexpression. Conclusion/Significance Znf202 overexpression in vivo reveals an important role of this transcriptional regulator in liver lipid homeostasis, while firmly establishing the proposed key role in the control of HDL levels. PMID:23469003

  19. Effect of ETC-1002 on Serum Low-Density Lipoprotein Cholesterol in Hypercholesterolemic Patients Receiving Statin Therapy.

    PubMed

    Ballantyne, Christie M; McKenney, James M; MacDougall, Diane E; Margulies, Janice R; Robinson, Paula L; Hanselman, Jeffrey C; Lalwani, Narendra D

    2016-06-15

    ETC-1002 is an oral, once-daily medication that inhibits adenosine triphosphate citrate lyase, an enzyme upstream of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, to reduce cholesterol biosynthesis. ETC-1002 monotherapy has demonstrated significant reduction in low-density lipoprotein cholesterol (LDL-C) compared with placebo in phase 2 studies. The objective of this study was to compare the lipid-lowering efficacy of ETC-1002 versus placebo when added to ongoing statin therapy in patients with hypercholesterolemia. This phase 2b, multicenter, double-blind trial (NCT02072161) randomized 134 hypercholesterolemic patients (LDL-C, 115 to 220 mg/dl) on stable background statin therapy to 12 weeks of add-on treatment with ETC-1002 120 mg, ETC-1002 180 mg, or placebo. The primary efficacy end point was the percent change in calculated LDL-C from baseline to week 12. For LDL-C, the least-squares mean percent change ± standard error from baseline to week 12 was significantly greater with ETC-1002 120 mg (-17 ± 4%, p = 0.0055) and ETC-1002 180 mg (-24 ± 4%, p <0.0001) than placebo (-4 ± 4%). ETC-1002 also dose dependently reduced apolipoprotein B by 15% to 17%, non-high-density lipoprotein cholesterol by 14% to 17%, total cholesterol by 13% to 15%, and LDL particle number by 17% to 21%. All these reductions in ETC-1002-treated cohorts were significantly greater than those with placebo. Rates of adverse events (AEs), muscle-related AEs, and discontinuations for AEs with ETC-1002 were similar to placebo. In conclusion, ETC-1002 120 mg or 180 mg added to stable statin therapy significantly reduced LDL-C compared to placebo and has a similar tolerability profile. PMID:27138185

  20. Changes in serum calcium, phosphorus, and magnesium levels in captive ruminants affected by diet manipulation.

    PubMed

    Miller, Michele; Weber, Martha; Valdes, Eduardo V; Neiffer, Donald; Fontenot, Diedre; Fleming, Gregory; Stetter, Mark

    2010-09-01

    A combination of low serum calcium (Ca), high serum phosphorus (P), and low serum magnesium (Mg) has been observed in individual captive ruminants, primarily affecting kudu (Tragelaphus strepsiceros), eland (Taurotragus oryx), nyala (Tragelaphus angasii), bongo (Tragelaphus eurycerus), and giraffe (Giraffa camelopardalis). These mineral abnormalities have been associated with chronic laminitis, acute tetany, seizures, and death. Underlying rumen disease secondary to feeding highly fermentable carbohydrates was suspected to be contributing to the mineral deficiencies, and diet changes that decreased the amount of starch fed were implemented in 2003. Serum chemistry values from before and after the diet change were compared. The most notable improvement after the diet change was a decrease in mean serum P. Statistically significant decreases in mean serum P were observed for the kudu (102.1-66.4 ppm), eland (73.3-58.4 ppm), and bongo (92.1-64.2 ppm; P < 0.05). Although not statistically significant, mean serum P levels also decreased for nyala (99.3-86.8 ppm) and giraffe (82.6-68.7 ppm). Significant increases in mean serum Mg were also observed for kudu (15.9-17.9 ppm) and eland (17.1-19.7 ppm). A trend toward increased serum Mg was also observed in nyala, bongo, and giraffe after the diet change. No significant changes in mean serum Ca were observed in any of the five species evaluated, and Ca was within normal ranges for domestic ruminants. The mean Ca:P ratio increased to greater than one in every species after the diet change, with kudu, eland, and bongo showing a statistically significant change. The results of this study indicate that the diet change had a generally positive effect on serum P and Mg levels. PMID:20945636

  1. A diet rich in monounsaturated rapeseed oil reduces the lipoprotein cholesterol concentration and increases the relative content of n-3 fatty acids in serum in hyperlipidemic subjects.

    PubMed

    Gustafsson, I B; Vessby, B; Ohrvall, M; Nydahl, M

    1994-03-01

    The effects of 3 wk on a diet rich in monounsaturated rapeseed oil were compared with those of a diet containing sunflower oil within a lipid-lowering diet. Ninety-five subjects with moderate hyperlipoproteinemia were randomly assigned to one of the two well-controlled diets prepared at the hospital kitchen. Total serum, low-density- and high-density-lipoprotein cholesterol concentrations decreased by 15%, 16%, and 11% (P < 0.001), respectively, on the rapeseed oil diet and by 16%, 14%, and 13% (P < 0.001) on the sunflower oil diet. Serum triglycerides decreased more markedly (by 29%, P < 0.001) on the sunflower oil than on the rapeseed oil diet (14%, P < 0.01). The n-3 fatty acids (20:5 and 22:5) in the serum phospholipids increased significantly on the rapeseed oil diet but decreased on the sunflower oil diet. There was an increase in the alpha-tocopherol concentrations after both diets. The findings indicate that low erucic acid rapeseed oil can replace oils and fats rich in polyunsaturated fatty acids in a lipid-lowering diet. PMID:8116547

  2. Amyloid Beta Peptides Affect Pregnenolone and Pregnenolone Sulfate Levels in PC-12 and SH-SY5Y Cells Depending on Cholesterol.

    PubMed

    Calan, Ozlem Gursoy; Akan, Pinar; Cataler, Aysenur; Dogan, Cumhur; Kocturk, Semra

    2016-07-01

    Increased amyloid beta (AB) peptide concentration is one of the initiating factors in the neurodegeneration process. It has been suggested that cholesterol induces the synthesis of AB peptide from amyloid precursor protein or facilitates the formation of amyloid plaque by lowering the aggregation threshold of the peptide. It is also shown that AB peptides may affect cholesterol metabolism and the synthesis of steroid hormones such as progesterone and estradiol. Pregnenolone (P) and pregnenolone sulfate (PS) are the major steroids produced from cholesterol in neural tissue. In toxicity conditions, the effect of AB peptides on P and PS levels has not yet been determined. Furthermore, it has not been clearly defined how changes in cellular P and PS levels affect neuronal cell survival. The aim of this study was to determine the effects of AB peptides on cellular changes in P and PS levels depending on the level of their main precursor, cholesterol. Cholesterol and toxic concentrations of AB fragments (AB 25-35, AB 1-40 and AB 1-42) were applied to PC-12 and SH-SY5Y cells. Changes in cellular cholesterol, P and PS levels were determined simultaneously in a dose-and time-dependent manner. The cell viability and cell death types were also evaluated. AB peptides affected both cell viability and P/PS levels. Steroid levels were altered depending on AB fragment type and the cholesterol content of the cells. Treatment with each of the AB fragments alone increased P levels by twofold. However, combined treatment with AB peptides and cholesterol increased P levels by approximately sixfold, while PS levels were increased only about 2.5 fold in both cell lines. P levels in the groups treated with AB 25-35 were higher than those in AB 1-40 and AB 1-42 groups. The cell viabilities were significantly low in the group treated by AB and cholesterol (9 mM). The effect of AB peptides on P levels might be a result of cellular self-defense. On the other hand, the rate of P increase

  3. Effects of inulin on performance, egg quality, gut microflora and serum and yolk cholesterol in laying hens.

    PubMed

    Shang, H M; Hu, T M; Lu, Y J; Wu, H X

    2010-12-01

    1. The present study was conducted to investigate the effects of inulin on laying hens. A total of 360 Brown Nick laying hens were divided randomly into 6 groups of 60 with 6 replicates of 10 hens and fed on diets containing 0 (control), 0·1, 0·5, 1·0, 1·5 or 2·0% inulin during the 4-week trial. 2. Dietary supplementation of inulin reduced cholesterol concentration (mg/g yolk) and content (mg/egg) in eggs. Cholesterol content in eggs decreased linearly with increasing levels of dietary inulin level. 3. Supplementation of inulin in diets decreased coliform bacteria counts and pH in the caecum. The lowest coliform bacteria counts (6·30 ± 0·03 log10 cfu/g) and pH (6·47 ± 0·01) were obtained in the 2·0% inulin group, the two indices decreasing by 21·6% and 3·0% respectively, compared with the control group. Coliform bacteria count and pH were changed linearly in accordance with increasing levels of dietary inulin level. Caecal Bifidobacteria counts were increased in the 2·0%-inulin group. 4. Inulin supplementation of layer diets did not appear to have any adverse effects on laying rate, egg weight, feed intake, feed conversion efficiency, cracked-egg rate, eggshell thickness or Haugh unit compared with the control laying hens. 5. Therefore, dietary supplementation with inulin may lead to the development of low-cholesterol chicken eggs as demanded by health-conscious consumers. PMID:21161786

  4. Cholesterol efflux and reverse cholesterol transport.

    PubMed

    Favari, Elda; Chroni, Angelika; Tietge, Uwe J F; Zanotti, Ilaria; Escolà-Gil, Joan Carles; Bernini, Franco

    2015-01-01

    Both alterations of lipid/lipoprotein metabolism and inflammatory events contribute to the formation of the atherosclerotic plaque, characterized by the accumulation of abnormal amounts of cholesterol and macrophages in the artery wall. Reverse cholesterol transport (RCT) may counteract the pathogenic events leading to the formation and development of atheroma, by promoting the high-density lipoprotein (HDL)-mediated removal of cholesterol from the artery wall. Recent in vivo studies established the inverse relationship between RCT efficiency and atherosclerotic cardiovascular diseases (CVD), thus suggesting that the promotion of this process may represent a novel strategy to reduce atherosclerotic plaque burden and subsequent cardiovascular events. HDL plays a primary role in all stages of RCT: (1) cholesterol efflux, where these lipoproteins remove excess cholesterol from cells; (2) lipoprotein remodeling, where HDL undergo structural modifications with possible impact on their function; and (3) hepatic lipid uptake, where HDL releases cholesterol to the liver, for the final excretion into bile and feces. Although the inverse association between HDL plasma levels and CVD risk has been postulated for years, recently this concept has been challenged by studies reporting that HDL antiatherogenic functions may be independent of their plasma levels. Therefore, assessment of HDL function, evaluated as the capacity to promote cell cholesterol efflux may offer a better prediction of CVD than HDL levels alone. Consistent with this idea, it has been recently demonstrated that the evaluation of serum cholesterol efflux capacity (CEC) is a predictor of atherosclerosis extent in humans. PMID:25522988

  5. Blood zinc protoporphyrin, serum total protein, and total cholesterol levels in automobile workshop workers in relation to lead toxicity: Our experience.

    PubMed

    Pachathundikandi, Suneesh Kumar; Varghese, Earaly Thomas

    2006-09-01

    Blood zinc protoporphyrin (ZPP), serum total protein (TP), and total cholesterol (TC) levels in automobile workshop workers in relation to lead toxicity were analysed. In the present study, automobile workshop workers (healthy male workers at an age between 28 and 35 from four major automobile workshops in Kottayam, Kerala State, India) and the control (male healthy adults at an age between 28 and 35 residing at Aymanam, a distant village at Kottayam District, Kerala having reduced or no chance of lead exposure) displayed significant difference in blood lead (BPb) and blood ZZP (BZPP) level. The mean value of BPb in automobile workshop workers was 15.76±0.33 μg/dl, while in the control it was 8.20±0.15 μg/dl. In automobile workshop workers, the mean value of BZPP was 34.2±0.62 μg/dl. The control group exhibited a mean of 11.5±0.22 μg/dl. Automobile workshop workers exhibited significant increase in BZPP was corresponding to the increase in BPb level. The total protein levels estimated in automobile workshop workers showed significant decrease compared to control individuals, but was within the reference range of healthy individuals. The mean value of TP level in automobile workshop workers and control was 6.9±0.13 g/dl and 7.71±0.18 g/dl, respectively. There was no significant difference in blood haemoglobin (BHb) level among the automobile workshop workers and control. The serum TC level in automobile workshop workers showed significant decrease compared to the control individuals, but was with in the reference range of healthy individuals. The mean level of serum TC in automobile workshop workers was 162.00±3.44 mg/dl and the same in control was 172.86±4.32 mg/dl. The present study affirms occupational lead toxicity in automobile workshop workers and its effect on serum protein and cholesterol levels. PMID:23105626

  6. Serum cholesterol and acute myocardial infarction: a case-control study from the GISSI-2 trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto-Epidemiologia dei Fattori di Rischio dell'Infarto Miocardico Investigators.

    PubMed Central

    Nobili, A.; D'Avanzo, B.; Santoro, L.; Ventura, G.; Todesco, P.; La Vecchia, C.

    1994-01-01

    OBJECTIVE--To examine the role of serum cholesterol in acute myocardial infarction in a population of patients with no history of coronary heart disease and to establish the nature of this association, the degree of risk, and the possible interaction between serum cholesterol and other major risk factors for acute myocardial infarction. DESIGN--Case-control study. SETTING--90 hospitals in northern, central, and southern Italy. PATIENTS--916 consecutive cases of newly diagnosed acute myocardial infarction and 1106 hospital controls admitted to hospital with acute conditions not related to known or suspected risk factors for coronary heart disease. DATA COLLECTION--Data were collected with a structured questionnaire and blood samples were taken by venepuncture as soon as possible after admission to hospital from cases and controls. Blood cholesterol concentrations were available for 614 cases and 792 controls. RESULTS--After adjustment by logistic regression for sex, age, education, geographical area, smoking status, body mass index, history of diabetes and hypertension, and family history of coronary heart disease the estimated relative risks of acute myocardial infarction for quintiles of serum cholesterol (from lowest to highest) were 2.3 (95% confidence interval (CI) 1.6 to 3.4), 3.1 (95% CI 2.1 to 4.6), 4.1 (95% CI 2.8 to 6.0), and 5.2 (95% CI 3.5 to 7.7). The estimated relative risk across selected covariates increased from the lowest to the highest quintile of serum cholesterol particularly for men, patients under 55 years of age, and smokers. When the possible interaction of known risk factors with serum cholesterol was examined, smoking habits, diabetes, and hypertension had approximately multiplicative effects on relative risk. CONCLUSIONS--This study indicates that serum cholesterol was an independent risk factor for acute myocardial infarction. This association was linear, with no threshold level. Moreover, there was a multiplicative effect between

  7. About Cholesterol

    MedlinePlus

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

  8. Restoring Mitochondrial Function: A Small Molecule-mediated Approach to Enhance Glucose Stimulated Insulin Secretion in Cholesterol Accumulated Pancreatic beta cells.

    PubMed

    Asalla, Suman; Girada, Shravan Babu; Kuna, Ramya S; Chowdhury, Debabrata; Kandagatla, Bhaskar; Oruganti, Srinivas; Bhadra, Utpal; Bhadra, Manika Pal; Kalivendi, Shasi Vardhan; Rao, Swetha Pavani; Row, Anupama; Ibrahim, A; Ghosh, Partha Pratim; Mitra, Prasenjit

    2016-01-01

    Dyslipidemia, particularly the elevated serum cholesterol levels, aggravate the pathophysiology of type 2 diabetes. In the present study we explored the relationship between fasting blood sugar and serum lipid parameters in human volunteers which revealed a significant linear effect of serum cholesterol on fasting blood glucose. Short term feeding of cholesterol enriched diet to rodent model resulted in elevated serum cholesterol levels, cholesterol accumulation in pancreatic islets and hyperinsulinemia with modest increase in plasma glucose level. To explore the mechanism, we treated cultured BRIN-BD11 pancreatic beta cells with soluble cholesterol. Our data shows that cholesterol treatment of cultured pancreatic beta cells enhances total cellular cholesterol. While one hour cholesterol exposure enhances insulin exocytosis, overnight cholesterol accumulation in cultured pancreatic beta cells affects cellular respiration, and inhibits Glucose stimulated insulin secretion. We further report that (E)-4-Chloro-2-(1-(2-(2,4,6-trichlorophenyl) hydrazono) ethyl) phenol (small molecule M1) prevents the cholesterol mediated blunting of cellular respiration and potentiates Glucose stimulated insulin secretion which was abolished in pancreatic beta cells on cholesterol accumulation. PMID:27282931

  9. Restoring Mitochondrial Function: A Small Molecule-mediated Approach to Enhance Glucose Stimulated Insulin Secretion in Cholesterol Accumulated Pancreatic beta cells

    PubMed Central

    Asalla, Suman; Girada, Shravan Babu; Kuna, Ramya S.; Chowdhury, Debabrata; Kandagatla, Bhaskar; Oruganti, Srinivas; Bhadra, Utpal; Bhadra, Manika Pal; Kalivendi, Shasi Vardhan; Rao, Swetha Pavani; Row, Anupama; Ibrahim, A; Ghosh, Partha Pratim; Mitra, Prasenjit

    2016-01-01

    Dyslipidemia, particularly the elevated serum cholesterol levels, aggravate the pathophysiology of type 2 diabetes. In the present study we explored the relationship between fasting blood sugar and serum lipid parameters in human volunteers which revealed a significant linear effect of serum cholesterol on fasting blood glucose. Short term feeding of cholesterol enriched diet to rodent model resulted in elevated serum cholesterol levels, cholesterol accumulation in pancreatic islets and hyperinsulinemia with modest increase in plasma glucose level. To explore the mechanism, we treated cultured BRIN-BD11 pancreatic beta cells with soluble cholesterol. Our data shows that cholesterol treatment of cultured pancreatic beta cells enhances total cellular cholesterol. While one hour cholesterol exposure enhances insulin exocytosis, overnight cholesterol accumulation in cultured pancreatic beta cells affects cellular respiration, and inhibits Glucose stimulated insulin secretion. We further report that (E)-4-Chloro-2-(1-(2-(2,4,6-trichlorophenyl) hydrazono) ethyl) phenol (small molecule M1) prevents the cholesterol mediated blunting of cellular respiration and potentiates Glucose stimulated insulin secretion which was abolished in pancreatic beta cells on cholesterol accumulation. PMID:27282931

  10. Replacing coconut santan with palm oil santan: impact on dietary C12-16 saturated fatty acids, serum total cholesterol and cardiovascular risk.

    PubMed

    Ng, T; Tee, E S

    1998-12-01

    The theoretical impact of the use of coconut cream (santan) powder and palm oil santan powder on the dietary levels of C12-16 saturated fatty acids (SFAs) and linoleic acid (18:2), and on serum total cholesterol (TC), was evaluated holding non-santan dietary variables constant. The prediction was based on a 2,300-kcal hypothetical diet, containing one santan-based dish or snack in each of the 5 daily meals with fat contributing 30% of total calories, while the santan contributed a total of 14% kcal (36g). Replacing coconut santan with palm oil santan reduced the overall dietary C12-16 SFAs from 10.8% kcal to 4.8% kcal (i.e. 6.0% kcal) and the virtual removal of lauric (12:0) + myristic (14:0) acids, while palmitic acid (16:0) rose by 3.3% kcal, and the polyunsaturated linoleic acid (18:2) increased by 1.13% kcal. Applying the Hegsted equation to these dietary fatty acid (FA) changes, predicted a serum TC reduction of 24 -31 mg/dL (0.62- 0.80 mM/L), with the hypocholesterolemic effect being influenced by the low-density lipoprotein receptor (LDLr) set-point of the individual(s) concerned. Thus, the prediction indicated that replacing coconut santan with palm oil santan in santan-based Malaysian dishes or snacks would have a significant beneficial impact on serum TC and hence, cardiovascular risk. PMID:22692342

  11. Effect of fasting during Ramadan on serum lithium level and mental state in bipolar affective disorder.

    PubMed

    Farooq, Saeed; Nazar, Zahid; Akhtar, Javaid; Akhter, Javed; Irfan, Muhammad; Irafn, Mohammad; Subhan, Fazal; Ahmed, Zia; Khan, Ejaz Hassan; Khatak, Ijaz Hassan; Naeem, Farooq

    2010-11-01

    The Muslims fast every year during the month of Ramadan. A fasting day can last 12-17 h. The effects of fasting on serum lithium levels and the mood changes in patients suffering from bipolar affective disorder during Ramadan are not well studied. We aimed to compare the serum lithium levels, side effects, toxicity and mental state in patients suffering from bipolar affective disorder and on prophylactic lithium therapy before, during and after Ramadan. Sixty-two patients meeting the International Classification of Diseases, Tenth Revision, Research Diagnostic Criteria of bipolar affective disorder receiving lithium treatment for prophylaxis were recruited in a tertiary care teaching hospital in Peshawar, Pakistan. Serum lithium, electrolytes, Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) were assessed at three points, 1 week before Ramadan, midRamadan and 1 week after Ramadan. The side effects and toxicity were measured by a symptoms and signs checklist. There was no significant difference in mean serum lithium levels at three time points (preRamadan=0.45±0.21, midRamadan=0.51±0.20 and postRamadan=0.44±0.23 milli equivalents/litre, P=0.116). The scores on HDRS and YMRS showed significant decrease during Ramadan (F=34.12, P=0.00, for HDRS and F=15.6, P=0.000 for YMRS). The side effects and toxicity also did not differ significantly at three points. In conclusion, the patients who have stable mental state and lithium levels before Ramadan can be maintained on lithium during Ramadan. Fasting in an average temperature of 28°C for up to 12 h per day did not result in elevated serum lithium levels or more side effects and did not have adverse effects on mental state of patients suffering from bipolar affective disorder. PMID:20827213

  12. Cholesterol absorption.

    PubMed

    Ostlund, Richard E

    2002-03-01

    Cholesterol absorption is a key regulatory point in human lipid metabolism because it determines the amount of endogenous biliary as well as dietary cholesterol that is retained, thereby influencing whole body cholesterol balance. Plant sterols (phytosterols) and the drug ezetimibe reduce cholesterol absorption and low-density lipoprotein cholesterol in clinical trials, complementing the statin drugs, which inhibit cholesterol biosynthesis. The mechanism of cholesterol absorption is not completely known but involves the genes ABC1, ABCG5, and ABCG8, which are members of the ATP-binding cassette protein family and appear to remove unwanted cholesterol and phytosterols from the enterocyte. ABC1 is upregulated by the liver X (LXR) and retinoid X (RXR) nuclear receptors. Acylcholesterol acytransferase-2 is an intestinal enzyme that esterifies absorbed cholesterol and increases cholesterol absorption when dietary intake is high. New clinical treatments based on better understanding of absorption physiology are likely to substantially improve clinical cholesterol management in the future. PMID:17033296

  13. Self-rated health showed a consistent association with serum HDL-cholesterol in the cross-sectional Oslo Health Study

    PubMed Central

    Tomten, Sissel E.; Høstmark, Arne T.

    2007-01-01

    Objective: To examine the association between serum HDL-cholesterol concentration (HDL-C) and self rated health (SRH) in several age groups of men and women. Study design and setting: The study had a cross-sectional design and included 18,770 men and women of the Oslo Health Study aged 30; 40 and 45; 69-60; 75-76 years. Results: In both sexes and all age groups, SRH (3 categories: poor, good, very good) was positively correlated with HDL-C. Logistic regression analysis on dichotomized values of SRH (i.e. poor vs. good health) in each age group of men and women showed that increasing HDL-C values were associated with increasing odds for reporting good health; the odds ratio (OR) was highest in young men, and was generally lower in women than in men. Odds ratios in the 4 age groups of men were 4.94 (2.63-9.29), 2.25 (1.63-3.09), 2.12 (1.58-2.86), 1.87 (1.37-2.54); and in women: 3.58 (2.46-5.21), 2.81 (2.23-3.53), 2.28 (1.84-2.82), 1.61 (1.31-1.99). In the whole material, 1 mmol/L increase in HDL-C increased the odds for reporting good health by 2.27 (2.06-2.50; p<0.001), when adjusting for sex, age group, time since food intake and use of cholesterol lowering drugs. Chronic diseases, pain, psychological distress, smoking, alcohol, length of education, and dietary items did not have any major influence on the pattern of the HDL-C vs. SRH association. Conclusion: There was a consistent positive association between HDL-C and SRH, in both men and women in four different age groups, with the strongest association in young people. PMID:18071582

  14. How to Get Your Cholesterol Tested

    MedlinePlus

    ... HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides. A small sample of blood will be drawn ... the amount of LDL (bad) cholesterol level and triglycerides can be affected by what you've recently ...

  15. Effects of consumption of whole grain foods rich in lignans in healthy postmenopausal women with moderate serum cholesterol: a pilot study.

    PubMed

    Durazzo, A; Carcea, M; Adlercreutz, H; Azzini, E; Polito, A; Olivieri, L; Zaccaria, M; Meneghini, C; Maiani, F; Bausano, G; Martiri, F; Samaletdin, A; Fumagalli, A; Raguzzini, A; Venneria, E; Foddai, M S; Ciarapica, D; Mauro, B; Volpe, F; Maiani, G

    2014-08-01

    This study aims at investigating the effect of an experimental period of intake of whole grain foods rich in lignans as part of an habitual diet on the plasma and urinary excretion of enterolignans, the biomarkers of lipid metabolism and the immunological and antioxidant status in a group of postmenopausal women with moderate serum cholesterol. A randomized double-blind crossover study was completed on 13 subjects in 12-weeks after protocol approval of an ethical committee. The subjects consumed whole grain foods high in lignans (30 g/d of breakfast cereals or biscuits, etc., 80 g/d of whole grain pasta) or refined grain foods for 4 weeks, separated by a 2-weeks wash-out period. A modest hypocholesterolemic effect (p < 0.05) of the whole grain diet was observed and the intake of whole grain products rich in lignans was also associated with an increase in urinary enterodiol excretion (p < 0.05). PMID:24611636

  16. Cholesterol (image)

    MedlinePlus

    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 ...

  17. Cholesterol metabolism in cholestatic liver disease and liver transplantation: From molecular mechanisms to clinical implications

    PubMed Central

    Nemes, Katriina; Åberg, Fredrik; Gylling, Helena; Isoniemi, Helena

    2016-01-01

    The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein (LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X (Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers - such as cholesterol precursor sterols, plant sterols, and cholestanol - may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation. PMID:27574546

  18. Cholesterol metabolism in cholestatic liver disease and liver transplantation: From molecular mechanisms to clinical implications.

    PubMed

    Nemes, Katriina; Åberg, Fredrik; Gylling, Helena; Isoniemi, Helena

    2016-08-01

    The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein (LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X (Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers - such as cholesterol precursor sterols, plant sterols, and cholestanol - may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation. PMID:27574546

  19. Facts about Blood Cholesterol. Revised.

    ERIC Educational Resources Information Center

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

    This fact sheet offers information on blood cholesterol and its implications for a healthy heart. An explanation is given of the known facts about cholesterol and how it affects the body. A chart is provided that lists various foods and their fat and cholesterol contents. (JD)

  20. Serum melatonin is not affected by glucocorticoid replacement in congenital adrenal hyperplasia.

    PubMed

    Waldhauser, F; Frisch, H; Krautgasser-Gasparotti, A; Schober, E; Bieglmayer, C

    1986-03-01

    Recently a hypothesis has been proposed suggesting a negative feedback in the regulation of cortisol (F) and melatonin (Mel). To study a possible influence of F on Mel regulation we examined 13 children with congenital adrenal hyperplasia (CAH) on two occasions: once 3 days after cessation of F substitution (group 1; n = 13) and once during treatment with dexamethasone (1 mg/m2/day) and fludrocortisone (0.1 mg/m2/day) (group 2; n = 11) 11 children matched by sex and age served as controls (group 3). While serum 17 OH-progesterone levels, an indicator for the activation of the hypothalamo-pituitary-adrenal axis in CAH, were significantly (P less than 0.001) elevated in untreated patients (group 1), serum Mel levels were not different among the 3 groups nor was the diurnal secretion pattern of Mel affected. Nocturnal serum Mel concentrations, however, correlated with the age of the subjects (r = 0.55, P less than 0.001 at 23.00 h), displaying high values in early childhood that declined with progressing age. The presented data do not support the view of a classical feedback mechanism in the regulation of Mel and F in humans. However, it confirms the description of a tremendous fall of nocturnal Mel concentrations during childhood. PMID:3962565

  1. Ibuprofen does not affect serum electrolyte concentrations after an ultradistance run

    PubMed Central

    Dumke, Charles L; Nieman, David C; Oley, Kevin; Lind, Robert H

    2007-01-01

    Objective To determine the effects of ibuprofen on serum electrolyte concentrations after a 160 km running race. Methods Twenty nine subjects (mean (SD) age 47.9 (7.4) years) ingested 600 mg ibuprofen the day before, and 1200 mg ibuprofen during, a 160 km competitive trail running race (approximately every 4 h in 200 mg doses). Twenty five control subjects (mean (SD) age 46.8 (10.3) years) avoided ingestion of ibuprofen before or during the race. Blood was drawn on the day before the race and immediately after the race. Serum biochemical profiles were analysed by a clinical laboratory. Significant effects of treatment and time were determined with a general linear model with repeated measures. Results Subjects in the two groups did not differ by age, training volume, race experience, body mass index, body fat, or finishing time (25.8 (3.3) vs 25.6 (3.9) h). Body weight did not change significantly over the race (measured before, mid‐race (90 km), and after). Ibuprofen ingestion did not significantly affect any of the serum markers including creatine kinase (p = 0.16). A significant decrease in serum sodium (p = 0.006), potassium (p = 0.001), chloride (p<0.001), calcium (p<0.001), albumin (p<0.001) and globulin (p<0.001) was observed after the race. Increases were seen in creatine kinase (p<0.001), creatinine (p<0.001), blood urea nitrogen (p<0.001), uric acid (p<0.001) and glucose (p<0.001) as the result of the race. Conclusions These data suggest that the non‐specific cyclo‐oxygenase inhibitor, ibuprofen, does not alter serum electrolyte concentrations during ultradistance running. However, the stress of ultradistance running appears to be related to significant changes in certain serum markers. PMID:17331976

  2. The mechanism of lowering cholesterol absorption by calcium studied by using an in vitro digestion model.

    PubMed

    Vinarova, Liliya; Vinarov, Zahari; Tcholakova, Slavka; Denkov, Nikolai D; Stoyanov, Simeon; Lips, Alex

    2016-01-01

    Studies in humans show that a calcium-enriched diet leads to lower cholesterol in blood serum. This phenomenon is usually explained in the literature with a reduced cholesterol absorption in the small intestine. Our study aims to clarify the effect of calcium on the solubilisation of cholesterol and fatty acid in the dietary mixed micelles (DMM), viz. on the bioaccessibility of these lipophilic substances in the gut. We use an in vitro digestion model which mimics very closely the intestinal pH-profile and the composition of the intestinal fluids. We quantified the effects of Ca(2+) concentration on the lipid solubilization for fats and oils with different saturated/unsaturated fatty acid (FA) contents. We found that the increase of calcium significantly decreases the solubilization of cholesterol, FA and MG. Most importantly, we observe a clear positive correlation between the amounts of solubilized cholesterol, on one side, and solubilized free fatty acids and monoglycerides, on the other side. The main conclusion is that Ca(2+) ions strongly affect the bioaccessibility of both cholesterol and saturated FA. Therefore, calcium may decrease the serum cholesterol via two complementary mechanisms: (1) fatty acid precipitation by calcium ions reduces the solubilisation capacity of the DMM, thus decreasing the levels of solubilised (bioaccessible) cholesterol; (2) the observed strong decrease of the bioaccessible saturated FA, in its own turn, may suppress the cholesterol synthesis in the liver. PMID:26481461

  3. Pyoverdine and proteases affect the response of Pseudomonas aeruginosa to gallium in human serum.

    PubMed

    Bonchi, Carlo; Frangipani, Emanuela; Imperi, Francesco; Visca, Paolo

    2015-09-01

    Gallium is an iron mimetic which has recently been repurposed as an antibacterial agent due to its capability to disrupt bacterial iron metabolism. In this study, the antibacterial activity of gallium nitrate [Ga(NO3)3] was investigated in complement-free human serum (HS) on 55 Pseudomonas aeruginosa clinical isolates from cystic fibrosis and non-cystic fibrosis patients. The susceptibility of P. aeruginosa to Ga(NO3)3 in HS was dependent on the bacterial ability to acquire iron from serum binding proteins (i.e., transferrin). The extent of serum protein degradation correlated well with P. aeruginosa growth in HS, while pyoverdine production did not. However, pyoverdine-deficient P. aeruginosa strains were unable to grow in HS and overcome iron restriction, albeit capable of releasing proteases. Predigestion of HS with proteinase K promoted the growth of all strains, irrespective of their ability to produce proteases and/or pyoverdine. The MICs of Ga(NO3)3 were higher in HS than in an iron-poor Casamino Acids medium, where proteolysis does not affect iron availability. Coherently, strains displaying high proteolytic activity were less susceptible to Ga(NO3)3 in HS. Our data support a model in which both pyoverdine and proteases affect the response of P. aeruginosa to Ga(NO3)3 in HS. The relatively high Ga(NO3)3 concentration required to inhibit the growth of highly proteolytic P. aeruginosa isolates in HS poses a limitation to the potential of Ga(NO3)3 in the treatment of P. aeruginosa bloodstream infections. PMID:26149986

  4. Pyoverdine and Proteases Affect the Response of Pseudomonas aeruginosa to Gallium in Human Serum

    PubMed Central

    Bonchi, Carlo; Frangipani, Emanuela; Imperi, Francesco

    2015-01-01

    Gallium is an iron mimetic which has recently been repurposed as an antibacterial agent due to its capability to disrupt bacterial iron metabolism. In this study, the antibacterial activity of gallium nitrate [Ga(NO3)3] was investigated in complement-free human serum (HS) on 55 Pseudomonas aeruginosa clinical isolates from cystic fibrosis and non-cystic fibrosis patients. The susceptibility of P. aeruginosa to Ga(NO3)3 in HS was dependent on the bacterial ability to acquire iron from serum binding proteins (i.e., transferrin). The extent of serum protein degradation correlated well with P. aeruginosa growth in HS, while pyoverdine production did not. However, pyoverdine-deficient P. aeruginosa strains were unable to grow in HS and overcome iron restriction, albeit capable of releasing proteases. Predigestion of HS with proteinase K promoted the growth of all strains, irrespective of their ability to produce proteases and/or pyoverdine. The MICs of Ga(NO3)3 were higher in HS than in an iron-poor Casamino Acids medium, where proteolysis does not affect iron availability. Coherently, strains displaying high proteolytic activity were less susceptible to Ga(NO3)3 in HS. Our data support a model in which both pyoverdine and proteases affect the response of P. aeruginosa to Ga(NO3)3 in HS. The relatively high Ga(NO3)3 concentration required to inhibit the growth of highly proteolytic P. aeruginosa isolates in HS poses a limitation to the potential of Ga(NO3)3 in the treatment of P. aeruginosa bloodstream infections. PMID:26149986

  5. Holoprosencephaly in RSH/Smith-Lemli-Opitz syndrome: Does abnormal cholesterol metabolism affect the function of sonic hedgehog?

    SciTech Connect

    Kelley, R.I.; Roessler, E.; Muenke, M.

    1996-12-30

    The RAH/Smith-Lemli-Opitz syndrome (RAH/SLOS) is an autosomal recessive malformation syndrome associated with increased levels of 7-dehydrocholesterol (7-DHC) and a defect of cholesterol biosynthesis at the level of 3{beta}-hydroxy-steroid-{Delta}{sup 7}-reductase (7-DHC reductase). Because rats exposed to inhibitors of 7-DHC reductase during development have a high frequency of holoprosencephaly (HPE), we have undertaken a search for biochemical evidence of RSH/SLOS and other possible defects of sterol metabolism among patients with various forms of HPE. We describe 4 patients, one with semilobar HPE and three others with less complete forms of the HPE sequence, in whom we have made a biochemical diagnosis of RAH/SLOS. The clinical and biochemical spectrum of these and other patients with RAH/SLOS suggests a role of abnormal sterol metabolism in the pathogenesis of their malformations. The association of HPE and RAH/SLOS is discussed in light of the recent discoveries that mutations in the embryonic patterning gene, Sonic Hedgehog (SHH), can cause HPE in humans and that the sonic hedgehog protein product undergoes autoproteolysis to form a cholesterol-modified active product. These clinical, biochemical, and molecular studies suggest that HPE and other malformations in SLOS may be caused by incomplete or abnormal modification of the sonic hedgehog protein and, possibly, other patterning proteins of the hedgehog class, a hypothesis testable in somatic cell systems. 37 refs., 1 fig.

  6. Foetal bovine serum-derived exosomes affect yield and phenotype of human cardiac progenitor cell culture

    PubMed Central

    Angelini, Francesco; Ionta, Vittoria; Rossi, Fabrizio; Miraldi, Fabio; Messina, Elisa; Giacomello, Alessandro

    2016-01-01

    Introduction: Cardiac progenitor cells (CPCs) represent a powerful tool in cardiac regenerative medicine. Pre-clinical studies suggest that most of the beneficial effects promoted by the injected cells are due to their paracrine activity exerted on endogenous cells and tissue. Exosomes are candidate mediators of this paracrine effects. According to their potential, many researchers have focused on characterizing exosomes derived from specific cell types, but, up until now, only few studies have analyzed the possible in vitro effects of bovine serum-derived exosomes on cell proliferation or differentiation. Methods: The aim of this study was to analyse, from a qualitative and quantitative point of view, the in vitro effects of bovine serum exosomes on human CPCs cultured either as cardiospheres or as monolayers of cardiosphere-forming cells. Results: Effects on proliferation, yield and molecular patterning were detected. We show, for the first time, that exogenous bovine exosomes support the proliferation and migration of human cardiosphere-forming cells, and that their depletion affects cardiospheres formation, in terms of size, yield and extra-cellular matrix production. Conclusion: These results stress the importance of considering differential biological effects of exogenous cell culture supplements on the final phenotype of primary human cell cultures.

  7. Compared with the intake of commercial vegetable juice, the intake of fresh fruit and komatsuna (Brassica rapa L. var. perviridis) juice mixture reduces serum cholesterol in middle-aged men: a randomized controlled pilot study

    PubMed Central

    2014-01-01

    Background Vegetables and fruits are rich in vitamins, minerals and, dietary fiber and contribute to the prevention and improvement of obesity and metabolic syndrome. However, inadequate intake of vegetable and fruit is a concern in Japan. We therefore produced a juice mixture of fresh fruit and komatsuna (Brassica rapa L. var. perviridis: B. rapa) with the aim to investigate the effects of this juice mixture on anthropometric data, blood parameters, and dietary intake differences. Methods This study was performed as a single blind and randomized controlled trial. Subjects were 16 men (mean age, 46.4 ± 7.1 years), and they were divided into two groups (control group and intervention group). The intervention group consumed the juice mixture of fresh fruit and B. rapa. The control group consumed commercial vegetable juice. Subjects consumed juice twice a day throughout the weekday, for 4 weeks. We prepared both juices with an equivalent energy balance. Results Weight and body mass index (BMI) of the control group after 4 weeks were significantly increased compared with baseline values. Serum total cholesterol (T-Chol) and low-density lipoprotein cholesterol (LDL-Chol) of the intervention group after 4 weeks were significantly reduced compared with baseline values. Furthermore, intake of total vegetables and fruits were significantly increased compared with baseline values in both groups. Conclusions Both vegetable juices contributed to improved intake of total vegetables and fruit. Compared with the intake of commercial vegetable juice, the intake of fresh fruit and B. rapa juice is highly effective in reducing serum cholesterol. Short-term intake of fresh fruit and B. rapa juice was shown to enhance cholesterol metabolism. PMID:24961537

  8. Glycosaminoglycan concentrations in horse plasma and serum. Differences with other animal species and identification of affecting factors.

    PubMed

    Ferlazzo, A M; Vinci, R; Panzera, M; Ferlazzo, A; Calatroni, A

    1991-01-01

    1. The measured values of acid glycosaminoglycan (GAG) concentration in plasma or in serum show significant differences between trained and untrained horses and among sedentary horses and other animal species (cattle, rabbit, sheep). 2. Diurnal variations in serum GAG levels are reported (cattle), and changes in plasma GAG concentrations after road transport (horses) and in late pregnancy (mares, cows), while sex, age and breed do not affect them. PMID:1782758

  9. A quinazoline-based HDAC inhibitor affects gene expression pathways involved in cholesterol biosynthesis and mevalonate in prostate cancer cells.

    PubMed

    Lin, Z; Bishop, K S; Sutherland, H; Marlow, G; Murray, P; Denny, W A; Ferguson, L R

    2016-03-01

    Chronic inflammation can lead to the development of cancers and resolution of inflammation is an ongoing challenge. Inflammation can result from dysregulation of the epigenome and a number of compounds that modify the epigenome are in clinical use. In this study the anti-inflammatory and anti-cancer effects of a quinazoline epigenetic-modulator compound were determined in prostate cancer cell lines using a non-hypothesis driven transcriptomics strategy utilising the Affymetrix PrimeView® Human Gene Expression microarray. GATHER and IPA software were used to analyse the data and to provide information on significantly modified biological processes, pathways and networks. A number of genes were differentially expressed in both PC3 and DU145 prostate cancer cell lines. The top canonical pathways that frequently arose across both cell lines at a number of time points included cholesterol biosynthesis and metabolism, and the mevalonate pathway. Targeting of sterol and mevalonate pathways may be a powerful anticancer approach. PMID:26759180

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

    PubMed Central

    Takeuchi, Hidekazu; Sata, Masataka

    2012-01-01

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

  11. Cholesterol depletion induces autophagy

    SciTech Connect

    Cheng, Jinglei; Ohsaki, Yuki; Tauchi-Sato, Kumi; Fujita, Akikazu; Fujimoto, Toyoshi . E-mail: tfujimot@med.nagoya-u.ac.jp

    2006-12-08

    Autophagy is a mechanism to digest cells' own components, and its importance in many physiological and pathological processes is being recognized. But the molecular mechanism that regulates autophagy is not understood in detail. In the present study, we found that cholesterol depletion induces macroautophagy. The cellular cholesterol in human fibroblasts was depleted either acutely using 5 mM methyl-{beta}-cyclodextrin or 10-20 {mu}g/ml nystatin for 1 h, or metabolically by 20 {mu}M mevastatin and 200 {mu}M mevalonolactone along with 10% lipoprotein-deficient serum for 2-3 days. By any of these protocols, marked increase of LC3-II was detected by immunoblotting and by immunofluorescence microscopy, and the increase was more extensive than that caused by amino acid starvation, i.e., incubation in Hanks' solution for several hours. The induction of autophagic vacuoles by cholesterol depletion was also observed in other cell types, and the LC3-positive membranes were often seen as long tubules, >50 {mu}m in length. The increase of LC3-II by methyl-{beta}-cyclodextrin was suppressed by phosphatidylinositol 3-kinase inhibitors and was accompanied by dephosphorylation of mammalian target of rapamycin. By electron microscopy, autophagic vacuoles induced by cholesterol depletion were indistinguishable from those seen after amino acid starvation. These results demonstrate that a decrease in cholesterol activates autophagy by a phosphatidylinositol 3-kinase-dependent mechanism.

  12. Effect of dietary vegetable (water convolvulus) on cholesterol metabolism in rats

    SciTech Connect

    Chen, M.L.; Chia, D.F.; Run, J.Q.

    1984-03-01

    Male rats were fed diets containing 0.5% cholesterol with or without vegetable (water convolvulus) or neutral detergent fiber supplementation. After 2 weeks, rats were given (4-14C)cholesterol i.p. Feces were collected for 1 week. Three hours prior to necropsy, (3H)acetate was administered i.p. Samples of serum, liver, adipose tissue, muscle and brain were obtained for analysis. Concentrations of total lipids and cholesterol and synthesis and recovery of labeled steroids are reported. Results showed that the growth of animals and food utilization were not significantly affected by different dietary treatments. The notable effect of vegetable was that the elevated liver and serum cholesterol levels due to increased intake can be nearly offset by increasing the fecal excretion. The high rate of excretion of 14C-labeled steroids shown in vegetable-fed rats indicated that both decreased absorption and increased endogenous excretion occurred in these animals. The synthesis of total lipids as demonstrated by (3H)acetate incorporation was not affected appreciably by diet. In liver, however, cholesterol synthesis appeared to be lower in rats receiving cholesterol-supplemented diet, but higher in rats fed vegetable diets. The ratio of 3H:14C of liver cholesterol was significantly higher in rats fed the vegetable diet. In brain cholesterol we also found consistently high 3H:14C ratios, which were not affected by dietary intake. It appears that brain cholesterol level is maintained mainly by synthesis in situ and not by uptake from dietary or other sources.

  13. Effect of dietary vegetable (water convolvulus) on cholesterol metabolism in rats.

    PubMed

    Chen, M L; Chia, D F; Run, J Q

    1984-03-01

    Male rats were fed diets containing 0.5% cholesterol with or without vegetable (water convolvulus) or neutral detergent fiber supplementation. After 2 weeks, rats were given [4-14C]cholesterol i.p. Feces were collected for 1 week. Three hours prior to necropsy, [3H]acetate was administered i.p. Samples of serum, liver, adipose tissue, muscle and brain were obtained for analysis. Concentrations of total lipids and cholesterol and synthesis and recovery of labeled steroids are reported. Results showed that the growth of animals and food utilization were not significantly affected by different dietary treatments. The notable effect of vegetable was that the elevated liver and serum cholesterol levels due to increased intake can be nearly offset by increasing the fecal excretion. The high rate of excretion of 14C-labeled steroids shown in vegetable-fed rats indicated that both decreased absorption and increased endogenous excretion occurred in these animals. The synthesis of total lipids as demonstrated by [3H]acetate incorporation was not affected appreciably by diet. In liver, however, cholesterol synthesis appeared to be lower in rats receiving cholesterol-supplemented diet, but higher in rats fed vegetable diets. The ratio of 3H:14C of liver cholesterol was significantly higher in rats fed the vegetable diet. In brain cholesterol we also found consistently high 3H:14C ratios, which were not affected by dietary intake. It appears that brain cholesterol level is maintained mainly by synthesis in situ and not by uptake from dietary or other sources. PMID:6321703

  14. Exposure to Palladium Nanoparticles Affects Serum Levels of Cytokines in Female Wistar Rats

    PubMed Central

    Iavicoli, Ivo; Fontana, Luca; Corbi, Maddalena; Leso, Veruscka; Marinaccio, Alessandro; Leopold, Kerstin; Schindl, Roland; Sgambato, Alessandro

    2015-01-01

    Background Information currently available on the impact of palladium on the immune system mainly derives from studies assessing the biological effects of palladium salts. However, in the last years, there has been a notable increase in occupational and environmental levels of fine and ultrafine palladium particles released from automobile catalytic converters, which may play a role in palladium sensitization. In this context, the evaluation of the possible effects exerted by palladium nanoparticles (Pd-NPs) on the immune system is essential to comprehensively assess palladium immunotoxic potential. Aim Therefore, the aim of this study was to investigate the effects of Pd-NPs on the immune system of female Wistar rats exposed to this xenobiotic for 14 days, by assessing possible quantitative changes in a number of cytokines: IL-1α, IL-2, IL-4, IL-6, IL-10, IL-12, GM-CSF, INF-γ and TNF-α. Methods Twenty rats were randomly divided into four exposure groups and one of control. Animals were given a single tail vein injection of vehicle (control group) and different concentrations of Pd-NPs (0.012, 0.12, 1.2 and 12 μg/kg). A multiplex biometric enzyme linked immunosorbent assay was used to evaluate cytokine serum levels. Results The mean serum concentrations of all cytokines decreased after the administration of 0.012 μg/kg of Pd-NPs, whereas exceeded the control levels at higher exposure doses. The highest concentration of Pd-NPs (12 μg/kg) induced a significant increase of IL-1α, IL-4, IL-6, IL-10, IL-12, GM-CSF and INF-γ compared to controls. Discussion and Conclusions These results demonstrated that Pd-NP exposure can affect the immune response of rats inducing a stimulatory action that becomes significant at the highest administered dose. Our findings did not show an imbalance between cytokines produced by CD4+ T helper (Th) cells 1 and 2, thus suggesting a generalized stimulation of the immune system with a simultaneous activation and polarization of the

  15. Lithium differentially affects clock gene expression in serum-shocked NIH-3T3 cells.

    PubMed

    Osland, Teresa M; Fernø, Johan; Håvik, Bjarte; Heuch, Ivar; Ruoff, Peter; Lærum, Ole Didrik; Steen, Vidar M

    2011-07-01

    Bipolar disorder has been associated with disturbances in circadian rhythms. Lithium is frequently used in the long-term treatment of bipolar disorder, and has been shown to prolong such rhythms in animals and humans. To examine whether lithium affects the expression of genes regulating the circadian clock, cultured NIH-3T3 cells were synchronized by serum-shocking, and the relative expression of the clock genes Period1 (Per1), Period2 (Per2), Period3 (Per3), Cryptochrome1 (Cry1), Cryptochrome2 (Cry2), Brain and muscle aryl hydrocarbon nuclear translocator-like 1 (Bmal1), Circadian locomotor output cycles kaput (Clock), Rev-Erb-α (Nr1d1), RAR-related orphan receptor α (Ror-α), Glycogen synthase kinase-3β (Gsk-3β), Casein kinase 1-ε (CK1-ε; Csnk1ε), E4 binding protein 4 (E4BP4; Nfil-3) and albumin D-binding protein (Dbp) was examined for three consecutive days in the presence of lithium (20 mM) or vehicle (20 mM NaCl). We found that lithium significantly increased the expression of Per2 and Cry1, whereas Per3, Cry2, Bmal1, E4BP4 and Rev-Erb-α expression was reduced. We also found that lithium prolonged the period of Per2. Taken together, these effects on clock gene expression may be relevant for the effects of lithium on biological rhythms and could also give new leads to further explore its mood-stabilizing actions in the treatment of bipolar disorder. PMID:20837565

  16. Serum From Advanced Heart Failure Patients Promotes Angiogenic Sprouting and Affects the Notch Pathway in Human Endothelial Cells.

    PubMed

    Pannella, Micaela; Caliceti, Cristiana; Fortini, Francesca; Aquila, Giorgio; Vieceli Dalla Sega, Francesco; Pannuti, Antonio; Fortini, Cinzia; Morelli, Marco Bruno; Fucili, Alessandro; Francolini, Gloria; Voltan, Rebecca; Secchiero, Paola; Dinelli, Giovanni; Leoncini, Emanuela; Ferracin, Manuela; Hrelia, Silvana; Miele, Lucio; Rizzo, Paola

    2016-12-01

    It is unknown whether components present in heart failure (HF) patients' serum provide an angiogenic stimulus. We sought to determine whether serum from HF patients affects angiogenesis and its major modulator, the Notch pathway, in human umbilical vein endothelial cells (HUVECs). In cells treated with serum from healthy subjects or from patients at different HF stage we determined: (1) Sprouting angiogenesis, by measuring cells network (closed tubes) in collagen gel. (2) Protein levels of Notch receptors 1, 2, 4, and ligands Jagged1, Delta-like4. We found a higher number of closed tubes in HUVECs treated with advanced HF patients serum in comparison with cells treated with serum from mild HF patients or controls. Furthermore, as indicated by the reduction of the active form of Notch4 (N4IC) and of Jagged1, advanced HF patients serum inhibited Notch signalling in HUVECs in comparison with mild HF patients' serum and controls. The circulating levels of NT-proBNP (N-terminal of the pro-hormone brain natriuretic peptide), a marker for the detection and evalutation of HF, were positively correlated with the number of closed tubes (r = 0.485) and negatively with Notch4IC and Jagged1 levels in sera-treated cells (r = -0.526 and r = -0.604, respectively). In conclusion, we found that sera from advanced HF patients promote sprouting angiogenesis and dysregulate Notch signaling in HUVECs. Our study provides in vitro evidence of an angiogenic stimulus arising during HF progression and suggests a role for the Notch pathway in it. J. Cell. Physiol. 231: 2700-2710, 2016. © 2016 Wiley Periodicals, Inc. PMID:26987674

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

    PubMed Central

    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 (p<0.05). Serum HDL cholesterol level tended to increase and hepatic total cholesterol level decreased and were comparable to the CON group (p>0.05). In HFY group, body weight and hepatic total lipid level significantly decreased over the HFCD group (p<0.05). Serum and hepatic total cholesterol level, kidney, and body fat weights decreased, and were compared to the CON group (p>0.05). 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. PMID:26761869

  18. Cholesterol-metabolizing cytochromes P450: implications for cholesterol lowering

    PubMed Central

    Pikuleva, Irina A.

    2010-01-01

    Cardiovascular disease (CVD) continues to be a leading cause of death worldwide. Elevated serum cholesterol is one of the classical risk factors for CVD which also include age, hypertension, smoking, diabetes mellitus, obesity and family history. A number of therapeutic drug classes have been developed to treat hypercholesterolemia, yet, an important percentage of patients do not reach their treatment goals. Therefore, new cholesterol-lowering medications, having a site of action different from that of currently available drugs need to be developed. This review summarizes new information about cytochrome P450 enzymes 7A1, 27A1, and 46A1, that play key roles in cholesterol elimination and that have potential to serve as targets for cholesterol-lowering. PMID:18950282

  19. Serum alkaline phosphatase negatively affects endothelium-dependent vasodilation in naïve hypertensive patients.

    PubMed

    Perticone, Francesco; Perticone, Maria; Maio, Raffaele; Sciacqua, Angela; Andreucci, Michele; Tripepi, Giovanni; Corrao, Salvatore; Mallamaci, Francesca; Sesti, Giorgio; Zoccali, Carmine

    2015-10-01

    Tissue nonspecific alkaline phosphatase, promoting arterial calcification in experimental models, is a powerful predictor of total and cardiovascular mortality in general population and in patients with renal or cardiovascular diseases. For this study, to evaluate a possible correlation between serum alkaline phosphatase levels and endothelial function, assessed by strain gauge plethysmography, we enrolled 500 naïve hypertensives divided into increasing tertiles of alkaline phosphatase. The maximal response to acetylcholine was inversely related to alkaline phosphatase (r=−0.55; P<0.001), and this association was independent (r=−0.61; P<0.001) of demographic and classical risk factors, body mass index, estimated glomerular filtration rate, serum phosphorus and calcium, C-reactive protein, and albuminuria. At multiple logistic regression analysis, the risk of endothelial dysfunction was ≈3-fold higher in patients in the third tertile than that of patients in the first tertile. We also tested the combined role of alkaline phosphatase and serum phosphorus on endothelial function. The steepness of the alkaline phosphatase/vasodilating response to acetylcholine relationship was substantially attenuated (P<0.001) in patients with serum phosphorus above the median value when compared with patients with serum phosphorus below the median (−5.0% versus −10.2% per alkaline phosphatase unit, respectively), and this interaction remained highly significant (P<0.001) after adjustment of all the previously mentioned risk factors. Our data support a strong and significant inverse relationship between alkaline phosphatase and endothelium-dependent vasodilation, which was attenuated by relatively higher serum phosphorus levels. PMID:26324506

  20. Does the antibody production ability affect the serum anti-Helicobacter pylori IgG titer?

    PubMed Central

    Chung, Hyun Ah; Lee, Sun-Young; Moon, Hee Won; Kim, Jeong Hwan; Sung, In-Kyung; Park, Hyung Seok; Shim, Chan Sup; Han, Hye Seung

    2016-01-01

    AIM To investigate the relationship between serum titers of anti-Helicobacter pylori (H. pylori) immunoglobulin G (IgG) and hepatitis B virus surface antibody (HBsAb). METHODS Korean adults were included whose samples had positive Giemsa staining on endoscopic biopsy and were studied in the hepatitis B virus surface antigen (HBsAg)/HBsAb serologic assay, pepsinogen (PG) assay, and H. pylori serologic test on the same day. Subjects were excluded if they were positive for HBsAg, had a recent history of medication, or had other medical condition(s). We analyzed the effects of the following factors on serum titers of HBsAb and the anti-H. pylori IgG: Age, density of H. pylori infiltration in biopsy samples, serum concentrations of PG I and PG II, PG I/II ratio, and white blood cell count. RESULTS Of 111 included subjects, 74 (66.7%) exhibited a positive HBsAb finding. The serum anti-H. pylori IgG titer did not correlate with the serum HBsAb titer (P = 0.185); however, it correlated with the degree of H. pylori infiltration on gastric biopsy (P < 0.001) and serum PG II concentration (P = 0.042). According to the density of H. pylori infiltration on gastric biopsy, subjects could be subdivided into those with a marked (median: 3.95, range 0.82-4.00) (P = 0.458), moderate (median: 3.37, range 1.86-4.00), and mild H. pylori infiltrations (median: 2.39, range 0.36-4.00) (P < 0.001). Subjects with a marked H. pylori infiltration on gastric biopsy had the highest serological titer, whereas in subjects with moderate and mild H. pylori infiltrations titers were correspondingly lower (P < 0.001). After the successful eradication, significant decreases of the degree of H. pylori infiltration (P < 0.001), serum anti-H. pylori IgG titer (P < 0.001), and serum concentrations of PG I (P = 0.028) and PG II (P = 0.028) were observed. CONCLUSION The anti-H. pylori IgG assay can be used to estimate the burden of bacteria in immunocompetent hosts with H. pylori infection, regardless

  1. Effects of Toxicologically Relevant Xenobiotics and the Lipid-Derived Electrophile 4-Hydroxynonenal on Macrophage Cholesterol Efflux: Silencing Carboxylesterase 1 Has Paradoxical Effects on Cholesterol Uptake and Efflux

    PubMed Central

    2015-01-01

    Cholesterol cycles between free cholesterol (unesterified) found predominantly in membranes and cholesteryl esters (CEs) stored in cytoplasmic lipid droplets. Only free cholesterol is effluxed from macrophages via ATP-binding cassette (ABC) transporters to extracellular acceptors. Carboxylesterase 1 (CES1), proposed to hydrolyze CEs, is inactivated by oxon metabolites of organophosphorus pesticides and by the lipid electrophile 4-hydroxynonenal (HNE). We assessed the ability of these compounds to reduce cholesterol efflux from foam cells. Human THP-1 macrophages were loaded with [3H]-cholesterol/acetylated LDL and then allowed to equilibrate to enable [3H]-cholesterol to distribute into its various cellular pools. The cholesterol-engorged cells were then treated with toxicants in the absence of cholesterol acceptors for 24 h, followed by a 24 h efflux period in the presence of toxicant. A concentration-dependent reduction in [3H]-cholesterol efflux via ABCA1 (up to 50%) was found for paraoxon (0.1–10 μM), whereas treatment with HNE had no effect. A modest reduction in [3H]-cholesterol efflux via ABCG1 (25%) was found after treatment with either paraoxon or chlorpyrifos oxon (10 μM each) but not HNE. No difference in efflux rates was found after treatments with either paraoxon or HNE when the universal cholesterol acceptor 10% (v/v) fetal bovine serum was used. When the re-esterification arm of the CE cycle was disabled in foam cells, paraoxon treatment increased CE levels, suggesting the neutral CE hydrolysis arm of the cycle had been inhibited by the toxicant. However, paraoxon also partially inhibited lysosomal acid lipase, which generates cholesterol for efflux, and reduced the expression of ABCA1 protein. Paradoxically, silencing CES1 expression in macrophages did not affect the percent of [3H]-cholesterol efflux. However, CES1 mRNA knockdown markedly reduced cholesterol uptake by macrophages, with SR-A and CD36 mRNA reduced 3- and 4-fold, respectively

  2. How cholesterol regulates endothelial biomechanics

    PubMed Central

    Hong, Zhongkui; Staiculescu, Marius C.; Hampel, Paul; Levitan, Irena; Forgacs, Gabor

    2012-01-01

    As endothelial cells form the barrier between blood flow and surrounding tissue, many of their functions depend on mechanical integrity, in particular those of the plasma membrane. As component and organizer of the plasma membrane, cholesterol is a regulator of cellular mechanical properties. Disruption of cholesterol balance leads to impairment of endothelial functions and eventually to disease. The mechanical properties of the membrane are strongly affected by the cytoskeleton. As Phosphatidylinositol-4,5-bisphosphate (PIP2) is a key mediator between the membrane and cytoskeleton, it also affects cellular biomechanical properties. Typically, PIP2 is concentrated in cholesterol-rich microdomains, such as caveolae and lipid rafts, which are particularly abundant in the endothelial plasma membrane. We investigated the connection between cholesterol and PIP2 by extracting membrane tethers from bovine aortic endothelial cells (BAEC) at different cholesterol levels and PIP2 conditions. Our results suggest that in BAEC the role of PIP2, as a mediator of membrane-cytoskeleton adhesion, is regulated by cholesterol. Our findings confirm the specific role of cholesterol in endothelial cells and may have implications for cholesterol-dependent vascular pathologies. PMID:23162471

  3. Women and Cholesterol

    MedlinePlus

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

  4. Cholesterol IQ Quiz

    MedlinePlus

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

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

    PubMed

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

    1989-01-01

    The effects of dietary cholesterol and fats on cholesterol metabolism later in life were studied in Mongolian gerbils. Three groups were given a basic diet with soybean oil, palm kernel oil amounting to 8.75% (w/w), or the basic diet only. In three other groups, cholesterol (0.05%) was added to the above diets. Measurements were done in animals of the third generation on the diets. On all diets, teh serum cholesterol of the sucklings was increased as compared to the young that were suckled by mothers on the basic diet only, while body cholesterol was highest in sucklings of mothers on the basic diet or palm-kernel-oil-enriched diets. When the diets were replaced by the basic diets at 6 months of age, serum cholesterol was still increased at 12 months of age in animals previously fed on the cholesterol-enriched diets. Tissue cholesterol did not differ. However, after a challenge with cholesterol at that age, the differences in serum cholesterol were not significantly different. PMID:2802529

  6. Krill oil supplementation lowers serum triglycerides without increasing low-density lipoprotein cholesterol in adults with borderline high or high triglyceride levels.

    PubMed

    Berge, Kjetil; Musa-Veloso, Kathy; Harwood, Melody; Hoem, Nils; Burri, Lena

    2014-02-01

    The aim of the study was to explore the effects of 12 weeks daily krill oil supplementation on fasting serum triglyceride (TG) and lipoprotein particle levels in subjects whose habitual fish intake is low and who have borderline high or high fasting serum TG levels (150-499 mg/dL). We hypothesized that Krill oil lowers serum TG levels in subjects with borderline high or high fasting TG levels. To test our hypothesis 300 male and female subjects were included in a double-blind, randomized, multi-center, placebo-controlled study with five treatment groups: placebo (olive oil) or 0.5, 1, 2, or 4 g/day of krill oil. Serum lipids were measured after an overnight fast at baseline, 6 and 12 weeks. Due to a high intra-individual variability in TG levels, data from all subjects in the four krill oil groups were pooled to increase statistical power, and a general time- and dose-independent one-way analysis of variance was performed to assess efficacy. Relative to subjects in the placebo group, those administered krill oil had a statistically significant calculated reduction in serum TG levels of 10.2%. Moreover, LDL-C levels were not increased in the krill oil groups relative to the placebo group. The outcome of the pooled analysis suggests that krill oil is effective in reducing a cardiovascular risk factor. However, owing to the individual fluctuations of TG concentrations measured, a study with more individual measurements per treatment group is needed to increase the confidence of these findings. PMID:24461313

  7. Quercetin regulates hepatic cholesterol metabolism by promoting cholesterol-to-bile acid conversion and cholesterol efflux in rats.

    PubMed

    Zhang, Min; Xie, Zongkai; Gao, Weina; Pu, Lingling; Wei, Jingyu; Guo, Changjiang

    2016-03-01

    Quercetin, a common member of the flavonoid family, is widely present in plant kingdom. Despite that quercetin is implicated in regulating cholesterol metabolism, the molecular mechanism is poorly understood. We hypothesized that quercetin regulates cholesterol homeostasis through regulating the key enzymes involved in hepatic cholesterol metabolism. To test this hypothesis, we compared the profile of key enzymes and transcription factors involved in the hepatic cholesterol metabolism in rats with or without quercetin supplementation. Twenty male Wistar rats were randomly divided into control and quercetin-supplemented groups. Serum total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total bile acids in feces and bile were measured. Hepatic enzymatic activities were determined by activity assay kit and high-performance liquid chromatography-based analyses. The messenger RNA (mRNA) and protein expressions were determined by reverse transcriptase polymerase chain reaction and Western blot analyses, respectively. The results showed that the activity of hepatic cholesterol 7α-hydroxylase, a critical enzyme in the conversion of cholesterol to bile acids, was significantly elevated by quercetin. The expression of cholesterol 7α-hydroxylase, as well as liver X receptor α, an important transcription factor, was also increased at both mRNA and protein levels by quercetin. However, quercetin exposure had no impact on the activity of hepatic HMG-CoA reductase, a rate-limiting enzyme in the biosynthesis of cholesterol. We also found that quercetin treatment significantly increased ATP binding cassette transporter G1 mRNA and protein expression in the liver, suggesting that quercetin may increase hepatic cholesterol efflux. Collectively, the results presented here indicate that quercetin regulates hepatic cholesterol metabolism mainly through the pathways that promote cholesterol-to-bile acid conversion and

  8. Carbon Inverse Opal Rods for Nonenzymatic Cholesterol Detection.

    PubMed

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

    2015-11-18

    Carbon inverse opal rods made from silica photonic crystal rods are used for nonenzymatic cholesterol sensing. The characteristic reflection peak originating from the physical periodic structure works as sensing signals for quantitatively estimating cholesterol concentrations. Carbon inverse opal rods work both in cholesterol standard solutions and human serum. They are suitable for practical use in clinical diagnose. PMID:26415111

  9. Cholesterol-lowering effect of rice bran protein containing bile acid-binding proteins.

    PubMed

    Wang, Jilite; Shimada, Masaya; Kato, Yukina; Kusada, Mio; Nagaoka, Satoshi

    2015-01-01

    Dietary plant protein is well known to reduce serum cholesterol levels. Rice bran is a by-product of rice milling and is a good source of protein. The present study examined whether feeding rats a high-cholesterol diet containing 10% rice bran protein (RBP) for 10 d affected cholesterol metabolism. Rats fed dietary RBP had lower serum total cholesterol levels and increased excretion of fecal steroids, such as cholesterol and bile acids, than those fed dietary casein. In vitro assays showed that RBP strongly bound to taurocholate, and inhibited the micellar solubility of cholesterol, compared with casein. Moreover, the bile acid-binding proteins of the RBP were eluted by a chromatographic column conjugated with cholic acid, and one of them was identified as hypothetical protein OsJ_13801 (NCBI accession No. EAZ29742) using MALDI-TOF mass spectrometry analysis. These results suggest that the hypocholesterolemic action of the RBP may be caused by the bile acid-binding proteins. PMID:25374002

  10. Changes in HDL-cholesterol and lipoprotein Lp(a) after 6-month treatment with finasteride in males affected by benign prostatic hyperplasia (BPH).

    PubMed

    Denti, L; Pasolini, G; Cortellini, P; Sanfelici, L; Benedetti, R; Cecchetti, A; Ferretti, S; Bruschieri, L; Ablondi, F; Valenti, G

    2000-09-01

    Androgen effects on lipoproteins, mainly high density lipoprotein (HDL), could be exerted by a direct interaction of testosterone (T) or dihydrotestosterone (DHT) with liver androgen receptors. To assess if T needs to be converted into DHT to affect lipid metabolism, 13 patients were studied, affected with benign prostatic hyperplasia (BPH) and treated with an inhibitor of 5 alpha-reductase (finasteride). They were compared with 15 untreated controls. At baseline and after 3 and 6 months of therapy, each patient was evaluated as for lipoprotein and hormone concentrations, as well as for nutritional status. Body composition was assessed by anthropometry and bio-impedance analysis (BIA). Treatment was associated with a significant increase of HDL-cholesterol (HDL-C), mainly HDL3 subclass, and lipoprotein(a) (Lp(a)), as well as a decline of DHT, whereas no significant changes were apparent for T, estradiol (E2), sex hormone binding hormone (SHBG) and body composition indexes. However, no significant associations between DHT and lipid relative changes were apparent at bivariate correlation analysis. This finding was confirmed by comparing patient subsets identified by cluster analysis, according to HDL subclass individual responses. Rather, a slight association with E2 for HDL2 (positive) and HDL3 (negative) was found. In conclusion, finasteride can modify HDL and Lp(a) concentrations. However, by the data, these effects cannot be definitively attributed to the changes in DHT synthesis induced by finasteride, since a direct and non-specific interference of the drug on liver metabolism cannot be excluded. PMID:10996351

  11. Step by Step: Eating To Lower Your High Blood Cholesterol. Revised.

    ERIC Educational Resources Information Center

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

    This booklet offers advice for adults who want to lower their blood cholesterol level. The first section, "What You Need To Know about High Blood Cholesterol," discusses blood cholesterol and why it matters, what cholesterol numbers mean, and what affects blood cholesterol levels. Section 2, "What You Need To Do To Lower Blood Cholesterol,"…

  12. Origin of Serum Affects Quality of Engineered Tissues Produced by the Self-Assembly Approach

    PubMed Central

    Chabaud, Stéphane; Simard, Melissa; Gendreau, Isabelle; Pouliot, Roxane; Bolduc, Stéphane

    2016-01-01

    Despite the emergence of serum-free media for cell culture, the use of serum to supplement the culture media is still essential in order to produce engineered urologic tissues using the self-assembly approach, not only for the stromal compartment but also for the uroepithelium. Effects of sera on thickness of these two compartments were measured and quality of the epithelial differentiation was evaluated. For bladder mucosa substitute reconstruction, the use of postnatal sera failed to produce an adequate uroepithelium whereas the fetal sera supplementation did. Postnatal sera also provided thinner stromal compartments than the one obtained using fetal sera, no matter if the fibroblasts from healthy or psoriatic donors were used to reconstruct human skin substitutes. PMID:27293972

  13. Interaction of Silver Nanoparticles with Serum Proteins Affects Their Antimicrobial Activity In Vivo

    PubMed Central

    Gnanadhas, Divya Prakash; Ben Thomas, Midhun; Thomas, Rony; Raichur, Ashok M.

    2013-01-01

    The emergence of multidrug-resistant bacteria is a global threat for human society. There exist recorded data that silver was used as an antimicrobial agent by the ancient Greeks and Romans during the 8th century. Silver nanoparticles (AgNPs) are of potential interest because of their effective antibacterial and antiviral activities, with minimal cytotoxic effects on the cells. However, very few reports have shown the usage of AgNPs for antibacterial therapy in vivo. In this study, we deciphered the importance of the chosen methods for synthesis and capping of AgNPs for their improved activity in vivo. The interaction of AgNPs with serum albumin has a significant effect on their antibacterial activity. It was observed that uncapped AgNPs exhibited no antibacterial activity in the presence of serum proteins, due to the interaction with bovine serum albumin (BSA), which was confirmed by UV-Vis spectroscopy. However, capped AgNPs [with citrate or poly(vinylpyrrolidone)] exhibited antibacterial properties due to minimized interactions with serum proteins. The damage in the bacterial membrane was assessed by flow cytometry, which also showed that only capped AgNPs exhibited antibacterial properties, even in the presence of BSA. In order to understand the in vivo relevance of the antibacterial activities of different AgNPs, a murine salmonellosis model was used. It was conclusively proved that AgNPs capped with citrate or PVP exhibited significant antibacterial activities in vivo against Salmonella infection compared to uncapped AgNPs. These results clearly demonstrate the importance of capping agents and the synthesis method for AgNPs in their use as antimicrobial agents for therapeutic purposes. PMID:23877702

  14. Interaction of silver nanoparticles with serum proteins affects their antimicrobial activity in vivo.

    PubMed

    Gnanadhas, Divya Prakash; Ben Thomas, Midhun; Thomas, Rony; Raichur, Ashok M; Chakravortty, Dipshikha

    2013-10-01

    The emergence of multidrug-resistant bacteria is a global threat for human society. There exist recorded data that silver was used as an antimicrobial agent by the ancient Greeks and Romans during the 8th century. Silver nanoparticles (AgNPs) are of potential interest because of their effective antibacterial and antiviral activities, with minimal cytotoxic effects on the cells. However, very few reports have shown the usage of AgNPs for antibacterial therapy in vivo. In this study, we deciphered the importance of the chosen methods for synthesis and capping of AgNPs for their improved activity in vivo. The interaction of AgNPs with serum albumin has a significant effect on their antibacterial activity. It was observed that uncapped AgNPs exhibited no antibacterial activity in the presence of serum proteins, due to the interaction with bovine serum albumin (BSA), which was confirmed by UV-Vis spectroscopy. However, capped AgNPs [with citrate or poly(vinylpyrrolidone)] exhibited antibacterial properties due to minimized interactions with serum proteins. The damage in the bacterial membrane was assessed by flow cytometry, which also showed that only capped AgNPs exhibited antibacterial properties, even in the presence of BSA. In order to understand the in vivo relevance of the antibacterial activities of different AgNPs, a murine salmonellosis model was used. It was conclusively proved that AgNPs capped with citrate or PVP exhibited significant antibacterial activities in vivo against Salmonella infection compared to uncapped AgNPs. These results clearly demonstrate the importance of capping agents and the synthesis method for AgNPs in their use as antimicrobial agents for therapeutic purposes. PMID:23877702

  15. Case report: A novel apolipoprotein A-I missense mutation apoA-I (Arg149Ser)Boston associated with decreased lecithin-cholesterol acyltransferase activation and cellular cholesterol efflux.

    PubMed

    Anthanont, Pimjai; Asztalos, Bela F; Polisecki, Eliana; Zachariah, Benoy; Schaefer, Ernst J

    2015-01-01

    We report a novel heterozygous apolipoprotein A-I (apoA-I) missense mutation (c.517C>A, p.Arg149Ser, designated as apoA-IBoston) in a 67-year-old woman and her 2 sons, who had mean serum high-density lipoprotein (HDL) cholesterol, apoA-I, and apoA-I in very large α-1 HDL that were 10%, 35%, and 16% of normal, respectively (all P < .05). The percentage of HDL cholesterol in the esterified form was also significantly (P < .05) reduced to 52% of control values. Cholesteryl ester tranfer protein (CETP) activity was normal. The mean global, adenosine triphosphate (ATP)-binding cassette transporter A1 and scavenger receptor B type I-mediated cellular cholesterol efflux capacity in apoB-depleted serum from affected family members were 41%, 37%, 47%, 54%, and 48% of control values, respectively (all P < .05). lecithin-cholesterol acyltransferase (LCAT) activity in plasma was 71% of controls, whereas in the cell-based assay, it was 73% of control values (P < .05). The data indicate that this novel apoA-I missense is associated with markedly decreased levels of HDL cholesterol and very large α-1 HDL, as well as decreased serum cellular cholesterol efflux and LCAT activity, but not with premature coronary heart disease, similar to other apoA-I mutations that have been associated with decreased LCAT activity. PMID:26073399

  16. Is the fact of parenting couples cohabitation affecting the serum levels of persistent organohalogen pollutants?

    PubMed

    Góralczyk, Katarzyna; Struciński, Paweł; Wojtyniak, Bogdan; Rabczenko, Daniel; Lindh, Christian H; Jönsson, Bo A G; Toft, Gunnar; Lenters, Virissa; Czaja, Katarzyna; Hernik, Agnieszka; Bonde, Jens Peter; Pedersen, Henning S; Zvyezday, Valentyna; Ludwicki, Jan K

    2015-06-01

    Organohalogen compounds constitute one of the important groups of persistent organic pollutants (POPs). Among them, due to their long-term health effects, one should pay attention on organochlorine pesticides, polychlorinated biphenyls (PCBs) and perfluoroalkylated substances (PFASs). This paper is an attempt to answer the question about relation between the fact of cohabitation by couples expecting a child and the level of the organohalogen compounds in the blood serum of both parents. The study was done on a population of parent couples from Greenland, Poland and Ukraine, from whom blood samples were collected in order to establish the levels of marker organohalogen compounds. We selected, as the representative of these compounds, the most persistent metabolite of DDT, i.e. p,p'-DDE, the most frequently detected PCB congener - CB-153, and PFOS and PFOA as the representatives of PFASs. The results show that in case of all compounds under study the highest concentrations were present always in men in relation to the levels detected in the blood serum of their female partners, regardless of the country of origin of the couple. A positive correlation was noted between the concentrations of the studied compounds in the blood serum of men and women in parenting couples. In some cases these correlations were statistically significant, e.g. for concentrations of p,p'-DDE in pairs from Greenland and Ukraine, of CB-153 in pairs from Poland and Ukraine, and of PFOS for parents from Greenland and Poland, while for PFOA - only for couples from Greenland. The concentrations of the compounds included in the study were similar to the levels found in general population in other countries. Our results show that the exposure to POPs resulting from cohabitation plays a role in the general exposure to these compounds. PMID:25836759

  17. Use of Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry to Demonstrate Decreased Serum Statin Levels after Extracorporeal LDL-Cholesterol Elimination

    PubMed Central

    Bláha, M.; Vlčková, H.; Nováková, L.; Solichová, D.; Solich, P.; Lánská, M.; Malý, J.; Bláha, V.

    2011-01-01

    Background. Using our statin analysis method, it was possible to uncover a significant drop in statin levels (atorvastatin, simvastatin, and metabolites) after extracorporeal LDL-cholesterol elimination (EE) in severe familial hypercholesterolemia (FH). The purpose of this work was to identify the mechanism underlying this drop and its clinical significance as well as to propose measures to optimize a pharmacotherapeutical regimen that can prevent the loss of statins. Methods. Ultra High Performance Liquid Chromatography (UHPLC) connected to the triple quadrupole MS/MS system was used. Patients. A group of long-term treated patients (3–12 years of treatment) with severe FH (12 patients) and treated regularly by LDL-apheresis (immunoadsorption) or haemorheopheresis (cascade filtration) were included in this study. Results. After EE, the level of statins and their metabolites decreased (atorvastatin before/after LDL-apheresis: 8.83/3.46 nmol/l; before/after haemorheopheresis: 37.02/18.94 nmol/l). A specific loss was found (concentration of atorvastatin for LDL-apheresis/haemorheopheresis: 0.28/3.04 nmol/l in washing fluids; 11.07 nmol/l in filters). To prevent substantial loss of statin concentrations, a pharmacotherapeutic regimen with a longer time interval between the dose of statins and EE is recommended (15 hours). Conclusions. A specific loss of statins was found in adsorbent columns and filters. The decrease can be prevented by the suggested dosage scheme. PMID:21076535

  18. Cholesterol strongly affects the organization of lipid monolayers studied as models of the milk fat globule membrane: Condensing effect and change in the lipid domain morphology.

    PubMed

    Murthy, Appala Venkata Ramana; Guyomarc'h, Fanny; Paboeuf, Gilles; Vié, Véronique; Lopez, Christelle

    2015-10-01

    The biological membrane that surrounds the milk fat globules exhibits phase separation of polar lipids that is poorly known. The objective of this study was to investigate the role played by cholesterol in the organization of monolayers prepared as models of the milk fat globule membrane (MFGM). Differential scanning calorimetry and X-ray diffraction experiments allowed characterization of the gel to liquid crystalline phase transition temperature of lipids, Tm ~35°C, in vesicles prepared with a MFGM lipid extract. For temperature below Tm, atomic force microscopy revealed phase separation of lipids at 30 mN·m(-1) in Langmuir-Blodgett monolayers of the MFGM lipid extract. The high Tm lipids form liquid condensed (LC) domains that protrude by about 1.5 nm from the continuous liquid expanded (LE) phase. Cholesterol was added to the MFGM extract up to 30% of polar lipids (cholesterol/milk sphingomyelin (MSM) molar ratio of 50/50). Compression isotherms evidenced the condensing effect of the cholesterol onto the MFGM lipid monolayers. Topography of the monolayers showed a decrease in the area of the LC domains and in the height difference H between the LC domains and the continuous LE phase, as the cholesterol content increased in the MFGM lipid monolayers. These results were interpreted in terms of nucleation effects of cholesterol and decrease of the line tension between LC domains and LE phase in the MFGM lipid monolayers. This study revealed the major structural role of cholesterol in the MFGM that could be involved in biological functions of this interface (e.g. mechanisms of milk fat globule digestion). PMID:26087463

  19. Tissue storage and control of cholesterol metabolism in man on high cholesterol diets.

    PubMed

    Quintão, E C; Brumer, S; Stechhahn, K

    1977-03-01

    The possibility of accumulation of tissue cholesterol in human beings submitted to high cholesterol feeding was investigated in liver biopsies and through fecal sterol balance studies. Feeding to 10 individuals 3.1 to 3.4 g/day of cholesterol for 3 weeks raised the mean serum level from 293 to 349 mg/100 ml, namely 19%, whereas the liver cholesterol content was 417 mg/100 g of wet weight. In 10 control cases eating 0.1--0.4 g/day of cholesterol serum cholesterol remained stable throughout the experimental period and the liver cholesterol content was 256 mg/100 g. Difference of liver colesterol level between the two groups was 62%. In 7 patients submitted to two periods of balance investigation on a cholesterol-free synthetic formula diet respectively prior to (PI) and after (PIII) eating the high cholesterol solid food from 4 to 15 weeks (PII), fecal steroid excretion in PIII exceeded PI in 3 patients. Such data are a direct evidence for the existence of an efficient system to release acutely stored cholesterol. In one patient bile acid excretion accounted for the difference between PIII and PI. PMID:849375

  20. The Role of Cholesterol in Cancer.

    PubMed

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

    2016-04-15

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

  1. Ethanol extract of Zhongtian hawthorn lowers serum cholesterol in mice by inhibiting transcription of 3-hydroxy-3-methylglutaryl-CoA reductase via nuclear factor-kappa B signal pathway.

    PubMed

    Hu, Hai-Jie; Luo, Xue-Gang; Dong, Qing-Qing; Mu, Ai; Shi, Guo-Long; Wang, Qiu-Tong; Chen, Xiao-Ying; Zhou, Hao; Zhang, Tong-Cun; Pan, Li-Wen

    2016-03-01

    Hawthorn is a berry-like fruit from the species of Crataegus. In China, it has another more famous name, Shan-Zha, which has been used to improve digestion as a traditional Chinese medicine or food for thousands of years. Moreover, during the last decades, hawthorn has received more attention because of its potential to treat cardiovascular diseases. However, currently, only fruits of C. pinnatifida and C. pinnatifida var. major are included as Shan-Zha in the Chinese Pharmacopoeia. In this study, our results showed that the ethanol extract of Zhongtian hawthorn, a novel grafted cultivar of C. cuneata (wild Shan-Zha), could markedly reduce body weight and levels of serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, and liver cholesterol of hyperlipidemia mice. It could suppress the stimulation effect of high-fat diet on the transcription of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and p65, and counteract the downregulation of CYP7A1 and LDLR. In addition, the results of luciferase reporter assay and Western blot showed that the transcriptional activity of HMGCR promoter was inhibited by Zhongtian hawthorn ethanol extract in a dose-dependent manner, while overexpression of p65 could reverse this transcriptional repression effect. These results suggested that Zhongtian hawthorn could provide health benefits by counteracting the high-fat diet-induced hypercholesteolemic and hyperlipidemic effects in vivo, and the mechanism underlying this event was mainly dependent on the suppressive effect of Zhongtian hawthorn ethanol extract on the transcription of HMGCR via nuclear factor-kappa B (NF-κB) signal pathway. Therefore, this novel cultivar of hawthorn cultivar which has much bigger fruits, early bearing, high yield, cold resistance, and drought resistance, might be considered as a good alternative to Shan-Zha and has great value in the food and medicine industry. In addition, to our best knowledge, this is also the first report that the

  2. Effect of Extended Release Niacin on Serum Lipids and on Endothelial Function in Adults with Sickle Cell Anemia and Low High-Density Lipoprotein Cholesterol Levels

    PubMed Central

    Scoffone, Heather M.; Krajewski, Megan; Zorca, Suzana; Bereal-Williams, Candice; Littel, Patricia; Seamon, Catherine; Mendelsohn, Laurel; Footman, Eleni; Jaoudeh, Nadine Abi; Sachdev, Vandana; Machado, Roberto F.; Cuttica, Michael; Shamburek, Robert; Cannon, Richard O.; Remaley, Alan; Minniti, Caterina P.; Kato, Gregory J.

    2014-01-01

    Through bound apolipoprotein A-I (apoA-I), high density lipoprotein cholesterol (HDL-C) activates endothelial nitric oxide synthase, inducing vasodilation. Because patients with sickle cell disease (SCD)have low apoA-I andendothelial dysfunction,we conducted a randomized, double-blinded, placebo-controlled trial to test whether extended-release niacin (niacin-ER) increases apoA-I-containing HDL-C, and improves vascular function in SCD. Twenty-seven SCD patientswith HDL-C <39 mg/dL or apoA-I <99 mg/dL were randomized to 12 weeks of niacin-ER, increased in 500mg increments to a maximum of 1500mg daily, or placebo. The primary outcome was the absolute change in HDL-C after 12 weeks, with endothelial function assessed before and at the end of treatment. Niacin-ER-treated patients trended to greater increase in HDL-C compared with placebo treatment at 12 weeks (5.1±7.7 vs. 0.9±3.8 mg/dL, one-tailed p=0.07), associated with significantly greater, improvements in the ratios of low-density lipoprotein to HDL-C (1.24 vs. 1.95, p = 0.003), and apolipoprotein B to apoA-I (0.46 vs. 0.58, p = 0.03) compared with placebo-treated patients. No improvements were detected in three independent vascular physiology assays of endothelial function. Thus, the relatively small changes in HDL-C achieved by the dose of niacin-ER used in our study are not associated with improved vascular function in patients with SCD with initially low levels of apoA-I or HDL-C. PMID:24035168

  3. Identification of Sequence Variation in the Apolipoprotein A2 Gene and Their Relationship with Serum High-Density Lipoprotein Cholesterol Levels

    PubMed Central

    Bandarian, Fatemeh; Daneshpour, Maryam Sadat; Hedayati, Mehdi; Naseri, Mohsen; Azizi, Fereidoun

    2016-01-01

    Background: Apolipoprotein A2 (APOA2) is the second major apolipoprotein of the high-density lipoprotein cholesterol (HDL-C). The study aim was to identify APOA2 gene variation in individuals within two extreme tails of HDL-C levels and its relationship with HDL-C level. Methods: This cross-sectional survey was conducted on participants from Tehran Glucose and Lipid Study (TLGS) at Research Institute for Endocrine Sciences, Tehran, Iran from April 2012 to February 2013. In total, 79 individuals with extreme low HDL-C levels (≤5th percentile for age and gender) and 63 individuals with extreme high HDL-C levels (≥95th percentile for age and gender) were selected. Variants were identified using DNA amplification and direct sequencing. Results: Screen of all exons and the core promoter region of APOA2 gene identified nine single nucleotide substitutions and one microsatellite; five of which were known and four were new variants. Of these nine variants, two were common tag single nucleotide polymorphisms (SNPs) and seven were rare SNPs. Both exonic substitutions were missense mutations and caused an amino acid change. There was a significant association between the new missense mutation (variant Chr.1:16119226, Ala98Pro) and HDL-C level. Conclusion: None of two common tag SNPs of rs6413453 and rs5082 contributes to the HDL-C trait in Iranian population, but a new missense mutation in APOA2 in our population has a significant association with HDL-C. PMID:26590203

  4. Perinatal Exposure to a Diet High in Saturated Fat, Refined Sugar and Cholesterol Affects Behaviour, Growth, and Feed Intake in Weaned Piglets.

    PubMed

    Clouard, Caroline; Gerrits, Walter J J; Kemp, Bas; Val-Laillet, David; Bolhuis, J Elizabeth

    2016-01-01

    The increased consumption of diets high in saturated fats and refined sugars is a major public health concern in Western human societies. Recent studies suggest that perinatal exposure to dietary fat and/or sugar may affect behavioural development. We thus investigated the effects of perinatal exposure to a high-fat high-sugar diet (HFS) on behavioural development and production performance of piglets. Thirty-two non-obese sows and their piglets were allocated to 1 of 4 treatments in a 2 × 2 factorial design, with 8-week prenatal (gestation) and 8-week postnatal (lactation and post-weaning) exposure to a HFS diet (12% saturated fat, 18.5% sucrose, 1% cholesterol) or control low-fat low-sugar high-starch diets as factors. From weaning onwards (4 weeks of age), piglets were housed in group of 3 littermates (n = 8 groups/treatment) and fed ad libitum. After the end of the dietary intervention (8 weeks of age), all the piglets were fed a standard commercial diet. Piglet behaviours in the home pens were scored, and skin lesions, growth, feed intake and feed efficiency were measured up to 8 weeks after the end of the dietary treatment, i.e. until 16 weeks of age. At the end of the dietary treatment (8 weeks of age), response to novelty was assessed in a combined open field and novel object test (OFT/NOT). During the weeks following weaning, piglets fed the postnatal HFS diet tended to be less aggressive (p = 0.06), but exhibited more oral manipulation of pen mates (p = 0.05) than controls. Compared to controls, piglets fed the prenatal or postnatal HFS diet walked more in the home pen (p ≤ 0.05), and tended to have fewer skin lesions (p < 0.10). Several behavioural effects of the postnatal HFS diet depended on the prenatal diet, with piglets subjected to a switch of diet at birth being more active, and exploring feeding materials, pen mates, and the environment more than piglets that remained on the same diet. Behaviours during the OFT/NOT were not affected by the

  5. Perinatal Exposure to a Diet High in Saturated Fat, Refined Sugar and Cholesterol Affects Behaviour, Growth, and Feed Intake in Weaned Piglets

    PubMed Central

    Gerrits, Walter J. J.; Kemp, Bas; Val-Laillet, David; Bolhuis, J. Elizabeth

    2016-01-01

    The increased consumption of diets high in saturated fats and refined sugars is a major public health concern in Western human societies. Recent studies suggest that perinatal exposure to dietary fat and/or sugar may affect behavioural development. We thus investigated the effects of perinatal exposure to a high-fat high-sugar diet (HFS) on behavioural development and production performance of piglets. Thirty-two non-obese sows and their piglets were allocated to 1 of 4 treatments in a 2 × 2 factorial design, with 8-week prenatal (gestation) and 8-week postnatal (lactation and post-weaning) exposure to a HFS diet (12% saturated fat, 18.5% sucrose, 1% cholesterol) or control low-fat low-sugar high-starch diets as factors. From weaning onwards (4 weeks of age), piglets were housed in group of 3 littermates (n = 8 groups/treatment) and fed ad libitum. After the end of the dietary intervention (8 weeks of age), all the piglets were fed a standard commercial diet. Piglet behaviours in the home pens were scored, and skin lesions, growth, feed intake and feed efficiency were measured up to 8 weeks after the end of the dietary treatment, i.e. until 16 weeks of age. At the end of the dietary treatment (8 weeks of age), response to novelty was assessed in a combined open field and novel object test (OFT/NOT). During the weeks following weaning, piglets fed the postnatal HFS diet tended to be less aggressive (p = 0.06), but exhibited more oral manipulation of pen mates (p = 0.05) than controls. Compared to controls, piglets fed the prenatal or postnatal HFS diet walked more in the home pen (p ≤ 0.05), and tended to have fewer skin lesions (p < 0.10). Several behavioural effects of the postnatal HFS diet depended on the prenatal diet, with piglets subjected to a switch of diet at birth being more active, and exploring feeding materials, pen mates, and the environment more than piglets that remained on the same diet. Behaviours during the OFT/NOT were not affected by the

  6. Investigation of gene expressions related to cholesterol metabolism in rats fed diets enriched in n-6 or n-3 fatty acid with a cholesterol after long-term feeding using quantitative-competitive RT-PCR analysis.

    PubMed

    Fukushima, M; Shimada, K; Ohashi, E; Saitoh, H; Sonoyama, K; Sekikawa, M; Nakano, M

    2001-06-01

    We have developed a method to quantitate hepatic apolipoprotein (apo) B, LDL receptor, 3-hydroxy-3-methylglutary coenzyme A reductase (HMG-CoA reductase) and cholesterol 7alpha-hydroxylase mRNA expression in rats fed a cholesterol-enriched diet after long-term feeding using competitive RT-RCR. Rats (8 wk of age) fed a conventional diet were shifted to diets containing 10% perilla oil (PEO, oleic acid+linoleic acid+alpha-linolenic acid), borage oil (BRO, oleic acid+linoleic acid+gamma-linolenic acid), evening primrose oil (EPO, linoleic acid+gamma-linolenic acid), mixed oil (MIO, oleic acid+linoleic acid+gamma-linolenic acid+alpha-linolenic acid), or palm oil (PLO, palmitic acid+oleic acid+linoleic acid) with 0.5% cholesterol for 15 wk. There were no significant differences in the food intake and body weight gain among the groups. The liver weight in the PEO and PLO groups was significantly higher than other groups. The serum total cholesterol and very low density lipoprotein (VLDL)+intermediate density lipoprotein (IDL)+low density lipoprotein (LDL)-cholesterol concentrations were consistently higher in PLO group than in the other groups. The serum high density lipoprotein cholesterol concentration was significantly lower in the PEO group than in the other groups. The liver cholesterol concentration group was significantly higher in the PEO than in the other groups. There were no significant differences in the hepatic LDL receptor mRNA level among the groups. Hepatic apo B, HMG-CoA reductase and cholesterol 7alpha-hydroxylase mRNA levels were not affected by the experimental conditions. However, hepatic cholesterol 7alpha-hydroxylase mRNA level in the PEO and MIO groups tended to be higher than in the other groups. The fecal cholesterol extraction was significantly higher in the MIO and PLO groups than in the PEO and EPO groups and the total bile acid extraction was significantly higher in the PEO and MIO groups than in the PLO group. The results of this study

  7. All about Cholesterol

    MedlinePlus

    ... are several kinds of fats in your blood. • LDL cholesterol is sometimes called “bad” cholesterol. It can narrow ... medicine to manage blood fats. They help lower LDL cholesterol. They also help lower your risk for a ...

  8. Cholesterol testing and results

    MedlinePlus

    ... lipoprotein (LDL cholesterol) High density lipoprotein (HDL cholesterol) Triglycerides (another type of fat in your blood) Very ... made of fat and protein. They carry cholesterol, triglycerides, and other fats, called lipids, in the blood ...

  9. High blood cholesterol levels

    MedlinePlus

    ... gov/ency/article/000403.htm High blood cholesterol levels To use the sharing features on this page, ... called "bad" cholesterol For many people, abnormal cholesterol levels are partly due to an unhealthy lifestyle. This ...

  10. HDL cholesterol: physiology, pathophysiology, and management.

    PubMed

    Link, Jeffrey J; Rohatgi, Anand; de Lemos, James A

    2007-05-01

    Numerous epidemiological studies have identified high-density lipoprotein cholesterol (HDL) to be an independent risk factor for coronary heart disease (CHD). HDL is an emerging therapeutic target that could rival the impact of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitors (statins) on LDL and CHD risk reduction. HDL metabolism, HDL kinetics, the concentration of various HDL subclasses, and other genetic factors affecting HDL functionality may all contribute to the anti-atherogenic properties of HDL; thus, standard plasma measurement may not capture the full range of HDL effects. Algorithms have been suggested to treat low HDL levels in subgroups of patients; however, no formal HDL target goals or treatment guidelines have been implemented as there is a lack of strong clinical evidence to support effective pharmacologic therapy for primary risk reduction. Available therapies have a modest impact on serum HDL levels; however, emerging therapies could have a more significant influence. PMID:17481993

  11. The Role of Dietary Cholesterol in Lipoprotein Metabolism and Related Metabolic Abnormalities: A Mini-review.

    PubMed

    Kapourchali, Fatemeh Ramezani; Surendiran, Gangadaran; Goulet, Amy; Moghadasian, Mohammed H

    2016-10-25

    Cholesterol plays a vital role in cell biology. Dietary cholesterol or "exogenous" cholesterol accounts for approximately one-third of the pooled body cholesterol, and the remaining 70% is synthesized in the body (endogenous cholesterol). Increased dietary cholesterol intake may result in increased serum cholesterol in some individuals, while other subjects may not respond to dietary cholesterol. However, diet-increased serum cholesterol levels do not increase the low-density lipoprotein/high-density lipoprotein (LDL/HDL) cholesterol ratio, nor do they decrease the size of LDL particles or HDL cholesterol levels. Elevated levels of LDL cholesterol, reduced HDL cholesterol levels, and small, dense LDL particles are independent risk factors for coronary artery disease. Dietary cholesterol is the primary approach for treatment of conditions such as the Smith-Lemli-Opitz syndrome. Recent studies have highlighted mechanisms for absorption of dietary cholesterol. These studies have help understand how dietary and/or pharmaceutical agents inhibit cholesterol absorption and thereby reduce LDL cholesterol concentrations. In this article, various aspects of cholesterol metabolism, including dietary sources, absorption, and abnormalities in cholesterol metabolism, have been summarized and discussed. PMID:26055276

  12. Reproductive effects of di(2-ethylhexyl)phthalate in immature male rats and its relation to cholesterol, testosterone, and thyroxin levels.

    PubMed

    Botelho, Giuliana G K; Golin, Munisa; Bufalo, Aedra C; Morais, Rosana N; Dalsenter, Paulo R; Martino-Andrade, Anderson J

    2009-11-01

    Phthalates are chemicals employed in several industrial products and there is a growing body of evidence demonstrating that they induce numerous adverse effects on the reproductive system. This study was carried out to assess possible alterations induced by the plasticizer di(2-ethylhexyl phthalate (DEHP) on cholesterol, testosterone, and thyroxine (total T4) levels, as well as to discuss the significance of these data in global changes observed in the reproductive tract of pubertal animals. Wistar rats aged 21 days received DEHP orally at 0, 250, 500, and 750 mg/kg/day for 30 days and were examined for different reproductive endpoints. At the end of the treatment, significant decreases in relative weight of testosterone-dependent organs, delayed preputial separation, and low serum testosterone were observed at the highest DEHP dose. The plot of the relationship between DEHP dose and serum cholesterol revealed a biphasic effect. The concentration of cholesterol in serum was significantly reduced at 250 mg/kg/day DEHP but returned to control values at 750 mg/kg/day. Cholesterol levels measured in testicular tissue increased with DEHP treatment. Serum T4 levels were not affected by DEHP at any dose, indicating the absence of a link between total thyroxin concentration and phthalate effects on cholesterol levels. Taken together these results indicate that effects observed in serum and testicular cholesterol levels may reflect distinct effects of DEHP on cholesterol synthesis and usage. These results confirm and extend previously reported findings showing that alterations in cholesterol balance may play a role in the suppression of steroidogenesis induced by DEHP in rats. PMID:19330368

  13. Size and molecular flexibility affect the binding of ellagitannins to bovine serum albumin.

    PubMed

    Dobreva, Marina A; Green, Rebecca J; Mueller-Harvey, Irene; Salminen, Juha-Pekka; Howlin, Brendan J; Frazier, Richard A

    2014-09-17

    Binding to bovine serum albumin of monomeric (vescalagin and pedunculagin) and dimeric ellagitannins (roburin A, oenothein B, and gemin A) was investigated by isothermal titration calorimetry and fluorescence spectroscopy, which indicated two types of binding sites. Stronger and more specific sites exhibited affinity constants, K1, of 10(4)-10(6) M(-1) and stoichiometries, n1, of 2-13 and dominated at low tannin concentrations. Weaker and less-specific binding sites had K2 constants of 10(3)-10(5) M(-1) and stoichiometries, n2, of 16-30 and dominated at higher tannin concentrations. Binding to stronger sites appeared to be dependent on tannin flexibility and the presence of free galloyl groups. Positive entropies for all but gemin A indicated that hydrophobic interactions dominated during complexation. This was supported by an exponential relationship between the affinity, K1, and the modeled hydrophobic accessible surface area and by a linear relationship between K1 and the Stern-Volmer quenching constant, K(SV). PMID:25162485

  14. Rapamycin selectively alters serum chemistry in diabetic mice

    PubMed Central

    Tabatabai-Mir, Hooman; Sataranatarajan, Kavithalakshmi; Lee, Hak Joo; Bokov, Alex F.; Fernandez, Elizabeth; Diaz, Vivian; Choudhury, Goutam Ghosh; Richardson, Arlan; Kasinath, Balakuntalam S.

    2012-01-01

    The study was undertaken to explore the effect of rapamycin, an anti-inflammatory agent, on the metabolic profile of type 2 diabetic mice. Seven-month-old diabetic db/db mice and their lean littermate non-diabetic controls (db/m) were randomized to receive control chow or chow mixed with rapamycin (2.24 mg/kg/day) (each group n =20, males and females) for 4 months and sacrificed. Serum samples were analyzed for the measurement of glucose, creatinine, blood urea nitrogen (BUN), alkaline phosphatase (ALP), alanine aminotransferase (ALT), total cholesterol, total triglyceride, and total protein, using the automated dry chemistry analysis. Rapamycin elevated serum glucose in female diabetic mice. Serum creatinine tended to be higher in diabetic mice but was not affected by rapamycin; there was no difference in BUN levels among the groups. Serum ALP was elevated in diabetic mice and rapamycin lowered it only in female diabetic mice; serum ALT levels were increased in female diabetic mice, unaffected by rapamycin. Serum total protein was elevated in diabetic mice of both genders but was not affected by rapamycin. Diabetic mice from both genders had elevated serum cholesterol and triglycerides; rapamycin did not affect serum cholesterol but decreased serum total triglycerides in male diabetic mice. We conclude that rapamycin elicits complex metabolic responses in aging diabetic mice, worsening hyperglycemia in females but improving ALP in female diabetic and total triglycerides in male diabetic mice, respectively. The metabolic effects of rapamycin should be considered while performing studies with rapamycin in mice. PMID:22953036

  15. Cholesterol and synaptic vesicle exocytosis

    PubMed Central

    Fratangeli, Alessandra

    2010-01-01

    Lipids may affect synaptic function in at least two ways: by acting as ligands for effector proteins [e.g., phosphatidylinositol (4,5) bisphosphate, diacylglycerol-mediated signaling] or by modifying the physicochemical properties and molecular organization of synaptic membranes. One that acts in the latter manner is cholesterol, an essential structural component of plasma membranes that is largely enriched in the membranes of synapses and synaptic vesicles, in which it may be involved in lipid-lipid and protein-lipid interactions. Cholesterol is an important constituent of the “membrane rafts” that may play a role in recruiting and organizing the specific proteins of the exocytic pathways. Furthermore, many synaptic proteins bind directly to cholesterol. The regulation of cholesterol and lipid levels may therefore influence the specific interactions and activity of synaptic proteins, and have a strong impact on synaptic functions. PMID:20798824

  16. Effects of dietary fucoxanthin on cholesterol metabolism in diabetic/obese KK-Ay mice

    PubMed Central

    2012-01-01

    Background Fucoxanthin is a xanthophyll present in brown seaweeds and has several beneficial effects, including anti-obesity and anti-diabetic effects. However, we and another group previously observed that fucoxanthin increases serum cholesterol levels in rodents. Cholesterol is an important component of cell membranes and biosynthesis of bile acids. Serum cholesterol levels are also closely associated with atherosclerosis. Therefore, we sought to identify the mechanism underlying the increase in serum cholesterol levels by fucoxanthin. Methods Diabetic/obese KK-Ay mice were fed a diet containing 0.2% fucoxanthin for 4 weeks. The mice were sacrificed, and total blood samples were collected for the measurement of serum total cholesterol, HDL-cholesterol and non-HDL-cholesterol levels. Cholesterol content in tissues was also analyzed. Real-time PCR and Western blotting were performed to determine hepatic mRNA and protein expression of genes involved in cholesterol metabolism, respectively. Results Dietary fucoxanthin significantly increased serum HDL and non-HDL cholesterol levels, and reduced hepatic cholesterol content. In liver, the expression of SREBP1, SREBP2 and their target genes involved in cholesterol biosynthesis significantly increased and tended to increase in the fucoxanthin-fed mice, respectively. In contrast, hepatic levels of LDLR and SR-B1 proteins which is important factors for LDL-cholesterol and HDL-cholesterol uptake in the liver from serum, decreased to 60% and 80% in the fucoxanthin-fed mice, respectively, compared with the control mice. Further, we found that dietary fucoxanthin significantly increased the mRNA expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), which enhances intracellular degradation of LDLR in lysosomes. Conclusions Fucoxanthin increased HDL-cholesterol and non-HDL-cholesterol levels in KK-Ay mice by inducing SREBP expression and reduced cholesterol uptake in the liver via down-regulation of LDLR and SR

  17. Performance, egg quality traits, and serum metabolite concentrations of laying hens affected by dietary supplemental chromium picolinate and vitamin C under a heat-stress condition.

    PubMed

    Torki, Mehran; Zangeneh, Samira; Habibian, Mahmood

    2014-02-01

    A 3 × 2 factorial experiment consisting three levels (0, 200, and 400 μg/kg) of chromium (chromium picolinate) and two levels (0 and 250 mg/kg) of vitamin C was employed to evaluate the effects of these dietary supplements on performance, egg quality traits, and serum biochemical parameters of heat-stressed laying hens (Lohmann LSL-Lite) from 66 to 74 weeks of age. Feed intake increased when birds were given either 400 μg/kg chromium or 250 mg/kg vitamin C (P < 0.05), but the birds that received both chromium and vitamin C consumed feed similar to those that received only chromium. Dietary treatments had no effect on egg production, egg mass, egg volume, feed conversion ratio, and body mass (P > 0.05). The birds that fed on diet with chromium or vitamin C produced eggs with higher shell mass and thickness compared to the control. Both eggshell mass and thickness decreased when vitamin C and chromium were supplemented simultaneously, and birds given the diet supplemented with 400 μg/kg chromium and 250 mg/kg vitamin C had eggshell mass and thickness similar to those of the control group. The serum concentration of chromium increased due to increasing level of dietary chromium (P < 0.05). The birds that received diet with chromium and vitamin C had higher serum concentrations of chromium compared to those that received only chromium (P < 0.05). Similarly, the hens that received chromium and vitamin C had higher serum concentrations of calcium and phosphorus compared to the hens fed with other treatments (P < 0.05). The birds given with supplemental chromium exhibited lower serum glucose, total cholesterol, and triglycerides concentrations but higher serum albumin and total protein concentrations compared to the other groups (P < 0.05). PMID:24347228

  18. Importance of cholesterol in dopamine transporter function

    PubMed Central

    Jones, Kymry T.; Zhen, Juan; Reith, Maarten E.A.

    2012-01-01

    The conformation and function of the dopamine transporter (DAT) can be affected by manipulating membrane cholesterol, yet there is no agreement as to the impact of cholesterol on the activity of lipid-raft localized DATs compared to non-raft DATs. Given the paucity of information regarding the impact of cholesterol on substrate efflux by the DAT, this study explores its influence on the kinetics of DAT-mediated DA efflux induced by dextroamphetamine, as measured by rotating disk electrode voltammetry (RDEV). Treatment with methyl-β-cyclodextrin (mβCD), which effectively depletes total membrane cholesterol- uniformly affecting cholesterol-DAT interactions in both raft and non-raft membrane domains- reduced both DA uptake and efflux rate. In contrast, disruption of raft localized DAT by cholesterol chelation with nystatin had no effect, arguing against a vital role for raft-localized DAT in substrate uptake or efflux. Supra-normal repletion of cholesterol depleted cells with the analogue desmosterol, a non-raft promoting sterol, was as effective as cholesterol itself in restoring transport rates. Further studies with Zn2+ and the conformationally-biased W84L DAT mutant supported the idea that cholesterol is important for maintaining the outward-facing DAT with normal rates of conformational interconversions. Collectively, these results point to a role for direct cholesterol-DAT interactions in regulating DAT function. PMID:22957537

  19. Consuming a buttermilk drink containing lutein-enriched egg yolk daily for 1 year increased plasma lutein but did not affect serum lipid or lipoprotein concentrations in adults with early signs of age-related macular degeneration.

    PubMed

    van der Made, Sanne M; Kelly, Elton R; Berendschot, Tos T J M; Kijlstra, Aize; Lütjohann, Dieter; Plat, Jogchum

    2014-09-01

    Dietary lutein intake is postulated to interfere with the development of age-related macular degeneration (AMD). Because egg yolk-derived lutein has a high bioavailability, long-term consumption of lutein-enriched eggs might be effective in preventing AMD development, but alternatively might increase cardiovascular disease risk. Here, we report the effect of 1-y daily consumption of a buttermilk drink containing 1.5 lutein-rich egg yolks on serum lipid and lipoprotein and plasma lutein concentrations. Additionally, subgroups that could potentially benefit the most from the intervention were identified. Men and women who had early signs of AMD in at least 1 eye, but were otherwise healthy, participated in a 1-y randomized, placebo-controlled parallel intervention trial. At the start of the study, 101 participants were included: 52 in the experimental (Egg) group and 49 in the control (Con) group. Final analyses were performed with 45 participants in the Egg group and 43 participants in the Con group. As expected, the increase in plasma lutein concentrations in the Egg group was 83% higher than that in the Con group (P < 0.001). Changes in serum total, HDL, and LDL cholesterol, as well as the ratio of total cholesterol to HDL cholesterol, were not different between the 2 groups. Interestingly, participants classified as cholesterol absorbers had higher serum HDL cholesterol concentrations than participants classified as cholesterol synthesizers or participants with average campesterol-to-lathosterol ratios (P < 0.05) at baseline. In addition, cholesterol absorbers had a 229% higher increase in plasma lutein concentrations than participants who were classified as having an average campesterol-to-lathosterol ratio upon consumption of the lutein-enriched egg yolk drink (P < 0.05). Moreover, the change in serum HDL cholesterol upon consumption was significantly different between these 3 groups (P < 0.05). We suggest that cholesterol absorbers particularly might benefit

  20. Lovastatin enhances adenovirus-mediated TRAIL induced apoptosis by depleting cholesterol of lipid rafts and affecting CAR and death receptor expression of prostate cancer cells.

    PubMed

    Liu, Youhong; Chen, Lin; Gong, Zhicheng; Shen, Liangfang; Kao, Chinghai; Hock, Janet M; Sun, Lunquan; Li, Xiong

    2015-02-20

    Oncolytic adenovirus and apoptosis inducer TRAIL are promising cancer therapies. Their antitumor efficacy, when used as single agents, is limited. Oncolytic adenoviruses have low infection activity, and cancer cells develop resistance to TRAIL-induced apoptosis. Here, we explored combining prostate-restricted replication competent adenovirus-mediated TRAIL (PRRA-TRAIL) with lovastatin, a commonly used cholesterol-lowering drug, as a potential therapy for advanced prostate cancer (PCa). Lovastatin significantly enhanced the efficacy of PRRA-TRAIL by promoting the in vivo tumor suppression, and the in vitro cell killing and apoptosis induction, via integration of multiple molecular mechanisms. Lovastatin enhanced PRRA replication and virus-delivered transgene expression by increasing the expression levels of CAR and integrins, which are critical for adenovirus 5 binding and internalization. Lovastatin enhanced TRAIL-induced apoptosis by increasing death receptor DR4 expression. These multiple effects of lovastatin on CAR, integrins and DR4 expression were closely associated with cholesterol-depletion in lipid rafts. These studies, for the first time, show correlations between cholesterol/lipid rafts, oncolytic adenovirus infection efficiency and the antitumor efficacy of TRAIL at the cellular level. This work enhances our understanding of the molecular mechanisms that support use of lovastatin, in combination with PRRA-TRAIL, as a candidate strategy to treat human refractory prostate cancer in the future. PMID:25605010

  1. Hypocholesterolemic activity of nut shell extract of Semecarpus anacardium (Bhilawa) in cholesterol fed rabbits.

    PubMed

    Sharma, A; Mathur, R; Dixit, V P

    1995-06-01

    Administration of S. anacardium nut shell extract to cholesterol fed rabbits resulted in a significant reduction in serum cholesterol (-73.3%) and serum LDL-Chol. (-80%). The extract feeding also prevented the accumulation of cholesterol/triglycerides in liver, heart muscle and aorta and caused a regression of plaques (75.3-83.5%). These results indicate that S. anacardium is hypocholesterolemic in action and prevents cholesterol induced atheroma. Possible mechanism of action is discussed. PMID:7590951

  2. PreImplantation factor prevents atherosclerosis via its immunomodulatory effects without affecting serum lipids.

    PubMed

    Chen, Yung Chih; Rivera, Jennifer; Fitzgerald, Melissa; Hausding, Christian; Ying, Ya-Lan; Wang, Xiaowei; Todorova, Krassimira; Hayrabedyan, Soren; Barnea, Eytan R; Peter, Karlheinz

    2016-05-01

    PreImplantation factor (PIF) is a 15-amino acid peptide endogenously secreted by viable embryos, regulating/enabling maternal (host) acceptance/tolerance to the "invading" embryo (allograft) all-while preserving maternal immunity to fight infections. Such attributes make PIF a potential therapeutic agent for chronic inflammatory diseases. We investigated whether PIF's immunomodulatory properties prevent progression of atherosclerosis in the hyper-cholesterolaemic ApoE-deficient murine model. Male, high-fat diet fed, ApoE-deficient (ApoE-/-) mice were administered either PBS, scrambled PIF (0.3-3 mg/kg) or PIF (0.3-3 mg/kg) for seven weeks. After treatment, PIF (3 mg/kg)-treated ApoE-/- mice displayed significantly reduced atherosclerosis lesion burden in the aortic sinus and aortic arch, without any effect on lipid profile. PIF also caused a significant reduction in infiltration of macrophages, decreased expression of pro-inflammatory adhesion molecules, cytokines and chemokines in the plaque, and reduced circulating IFN-γ levels. PIF preferentially binds to monocytes/neutrophils. In vitro, PIF attenuated monocyte migration (MCP-1-induced chemotaxis assay) and in vivo in LPS peritonitis model. Also PIF prevented leukocyte extravasation (peritonitis thioglycollate-induced model), demonstrating that PIF exerts its effect in part by modulation of monocyte function. Inhibition of the potassium channel KCNAB3 (Kv1.3) and of the insulin degrading enzyme (IDE) was demonstrated as potential mechanism of PIF's immunomodulatory effects. In conclusion, PIF regulates/lowers inflammation and prevents atherosclerosis development without affecting circulating lipids. Overall our findings establish PIF as a strong immunomodulatory drug candidate for atherosclerosis therapy. PMID:26842698

  3. Interaction between dietary lipids and gut microbiota regulates hepatic cholesterol metabolism.

    PubMed

    Caesar, Robert; Nygren, Heli; Orešič, Matej; Bäckhed, Fredrik

    2016-03-01

    The gut microbiota influences many aspects of host metabolism. We have previously shown that the presence of a gut microbiota remodels lipid composition. Here we investigated how interaction between gut microbiota and dietary lipids regulates lipid composition in the liver and plasma, and gene expression in the liver. Germ-free and conventionally raised mice were fed a lard or fish oil diet for 11 weeks. We performed lipidomics analysis of the liver and serum and microarray analysis of the liver. As expected, most of the variation in the lipidomics dataset was induced by the diet, and abundance of most lipid classes differed between mice fed lard and fish oil. However, the gut microbiota also affected lipid composition. The gut microbiota increased hepatic levels of cholesterol and cholesteryl esters in mice fed lard, but not in mice fed fish oil. Serum levels of cholesterol and cholesteryl esters were not affected by the gut microbiota. Genes encoding enzymes involved in cholesterol biosynthesis were downregulated by the gut microbiota in mice fed lard and were expressed at a low level in mice fed fish oil independent of microbial status. In summary, we show that gut microbiota-induced regulation of hepatic cholesterol metabolism is dependent on dietary lipid composition. PMID:26783361

  4. Influence of cholesterol on survival after stroke: retrospective study.

    PubMed Central

    Dyker, A. G.; Weir, C. J.; Lees, K. R.

    1997-01-01

    OBJECTIVE: To investigate the association between serum cholesterol concentration and cerebrovascular disease. DESIGN: Retrospective study. SETTING: Acute stroke unit of inner city general hospital. SUBJECTS: 977 patients with acute stroke. MAIN OUTCOME MEASURES: Serum total cholesterol concentration, type of stroke investigated by computed tomography or magnetic resonance imaging, three month outcome (good (alive at home) or bad (dead or in care)), long term mortality. RESULTS: After adjustment for known prognostic factors, higher serum cholesterol concentrations were associated with reduced long term mortality after stroke (relative hazard 0.91 (95% confidence interval 0.84 to 0.98) per mmol/l increase in cholesterol) independently of stroke type, vascular territory and extent, age, and hyperglycaemia. Three month outcome was also influenced independently by serum cholesterol (P = 0.024). CONCLUSIONS: Our data suggest an association between poor stroke outcome and lower serum cholesterol concentration. Until a prospective controlled study has confirmed the benefits of lowering cholesterol concentration in elderly subjects, the application of cholesterol lowering guidelines cannot be justified as secondary prevention of acute stroke. PMID:9169402

  5. Cholesterol dynamics in membranes.

    PubMed Central

    Yeagle, P L; Albert, A D; Boesze-Battaglia, K; Young, J; Frye, J

    1990-01-01

    Time-resolved fluorescence anisotropy of the sterol analogue, cholestatrienol, and 13C nuclear magnetic resonance (NMR) spin lattice relaxation time (T1c) measurements of [13C4] labeled cholesterol were exploited to determine the correlation times characterizing the major modes of motion of cholesterol in unsonicated phospholipid multilamellar liposomes. Two modes of motion were found to be important: (a) rotational diffusion and (b) time dependence of the orientation of the director for axial diffusion, or "wobble." From the time-resolved fluorescence anisotropy decays of cholestatrienol in egg phosphatidylcholine (PC) bilayers, a value for tau perpendicular, the correlation time for wobble, of 0.9 x 10(-9) s and a value for S perpendicular, the order parameter characterizing the same motion, of 0.45 s were calculated. Both tau perpendicular and S perpendicular were relatively insensitive to temperature and cholesterol content of the membranes. The T1c measurements of [13C4] labeled cholesterol did not provide a quantitative determination of tau parallel, the correlation time for axial diffusion. T1c from the lipid hydrocarbon chains suggested a value for tau perpendicular similar to that for cholesterol. Steady-state anisotropy measurements and time-resolved anisotropy measurements of cholestatrienol were used to probe sterol behavior in a variety of pure and mixed lipid multilamellar liposomes. Both the lipid headgroups and the lipid hydrocarbons chains contributed to the determination of the sterol environment in the membrane, as revealed by these fluorescence measurements. In particular, effects of the phosphatidylethanolamine (PE) headgroup and of multiple unsaturation in the lipid hydrocarbon chains were observed. However, while the steady-state anisotropy was sensitive to these factors, the time-resolved fluorescence analysis indicated that tau perpendicular was not strongly affected by the lipid composition of the membrane. S perpendicular may be increased

  6. Enhanced vascular permeability facilitates entry of plasma HDL and promotes macrophage-reverse cholesterol transport from skin in mice.

    PubMed

    Kareinen, Ilona; Cedó, Lídia; Silvennoinen, Reija; Laurila, Pirkka-Pekka; Jauhiainen, Matti; Julve, Josep; Blanco-Vaca, Francisco; Escola-Gil, Joan Carles; Kovanen, Petri T; Lee-Rueckert, Miriam

    2015-02-01

    Reverse cholesterol transport (RCT) pathway from macrophage foam cells initiates when HDL particles cross the endothelium, enter the interstitial fluid, and induce cholesterol efflux from these cells. We injected [(3)H]cholesterol-loaded J774 macrophages into the dorsal skin of mice and measured the transfer of macrophage-derived [(3)H]cholesterol to feces [macrophage-RCT (m-RCT)]. Injection of histamine to the macrophage injection site increased locally vascular permeability, enhanced influx of intravenously administered HDL, and stimulated m-RCT from the histamine-treated site. The stimulatory effect of histamine on m-RCT was abolished by prior administration of histamine H1 receptor (H1R) antagonist pyrilamine, indicating that the histamine effect was H1R-dependent. Subcutaneous administration of two other vasoactive mediators, serotonin or bradykinin, and activation of skin mast cells to secrete histamine and other vasoactive compounds also stimulated m-RCT. None of the studied vasoactive mediators affected serum HDL levels or the cholesterol-releasing ability of J774 macrophages in culture, indicating that acceleration of m-RCT was solely due to increased availability of cholesterol acceptors in skin. We conclude that disruption of the endothelial barrier by vasoactive compounds enhances the passage of HDL into interstitial fluid and increases the rate of RCT from peripheral macrophage foam cells, which reveals a novel tissue cholesterol-regulating function of these compounds. PMID:25473102

  7. Effects of diets enriched in n-6 or n-3 fatty acids on cholesterol metabolism in older rats chronically fed a cholesterol-enriched diet.

    PubMed

    Fukushima, M; Ohhashi, T; Ohno, S; Saitoh, H; Sonoyama, K; Shimada, K; Sekikawa, M; Nakano, M

    2001-03-01

    Hypocholesterolemic effects in older animals after long-term feeding are unknown. Therefore, aged rats (24 wk of age) fed a conventional diet were shifted to diets containing 10% perilla oil [PEO; oleic acid + linoleic acid + alpha-linolenic acid; n-6/n-3, 0.3; polyunsaturated fatty acid/saturated fatty acid (P/S), 9.6], borage oil [oleic acid + linoleic acid + alpha-linolenic acid; n-6/n-3, 15.1; P/S, 5.3], evening primrose oil (EPO; linoleic acid + gamma-linolenic acid; P/S, 10.5), mixed oil (MIO; oleic acid + linoleic acid + gamma-linolenic acid + alpha-linolenic acid; n-6/n-3, 1.7; P/S, 6.7), or palm oil (PLO; palmitic acid + oleic acid + linoleic acid; n-6/n-3, 25.3; P/S, 0.2) with 0.5% cholesterol for 15 wk in this experiment. There were no significant differences in the food intake and body weight gain among the groups. The liver weight in the PEO (n-6/n-3, 0.3) group was significantly higher than those of other groups in aged rats. The serum total cholesterol and very low density lipoprotein (VLDL) + intermediate density lipoprotein (IDL) + low density lipoprotein (LDL)-cholesterol concentrations of the PLO (25.3) group were consistently higher than those in the other groups. The serum high density lipoprotein cholesterol concentrations of the PEO (0.3) and EPO groups were significantly lower than in the other groups at the end of the 15-wk feeding period. The liver cholesterol concentration of the PLO (25.3) group was significantly higher than those of other groups. There were no significant differences in the hepatic LDL receptor mRNA level among the groups. Hepatic apolipoprotein (apo) B mRNA levels were not affected by the experimental conditions. The fecal neutral steroid excretion of the PLO (25.3) group tended to be low compared to the other groups. The results of this study demonstrate that both n-6 fatty acid and n-3 fatty acids such as gamma-linolenic acid and alpha-linolenic acid inhibit the increase of serum total cholesterol and VLDL + IDL

  8. Taurine ameliorates cholesterol metabolism by stimulating bile acid production in high-cholesterol-fed rats.

    PubMed

    Murakami, Shigeru; Fujita, Michiko; Nakamura, Masakazu; Sakono, Masanobu; Nishizono, Shoko; Sato, Masao; Imaizumi, Katsumi; Mori, Mari; Fukuda, Nobuhiro

    2016-03-01

    This study was designed to investigate the effects of dietary taurine on cholesterol metabolism in high-cholesterol-fed rats. Male Sprague-Dawley rats were randomly divided into two dietary groups (n = 6 in each group): a high-cholesterol diet containing 0.5% cholesterol and 0.15% sodium cholate, and a high-cholesterol diet with 5% (w/w) taurine. The experimental diets were given for 2 weeks. Taurine supplementation reduced the serum and hepatic cholesterol levels by 37% and 32%, respectively. Faecal excretion of bile acids was significantly increased in taurine-treated rats, compared with untreated rats. Biliary bile acid concentrations were also increased by taurine. Taurine supplementation increased taurine-conjugated bile acids by 61% and decreased glycine-conjugated bile acids by 53%, resulting in a significant decrease in the glycine/taurine (G/T) ratio. Among the taurine-conjugated bile acids, cholic acid and deoxycholic acid were significantly increased. In the liver, taurine supplementation increased the mRNA expression and enzymatic activity of hepatic cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme for bile acid synthesis, by three- and two-fold, respectively. Taurine also decreased the enzymatic activity of acyl-CoA:cholesterol acyltransferase (ACAT) and microsomal triglyceride transfer protein (MTP). These observations suggest that taurine supplementation increases the synthesis and excretion of taurine-conjugated bile acids and stimulates the catabolism of cholesterol to bile acid by elevating the expression and activity of CYP7A1. This may reduce cholesterol esterification and lipoprotein assembly for very low density lipoprotein (VLDL) secretion, leading to reductions in the serum and hepatic cholesterol levels. PMID:26710098

  9. Serum proprotein convertase subtilisin/kexin type 9 concentration is not increased by plant stanol ester consumption in normo- to moderately hypercholesterolaemic non-obese subjects. The BLOOD FLOW intervention study.

    PubMed

    Simonen, Piia; Stenman, Ulf-Håkan; Gylling, Helena

    2015-09-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates low-density lipoprotein (LDL) cholesterol (LDL-C) metabolism by targeting LDL receptors for degradation. Statins increase serum PCSK9 concentration limiting the potential of statins to reduce LDL-C, whereas ezetimibe, inhibitor of cholesterol absorption, has ambiguous effects on circulating PCSK9 levels. Plant stanols also reduce cholesterol absorption, but their effect on serum PCSK9 concentration is not known. Therefore, we performed a controlled, randomized, double-blind study, in which 92 normo- to moderately hypercholesterolaemic subjects (35 males and 57 females) consumed vegetable-oil spread 20 g/day enriched (plant stanol group, n=46) or not (control group, n=46) with plant stanols 3 g/day as ester for 6 months. Fasting blood samples were drawn at baseline and at the end of the study. Serum PCSK9 concentration was analysed with Quantikine Elisa Immunoassay, serum and lipoprotein lipids enzymatically and serum non-cholesterol sterols with GLC. At baseline, PCSK9 concentration varied from 91 to 716 ng/ml with a mean value of 278±11 (S.E.M.) ng/ml with no gender difference. It correlated with serum and LDL-C, serum triglycerides, age, body mass index (BMI) and plasma glucose concentration, but not with variables of cholesterol metabolism when adjusted to serum cholesterol. Plant stanols reduced LDL-C by 10% from controls (P<0.05), but PCSK9 levels were unchanged and did not differ between the groups. In conclusion, the present study demonstrated for the first time that inhibition of cholesterol absorption with plant stanol esters did not affect serum PCSK9 concentration. Thus, plant stanol esters provide an efficient dietary means to lower LDL-C without interfering with the PCSK9 metabolism and in this regard the LDL receptor-mediated cellular cholesterol uptake and removal. PMID:25857271

  10. Association between Plasma PFOA and PFOS Levels and Total Cholesterol in a Middle-Aged Danish Population

    PubMed Central

    Eriksen, Kirsten T.; Raaschou-Nielsen, Ole; McLaughlin, Joseph K.; Lipworth, Loren; Tjønneland, Anne; Overvad, Kim; Sørensen, Mette

    2013-01-01

    Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are used in a variety of consumer products and have been detected worldwide in human blood. Recent studies mainly of highly exposed populations have indicated that PFOA and PFOS may affect serum cholesterol levels, but the magnitude of the effect may be inconsistent across exposure levels. The aim of the present cross-sectional study was to investigate the association between plasma PFOA and PFOS and total cholesterol in a general, middle-aged Danish population. The study population comprised 753 individuals (663 men and 90 women), 50–65 years of age, nested within a Danish cohort of 57,053 participants. Blood samples were taken from all cohort members at enrolment (1993–1997) and stored in a biobank at -150°C. Plasma levels of PFOA and PFOS and serum levels of total cholesterol were measured. The associations between plasma PFOA and PFOS levels and total cholesterol levels were analysed by generalized linear models, both crude and adjusted for potential confounders. We observed statistically significant positive associations between both perfluorinated compounds and total cholesterol, e.g. a 4.4 [95% CI  =  1.1–7.8] higher concentration of total cholesterol (mg/dL) per interquartile range of PFOA plasma level. Sex and prevalent diabetes appeared to modify the association between PFOA and PFOS, respectively, and cholesterol. In conclusion, this study indicated positive associations between plasma PFOA and PFOS levels and total cholesterol in a middle-aged Danish population, although whether the observed pattern of results reflects a causal association is unclear. PMID:23441227

  11. Cholesterol reduction impairs exocytosis of synaptic vesicles.

    PubMed

    Linetti, Anna; Fratangeli, Alessandra; Taverna, Elena; Valnegri, Pamela; Francolini, Maura; Cappello, Valentina; Matteoli, Michela; Passafaro, Maria; Rosa, Patrizia

    2010-02-15

    Cholesterol and sphingolipids are abundant in neuronal membranes, where they help the organisation of the membrane microdomains involved in major roles such as axonal and dendritic growth, and synapse and spine stability. The aim of this study was to analyse their roles in presynaptic physiology. We first confirmed the presence of proteins of the exocytic machinery (SNARES and Ca(v)2.1 channels) in the lipid microdomains of cultured neurons, and then incubated the neurons with fumonisin B (an inhibitor of sphingolipid synthesis), or with mevastatin or zaragozic acid (two compounds that affect the synthesis of cholesterol by inhibiting HMG-CoA reductase or squalene synthase). The results demonstrate that fumonisin B and zaragozic acid efficiently decrease sphingolipid and cholesterol levels without greatly affecting the viability of neurons or the expression of synaptic proteins. Electron microscopy showed that the morphology and number of synaptic vesicles in the presynaptic boutons of cholesterol-depleted neurons were similar to those observed in control neurons. Zaragozic acid (but not fumonisin B) treatment impaired synaptic vesicle uptake of the lipophilic dye FM1-43 and an antibody directed against the luminal epitope of synaptotagmin-1, effects that depended on the reduction in cholesterol because they were reversed by cholesterol reloading. The time-lapse confocal imaging of neurons transfected with ecliptic SynaptopHluorin showed that cholesterol depletion affects the post-depolarisation increase in fluorescence intensity. Taken together, these findings show that reduced cholesterol levels impair synaptic vesicle exocytosis in cultured neurons. PMID:20103534

  12. Hypocholesterolemic effect of ursodeoxycholylcysteic acid in hamsters fed a high cholesterol diet.

    PubMed

    Shimizu, H; Yoshii, M; Seki, A; Une, M; Hoshita, T

    1992-10-01

    We studied the effect of feeding ursodeoxycholylcysteic acid, the cysteic acid conjugated analog of ursodeoxycholyltaurine, on serum and liver cholesterol levels and on intestinal absorption of cholesterol and bile salts in hamsters. Addition of ursodeoxycholylcysteic acid to the cholesterol-enriched diet reduced the elevation of serum and liver cholesterol levels caused by feeding cholesterol. However, supplementation with ursodeoxycholylcysteic acid to the standard diet did not show any significant change in serum and liver cholesterol levels. Administration of ursodeoxycholylcysteic acid caused a decrease in dietary cholesterol absorption but did not interfere with the ileal transport of endogenous bile salts. Hence the hypocholesterolemic activity of dietary ursodeoxycholylcysteic acid is thought to be the effect on intestinal absorption of cholesterol but not to be the interruption of the enterohepatic circulation of bile salts. PMID:1494107

  13. Cholesterol aided etching of tomatine gold nanoparticles: a non-enzymatic blood cholesterol monitor.

    PubMed

    Raj, Vidya; Johnson, Teslin; Joseph, Kuruvilla

    2014-10-15

    Colloidal gold is extensively used for molecular sensing because of the wide flexibilities it offers in terms of modifications of the gold nanoparticles (GNPs) surface with a variety of functional groups. We describe a simple, enzyme free assay for the detection of cholesterol, and demonstrate its applicability by estimating cholesterol in human serum samples. To enable cholesterol detection, we functionalized GNPs with tomatine, a glycoalkaloid found in the leaves and stem of tomato plants. The binding of cholesterol onto tomatine functionalized gold nanoparticles (TGNPs) was characterized by a blue shift in the plasmon absorption spectra (SPR) followed by reduction in the particle size. The TGNPs have been core etched with increasing concentration of cholesterol and with 800 ng/mL of cholesterol particles in the size range of 10-12 nm have been obtained. This behavior was attributed to the enhanced hydrophobicity of the surface acquired by cholesterol binding resulting in the folding or shrinkage of molecule in turn leading to core etching. The method was successfully applied for the detection of cholesterol in real samples and agrees well with values obtained from the conventional method. Because of its significant plasmonic shift and simplicity, this biosensor could be used for cholesterol detection as it does not demand either any hazardous and costly chemicals or any complex synthetic routes. PMID:24811192

  14. The role of developing breast cancer in alteration of serum lipid profile

    PubMed Central

    Abdelsalam, Kamal Eldin A.; Hassan, Ikhlas K.; Sadig, Isam A.

    2012-01-01

    Aims: The major aim of this study is to examine the role of alterations in lipid profile in women developing breast cancer. This study was carried out between May 2009 and December 2010. Background: The relationship between lipids and breast cancer is undistinguished. Until now, conflicting results have been reported on the association between lipids and risk of breast cancer development in women. Materials and Methods: Plasma lipids (i.e., total cholesterol [TC], high-density lipoprotein [HDL], low-density lipoprotein [LDL], and triglycerides [TG] were analyzed from 60 controls and 120 untreated breast cancer patients with clinical and histopathological evidence, under aseptic conditions. Venous blood was drawn from the cases and controls and estimations of lipid profile were done utilizing the standard procedures. Statistical Analysis Used: Independent sample t-test to compare the mean serum levels of lipid profile and TC/HDL ratio between patients and controls. Results: A significant rise in serum total cholesterol, low-density lipoprotein cholesterol, and ratio of total cholesterol: high density lipoprotein cholesterol values, whereas high density lipoprotein cholesterol and very low density lipoprotein cholesterol were not affected significantly by the breast cancer. Conclusions: The developing breast cancer might be considered as one of the factors in alterations in lipid profile levels. PMID:23626635

  15. An amperometric cholesterol biosensor based on epoxy resin membrane bound cholesterol oxidase

    PubMed Central

    Pundir, C.S.; Narang, Jagriti; Chauhan, Nidhi; Sharma, Preety; Sharma, Renu

    2012-01-01

    Background & objectives: The use of epoxy resin membrane as a support for immobilization of enzyme has resulted into improved sensitivity and stability of biosensors for uric acid, ascorbic acid and polyphenols. The present work was aimed to prepare an improved amperometric biosensor for determination of serum cholesterol required in the diagnostics and management of certain pathological conditions. Methods: Epoxy resin membrane with immobilized cholesterol oxidase was mounted on the cleaned platinum (Pt) electrode with a parafilm to construct a working electrode. This working electrode along with Ag/AgCl as reference and Ag wire as an auxiliary electrode were connected through a three terminal electrometer to construct a cholesterol biosensor. Results: The sensor showed optimum response within 25 sec at pH 7.0 and 45°C. The linear working range of biosensor was 1.0 to 8.0 mM cholesterol. Km and Imax for cholesterol were 5.0 mM and 9.09 μA, respectively. The biosensor measured serum cholesterol. The minimum detection limit of the sensor was 1.0 mM. The mean analytical recoveries of added cholesterol in serum (2.84 and 4.13 mM) were 91.4±2.8 and 92.3±3.1 per cent (n=6), respectively. Within and between assay coefficient of variation (CV) were <2 and <4 per cent, respectively. Biosensor had a storage life of 6 months at 4°C. Interpretation & conclusions: The use of epoxy resin membrane as a support for immobilization of cholesterol oxidase has resulted into an improved amperometric cholesterol biosensor. The present biosensor had an advantage over the existing biosensors as it worked at comparatively lower potential. PMID:23168704

  16. Quantification of In Vitro Macrophage Cholesterol Efflux and In Vivo Macrophage-Specific Reverse Cholesterol Transport.

    PubMed

    Escolà-Gil, Joan Carles; Lee-Rueckert, Miriam; Santos, David; Cedó, Lídia; Blanco-Vaca, Francisco; Julve, Josep

    2015-01-01

    Promotion of reverse cholesterol transport (RCT) is thought to be a major HDL-mediated mechanism for protecting against atherosclerosis. Preclinical studies support the concept that increasing cholesterol efflux from macrophages may confer atheroprotective benefits independently of the plasma HDL-cholesterol concentration. The application of the macrophage-to-feces RCT method in genetically engineered mice has provided evidence that this major HDL property correlates closely with changes in atherosclerosis susceptibility. This chapter provides details on the methodologies currently used to measure in vitro cholesterol efflux from macrophages or in vivo macrophage-specific RCT. The general principles and techniques described herein may be applied to measure the in vitro cholesterol efflux capacity of human serum in macrophage cultures and to evaluate the effect of different experimental pathophysiological conditions or the efficacy of different therapeutic strategies on the modulation of in vivo macrophage-RCT in mice. PMID:26445792

  17. Get Your Cholesterol Checked

    MedlinePlus

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

  18. Lysobisphosphatidic acid controls endosomal cholesterol levels.

    PubMed

    Chevallier, Julien; Chamoun, Zeina; Jiang, Guowei; Prestwich, Glenn; Sakai, Naomi; Matile, Stefan; Parton, Robert G; Gruenberg, Jean

    2008-10-10

    Most cell types acquire cholesterol by endocytosis of circulating low density lipoprotein, but little is known about the mechanisms of intra-endosomal cholesterol transport and about the primary cause of its aberrant accumulation in the cholesterol storage disorder Niemann-Pick type C (NPC). Here we report that lysobisphosphatidic acid (LBPA), an unconventional phospholipid that is only detected in late endosomes, regulates endosomal cholesterol levels under the control of Alix/AlP1, which is an LBPA-interacting protein involved in sorting into multivesicular endosomes. We find that Alix down-expression decreases both LBPA levels and the lumenal vesicle content of late endosomes. Cellular cholesterol levels are also decreased, presumably because the storage capacity of endosomes is affected and thus cholesterol clearance accelerated. Both lumenal membranes and cholesterol can be restored in Alix knockdown cells by exogenously added LBPA. Conversely, we also find that LBPA becomes limiting upon pathological cholesterol accumulation in NPC cells, because the addition of exogenous LBPA, but not of LBPA isoforms or analogues, partially reverts the NPC phenotype. We conclude that LBPA controls the cholesterol capacity of endosomes. PMID:18644787

  19. Cholesterol modulates Orai1 channel function.

    PubMed

    Derler, Isabella; Jardin, Isaac; Stathopulos, Peter B; Muik, Martin; Fahrner, Marc; Zayats, Vasilina; Pandey, Saurabh K; Poteser, Michael; Lackner, Barbara; Absolonova, Marketa; Schindl, Rainer; Groschner, Klaus; Ettrich, Rüdiger; Ikura, Mitsu; Romanin, Christoph

    2016-01-26

    STIM1 (stromal interaction molecule 1) and Orai proteins are the essential components of Ca(2+) release-activated Ca(2+) (CRAC) channels. We focused on the role of cholesterol in the regulation of STIM1-mediated Orai1 currents. Chemically induced cholesterol depletion enhanced store-operated Ca(2+) entry (SOCE) and Orai1 currents. Furthermore, cholesterol depletion in mucosal-type mast cells augmented endogenous CRAC currents, which were associated with increased degranulation, a process that requires calcium influx. Single point mutations in the Orai1 amino terminus that would be expected to abolish cholesterol binding enhanced SOCE to a similar extent as did cholesterol depletion. The increase in Orai1 activity in cells expressing these cholesterol-binding-deficient mutants occurred without affecting the amount in the plasma membrane or the coupling of STIM1 to Orai1. We detected cholesterol binding to an Orai1 amino-terminal fragment in vitro and to full-length Orai1 in cells. Thus, our data showed that Orai1 senses the amount of cholesterol in the plasma membrane and that the interaction of Orai1 with cholesterol inhibits its activity, thereby limiting SOCE. PMID:26814231

  20. Rapid turn-over of plasma membrane sphingomyelin and cholesterol in baby hamster kidney cells after exposure to sphingomyelinase.

    PubMed

    Slotte, J P; Härmälä, A S; Jansson, C; Pörn, M I

    1990-12-14

    Plasma membrane sphingomyelin in baby hamster kidney (BHK-21) cells was hydrolyzed with sphingomyelinase (Staphylococcus aureus) and the effects on membrane cholesterol translocation and the properties of membrane bound adenylate cyclase and Na+/K(+)-ATPase were determined. Exposure of confluent BHK-21 cells to 0.1 U/ml of sphingomyelinase led to the degradation (at 37 degrees C) of about 60% of cell sphingomyelin. No simultaneous hydrolysis of phosphatidylcholine occurred. The hydrolysis of sphingomyelin subsequently led to the translocation (within 40 min) of about 50-60% of cell [3H]cholesterol from a cholesterol oxidase susceptible pool to an oxidase resistant compartment. The translocation of [3H]cholesterol from the cell surface to intracellular membranes was accompanied by a paralleled increase in [3H]cholesterol ester formation. When cells were first exposed to sphingomyelinase (to degrade sphingomyelin) and then incubated without the enzyme in serum-free media, the mass of cell sphingomyelin decreased initially (by 60%), but then began to increase and reached control levels within 3-4 h. The rapid re-synthesis of sphingomyelin was accompanied by an equally rapid normalization of cell [3H]cholesterol distribution. The re-formation of cell sphingomyelin also led to a decreased content of cellular [3H]cholesterol esters, indicating that unesterified [3H]cholesterol was pulled out of the cholesterol ester cycle and transported to the cell surface. Exposure of BHK-21 cells to sphingomyelinase further led to a dramatically decreased activity of ouabain-sensitive Na+/K(+)-ATPase, whereas forskolin-stimulated adenylate cyclase activity was not affected. The activity of Na+/K(+)-ATPase returned to normal in parallel with the normalization of cell sphingomyelin mass and cholesterol distribution. We conclude that sphingomyelin has profound effects on the steady-state distribution of cell cholesterol, and that manipulations of cell sphingomyelin levels directly and

  1. Cholesterol and Plants

    ERIC Educational Resources Information Center

    Behrman, E. J.; Gopalan, Venkat

    2005-01-01

    There is a widespread belief among the public and even among chemist that plants do not contain cholesterol. This wrong belief is the result of the fact that plants generally contain only small quantities of cholesterol and that analytical methods for the detection of cholesterol in this range were not developed until recently.

  2. Long-term garlic or micronutrient supplementation, but not anti-Helicobacter pylori therapy, increases serum folate or glutathione without affecting serum vitamin B-12 or homocysteine in a rural Chinese population.

    PubMed

    Wang, Yujue; Zhang, Lian; Moslehi, Roxana; Ma, Junling; Pan, Kaifeng; Zhou, Tong; Liu, Weidong; Brown, Linda Morris; Hu, Yuangreng; Pee, David; Gail, Mitchell H; You, Weicheng

    2009-01-01

    The effects of a 7.3-y supplementation with garlic and micronutrients and of anti-Helicobacter pylori treatment with amoxicillin (1 g twice daily) and omeprazole (20 mg twice daily) on serum folate, vitamin B-12, homocysteine, and glutathione concentrations were assessed in a rural Chinese population. A randomized, double-blind, placebo-controlled, factorial trial was conducted to compare the ability of 3 treatments to retard the development of precancerous gastric lesions in 3411 subjects. The treatments were: 1) anti-H. pylori treatment with amoxicillin and omeprazole; 2) 7.3-y supplementation with aged garlic and steam-distilled garlic oil; and 3) 7.3-y supplementation with vitamin C, vitamin E, and selenium. All 3 treatments were given in a 2(3) factorial design to subjects seropositive for H. pylori infection; only the garlic supplement and vitamin and selenium supplement were given in a 2(2) factorial design to the other subjects. Thirty-four subjects were randomly selected from each of the 12 treatment strata. Sera were analyzed after 7.3 y to measure effects on folate, vitamin B-12, homocysteine, and glutathione concentrations. Regression analyses adjusted for age, gender, and smoking indicated an increase of 10.2% (95%CI: 2.9-18.1%) in serum folate after garlic supplementation and an increase of 13.4% (95%CI: 5.3-22.2%) in serum glutathione after vitamin and selenium supplementation. The vitamin and selenium supplement did not affect other analytes and the amoxicillin and omeprazole therapy did not affect any of the variables tested. In this rural Chinese population, 7.3 y of garlic supplementation increased the serum folate concentration and the vitamin and selenium supplement increased that of glutathione, but neither affected serum concentrations of vitamin B-12 or homocysteine. PMID:19056661

  3. Manufacture of Cheddar cheese using probiotic Lactobacillus plantarum K25 and its cholesterol-lowering effects in a mice model.

    PubMed

    Zhang, Li; Zhang, Xue; Liu, Chunhong; Li, Changying; Li, Shengyu; Li, Tiezhu; Li, Da; Zhao, Yujuan; Yang, Zhennai

    2013-01-01

    The probiotic adjunct Lactobacillus plantarum K25 was inoculated into milk to produce probiotic cheese. The effect of Lb. plantarum K25 on cheese composition, microbiological growth and survival during the manufacturing and ripening period, primary and secondary proteolysis during cheese ripening, and the in vivo cholesterol-lowering ability of the probiotic cheese were investigated. The results showed that the use of adjunct Lb. plantarum K25 in Cheddar cheese did not affect the cheese components including moisture, protein, fat, salt content and the pH value of cheese. During the whole ripening period, the probiotic adjunct maintained its viability, suggesting the effectiveness of Cheddar cheese as a vehicle for delivery of probiotic bacteria. No significant differences were observed in water-soluble nitrogen, 70 % ethanol-soluble nitrogen, 5 % phosphotungstic acid-soluble nitrogen, free amino acids and urea-PAGE patterns between the control and probiotic cheeses. Assessment of the in vivo cholesterol-lowering property of cheese with Lb. plantarum K25 showed that the levels of serum total cholesterol, low-density lipoprotein cholesterol and triglycerides decreased significantly, and the level of serum high-density lipoprotein cholesterol increased in mice fed with the probiotic cheese. The results indicated the potential function as a dietary item of the probiotic cheese with Lb. plantarum K25 to reduce the risk of cardiovascular diseases. PMID:22956024

  4. Concurrent increase of cholesterol, sphingomyelin and glucosylceramide in the spleen from non-neurologic Niemann-Pick type C patients but also patients possibly affected with other lipid trafficking disorders.

    PubMed

    Harzer, Klaus; Massenkeil, Gero; Fröhlich, Eckhart

    2003-02-27

    Niemann-Pick type C disease (NPC) is a neurovisceral (or, extremely rarely, only visceral) lipidosis caused by mutations in the NPC1 gene or, in a few patients, the HE1 gene, which encode sterol regulating proteins. NPC is characterised by a complex lipid anomaly including a disturbed cellular trafficking of cholesterol but also multi-lipid storage in visceral organs and brain. Lipids were studied using conventional methods in enlarged spleens that had been removed from five patients for different therapeutic and diagnostic reasons and found to have microscopic signs of lysosomal storage disease not suspected clinically. The spleen lipid findings with a concurrent accumulation of cholesterol, sphingomyelin and glucosylceramide (Acc-CSG) allowed us to suggest NPC diagnoses for these patients, who were free of neurologic symptoms. From two patients no material for confirmatory studies was available, but in two other patients NPC diagnoses could be confirmed with the filipin cytochemical cholesterol assay and NPC1 gene analysis, respectively. However, these tests and also HE1 gene analysis were negative in a third patient. Since the Acc-CSG lipid pattern seems to indicate a multi-lipid trafficking defect rather than being highly specific for NPC, this patient, if not affected with very atypical NPC, may be a candidate for a different lipid trafficking disorder. The Acc-CSG pattern was considered to be similar to the lipid pattern known for the lipid rafts, these functional cell structures being probably disorganised and accumulated in late endosomes and lysosomes of NPC cells. PMID:12606053

  5. Total cholesterol, low density lipoprotein cholesterol, and high density lipoprotein cholesterol and coronary heart disease in Scotland.

    PubMed Central

    Hargreaves, A D; Logan, R L; Thomson, M; Elton, R A; Oliver, M F; Riemersma, R A

    1991-01-01

    OBJECTIVE--To investigate long term changes in total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol concentrations and in measures of other risk factors for coronary heart disease and to assess their importance for the development of coronary heart disease in Scottish men. DESIGN--Longitudinal study entailing follow up in 1988-9 of men investigated during a study in 1976. SETTING--Edinburgh, Scotland. SUBJECTS--107 men from Edinburgh who had taken part in a comparative study of risk factors for heart disease with Swedish men in 1976 when aged 40. INTERVENTION--The men were invited to attend a follow up clinic in 1988-9 for measurement of cholesterol concentrations and other risk factor measurements. Eighty three attended and 24 refused to or could not attend. MAIN OUTCOME MEASURES--Changes in total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol concentrations, body weight, weight to height index, prevalence of smoking, and alcohol intake; number of coronary artery disease events. RESULTS--Mean serum total cholesterol concentration increased over the 12 years mainly due to an increase in the low density lipoprotein cholesterol fraction (from 3.53 (SD 0.09) to 4.56 (0.11) mmol/l) despite a reduction in high density lipoprotein cholesterol concentration. Body weight and weight to height index increased. Fewer men smoked more than 15 cigarettes/day in 1988-9 than in 1976. Blood pressure remained stable and fasting triglyceride concentrations did not change. The frequency of corneal arcus doubled. Alcohol consumption decreased significantly. Eleven men developed clinical coronary heart disease. High low density lipoprotein and low high density lipoprotein cholesterol concentrations in 1976, but not total cholesterol concentration, significantly predicted coronary heart disease (p = 0.05). Almost all of the men who developed coronary heart disease were smokers (91% v 53%, p less than

  6. Gene-environment interactions reveal a homeostatic role for cholesterol metabolism during dietary folate perturbation in mice

    PubMed Central

    Kitami, Toshimori; Rubio, Renee; O'Brien, William; Quackenbush, John; Nadeau, Joseph H.

    2008-01-01

    Dietary folate supplementation can dramatically reduce the severity and incidence of several common birth defects and adult diseases that are associated with anomalies in homocysteine and folate metabolism. The common polymorphisms that adversely affect these metabolic pathways do not fully account for the particular birth defects and adult diseases that occur in at-risk individuals. To test involvement of folate, homocysteine, and other pathways in disease pathogenesis and treatment response, we analyzed global and pathway-specific changes in gene expression and levels of selected metabolites after depletion and repletion of dietary folate in two genetically distinct inbred strains of mice. Compared with the C57BL/6J strain, A/J showed greater homeostatic response to folate perturbation by retaining a higher serum folate level and minimizing global gene expression changes. Remarkably, folate perturbation led to systematic strain-specific differences only in the expression profile of the cholesterol biosynthesis pathway and to changes in levels of serum and liver total cholesterol. By genetically increasing serum and liver total cholesterol levels in APOE-deficient mice, we modestly but significantly improved folate retention during folate depletion, suggesting that homeostasis among the homocysteine, folate and cholesterol metabolic pathways contributes to the beneficial effects of dietary folate supplementation. PMID:18697859

  7. Antigen presentation of detergent free glutamate decarboxylase (GAD65) is affected by human serum albumin as carrier protein

    PubMed Central

    Steed, Jordan; Gilliam, Lisa K.; Harris, Robert A.; Lernmark, Åke; Hampe, Christiane S.

    2008-01-01

    1. Summary The smaller isoform of glutamate decarboxylase (GAD65) is a major autoantigen in type 1 diabetes (TID). Its hydrophobic character requires detergent to keep the protein in solution, which complicates studies of antigen processing and presentation. In this study an attempt was made to replace detergent with human serum albumin (HSA) for in vitro antigen presentation. Different preparations of recombinant human GAD65 complexed with HSA were incubated with Priess B cells (HLA DRB1*0401) and antigen presentation was tested with HLA DRB1*0401-restricted and epitope-specific T33.1 (GAD65 epitope 274-286) and T35 (GAD65 epitope 115-127) T cell hybridomas. Specific epitope recognition by T33.1 (274-286) and T35 (115-127) cells varied between the different GAD65/HSA preparations, and a reverse pattern of antigen presentation were detected by the two hybridoma. The HSA-specific T-cell hybridoma 17.9 response to the different GAD65/HSA preparations followed the same pattern as that observed for the T33.1 cells. The content of immunoreactive GAD65 measured with four GAD65 antibodies indicated that the lowest GAD65 concentration resulted in the highest 274-286, but the lowest 115-127 presentation. This suggests that HSA-GAD65 complexes qualitatively affect the epitope specificity of GAD65 presentation. HSA may enhance the 274-286 epitope presentation, while suppressing the 115-127 epitope. PMID:18353353

  8. Normocaloric Low Cholesterol Diet Modulates Th17/Treg Balance in Patients with Chronic Hepatitis C Virus Infection

    PubMed Central

    Maggio, Roberta; Viscomi, Carmela; Andreozzi, Paola; D'Ettorre, Gabriella; Viscogliosi, Giovanni; Barbaro, Barbara; Gori, Manuele; Vullo, Vincenzo; Balsano, Clara

    2014-01-01

    Hepatitis C virus (HCV) infection is associated with hepatic and extrahepatic manifestations, including immunological disorders. Chronic Hepatitis C (CHC) is often characterized by cholesterol and lipid metabolism alterations, leading to hepatic steatosis. Cholesterol metabolism, in fact, is crucial for the viral life cycle. Recent works described that a higher dietary cholesterol intake is associated with the progression of HCV-related liver disease. CHC patients have increased levels of T helper 17 (Th17)-cells, a lymphocytic population involved in the pathogenesis of liver inflammation and autoimmune hepatitis. The balance between Th17 and regulatory T (Treg) cells is crucial for chronic inflammation and autoimmunity. Th17-cell differentiation is deeply influenced by the activation LXRs, nuclear receptors modulating cholesterol homeostasis. Moreover, HCV may affect these nuclear receptors, and cholesterol metabolism, through both direct and indirect mechanisms. On these bases, we hypothesized that modulation of cholesterol levels through Normocaloric Low Cholesterol Diet (NLCD) may represent an innovative strategy to reduce the progression of HCV infection, through the modulation of peripheral Th17/Treg balance. To this end, we performed a pilot study to investigate whether a Normocaloric Low Cholesterol Diet may be able to modulate Th17/Treg balance in patients affected by chronic HCV infection. After 30 days of NLCD CHC patients showed a significant reduction in Th17 cells frequency, which correlated with strong reduction of IL-17 and IL-22 serum levels. At the same time, we appreciated an increase in the percentage of Treg cells, thus improving Treg/Th17balance. Moreover, we observed an increased expression of LXRs and their target genes: SREBP-1c and ABCA-1. In conclusion, NLCD finely regulates Th17/Treg balance, improving immune system response in CHC patients. This study could pave the way for new treatments of CHC patients, suggesting that change in

  9. Use of BODIPY-Cholesterol (TF-Chol) for Visualizing Lysosomal Cholesterol Accumulation.

    PubMed

    Hölttä-Vuori, Maarit; Sezgin, Erdinc; Eggeling, Christian; Ikonen, Elina

    2016-09-01

    Dipyrromethene difluoride-cholesterol (TopFluor-Cholesterol, TF-Chol) is a widely used cholesterol analogue due to its excellent fluorescence properties and considerable similarity with natural cholesterol in terms of membrane partitioning. However, the suitability of TF-Chol for detecting lysosomal cholesterol deposition has recently been questioned. Here, we highlight the fact that the method of lipid delivery and the analysis of time-point both affect the membrane distribution and labeling pattern of TF-Chol, similarly as with radiolabeled cholesterol. Lysosomal sterol accumulation characteristic to a lysosomal storage disease is most readily detected when the probe is introduced via the physiological route, i.e. as a sterol fatty acid ester in low-density lipoprotein particles. When administered to cells from solvent, lysosomal sterol sequestration becomes evident after an overnight equilibration between membranes. PMID:27187581

  10. Human FABP1 T94A variant enhances cholesterol uptake.

    PubMed

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

    2015-07-01

    Although expression of the human liver fatty acid binding protein (FABP1) T94A variant alters serum lipoprotein cholesterol levels in human subjects, nothing is known whereby the variant elicits these effects. This issue was addressed by in vitro cholesterol binding assays using purified recombinant wild-type (WT) FABP1 T94T and T94A variant proteins and in cultured primary human hepatocytes expressing the FABP1 T94T (genotyped as TT) or T94A (genotyped as CC) proteins. The human FABP1 T94A variant protein had 3-fold higher cholesterol-binding affinity than the WT FABP1 T94T as shown by NBD-cholesterol fluorescence binding assays and by cholesterol isothermal titration microcalorimetry (ITC) binding assays. CC variant hepatocytes also exhibited 30% higher total FABP1 protein. HDL- and LDL-mediated NBD-cholesterol uptake was faster in CC variant than TT WT human hepatocytes. VLDL-mediated uptake of NBD-cholesterol did not differ between CC and TT human hepatocytes. The increased HDL- and LDL-mediated NBD-cholesterol uptake was not associated with any significant change in mRNA levels of SCARB1, LDLR, CETP, and LCAT encoding the key proteins in lipoprotein cholesterol uptake. Thus, the increased HDL- and LDL-mediated NBD-cholesterol uptake by CC hepatocytes may be associated with higher affinity of T94A protein for cholesterol and/or increased total T94A protein level. PMID:25732850

  11. Effects of Moxibustion Temperature on Blood Cholesterol Level in a Mice Model of Acute Hyperlipidemia: Role of TRPV1

    PubMed Central

    Wang, Gui-Ying; Wang, Ling-Ling; Xu, Bin; Zhang, Jian-Bin; Jiang, Jin-Feng

    2013-01-01

    Objectives. To compare the effects of moxibustion at two different temperatures (38°C and 46°C) on the blood cholesterol level in a mice model of acute hyperlipidemia, to detect the different expression levels of transient receptor potential vanilloid subfamily 1 (TRPV1) in the dorsal root ganglions of the wild mice, and to explore the correlation between TRPV1 and moxibustion's cholesterol-lowering effects. Method. Two different mice models were used: C57BL/6J wild type (WT) and TRPV1 gene knockout (TRPV1−/−). Each model was randomly divided into control group and model group with three subgroups after acute hyperlipidemia was established: model control group, 38°C moxibustion group, and 46°C moxibustion group. The mice in 38°C group and 46°C group were subject to moxibustion. After the therapy, the cholesterol concentration in serum was measured, and the expression of TRPV1 was quantified. Results. In WT mice, moxibustion caused a decrease in blood cholesterol level and upregulation of TRPV1 at the mRNA level, which was significantly greater in the 46°C group. In contrast, in TRPV1−/− mice, the differences of cholesterol-lowering effects of moxibustion were lost. Conclusions. Temperature is one of the important factors affecting the effects of moxibustion, and the cholesterol -lowering effect of moxibustion is related to the activation of TRPV1. PMID:23935685

  12. Hematology and serum chemistry of cottontail rabbits of southern Illinois.

    PubMed

    Lepitzki, D A; Woolf, A

    1991-10-01

    In 1983 and 1984 blood was collected from 79 cottontail rabbits (Sylvilagus floridanus) confined to an outdoor enclosure in southern Illinois to establish reference values for hematology and serum chemistry. Packed cell volume, sodium, potassium, chloride, glucose, calcium, carbon dioxide, blood urea nitrogen, creatinine, uric acid, cholesterol, albumin, bilirubin, alkaline phosphatase, aspartate transaminase, alanine aminotransaminase, total protein, albumin/globulin ratio, and osmolality were measured. Sex and age (adult versus juvenile) of rabbit as well as season (June to September versus October to May) and method of capture (trap versus shot) variously affected most hematology and serum chemistry variables. PMID:1758030

  13. Role of cholesterol in parasitic infections

    PubMed Central

    Bansal, Devendra; Bhatti, Harinderpal Singh; Sehgal, Rakesh

    2005-01-01

    The requirement of cholesterol for internalization of eukaryotic pathogens like protozoa (Leishmaniasis, Malaria and Toxoplasmosis) and the exchange of cholesterol along with other metabolites during reproduction in Schistosomes (helminths) under variable circumstances are poorly understood. In patients infected with some other helminthes, alterations in the lipid profile have been observed. Also, the mechanisms involved in lipid changes especially in membrane proteins related to parasite infections remain uncertain. Present review of literature shows that parasites induce significant changes in lipid parameters, as has been shown in the in vitro study where substitution of serum by lipid/cholesterol in medium and in experimental models (in vivo). Thus changes in lipid profile occur in patients having active infections with most of the parasites. Membrane proteins are probably involved in such reactions. All parasites may be metabolising cholesterol, but the exact relationship with pathogenic mechanism is not clear. So far, studies suggest that there may be some factors or enzymes, which allow the parasite to breakup and consume lipid/cholesterol. Further studies are needed for better understanding of the mechanisms involved in vivo. The present review analysis the various studies till date and the role of cholesterol in pathogenesis of different parasitic infections. PMID:15882457

  14. Perturbed cholesterol homeostasis in aging spinal cord.

    PubMed

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

    2016-09-01

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

  15. The perspective on cholesterol-lowering mechanisms of probiotics.

    PubMed

    Ishimwe, Nestor; Daliri, Eric B; Lee, Byong H; Fang, Fang; Du, Guocheng

    2015-01-01

    The use of probiotics as food components combats not only cardiovascular diseases but also many gastrointestinal tract disorders. Their health benefits along with their increased global market have interested scientists for better formulation and appropriate administration to the consumers. However, the lack of clear elucidation of their cholesterol-lowering mechanisms has complicated their proper dosage and administration to the beneficiaries. In this review, proposed mechanisms of cholesterol reduction such as deconjugation of bile via bile salt hydrolase activity, binding of cholesterol to probiotic cellular surface and incorporation into their cell membrane, production of SCFAs from oligosaccharides, coprecipitation of cholesterol with deconjugated bile, and cholesterol conversion to coprostanol have been discussed. Also, hypocholesterolemic effects on human- and animal-trial results, commonly used probiotics and synbiotics with effect on serum cholesterol regulation, types of bile salt hydrolase genes, and substrate specificities have been discussed. PMID:25403164

  16. [Effect of raw and cooked nopal (Opuntia ficus indica) ingestion on growth and profile of total cholesterol, lipoproteins, and blood glucose in rats].

    PubMed

    Cárdenas Medellín, M L; Serna Saldívar, S O; Velazco de la Garza, J

    1998-12-01

    Two different concentrations (approx. 6 and 12%) and two presentations (raw and cooked) of dehydrated nopal were fed to laboratory rats and growth and serum total cholesterol, lipoprotein profile and glucose determined. Samples of raw and cooked nopal were chemically characterized for moisture, protein, ash, crude fiber, ether extract, total dietary fiber, reducing sugars, amino acids, minerals and gross energy. Cooking slightly affected some of the nutrients analyzed. After one month feeding, blood was withdrawn via intracardiac puncture and serum glucose, total cholesterol, HDL, LDL, and VLDL were determined. Rats fed 12% nopal had lower weight gains (P < 0.05) when compared with counterparts fed 6% nopal or the control diet. Consumption of nopal did not affect (P > 0.05) glucose, total cholesterol and HDL cholesterol levels. However, rats fed raw nopal at the 12% concentration level had a 34% reduction in LDL cholesterol levels; thus, it was concluded that raw nopal had a potentially beneficial effect for hypercholesterolemic individuals. PMID:10347696

  17. Effect of plant sterol-enriched diets on plasma and egg yolk cholesterol concentrations and cholesterol metabolism in laying hens.

    PubMed

    Liu, X; Zhao, H L; Thiessen, S; House, J D; Jones, P J H

    2010-02-01

    Egg exists as a major dietary source of cholesterol in Western diets. In North America, laying hen diets are usually devoid of cholesterol when diets are formulated to exclude animal-based products. Hence, laying hens meet their physiological cholesterol requirement through de novo synthesis. Plant sterols exert a cholesterol-lowering effect in humans by interfering with intestinal sterol absorption. However, it is unknown whether plant sterol supplementation could be effective in reducing intestinal reabsorption of biliary cholesterol in laying hens, thus modulating whole body cholesterol in favor of lower plasma and yolk cholesterol content. The current study was designed to investigate the effect of diets enriched with 0, 0.5, 1, and 2% plant sterols on cholesterol absorption, synthesis, as well as plasma, liver, and egg yolk cholesterol concentrations in laying hens. After 8 wk of plant sterol intervention (first 2 wk were acclimatization), feed intake, BW, egg weight, egg yolk weight, egg production, Haugh units, liver mass, plasma, and hepatic cholesterol concentrations did not differ as a function of plant sterol supplementation. Egg cholesterol concentrations (mg/g) fluctuated during the 6-wk experimental period. At wk 6, a minor reduction in egg yolk cholesterol concentration (mg per g of yolk, P<0.05, vs. control) was observed in hens fed 1 and 2% cholesterol-enriched diets, respectively. However, such result failed to affect total egg cholesterol content. No statistical difference was observed across treatments over 6 wk. Neither cholesterol absorption rates nor synthesis differed as a function of treatment. Results suggested that overall cholesterol content in egg yolk was not affected by feeding hens plant sterol-enriched diets over 6 wk. PMID:20075279

  18. Gene-by-Diet Interactions Affect Serum 1,25-Dihydroxyvitamin D Levels in Male BXD Recombinant Inbred Mice.

    PubMed

    Fleet, James C; Replogle, Rebecca A; Reyes-Fernandez, Perla; Wang, Libo; Zhang, Min; Clinkenbeard, Erica L; White, Kenneth E

    2016-02-01

    1,25-Dihydroxyvitamin D (1,25[OH]2D) regulates calcium (Ca), phosphate, and bone metabolism. Serum 1,25(OH)2D levels are reduced by low vitamin D status and high fibroblast growth factor 23 (FGF23) levels and increased by low Ca intake and high PTH levels. Natural genetic variation controls serum 25-hydroxyvitamin D (25[OH]D) levels, but it is unclear how it controls serum 1,25(OH)2D or the response of serum 1,25(OH)2D levels to dietary Ca restriction (RCR). Male mice from 11 inbred lines and from 51 BXD recombinant inbred lines were fed diets with either 0.5% (basal) or 0.25% Ca from 4 to 12 weeks of age (n = 8 per line per diet). Significant variation among the lines was found in basal serum 1,25(OH)2D and in the RCR as well as basal serum 25(OH)D and FGF23 levels. 1,25(OH)2D was not correlated to 25(OH)D but was negatively correlated to FGF23 (r = -0.5). Narrow sense heritability of 1,25(OH)2D was 0.67 on the 0.5% Ca diet, 0.66 on the 0.25% Ca diet, and 0.59 for the RCR, indicating a strong genetic control of serum 1,25(OH)2D. Genetic mapping revealed many loci controlling 1,25(OH)2D (seven loci) and the RCR (three loci) as well as 25(OH)D (four loci) and FGF23 (two loci); a locus on chromosome 18 controlled both 1,25(OH)2D and FGF23. Candidate genes underlying loci include the following: Ets1 (1,25[OH]2D), Elac1 (FGF23 and 1,25[OH]2D), Tbc1d15 (RCR), Plekha8 and Lyplal1 (25[OH]D), and Trim35 (FGF23). This report is the first to reveal that serum 1,25(OH)2D levels are controlled by multiple genetic factors and that some of these genetic loci interact with the dietary environment. PMID:26587785

  19. Supplemental leucine and isoleucine affect expression of cationic amino acid transporters and myosin, serum concentration of amino acids, and growth performance of pigs.

    PubMed

    Cervantes-Ramírez, M; Mendez-Trujillo, V; Araiza-Piña, B A; Barrera-Silva, M A; González-Mendoza, D; Morales-Trejo, A

    2013-01-01

    Leucine (Leu) participates in the activity of cationic amino acid (aa) transporters. Also, branched-chain aa [Leu, isoleucine (Ile), and valine (Val)] share intestinal transporters for absorption. We conducted an experiment with 16 young pigs (body weight of about 16 kg) to determine whether Leu and Ile affect expression of aa transporters b(0,+) and CAT-1 in the jejunum and expression of myosin in muscle, as well as serum concentration of essential aa, and growth performance in pigs. Dietary treatments were: wheat-based diets fortified with Lys, Thr, and Met; basal diet plus 0.50% Leu; basal diet plus 0.50% Ile, and basal diet plus 0.50% Leu and 0.50% Ile. After 28 days, the pigs were sacrificed to collect blood, jejunum, and semitendinosus and longissimus muscle samples. The effects of single and combined addition of Leu and Ile were analyzed. Leu alone or combined with Ile significantly decreased daily weight gain and reduced feed conversion. Leu and Ile, alone or in combination, significantly decreased expression of b(0,+) and significantly increased CAT-1. Ile alone or combined with Leu significantly decreased myosin expression in semitendinosus and significantly decreased it in longissimus muscle. Leu alone significantly decreased Lys, Ile and Thr serum concentrations; Ile significantly decreased Thr serum concentration; combined Leu and Ile significantly decreased Thr and significantly increased Val serum concentration. We conclude that dietary levels of Leu and Ile affect growth performance, expression of aa transporters and myosin, and aa serum concentrations in pigs. PMID:23408397

  20. Home-Use Tests - Cholesterol

    MedlinePlus

    ... this test does: This is a home-use test kit to measure total cholesterol. What cholesterol is: Cholesterol is a fat (lipid) in your blood. High-density lipoprotein (HDL) ("good" cholesterol) helps protect your heart, but low-density lipoprotein (LDL) ("bad" cholesterol) can clog the arteries of your ...

  1. Oral vitamin D supplementation at five times the recommended allowance marginally affects serum 25-hydroxyvitamin D concentrations in dogs.

    PubMed

    Young, Lauren R; Backus, Robert C

    2016-01-01

    Little is known regarding optimal vitamin D status in adult dogs. To date no studies on vitamin D supplementation for improving vitamin D status have been reported for adult dogs. The aims of this study were to identify dogs with low vitamin D status and evaluate an oral dosage of cholecalciferol (D3) for effectiveness in increasing vitamin D status. For this, forty-six privately owned dogs were evaluated. Of the dogs, thirty-three (or 71·7 %) had serum 25-hydroxyvitamin D (25(OH)D) concentrations less than 100 ng/ml, a minimum previously suggested for vitamin D sufficiency in dogs. Subsequently, thirteen dogs were enrolled in a supplementation trial. Dogs were given either a D3 supplement (n 7; 2·3 µg/kg(0·75)) or olive oil placebo (n 6) daily with food. Serum concentrations of 25(OH)D were determined at weeks 1, 3 and 6, and at the trial end. Only at the trial end (weeks 9-10) was 25(OH)D significantly greater (P = 0·05) in supplemented v. placebo dogs. Serum concentrations of 24R,25-dihydroxycholecalciferol determined at the trial end were about 40 % of that of 25(OH)D3 and not significantly different between the groups. Concentrations of parathyroid hormone, ionised Ca, P and creatinine measured in initial and final serum samples indicated supplementation caused no toxicity. We conclude that vitamin D3 supplementation at a dosage near the National Research Council recommended safe-upper limit was not effective for rapidly raising serum 25(OH)D concentrations in healthy, adult dogs. Further work is needed in evaluating the metabolism of orally administered D3 in dogs before dosing recommendations can be made. PMID:27547394

  2. Absorption and transport of cholesterol autoxidation derivatives in rabbits

    SciTech Connect

    Peng, S.K.; Morin, R.J.; Phillips, G.A.; Xia, G.Z.

    1986-03-01

    Spontaneously autoxidized products of cholesterol have been demonstrated to be angiotoxic and possibly atherogenic. This study investigates the absorption and transport of these cholesterol oxidation derivatives (COD's) as compared to cholesterol. /sup 14/C-labeled cholesterol autoxidized by incubation in a 60/sup 0/C water bath for 5 weeks, then suspended in gelatin and given to New Zealand white rabbits by gastric gavage. Rabbits were sacrificed 24 hours after treatment. COD's were separated by thin layer chromatography (TLC) and radioactivities of each COD and cholesterol were measured. Percentages of each COD and cholesterol in the original mixture before administration and in the rabbits' serum after administration are almost identical, suggesting that the rates of absorption of COD's are not significantly different from that of cholesterol. Lipoproteins were fractionated by ultracentrifugation into VLDL, LDL and HDL. Radioactivities of each COD separated by TLC in each lipoprotein fraction showed that cholestane-3..beta..,5..cap alpha..,6..beta..-triol, 7..cap alpha..- and 7..beta..-hydroxycholesterol and 7-ketocholesterol were predominantly present in VLDL (3 x serum concentration) and 25-hydroxycholesterol was predominantly in LDL (2.5 x serum concentration). HDL contained only minute amounts of COD's. The increased levels of COD's in VLDL and LDL may contribute to the atherogenicity of these lipoprotein.

  3. The relationship of drinking water chlorination and serum lipids in human populations

    SciTech Connect

    Zeighami, E.A.; Watson, A.P.; Craun, G.C.

    1987-01-01

    This research tests hypotheses concerning the relationship between drinking water characteristics and the cardiovascular disease risk factors blood pressure and serum lipids, as well as thyroid function. The study used a cross-sectional survey design to examine the characteristics of the cardiovascular disease risk factors in residents of forty-six small communities in central Wisconsin. Twenty of the communities chlorinated the water supply, and twenty-six did not. Within each of the chlorination groups, approximately half the communities had hard water and the other half had soft drinking water. This report examines the relationship of chlorination to serum lipid levels in the forty-six communities. Serum cholesterol levels were significantly higher in chlorinated communities for females. Levels of serum cholesterol were also higher in chlorinated communities for males, but the difference was not as great, nor was it statistically significant. LDL levels were higher in chlorinated communities, but did not reach statistical significance for either sex. Levels of high-density lipoprotein cholesterol were related to calcium level of the drinking water within the hardness categories, but only in the chlorinated communities. Thus chlorine and calcium level in the drinking water may interact in some way which affects levels of HDL cholesterol. 24 refs., 1 fig., 2 tabs.

  4. Spent Mushroom Substrate Influences Elk (Cervus Elaphus Canadensis) Hematological and Serum Biochemical Parameters

    PubMed Central

    Park, Jae Hong; Kim, Sang Woo; Do, Yoon Jung; Kim, Hyun; Ko, Yeoung Gyu; Yang, Boh Suk; Shin, Daekeun; Cho, Young Moo

    2012-01-01

    The objective of this study was to evaluate the effect of spent mushroom substrate (SMS) derived from Pleurotus eryngii on the hematological and biochemical blood properties of elk. A total of 18, two and three-year-old elk were fed three different levels of SMS (0, 15 and 20%) in a corn-wheat bran diet for 80 days. The results indicated significantly high levels of blood monocytes, hemoglobin (Hb), and hematocrit (HCT) in elk fed 15% or 20% SMS (p<0.05) compared to control animals. Serum blood urea nitrogen (BUN) and glucose concentrations were also significantly elevated in elk fed both 15% and 20% SMS. The inclusion of SMS in the elk diet did not affect serum total cholesterol, triglyceride, or low density lipoprotein (LDL)-cholesterol concentrations; however, high density lipoprotein (HDL)-cholesterol concentration was significantly increased in SMS-fed groups. In addition, 20% SMS in the diet increased serum iron and testosterone concentrations in elk. These results indicate that adding SMS to the diet of elk can increase their Hgb, serum BUN, glucose, and HDL-cholesterol concentration; therefore, diets containing SMS may enhance the physiologic condition of elk during growth. PMID:25049569

  5. Effect of dietary Maitake (Grifola frondosa) mushrooms on plasma cholesterol and hepatic gene expression in cholesterol-fed mice.

    PubMed

    Sato, Mayumi; Tokuji, Yoshihiko; Yoneyama, Shozo; Fujii-Akiyama, Kyoko; Kinoshita, Mikio; Chiji, Hideyuki; Ohnishi, Masao

    2013-01-01

    To investigate the effects of dietary Grifola frondosa on cholesterol, normal mice were fed a diet containing 1% cholesterol (HC group) or 1% cholesterol and 10% freeze-dried G. frondosa powder (HC+G group) for 4 weeks and hepatic and plasma lipid levels were compared with those of a cholesterol-free diet-fed mice (N group). Hepatic total cholesterol (TC), triacylglycerol contents were considerably increased and plasma TC / phospholipid (PL) was also increased significantly in the HC group compared with the N group. However, plasma TC content decreased in the HC+G group compared with the HC group. To characterize the mechanisms responsible for lowered plasma cholesterol in G. frondosa-supplemented mice, hepatic gene expression was profiled using DNA microarray and gene ontology. Genome analyses revealed that de novo cholesterol synthesis genes were suppressed following cholesterol intake. However, expression of bile acid biosynthesis and low-density lipoprotein receptor genes showed little change. Scarb1, Abcg5, and Abcg8, involved in cholesterol transport and excretion, were slightly upregulated in the HC+G group compared with the HC group. These data indicate the plasma cholesterol-lowering effect of G. frondosa. Moreover, fatty acid (FA) β-oxidation was promoted via adipocytokine signaling pathways, and Saa, encodes serum amyloid A related to arteriosclerosis, was suppressed in the HC+G group. PMID:24292357

  6. Isoform dependent regulation of human HCN channels by cholesterol

    PubMed Central

    Fürst, Oliver; D’Avanzo, Nazzareno

    2015-01-01

    Cholesterol has been shown to regulate numerous ion channels. HCN channels represent the molecular correlate of If or Ih in sinoatrial node (SAN) and neuronal cells. Previous studies have implicated a role for cholesterol in the regulation of rabbit HCN4 channels with effects on pacing in the rabbit SAN. Using electrophysiological and biochemical approaches, we examined the effect of cholesterol modulation on human HCN1, HCN2 and HCN4 isoforms. Patch-clamp experiments uncovered isoform specific differences in the effect of cholesterol on gating kinetics upon depletion by MβCD or mevastatin or enrichment using MβCD/cholesterol. Most dramatically cholesterol had isoform specific effects on mode-shifting, which has been suggested to play a key role in stabilizing firing rate and preventing arrhythmic firing in SAN cells and neurons. Mode-shifting in HCN1 channels was insensitive to cholesterol manipulation, while HCN2 and HCN4 were strongly affected. Trafficking of each isoform to the plasma membrane was also affected by cholesterol modulation differentially between isoforms, however, each isoform remained localized in lipid raft domains after cholesterol depletion. These effects may contribute to the side effects of cholesterol reducing therapies including disrupted heart rhythm and neuropathic pain, as well as the susceptibility of sinus dysfunction in patients with elevated cholesterol. PMID:26404789

  7. Children and Cholesterol

    MedlinePlus

    ... a coronary artery procedure; or who suffered a heart attack or sudden cardiac death before age 55. Those with a parent who has a history of high total cholesterol levels (240 mg/dL or higher). Talk to your child’s pediatrician ... Risk Calculator Printable Cholesterol Information Sheets Heart360 Health ...

  8. Kids and Cholesterol.

    ERIC Educational Resources Information Center

    Ficklen, Ellen

    1992-01-01

    According to a 1991 National Cholesterol Education Program report, the best way to avoid heart trouble is to take early preventive measures. This means that children over age two should follow the same low-fat, low-cholesterol guidelines already recommended for adults. Sidebars contain a fat glossary and tips for cutting fat in school lunches.…

  9. Electrochemical oxidation of cholesterol

    PubMed Central

    2015-01-01

    Summary Indirect cholesterol electrochemical oxidation in the presence of various mediators leads to electrophilic addition to the double bond, oxidation at the allylic position, oxidation of the hydroxy group, or functionalization of the side chain. Recent studies have proven that direct electrochemical oxidation of cholesterol is also possible and affords different products depending on the reaction conditions. PMID:25977713

  10. Cholesterol and Your Child

    MedlinePlus

    ... traveling together are called lipoproteins . Two kinds — low-density lipoprotein (LDL) and high-density lipoprotein (HDL) — are the ones that most of us have heard about. Low-density lipoproteins , or "bad cholesterol," are the primary cholesterol ...

  11. Cholesterol reduction in the workplace and in community settings.

    PubMed

    Wilson, M G

    1991-02-01

    Recent emphasis has been placed on the role of serum cholesterol in the development of cardiovascular disease and on reducing high serum cholesterol levels through a screening followed by a behavioral intervention. However, evidence about the effectiveness of this technique in reducing cholesterol has yet to be evaluated. A review of the biomedical and allied health literature was conducted to determine the effectiveness of reducing serum cholesterol levels in the general population through the use of a screening to identify those at risk followed by a behavioral intervention. Only worksite and community based studies published from 1980-89 were reviewed. Seven worksite and four community studies were identified. All studies used total serum cholesterol as the dependent variable while some included other physiological measures. The majority of studies used a multicomponent intervention involving dietary education, exercise, smoking cessation, or weight reduction components. The interventions tested lasted from 14 weeks to five years and varied from low intensity to high intensity. The methods of intervention ranged from face-to-face interaction to mail and telephone counseling. Although many of the studies reviewed contain methodological flaws, certain findings are evident. The studies show that cholesterol can be reduced through a screening followed by a behavioral intervention, the multicomponent program is the most effective intervention, and low intensive interventions are as equally effective as high intensive interventions. Program implications and future research directions are discussed. PMID:2010571

  12. Rifampin affects polymorphonuclear leukocyte interactions with bacterial and synthetic chemotaxins but not interactions with serum-derived chemotaxins.

    PubMed Central

    Gray, G D; Smith, C W; Hollers, J C; Chenoweth, D E; Fiegel, V D; Nelson, R D

    1983-01-01

    Three independent experimental approaches support the hypothesis that rifampin competes for receptors on polymorphonuclear leukocytes (PMLs) with small peptide chemoattractants, e.g., N-formylmethionylleucylphenylalanine (FMLP), but not with serum-derived chemoattractants (C5a). First, rifampin inhibited chemotaxis induced with FMLP but reversed the immobilization of PMLs that occurred at high FMLP concentrations. Second, rifampin competed with radiolabeled FMLP for binding sites on PMLs and displaced already-bound radiolabeled FMLP. Third, rifampin blocked and reversed the bipolar shape changes induced in PMLs by FMLP. These effects occurred at concentrations attained during rifampin therapy and were not due to rifampin toxicity. In contrast, no effect of rifampin was observed on serum-derived chemoattractants (C5a) in any of the three systems. The evidence suggests, therefore, that rifampin is a ligand for FMLP-type receptors on PMLs. PMID:6318656

  13. Bile acid sequestrants for cholesterol

    MedlinePlus

    ... 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 ...

  14. What Your Cholesterol Levels Mean

    MedlinePlus

    ... Pressure Tools & Resources Stroke More What Your Cholesterol Levels Mean Updated:Aug 17,2016 How’s your cholesterol? Time to get it checked! Keeping your cholesterol levels healthy is a great way to keep your ...

  15. Computational investigation of cholesterol binding sites on mitochondrial VDAC.

    PubMed

    Weiser, Brian P; Salari, Reza; Eckenhoff, Roderic G; Brannigan, Grace

    2014-08-21

    The mitochondrial voltage-dependent anion channel (VDAC) allows passage of ions and metabolites across the mitochondrial outer membrane. Cholesterol binds mammalian VDAC, and we investigated the effects of binding to human VDAC1 with atomistic molecular dynamics simulations that totaled 1.4 μs. We docked cholesterol to specific sites on VDAC that were previously identified with NMR, and we tested the reliability of multiple docking results in each site with simulations. The most favorable binding modes were used to build a VDAC model with cholesterol occupying five unique sites, and during multiple 100 ns simulations, cholesterol stably and reproducibly remained bound to the protein. For comparison, VDAC was simulated in systems with identical components but with cholesterol initially unbound. The dynamics of loops that connect adjacent β-strands were most affected by bound cholesterol, with the averaged root-mean-square fluctuation (RMSF) of multiple residues altered by 20-30%. Cholesterol binding also stabilized charged residues inside the channel and localized the surrounding electrostatic potentials. Despite this, ion diffusion through the channel was not significantly affected by bound cholesterol, as evidenced by multi-ion potential of mean force measurements. Although we observed modest effects of cholesterol on the open channel, our model will be particularly useful in experiments that investigate how cholesterol affects VDAC function under applied electrochemical forces and also how other ligands and proteins interact with the channel. PMID:25080204

  16. Critical role of cellular cholesterol in bovine rotavirus infection

    PubMed Central

    2014-01-01

    Background Bovine rotavirus (BRV) is a non-enveloped dsRNA virus that cause neonatal calf diarrhea. Lipid rafts are cholesterol-enrich membrane mircodomains that play a vital role in many cellular processes. In this study, the effect of cellular cholesterol depletion on infection of MA-104 cells with bovine rotavirus was investigated. Results We demonstrated that cholesterol depletion of the plasma membrane by MβCD had no effect on BRV binding to cells but significantly impaired BRV entry in a dose-dependent manner and the effect was partially reversed by addition of exogenous cholesterol, suggesting the reduction of BRV infection by MβCD was specifically due to cholesterol depletion. Cholesterol depletion after virus entry did not reduce BRV replication, whereas affected virus assembly. Conclusions Taken together, our results demonstrate that cell membrane cholesterol is essential to BRV infectivity. PMID:24884772

  17. Elasticity of ligated carotid arteries of rabbits with and without a cholesterol-rich diet.

    PubMed

    Lim, K O; Terpin, T; Roach, M R

    1980-02-01

    Elasticity of carotid arterial segments of rabbits proximal and distal to an induced ligation was examined. In the presence of both ligation and hypercholesterolemia, longitudinal distensibility was decreased while circumferential distensibility increased. The decrease in longitudinal distensibility was attributed to a decrease in the slack of collagen while the increase in circumferential distensibility was attributed to an increase in the slack of collagen as well as a decrease in the elastances of elastin and collagen. Cholesterol alone was found not to affect the elasticity, while ligation acting alone slightly decreased the circumferential distensibility while leaving the longitudinal distensibility unchanged. High serum cholesterol was also found to accelerate intimal proliferation in regions near the ligature. Some intimal proliferation was seen near the ligature, but this could not be quantitated as the sections were too short for pressure fixation. If intimal proliferation is a precursor of atherosclerotic lesions, then formation of these lesions might be accelerated near occluded regions and maybe also in regions of disturbed blood flow when high serum cholesterol is present. PMID:7378919

  18. Cholesterol oxidation products and their biological importance.

    PubMed

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

    2016-09-01

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

  19. Clot dissolution is better with ultrasound assisted thrombolysis for fresh clots with higher cholesterol content

    NASA Astrophysics Data System (ADS)

    Zhou, Yufeng; Sharma, Vijay Kumar; Murugappan, Kanna Suresh; Ahmad, Aftab

    2012-11-01

    Tissue plasminogen activator (tPA) remains the only drug for recanalization in acute ischemic stroke, and the dose is determined by the patient's body-weight. Properties of the blood clot as well as ultrasound exposure might affect the thrombolysis outcome. In this study, clot was prepared by mixing horse blood with CaCl2 solution and cholesterin up to 1.0 mg/ml. To simulate the aging effect serum was replaced by fresh blood periodically. 225 IU/ml of tPA was used to initiate lysis. Clot was exposed to continuous 2 MHz transcranial Doppler ultrasound at acoustic intensity of 340 mW/cm2. The weight of the blood clot increased with its age (from 37.28±2.87 mg at 2 hrs to 51.56±5.34 mg at 10 hrs, p < 0.05). Although no difference between clot-cholesterol levels and thrombolysis with ultrasound or tPA alone was found, combination of these modalities induced significant lysis in the clots with cholesterol levels of more than 0.5 mg/ml (clot-weight reduced by 41.68±2.3%) as compared to clots with normal cholesterol (30.60±4.10%; p < 0.05). Altogether, sonothrombolysis seems to work better in fresh thrombi with high-cholesterol levels.

  20. Zearalenone Affects Immune-Related Parameters in Lymphoid Organs and Serum of Rats Vaccinated with Porcine Parvovirus Vaccine

    PubMed Central

    Choi, Byung-Kook; Cho, Joon-Hyung; Jeong, Sang-Hee; Shin, Hyo-Sook; Son, Seong-Wan; Yeo, Young-Keun; Kang, Hwan-Goo

    2012-01-01

    Rats were administered zearalenone (ZEA) via gavage at dosages of 0, 1, 5, and 30 mg/kg for 36 days. On treatment day 8, inactivated porcine parvovirus vaccine (Vac) was injected intraperitoneally. Antibody production against porcine parvovirus was then measured as a function of ZEA treatment. Compared to the vaccine alone, ZEA treatment, with or without Vac, decreased the serum level of IgG. The level of IgM decreased in all ZEA groups at day 22, but the decrease was sustained only in the medium-dose ZEA group at day 36. The level of IgA was unchanged in the Vac only and ZEA groups at day 22, but was decreased in the 5 mg/kg ZEA plus Vac group compared to the Vac only group at day 36. The level of IgE was decreased by all doses of ZEA at day 22, but was unaffected in ZEA plus Vac groups compared to the Vac only group. The levels of IL-1 in the thymus and spleen; INF-γ in serum; IL-2, IL-6, and IL-10 in the thymus; and IL-10 and IFN-γ in the spleen decreased after ZEA administration. Furthermore, the levels of IL-1β in the spleen and mesenteric lymph node, IL-1β in the thymus, IL-2 in the thymus and spleen, IL-6 in the thymus, IL-10 and IFN-γ in the spleen, and GM-CSF and TNF-α in the thymus decreased after vaccination in rats exposed to ZEA. In conclusion, these results suggest that ZEA exposure via drinking water can cause an immunosuppressive effect by decreasing immunoglobulins in serum and cytokines in lymphoid organs. PMID:24278621

  1. VEGF Gene Polymorphisms Affect Serum Protein Levels and Alter Disease Activity and Synovial Lesions in Rheumatoid Arthritis

    PubMed Central

    Yi, Jin-Ping; Wu, Yu-Zhang; Yu, Nan; Yu, Zhi-Wu; Xie, Fu-Yuan; Yuan, Quan

    2016-01-01

    Background Our study investigated 2 common single-nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) for their influences on serum VEGF levels, disease activity, and synovial lesions in rheumatoid arthritis (RA). Material/Methods Clinical information and venous blood samples were collected from 98 RA patients and 100 healthy controls. Genotyping on samples from the subjects was performed using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). Serum VEGF levels were determined using the enzyme-linked immunosorbent assay (ELISA). The synovial thickness and joint effusion of 28 joints were measured in RA patients, and total sharp score (TSS) and disease activity score (DAS) of 28 joints were recorded. Results The genotype and allele frequencies of VEGF rs833070 (G>A) and rs3025030 (G>C) were significantly different between RA group and control group (all P<0.05). VEGF rs833070 and rs3025030 polymorphisms were associated with increasing VEGF serum levels in the RA group (all P<0.01). Statistically significant difference was observed in DAS28 between the different genotypes of VEGF rs833070 in RA patients (P<0.05). Importantly, significant differences in synovial thickening, joint effusion and synovial angiogenesis were observed between the different genotypes of VEGF rs833070 and rs3025030 polymorphisms (all P<0.05). Conclusions Our study provides evidence that VEGF polymorphisms might be important indicators of disease activity and synovial lesions, and prognostic factors in evaluating the treatment effectiveness in RA. PMID:26825024

  2. Chromatographic separation of cholesterol in foods.

    PubMed

    Fenton, M

    1992-10-30

    mass spectrometry has been widely accepted as a reliable analytical method for highly accurate determination of cholesterol in serum and several definitive methods have been reported. The combination of capillary gas chromatography with mass spectrometry has become an excellent approach for the determination of cholesterol in complex mixtures of sterols and tocopherols, providing high resolution with positive identification. When used to determine cholesterol in multi-component foods, spectrophotometric methods have been documented to overestimate significantly the amount of cholesterol owing to the presence of other interfering substances. A re-evaluation of food products should be undertaken using the more specific chromatographic methods to accumulate data that will more accurately reflect the true cholesterol content. PMID:1494014

  3. Altitude, pasture type, and sheep breed affect bone metabolism and serum 25-hydroxyvitamin D in grazing lambs.

    PubMed

    Willems, Helen; Leiber, Florian; Kohler, Martina; Kreuzer, Michael; Liesegang, Annette

    2013-05-15

    This study aimed to investigate the bone development of two mountain sheep breeds during natural summer grazing either in the lowlands or on different characteristic alpine pastures. Pasture types differed in topographic slope, plant species composition, general nutritional feeding value, Ca and P content, and Ca:P ratio of herbage. Twenty-seven Engadine sheep (ES) lambs and 27 Valaisian Black Nose sheep (VS) lambs were divided into four groups of 6 to 7 animals per breed and allocated to three contrasting alpine pasture types and one lowland pasture type. The lambs were slaughtered after 9 wk of experimental grazing. The steep alpine pastures in combination with a high (4.8) to very high (13.6) Ca:P ratio in the forage decreased total bone mineral content as measured in the middle of the left metatarsus of the lambs from both breeds, and cortical bone mineral content and cortical bone mineral density of ES lambs. Breed × pasture type interactions occurred in the development of total and cortical bone mineral content, and in cortical thickness, indicating that bone metabolism of different genotypes obviously profited differently from the varying conditions. An altitude effect occurred for 25-hydroxyvitamin D with notably higher serum concentrations on the three alpine sites, and a breed effect led to higher concentrations for ES than VS. Despite a high variance, there were pasture-type effects on serum markers of bone formation and resorption. PMID:23471950

  4. High dose flaxseed oil supplementation may affect fasting blood serum glucose management in human type 2 diabetics.

    PubMed

    Barre, Douglas E; Mizier-Barre, Kazimiera A; Griscti, Odette; Hafez, Kevin

    2008-01-01

    Type 2 diabetes is characterized partially by elevated fasting blood serum glucose and insulin concentrations and the percentage of hemoglobin as HbA1c. It was hypothesized that each of blood glucose and its co-factors insulin and HbA1c and would show a more favorable profile as the result of flaxseed oil supplementation. Patients were recruited at random from a population pool responding to a recruitment advertisement in the local newspaper and 2 area physicians. Completing the trial were 10 flaxseed oil males, 8 flaxseed oil females, 8 safflower (placebo) oil males and 6 safflower oil females. Patients visited on two pre-treatment occasions each three months apart (visits 1 and 2). At visit 2 subjects were randomly assigned in double blind fashion and in equal gender numbers to take flaxseed oil or safflower oil for three further months until visit 3. Oil consumption in both groups was approximately 10 g/d. ALA intake in the intervention group was approximately 5.5 g/d. Power was 0.80 to see a difference of 1 mmol of glucose /L using 12 subjects per group with a p < 0.05. Flaxseed oil had no impact on fasting blood serum glucose, insulin or HbA1c levels. It is concluded that high doses of flaxseed oil have no effect on glycemic control in type 2 diabetics. PMID:18391475

  5. Policosanol inhibits cholesterol synthesis in hepatoma cells by activation of AMP-kinase.

    PubMed

    Singh, Dev K; Li, Li; Porter, Todd D

    2006-09-01

    Policosanol is a mixture of long-chain primary alcohols that has been shown to decrease serum cholesterol in animals and in humans. The hypocholesterolemic effect results from a decrease in cholesterol synthesis by suppression of HMG-CoA reductase activity, but the mechanism of this suppression and the active components of policosanol have not been established. In the present study, we investigated the ability of policosanol and its principal components to inhibit cholesterol synthesis in cultured rat hepatoma cells. Maximal inhibition by policosanol yielded a 30% decrease in [(14)C]acetate incorporation without evidence of cellular toxicity. Octacosanol (C28, the major constituent of policosanol), heptacosanol (C27), and hexacosanol (C26) yielded smaller and statistically insignificant decreases in cholesterol synthesis, whereas triacontanol (1-hydroxytriacontane; C30) replicated the inhibition obtained with policosanol. At pharmacological concentrations (<5 microg/ml), policosanol and triacontanol decreased [(14)C]acetate incorporation into cholesterol without affecting the incorporation of [(14)C]mevalonate, indicating that these compounds act at or above HMG-CoA reductase. Policosanol and triacontanol did not directly inhibit HMG-CoA reductase, and incubation of these compounds with hepatoma cells did not affect reductase enzyme levels. However, reductase activity was decreased by up to 55% in lysates prepared from these cells, suggesting that HMG-CoA reductase activity was down-regulated by policosanol treatment. Consistent with this hypothesis, a 3-fold increase in AMP-kinase phosphorylation was noted in policosanol-treated cells. Because AMP-kinase is activated by phosphorylation and is well established to suppress HMG-CoA reductase activity, these results suggest that policosanol or a metabolite decreases HMG-CoA reductase activity by activating AMP-kinase. PMID:16714400

  6. Dietary Fat and Cholesterol

    MedlinePlus

    ... Gynecology Medical Conditions Nutrition & Fitness Emotional Health Dietary Fat and Cholesterol Posted under Health Guides . Updated 23 ... warm What are the different types of dietary fat? The four main types of fat found in ...

  7. Get Your Cholesterol Checked

    MedlinePlus

    ... is checked with a blood test called a lipid profile. During the test, a nurse will take ... blood tests that can check cholesterol, but a lipid profile gives the most information. Find out more ...

  8. High Blood Cholesterol

    MedlinePlus

    ... of cholesterol is called plaque. Plaque Buildup Can Lead to… Click for more information Artherosclerosis. Over time, ... disease (CHD). Angina. The buildup of plaque can lead to chest pain called angina. Angina is a ...

  9. Common Misconceptions about Cholesterol

    MedlinePlus

    ... most (and preferably all) days; and stressing the importance of avoiding tobacco products. Learn more about cholesterol ... Privacy Policy Popular Articles 1 Understanding Blood Pressure Readings 2 Sodium and Salt 3 Low Blood Pressure ...

  10. Cholesterol and Statins

    MedlinePlus

    ... the liver makes ldl & hdl In the liver, triglycerides, cholesterol, and proteins form together to make LDL ... This is especially important for individuals with high triglyceride and/or low HDL levels who are overweight ...

  11. Cholesterol in unusual places

    NASA Astrophysics Data System (ADS)

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

    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).

  12. MD-2 binds cholesterol.

    PubMed

    Choi, Soo-Ho; Kim, Jungsu; Gonen, Ayelet; Viriyakosol, Suganya; Miller, Yury I

    2016-02-19

    Cholesterol is a structural component of cellular membranes, which is transported from liver to peripheral cells in the form of cholesterol esters (CE), residing in the hydrophobic core of low-density lipoprotein. Oxidized CE (OxCE) is often found in plasma and in atherosclerotic lesions of subjects with cardiovascular disease. Our earlier studies have demonstrated that OxCE activates inflammatory responses in macrophages via toll-like receptor-4 (TLR4). Here we demonstrate that cholesterol binds to myeloid differentiation-2 (MD-2), a TLR4 ancillary molecule, which is a binding receptor for bacterial lipopolysaccharide (LPS) and is indispensable for LPS-induced TLR4 dimerization and signaling. Cholesterol binding to MD-2 was competed by LPS and by OxCE-modified BSA. Furthermore, soluble MD-2 in human plasma and MD-2 in mouse atherosclerotic lesions carried cholesterol, the finding supporting the biological significance of MD-2 cholesterol binding. These results help understand the molecular basis of TLR4 activation by OxCE and mechanisms of chronic inflammation in atherosclerosis. PMID:26806306

  13. The steady-state serum concentration of genistein aglycone is affected by formulation: a bioequivalence study of bone products.

    PubMed

    Bitto, Alessandra; Burnett, Bruce P; Polito, Francesca; Russo, Silvia; D'Anna, Rosario; Pillai, Lakshmi; Squadrito, Francesco; Altavilla, Domenica; Levy, Robert M

    2013-01-01

    An FDA-regulated, prescription medical food (Fosteum; 27 mg natural genistein, 200 IU cholecalciferol, 20 mg citrated zinc bisglycinate (4 mg elemental zinc) per capsule) and an over-the-counter (OTC) supplement (Citracal Plus Bone Density Builder; 27 mg synthetic genistein, 600 mg elemental calcium (calcium citrate), 400 IU vitamin D3, 50 mg magnesium, 7.5 mg zinc, 1 mg copper, 75 μ g molybdenum, 250 μ g boron per two tablets) were compared to a clinically proven bone formulation (27 mg natural genistein, 400 IU cholecalciferol, 500 mg elemental calcium (calcium carbonate) per tablet; the Squadrito formulation) in an 8-day steady-state pharmacokinetic (PK) study of healthy postmenopausal women (n = 30) randomized to receive 54 mg of genistein per day. Trough serum samples were obtained before the final dose on the morning of the ninth day followed by sampling at 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hrs. Total serum genistein, after β -glucuronidase/sulfatase digestion, was measured by time-resolved fluorometric assay. Maximal time (Tmax), concentration (Cmax), half-life (T1/2), and area under the curve (AUC) were determined for genistein in each formulation. Fosteum and the Squadrito study formulation were equivalent for genistein Tmax (2 hrs), Cmax (0.7 μM), T1/2 (18 ± 6.9 versus 21 ± 4.9 hrs), and AUC (9221 ± 413 versus 9818 ± 1370 ng·hr/mL). The OTC supplement's synthetically derived genistein, however, showed altered Tmax (6 hrs), Cmax (0.57 μ M), T1/2 (8.3 ± 1.9 hrs), and AUC (6474 ± 287 ng·hr/mL). Differences in uptake may be due to multiple ingredients in the OTC supplement which interfere with genistein absorption. PMID:23484100

  14. Dietary Cholesterol Modulates Pathogen Blocking by Wolbachia

    PubMed Central

    Caragata, Eric P.; Rancès, Edwige; Hedges, Lauren M.; Gofton, Alexander W.; Johnson, Karyn N.; O'Neill, Scott L.; McGraw, Elizabeth A.

    2013-01-01

    The bacterial endosymbiont Wolbachia pipientis protects its hosts from a range of pathogens by limiting their ability to form infections inside the insect. This “pathogen blocking” could be explained by innate immune priming by the symbiont, competition for host-derived resources between pathogens and Wolbachia, or the direct modification of the cell or cellular environment by Wolbachia. Recent comparative work in Drosophila and the mosquito Aedes aegypti has shown that an immune response is not required for pathogen blocking, implying that there must be an additional component to the mechanism. Here we have examined the involvement of cholesterol in pathogen blocking using a system of dietary manipulation in Drosophila melanogaster in combination with challenge by Drosophila C virus (DCV), a common fly pathogen. We observed that flies reared on cholesterol-enriched diets infected with the Wolbachia strains wMelPop and wMelCS exhibited reduced pathogen blocking, with viral-induced mortality occurring 2–5 days earlier than flies reared on Standard diet. This shift toward greater virulence in the presence of cholesterol also corresponded to higher viral copy numbers in the host. Interestingly, an increase in dietary cholesterol did not have an effect on Wolbachia density except in one case, but this did not directly affect the strength of pathogen blocking. Our results indicate that host cholesterol levels are involved with the ability of Wolbachia-infected flies to resist DCV infections, suggesting that cholesterol contributes to the underlying mechanism of pathogen blocking. PMID:23825950

  15. The link between cholesterol and Alzheimer's disease.

    PubMed

    Sjögren, Magnus; Blennow, Kaj

    2005-01-01

    A leading hypothesis on the pathophysiology of Alzheimer's disease (AD) is the mis-metabolism of amyloid precursor protein. This mis-metabolism causes the 42-amino acid form of A beta(Abeta42) to form oligomers that in turn start a chain of events leading to the accumulation of amyloid plaques. Vascular factors such as hypertension, hypercholesterolemia and diabetes as well as the inheritance of the epsilon4 allele of the ApoE gene are risk factors for AD. These risks are thought to promote the production of beta-amyloid (Abeta). An association between cholesterol and the development of AD was suggested in 1994 and since then, research has confirmed a link between cholesterol and the development of AD. A high cholesterol level in mid-life is a risk for AD and statins i.e. cholesterol-lowering drugs, reduce this risk. Statins inhibit enzymes involved in the endogenous synthesis of cholesterol and evidence is mounting that they also affect enzymes in Abeta metabolism i.e. beta-secretase. This normalises the breakdown of the precursor of Abeta, amyloid precursor protein, thereby promoting the nonamyloidogenic pathway. This review focusses on the link between cholesterol and Alzheimer's disease. PMID:16156481

  16. Mitochondrial cholesterol: mechanisms of import and effects on mitochondrial function.

    PubMed

    Martin, Laura A; Kennedy, Barry E; Karten, Barbara

    2016-04-01

    Mitochondria require cholesterol for biogenesis and membrane maintenance, and for the synthesis of steroids, oxysterols and hepatic bile acids. Multiple pathways mediate the transport of cholesterol from different subcellular pools to mitochondria. In steroidogenic cells, the steroidogenic acute regulatory protein (StAR) interacts with a mitochondrial protein complex to mediate cholesterol delivery to the inner mitochondrial membrane for conversion to pregnenolone. In non-steroidogenic cells, several members of a protein family defined by the presence of a StAR-related lipid transfer (START) domain play key roles in the delivery of cholesterol to mitochondrial membranes. Subdomains of the endoplasmic reticulum (ER), termed mitochondria-associated ER membranes (MAM), form membrane contact sites with mitochondria and may contribute to the transport of ER cholesterol to mitochondria, either independently or in conjunction with lipid-transfer proteins. Model systems of mitochondria enriched with cholesterol in vitro and mitochondria isolated from cells with (patho)physiological mitochondrial cholesterol accumulation clearly demonstrate that mitochondrial cholesterol levels affect mitochondrial function. Increased mitochondrial cholesterol levels have been observed in several diseases, including cancer, ischemia, steatohepatitis and neurodegenerative diseases, and influence disease pathology. Hence, a deeper understanding of the mechanisms maintaining mitochondrial cholesterol homeostasis may reveal additional targets for therapeutic intervention. Here we give a brief overview of mitochondrial cholesterol import in steroidogenic cells, and then focus on cholesterol trafficking pathways that deliver cholesterol to mitochondrial membranes in non-steroidogenic cells. We also briefly discuss the consequences of increased mitochondrial cholesterol levels on mitochondrial function and their potential role in disease pathology. PMID:25425472

  17. Serum Immunoglobulin G Levels to Porphyromonas gingivalis Peptidylarginine Deiminase Affect Clinical Response to Biological Disease-Modifying Antirheumatic Drug in Rheumatoid Arthritis

    PubMed Central

    Kobayashi, Tetsuo; Ito, Satoshi; Kobayashi, Daisuke; Shimada, Atsushi; Narita, Ichiei; Murasawa, Akira; Nakazono, Kiyoshi; Yoshie, Hiromasa

    2016-01-01

    Objectives To determine whether serum immunity to Porphyromonas gingivalis peptidylarginine deiminase (PPAD) affects the clinical response to biological disease-modifying antirheumatic drug (bDMARD) in patients with rheumatoid arthritis (RA). Methods In a retrospective study, rheumatologic and periodontal conditions of 60 patients with RA who had been treated with conventional synthetic DMARD were evaluated before (baseline) and after 3 and 6 months of bDMARD therapy. After serum levels of anti-PPAD immunoglobulin G (IgG) were determined at baseline, the patients were respectively divided into two groups for high and low anti-PPAD IgG titers according to the median measurements. Genotypes at 8 functional single nucleotide polymorphisms (SNPs) related to RA were also determined. Results After 3 and 6 months of therapy, patients with low anti-PPAD IgG titers showed a significantly greater decrease in changes in the Disease Activity Score including 28 joints using C-reactive protein (DAS28-CRP) (P = 0.04 for both) and anti-cyclic citrullinated peptide (CCP) IgG levels (P = 0.03 and P = 0.04) than patients with high anti-PPAD IgG titers, although these parameter values were comparable at baseline. The anti-PPAD IgG titers were significantly positively correlated with changes in the DAS28-CRP (P = 0.01 for both) and the anti-CCP IgG levels (P = 0.02 for both) from baseline to 3 and 6 months later. A multiple regression analysis revealed a significantly positive association between the anti-PPAD IgG titers and changes in the DAS28-CRP after 6 months of bDMARD therapy (P = 0.006), after adjusting for age, gender, smoking, periodontal condition, and RA-related SNPs. Conclusion The serum IgG levels to PPAD affect the clinical response to bDMARD in patients with RA. PMID:27111223

  18. Relationships existing between the serum cytokine levels and bone mineral density in women in the premenopausal period affected by Graves' disease with subclinical hyperthyroidism.

    PubMed

    Ugur-Altun, Betül; Altun, Armagan; Arikan, Ender; Guldiken, Sibel; Tugrul, Armagan

    2003-11-01

    We examined the relationships existing between serum cytokine levels and bone mineral density (BMD) in women of premenopausal age affected by Graves' disease with subclinical hyperthyroidism. The study population consisted of 21 women with untreated hyperthyroid Graves' disease (group H) (age, 36 +/- 2 years), eight women with untreated subclinical hyperthyroid status (group SH) (age, 33 +/- 5 years) and 10 healthy women (group N) (age, 35 +/- 3 years). The following measurements were made in all patients: free T4 (fT4), free T3 (fT3), thyroid stimulating hormone (TSH), TSH receptor antibody (TRab), anti-thyroid peroxidase antibody (anti-TPO), anti-thyroglobulin antibody (anti-Tg), interleukin-2 receptor (IL-2r), interleukin-4 (IL-4), interleukin-8 (IL-8) and interleukin-13 (IL-13). IL-2r and IL-8 levels significantly increased in group H compared with group SH (p < 0.01 and p = 0.05, respectively) and group N (p < 0.001 and p = 0.02, respectively). IL-4 and IL-13 levels tended to be lower in groups H and SH compared with group N, although this difference did not reach statistical significance. Bone mineral density was significantly reduced in only two areas of the femur in group H compared with group N. There was no difference in BMD between groups SH and N. There was no correlation between thyroid hormones, serum cytokine levels and BMD in either group. In conclusion, these results suggest that there were no relationships existing between the serum level of these cytokines and BMD in women of premenopausal age affected by Graves' disease with subclinical hyperthyroidism. PMID:14682468

  19. A critical analysis of the role of cholesterol in atherogenesis.

    PubMed

    Sloop, G D

    1999-02-01

    Serum hypercholesterolemia is theorized to accelerate atherogenesis by augmenting cholesterol accumulation (insudation) in the arterial intima. The author views this theory as an example of what the noted philosopher of science Imre Lakatos called 'degenerative science', because data have forced several modifications of the theory. Although the theory that some fraction of intimal cholesterol causes atherosclerosis is not yet disproved, the author favors the hypothesis that serum hypercholesterolemia accelerates atherogenesis and contributes to symptomatic atherosclerosis by increasing blood viscosity and the mechanical fragility of atherosclerotic plaques, making them vulnerable to rupture and thrombosis. PMID:10030376

  20. Effect of black tea intake on blood cholesterol concentrations in individuals with mild hypercholesterolemia: A diet-controlled randomized trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Habitual intake of black tea has predominantly been associated with relatively lower serum cholesterol concentrations in observational studies. However, clinical trials evaluating the potential effects of black tea on serum cholesterol have had inconsistent results. These mixed results could be expl...

  1. High Uric Acid (UA) Negatively Affects Serum Tartrate-Resistant Acid Phosphatase 5b (TRACP 5b) Immunoassay

    PubMed Central

    Wu, Zhi-Qi; Zhang, Yan; Xie, Erfu; Song, Wei-Juan; Yang, Rui-Xia; Yan, Cheng-Jing; Zhang, Bing-Feng; Xu, Hua-Guo

    2016-01-01

    Background Bone metastases often occur in the majority of patients with advanced cancer, such as prostate cancer, lung cancer and breast cancer. Serum tartrate-resistant acid phosphatase 5b (TRACP 5b), a novel bone resorption marker, has been used gradually in the clinics as a specific and sensitive marker of bone resorption for the early diagnosis of cancer patients with bone metastasis. Here, we reported that high concentrations of uric acid (UA) lead to decrease of TRACP 5b levels and determined whether TRACP 5b level was associated with UA in interference experiment. Methods A total of 77 patients with high concentrations of UA and 77 healthy subjects were tested to evaluate the differences in their TRACP 5b levels. Serial dilutions of UA were respectively spiked with a known concentration of TRACP 5b standard sample, then Serum TRACP 5b was detected by using bone TRAP® Assay. A correction equation was set to eliminate UA-derived TRACP 5b false-decrease. The effect of this correction was evaluated in high-UA individuals. Results The average TRACP level of the high-UA individuals (1.47± 0.62 U/L) was significantly lower than that of the healthy subjects (2.62 ± 0.63 U/L) (t-test, p<0.0001). The UA correction equation derived: ΔTRACP 5b = -1.9751lgΔUA + 3.7365 with an R2 = 0.98899. Application of the UA correction equation resulted in a statistically non-significant difference in TRACP 5b values between the healthy subjects and high-UA individuals (p = 0.24). Conclusions High UA concentrations can falsely decrease TRACP 5b levels due to a method-related systematic error. To avoid misdiagnoses or inappropriate therapeutic decisions, increased attention should be paid to UA interference, when TRACP 5b is used for early diagnosis of cancer patients with bone metastasis, evaluation of the aggressiveness of osteosarcoma or prediction of survival in prostate cancer and breast cancer with bone metastases. PMID:26800211

  2. The Steady-State Serum Concentration of Genistein Aglycone Is Affected by Formulation: A Bioequivalence Study of Bone Products

    PubMed Central

    Bitto, Alessandra; Burnett, Bruce P.; Polito, Francesca; Russo, Silvia; D'Anna, Rosario; Pillai, Lakshmi; Squadrito, Francesco; Altavilla, Domenica; Levy, Robert M.

    2013-01-01

    An FDA-regulated, prescription medical food (Fosteum; 27 mg natural genistein, 200 IU cholecalciferol, 20 mg citrated zinc bisglycinate (4 mg elemental zinc) per capsule) and an over-the-counter (OTC) supplement (Citracal Plus Bone Density Builder; 27 mg synthetic genistein, 600 mg elemental calcium (calcium citrate), 400 IU vitamin D3, 50 mg magnesium, 7.5 mg zinc, 1 mg copper, 75 μg molybdenum, 250 μg boron per two tablets) were compared to a clinically proven bone formulation (27 mg natural genistein, 400 IU cholecalciferol, 500 mg elemental calcium (calcium carbonate) per tablet; the Squadrito formulation) in an 8-day steady-state pharmacokinetic (PK) study of healthy postmenopausal women (n = 30) randomized to receive 54 mg of genistein per day. Trough serum samples were obtained before the final dose on the morning of the ninth day followed by sampling at 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hrs. Total serum genistein, after β-glucuronidase/sulfatase digestion, was measured by time-resolved fluorometric assay. Maximal time (Tmax), concentration (Cmax), half-life (T1/2), and area under the curve (AUC) were determined for genistein in each formulation. Fosteum and the Squadrito study formulation were equivalent for genistein Tmax (2 hrs), Cmax (0.7 μM), T1/2 (18 ± 6.9 versus 21 ± 4.9 hrs), and AUC (9221 ± 413 versus 9818 ± 1370 ng·hr/mL). The OTC supplement's synthetically derived genistein, however, showed altered Tmax (6 hrs), Cmax (0.57 μM), T1/2 (8.3 ± 1.9 hrs), and AUC (6474 ± 287 ng·hr/mL). Differences in uptake may be due to multiple ingredients in the OTC supplement which interfere with genistein absorption. PMID:23484100

  3. The Effects of Cholesterol on Learning and Memory

    PubMed Central

    Schreurs, Bernard G.

    2010-01-01

    Cholesterol is vital to normal brain function including learning and memory but that involvement is as complex as the synthesis, metabolism and excretion of cholesterol itself. Dietary cholesterol influences learning tasks from water maze to fear conditioning even though cholesterol does not cross the blood brain barrier. Excess cholesterol has many consequences including peripheral pathology that can signal brain via cholesterol metabolites, proinflammatory mediators and antioxidant processes. Manipulations of cholesterol within the central nervous system through genetic, pharmacological, or metabolic means circumvent the blood brain barrier and affect learning and memory but often in animals already otherwise compromised. The human literature is no less complex. Cholesterol reduction using statins improves memory in some cases but not others. There is also controversy over statin use to alleviate memory problems in Alzheimer’s disease. Correlations of cholesterol and cognitive function are mixed and association studies find some genetic polymorphisms are related to cognitive function but others are not. In sum, the field is in flux with a number of seemingly contradictory results and many complexities. Nevertheless, understanding cholesterol effects on learning and memory is too important to ignore. PMID:20470821

  4. Cholesterol Absorption and Metabolism.

    PubMed

    Howles, Philip N

    2016-01-01

    Inhibitors of cholesterol absorption have been sought for decades as a means to treat and prevent cardiovascular diseases (CVDs) associated with hypercholesterolemia. Ezetimibe is the one clear success story in this regard, and other compounds with similar efficacy continue to be sought. In the last decade, the laboratory mouse, with all its genetic power, has become the premier experimental model for discovering the mechanisms underlying cholesterol absorption and has become a critical tool for preclinical testing of potential pharmaceutical entities. This chapter briefly reviews the history of cholesterol absorption research and the various gene candidates that have come under consideration as drug targets. The most common and versatile method of measuring cholesterol absorption is described in detail along with important considerations when interpreting results, and an alternative method is also presented. In recent years, reverse cholesterol transport (RCT) has become an area of intense new interest for drug discovery since this process is now considered another key to reducing CVD risk. The ultimate measure of RCT is sterol excretion and a detailed description is given for measuring neutral and acidic fecal sterols and interpreting the results. PMID:27150091

  5. A freshwater clam (Corbicula fluminea) extract improves cholesterol metabolism in rats fed on a high-cholesterol diet.

    PubMed

    Chijimatsu, Takeshi; Tatsuguchi, Iwao; Abe, Kazuaki; Oda, Hiroaki; Mochizuki, Satoshi

    2008-10-01

    The effect of a freshwater clam (Corbicula fluminea) extract (FCE) on cholesterol metabolism in rats fed on a high-cholesterol diet was investigated. When rats were fed various amounts of FCE in addition to the high-cholesterol diet for 2 wk, the serum and hepatic cholesterol levels were gradually reduced in a dose-dependent manner, as compared with the control group. The excretion of neutral sterols and bile acids into the feces was increased by feeding FCE. Several phytosterols were detected in the feces of rats fed on the FCE-containing diet. In addition, substantial amounts of phytosterols were found in FCE. Cholesterol 7alpha-hydroxylase (CYP7A1) mRNA in the liver of the rats fed on the FCE-containing diets was higher than that of rats fed on the high-cholesterol diets without FCE. These results may suggest that enhanced cholesterol degradation and the excretion of neutral sterols and bile acids contributed to the hypocholesterolemic effect of FCE observed in the hypercholesterolemic rats fed on the high-cholesterol diet. PMID:18838816

  6. The plasma dilution factor: predicting how concentrations in plasma and serum are affected by blood volume variations and blood loss.

    PubMed

    Flordal, A

    1995-10-01

    To determine the effects of therapeutic interventions on plasma protein concentrations, it is often desirable to rule out nonspecific effects of hemodilution. Because red cells are restricted to the vascular space, the hematocrit (Hct) is a convenient marker. At the bedside--and even in scientific reports--a simple ratio of Hcts (obtained before and after the change in plasma volume) is often used to "correct" the value of interest. This is incorrect, and it may introduce a sizeable error. A new method, the plasma dilution factor (PDF), has been mathematically deduced. It accounts for the influence of any blood loss, plasma osmolality changes, and blood volume variations on plasma and serum concentrations. In an in vitro experiment, blood loss and osmolality and blood volume changes were simulated through the withdrawal of various volumes of blood, which were replaced with smaller, identical, or larger volumes of hypotonic, isotonic, or hypertonic solutions. The PDF accurately predicted changes in concentrations of albumin, fibrinogen, and antithrombin III. In contrast, the Hct ratio significantly underestimated the effects of dilution. Von Willebrand factor concentrations after hemodilution through dextran infusion in volunteers were the same as predicted by the PDF. In patients undergoing orthopedic surgery who were also given dextran, the postdilution von Willebrand factor concentrations were higher than predicted by the PDF. The Hct gave a false impression of a decrease in the volunteers that was not explained by hemodilution, and it failed to detect the von Willebrand factor response to trauma in the surgical patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7561443

  7. Mathematically modelling the dynamics of cholesterol metabolism and ageing.

    PubMed

    Morgan, A E; Mooney, K M; Wilkinson, S J; Pickles, N A; Mc Auley, M T

    2016-07-01

    Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the UK. This condition becomes increasingly prevalent during ageing; 34.1% and 29.8% of males and females respectively, over 75 years of age have an underlying cardiovascular problem. The dysregulation of cholesterol metabolism is inextricably correlated with cardiovascular health and for this reason low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) are routinely used as biomarkers of CVD risk. The aim of this work was to use mathematical modelling to explore how cholesterol metabolism is affected by the ageing process. To do this we updated a previously published whole-body mathematical model of cholesterol metabolism to include an additional 96 mechanisms that are fundamental to this biological system. Additional mechanisms were added to cholesterol absorption, cholesterol synthesis, reverse cholesterol transport (RCT), bile acid synthesis, and their enterohepatic circulation. The sensitivity of the model was explored by the use of both local and global parameter scans. In addition, acute cholesterol feeding was used to explore the effectiveness of the regulatory mechanisms which are responsible for maintaining whole-body cholesterol balance. It was found that our model behaves as a hypo-responder to cholesterol feeding, while both the hepatic and intestinal pools of cholesterol increased significantly. The model was also used to explore the effects of ageing in tandem with three different cholesterol ester transfer protein (CETP) genotypes. Ageing in the presence of an atheroprotective CETP genotype, conferring low CETP activity, resulted in a 0.6% increase in LDL-C. In comparison, ageing with a genotype reflective of high CETP activity, resulted in a 1.6% increase in LDL-C. Thus, the model has illustrated the importance of CETP genotypes such as I405V, and their potential role in healthy ageing. PMID:27157786

  8. Serum lipid and fatty acid profiles in adriamycin-treated rats after administration of L-carnitine.

    PubMed

    Hong, Young Mi; Kim, Hae Soon; Yoon, Hye-Ran

    2002-02-01

    Cardiomyopathy induced by Adriamycin (ADR) is a cause of congestive heart failure. Recently, it has been suggested that ADR inhibits the carnitine palmitoyltransferase system (CPT I) and consequently the transport of long-chain fatty acids across mitochondrial membranes. This study was devised to ascertain how ADR affects serum lipid and fatty acid metabolism in rats given ADR with and without L-carnitine supplementation. Male Sprague-Dawley rats were divided into four groups. The first group was the control. The second group was given intraperitoneal injections of ADR (5 mg/kg) twice a week over a period of 2 wk. The third group received the same dose of ADR plus L-carnitine (200 mg/kg). The fourth group was injected with L-carnitine only. Serum lipids (total cholesterol, triglyceride, HDL cholesterol, and LDL cholesterol) and fatty acid levels were determined on the first, eighth, and 15th d after injection of ADR. ADR caused an increase of serum total cholesterol, triglyceride, and LDL cholesterol compared with the control group. HDL cholesterol was similar between two groups. Similarly, total fatty acids, especially C16-C18 fatty acids, were significantly elevated after injection of ADR. Striking reduction in these substances was observed when L-carnitine was added (p < 0.05). This study is the first report regarding the reversal effect of L-carnitine in connection with FFA profiles (C6-C18) in the serum of ADR-induced cardiomyopathic rats. This study also supports the view that ADR causes cardiomyopathy because it interferes with fatty acid metabolism, and we hypothesize that there is a possible protective effect of L-carnitine. PMID:11809922

  9. Bu-Shen-Ning-Xin Decoction ameliorated the osteoporotic phenotype of ovariectomized mice without affecting the serum estrogen concentration or uterus

    PubMed Central

    Wang, Ling; Qiu, Xue-Min; Gui, Yu-Yan; Xu, Ying-Ping; Gober, Hans-Jürgen; Li, Da-Jin

    2015-01-01

    Introduction Bu-Shen-Ning-Xin Decoction (BSNXD), a traditional Chinese medicinal composition, has been used as a remedy for postmenopausal osteoporosis, but its effects on bone metabolism and the uterus have not been reported. Purpose We aimed to determine the respective effects of BSNXD on the bones and the uterus of ovariectomized (OVX) mice to evaluate the efficacy and safety of this herbal formula. Materials and methods Postmenopausal osteoporosis animal models that were generated by ovariectomy were treated with BSNXD. Dual-energy X-ray absorptiometry was performed to analyze the bone mineral density, and histomorphometric analysis was performed to measure the parameters related to bone metabolism. Calcein labeling was performed to detect bone formation. The uteruses from the mice were weighed, and the histomorphometry was analyzed. Drug-derived serum was prepared to assess the 17-β-estradiol concentration via enzyme immunoassay. Results BSNXD administration ameliorated the osteoporotic phenotype of OVX mice, as evidenced by an increase in the bone mineral density and bone volume; these effects could not be abolished by the administration of the aromatase inhibitor letrozole. Moreover, BSNXD had no effect on the serum estrogen concentration or uterus. Conclusion These results suggest that BSNXD has ameliorating effects on bone loss due to estrogen deprivation without affecting the peripheral blood estrogen concentration or the uterus in OVX mice. PMID:26357466

  10. Cholesterol exchange and lateral cholesterol pools in synaptosomal membranes of pair-fed control and chronic ethanol-treated mice.

    PubMed

    Wood, W G; Rao, A M; Igbavboa, U; Semotuk, M

    1993-04-01

    Most studies on effects of ethanol on membrane cholesterol have reported on changes in the total or bulk amount of cholesterol. Membrane cholesterol, however, can be described in terms of its kinetics and domains. The kinetics and size of lateral cholesterol exchangeable and nonexchangeable pools were examined in synaptosomes of pair-fed controls and chronic ethanol-treated mice. Effects of sphingomyelin, an exofacial leaflet phospholipid, that has been shown to affect cholesterol pools, were also examined. Radiolabeled small unilamellar vesicles were used to exchange cholesterol with synaptosomes. The total amounts of membrane cholesterol, phospholipid phosphorus, and the ratio of cholesterol to phospholipid did not differ between the pair-fed control and ethanol groups. In control mice, the rate constant (hr-1) and the t1/2 (hr) of cholesterol exchange were 0.065 +/- 0.001 and 10.7 +/- 0.25 (hr), respectively. The rate constant was significantly slower (0.053 +/- 0.001, p < 0.05) and the t1/2 significantly longer (13.33 +/- 0.58, p < 0.05) in synaptosomes of the ethanol group compared with the control group. The size of the exchangeable pool of cholesterol did not differ significantly between the two groups. Sphingomyelinase-induced hydrolysis of sphingomyelin significantly slowed cholesterol exchange with the largest effect in synaptosomes of the control group as compared with the ethanol group (p < 0.05). Hydrolysis of sphingomyelin had significantly (p < 0.05) less of an effect on cholesterol exchange in synaptosomes of the ethanol group. Membrane cholesterol can be described in terms of total content, transbilayer distribution, kinetics, and size of lateral pools.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8488977

  11. Metabolic effects of fluvastatin extended release 80 mg and atorvastatin 20 mg in patients with type 2 diabetes mellitus and low serum high-density lipoprotein cholesterol levels: a 4-month, prospective, open-label, randomized, blinded—end point (probe) trial

    PubMed Central

    Bevilacqua, Maurizio; Guazzini, Barbara; Righini, Velella; Barrella, Massimo; Toscano, Rosanna; Chebat, Enrica

    2004-01-01

    Background Diabetic dyslipidemia is characterized by greater triglyceridation of all lipoproteins and low levels of plasma high-density lipoprotein cholesterol (HDL-C). In this condition, the serum level of low-density lipoprotein cholesterol (LDL-C) is only slightly elevated. The central role of decreased serum HDL-C level in diabetic cardiovascular disease has prompted the establishment of a target of ≥50 mg/dL in patients with diabetes mellitus (DM). Objective The aim of the study was to assess the effects of once-daily administration of fluvastatin extended release (XL) 80 mg or atorvastatin 20 mg on serum HDL-C levels in patients with type 2 DM and low levels of serum HDL-C. Methods This 4-month, prospective, open-label, randomized, blinded—end point (PROBE) trial was conducted at Endocrinology and Diabetology Service, L. Sacco-Polo University Hospital (Milan, Italy). Patients aged 45 to 71 years with type 2 DM receiving standard oral antidiabetic therapy, with serum HDL-C levels <50 mg/dL, and with moderately high serum levels of LDL-C and triglycerides (TG) were enrolled. After 1 month of lifestyle modification and dietary intervention, patients who were still showing a decreased HDL-C level were randomized, using a 1:1 ratio, to receive fluvastatin XL 80-mg tablets or atorvastatin 20-mg tablets, for 3 months. Lipoprotein metabolism was assessed by measuring serum levels of LDL-C, HDL-C, TG, apolipoprotein (apo) A-I (the lipoprotein that carries HDL), and apo B (the lipoprotein that binds very low-density lipoprotein cholesterol, intermediate-density lipoprotein, and LDL on a molar basis). Patients were assessed every 2 weeks for treatment compliance and subjective adverse events. Serum creatine phosphokinase and liver enzymes were assessed before the run-in period, at the start of the trial, and at 1 and 3 months during the study. Results One hundred patients were enrolled (50 patients per treatment group; fluvastatin XL group: 33 men, 17 women; mean

  12. Relationship between the plasma fentanyl and serum 4β-hydroxycholesterol based on CYP3A5 genotype and gender in patients with cancer pain.

    PubMed

    Ishida, Takuya; Naito, Takafumi; Sato, Hikaru; Kawakami, Junichi

    2016-06-01

    This study aimed to evaluate the relationship between the concentrations of plasma fentanyl and serum 4β-hydroxycholesterol based on CYP3A5 genotype and gender in cancer patients. Thirty-three Japanese cancer patients treated with transdermal fentanyl were enrolled. The concentrations of plasma fentanyl and norfentanyl, and serum 4β-hydroxycholesterol and total cholesterol were determined at day 8 or later after starting the medication. The plasma fentanyl concentration was significantly higher in the CYP3A5*3/*3 group than in the *1 allele carrier group. The *3/*3 group had a lower metabolic ratio of fentanyl. The serum 4β-hydroxycholesterol concentration and its ratio to total cholesterol were significantly lower in the CYP3A5*3/*3 group than in the *1 allele carrier group. The concentrations of plasma fentanyl and serum 4β-hydroxycholesterol were significantly higher in women than in men. Gender did not affect the metabolic ratio of fentanyl or the concentration ratio of 4β-hydroxycholesterol. The plasma fentanyl concentration was not correlated with the serum 4β-hydroxycholesterol concentration, while the metabolic ratio of fentanyl was slightly correlated with the serum concentration ratio of 4β-hydroxycholesterol. In conclusion, CYP3A5*3 and gender affected the plasma fentanyl and serum 4β-hydroxycholesterol concentrations in cancer patients. However, the plasma disposition of fentanyl was not determined using the serum 4β-hydroxycholesterol concentration. PMID:27236640

  13. A common genetic variant of fucosyltransferase 2 correlates with serum carcinoembryonic antigen levels and affects cancer screening in patients with primary sclerosing cholangitis

    PubMed Central

    Wannhoff, Andreas; Folseraas, Trine; Brune, Maik; Rupp, Christian; Friedrich, Kilian; Knierim, Johannes; Weiss, Karl Heinz; Sauer, Peter; Flechtenmacher, Christa; Schirmacher, Peter; Stremmel, Wolfgang; Hov, Johannes R

    2015-01-01

    Background Primary sclerosing cholangitis (PSC) patients are at increased risk of biliary tract cancer, and carcinoembryonic antigen (CEA) serum levels might be used for screening. Objective To examine cancer screening with CEA in PSC patients and analyse how serum CEA levels are affected by genetic variants of fucosyltransferase (FUT) 2 and 3. Methods In a retrospective cohort analysis we evaluated CEA levels in 226 PSC patients, including 19 with biliary malignancy, and investigated how FUT2 and FUT3 SNPs affected CEA levels. Receiver-operating-characteristic (ROC) analysis was performed and cut-off values were determined based on Youden’s index. A control cohort contained 240 patients, including 28 with biliary malignancy. Results Median CEA concentration was lower in cancer-free patients (1.4 ng/mL) than in cancer patients (2.0 ng/mL, P = 0.014). ROC analysis revealed an area under the curve (AUC) of 0.671, the optimal cut-off was 3.2 ng/mL. The FUT2 variant rs601338 (G428A) correlated with CEA levels, and the effect was most prominent in a subgroup of patients genetically incapable of expressing CA19-9. The AUC improved if ROC analysis was performed separately for wild-type (AUC: 0.731) and homozygous mutant (AUC: 0.816) G428A. The influence of FUT2 on CEA was confirmed in the control cohort. Conclusions CEA is interesting for biliary-malignancy screening in PSC patients, especially in patients who do not express CA19-9. This is the first study to show that the combined use of CEA measurement and FUT genotyping is clinically beneficial and that it might enhance the early detection of biliary malignancy in clinical practice. This approach could also be effective when screening for other common gastrointestinal malignancies. PMID:26966527

  14. High blood cholesterol levels

    MedlinePlus

    Steps you can take to improve their cholesterol levels, and help prevent heart disease and a heart attack include: Quit smoking. This is the single biggest change you can make to reduce your risk of heart attack and stroke. Eat foods ...

  15. Niacin for cholesterol

    MedlinePlus

    ... this page, please enable JavaScript. Niacin is a B-vitamin. When taken as a prescription in larger doses, ... A.M. Editorial team. Related MedlinePlus Health Topics B Vitamins Cholesterol Browse the Encyclopedia A.D.A.M., ...

  16. Cholesterol, inflammasomes, and atherogenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plasma cholesterol levels have been strongly associated with atherogenesis, underscoring the role of lipid metabolism in defining cardiovascular disease risk. However, atherosclerotic plaque is highly dynamic and contains elements of both the innate and adaptive immune system that respond to the abe...

  17. Anti-cancer activity of the cholesterol exporter ABCA1 gene

    PubMed Central

    Smith, Bradley; Land, Hartmut

    2012-01-01

    Summary The ABCA1 protein mediates the transfer of cellular cholesterol across the plasma membrane to apolipoprotein A-I. Loss-of-function mutations in the ABCA1 gene induce Tangier disease and familial hypoalphalipoproteinemia, both cardio-vascular conditions characterized by abnormally low levels of serum cholesterol, increased cholesterol in macrophages and subsequent formation of vascular plaque. Increased intra-cellular cholesterol levels are also frequently found in cancer cells. Here we demonstrate anti-cancer activity of ABCA1 efflux function, which is compromised following inhibition of ABCA1 gene expression by oncogenic mutations or cancer-specific ABCA1 loss-of-function mutations. In concert with elevated cholesterol synthesis found in cancer cells, ABCA1 deficiency allows for increased mitochondrial cholesterol, inhibits release of mitochondrial cell death-promoting molecules and thus facilitates cancer cell survival, overall suggesting that elevated mitochondrial cholesterol is essential to the cancer phenotype. PMID:22981231

  18. Resveratrol Protects Rabbits Against Cholesterol Diet-Induced Hyperlipidaemia.

    PubMed

    Tanko, Y; Jimoh, A; Ahmed, A; Mohammed, A; Ayo, J O

    2016-01-01

    The excessive consumption of high cholesterol diet has been associated with an increased incidence oflipidaemia. Lipidaemia is enhanced by formation of oxidative stress, lipid peroxidation and hyperglycaemia. The aim ofthese experiments was to investigate the protective effect of resveratrol co-administered with cholesterol diet inducedhyperlipidaemia in rabbits. Thirty rabbits divided into six groups of five animal (group= 5) each: group 1 = normal control,group 2 = cholesterol diet/high fat diet group only (HFD), group 3 = resveratrol 200 mg/kg (R200), group 4 = resveratrol400 mg/kg (R400), group 5 = HFD + R200 and group 6 = HFD + R400. The normal group was fed with standard animalfeeds only; while the HFD groups were fed with standard animal feeds + cholesterol diet (10% Groundnut oil, 20%Groundnut mill and 2% cholesterol). Resveratrol-treated rabbits received resveratrol suspended in 10 g/Lcarboxymethylcellulose (CMC) and the control group received the vehicle only, CMC. The preparations were administeredfor 8 weeks of experimental protocol. At the end of the study period, the animals were sacrificed. Blood and plasma sampleswere collected. Serum evaluation of lipid profile such as total cholesterol (TC), triacylglycerol (Tg), low density lipoproteincholesterol (LDP-c) and high density lipoprotein cholesterol (HDL-c) were also assessed. The results obtained showsignificant (P < 0.05) decrease in total cholesterol (TC), Low density lipoprotein cholesterol (LDP-c), total triacylglyceroland an increase in high density lipoprotein cholesterol (HDL-c) in resveratrol treated groups compared to HFD group only.In conclusion, the findings indicated that Resveratrol may contain polar products able to lower plasma lipid concentrationsand might be beneficial in treatment of hyperlipidemia and atherosclerosis. PMID:27574767

  19. What's so special about cholesterol?

    PubMed

    Mouritsen, Ole G; Zuckermann, Martin J

    2004-11-01

    Cholesterol (or other higher sterols such as ergosterol and phytosterols) is universally present in large amounts (20-40 mol%) in eukaryotic plasma membranes, whereas it is universally absent in the membranes of prokaryotes. Cholesterol has a unique ability to increase lipid order in fluid membranes while maintaining fluidity and diffusion rates. Cholesterol imparts low permeability barriers to lipid membranes and provides for large mechanical coherence. A short topical review is given of these special properties of cholesterol in relation to the structure of membranes, with results drawn from a variety of theoretical and experimental studies. Particular focus is put on cholesterol's ability to promote a special membrane phase, the liquid-ordered phase, which is unique for cholesterol (and other higher sterols like ergosterol) and absent in membranes containing the cholesterol precursor lanosterol. Cholesterol's role in the formation of special membrane domains and so-called rafts is discussed. PMID:15726825

  20. Bile acid sequestrants for cholesterol

    MedlinePlus

    Bile acid sequestrants are medicines that help lower your LDL (bad) cholesterol . Too much cholesterol in your blood can ... block them. These medicines work by blocking bile acid in your stomach from being absorbed in your ...

  1. Randomized controlled trial of a nonpharmacologic cholesterol reduction program at the worksite.

    PubMed

    Bruno, R; Arnold, C; Jacobson, L; Winick, M; Wynder, E

    1983-07-01

    Under experimental clinical conditions diet modification has been shown to reduce serum cholesterol levels. This paper reports such a positive response to a nonpharmacologic, behavioral education program at the worksite. Employees at the New York Telephone Company corporate headquarters were assigned randomly to treatment and control groups. Treatment consisted of an 8-week group cholesterol reduction program conducted during employee lunch hours. It comprised a multiple-treatment approach--food behavior change techniques combined with nutrition education, physical activity planning, and self-management skills. The treatment group showed substantial change compared with the control group at the program's completion. Those treated displayed a significant 6.4% reduction in total serum cholesterol (266 mg% average at baseline) as compared with control subjects with a corresponding decrease in high-density lipoprotein levels. A significant increase in nutrition knowledge and moderate weight loss were also documented for this group. The magnitudes of a participant's baseline serum cholesterol level and his/her reduction in percentage of ideal body weight were positively and independently correlated with percentage changes in serum cholesterol levels. Over the same period, decreases in high-density lipoprotein levels and no changes in serum cholesterol, weight, and nutrition knowledge were observed for the control group. Overall, participants in the treatment program successfully reduced the coronary heart disease risk factors of elevated cholesterol and weight. Directions for future study are suggested. PMID:6622436

  2. Factors that affect postdialysis rebound in serum urea concentration, including the rate of dialysis: results from the HEMO Study.

    PubMed

    Daugirdas, John T; Greene, Tom; Depner, Thomas A; Leypoldt, John; Gotch, Frank; Schulman, Gerald; Star, Robert

    2004-01-01

    Previous studies have suggested that postdialysis urea rebound is related to K/V, the rate of dialysis, but a systematic analysis of factors that affect rebound has not been reported. With the use of 30-min and, in a subset, 60-min postdialysis samples, postdialysis urea rebound was measured to (1) determine how well previously proposed equations based on the rate of dialysis (K/V) predict rebound in a large sample of patients with varying characteristics, (2) determine whether other factors besides K/V affect rebound, and (3) estimate more precise values for coefficients in prediction equations for rebound. Rebound was calculated relative to both immediate and 20-s postdialysis samples to study early components of rebound unrelated to access recirculation. The equilibrated Kt/V (eKt/V) computed by fitting the two-pool variable volume model to the 30-min postdialysis sample agreed well with eKt/V based on the 60-min postdialysis sample. Using the pre-, post-, and 30-min postdialysis samples for 1245 patients with arteriovenous (AV) accesses, the median intercompartmental mass transfer coefficient (Kc) was 797 ml/min for rebound computed relative to the 20-s postdialysis samples and 592 ml/min relative to the immediate postdialysis samples. K/V was the strongest predictor of rebound among 22 factors considered. Other factors associated with greater rebound for 1331 patients using AV accesses or venous catheters included access type, black race, male gender, absence of congestive heart failure, greater age, ultrafiltration rate, and low predialysis or intradialysis systolic BP. Equations of the form eKt/V = single-pool Kt/V - B x (K/V) were fit to the data. With AV access, the optimum values for the slope term (B) were 0.39 and 0.46 (in h(-1)) for single-pool Kt/V calculated based on 20-s postdialysis or immediate postdialysis samples, respectively. For patients using venous catheters, the respective values for B were 0.22 and 0.29. Postdialysis urea rebound can be

  3. EHD1 regulates cholesterol homeostasis and lipid droplet storage

    PubMed Central

    Naslavsky, Naava; Rahajeng, Juliati; Rapaport, Debora; Horowitz, Mia; Caplan, Steve

    2007-01-01

    Endocytic transport is critical for the subcellular distribution of free cholesterol and the endocytic recycling compartment (ERC) is an important organelle that stores cholesterol and regulates its trafficking. The C-terminal EHD protein, EHD1, controls receptor recycling through the ERC and affects free cholesterol distribution in the cell. We utilized embryonic fibroblasts from EHD1 knockout mice (Ehd1-/-MEF) and SiRNA in normal MEF cells to assess the role of EHD1 in intracellular transport of cholesterol. Surprisingly, Ehd1-/-MEFs displayed reduced levels of esterified and free cholesterol, which returned to normal level upon re-introduction of wild-type, but not dysfunctional EHD1. Moreover, triglyceride and cholesterol storage organelles known as ‘lipid droplets’ were smaller in size in cells lacking EHD1, indicating that less esterified cholesterol and triglycerides were being stored. Decreased cellular cholesterol and reduced lipid droplet size in Ehd1-/-MEFs correlated with ineffectual cholesterol uptake via LDL receptor, suggesting involvement of EHD1 in LDL receptor internalization. PMID:17451652

  4. New horizons for cholesterol ester transfer protein inhibitors.

    PubMed

    Schwartz, Gregory G

    2012-02-01

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

  5. Does dietary vitamin E or C decrease egg yolk cholesterol?

    PubMed

    Mohiti-Asli, Maziar; Zaghari, Mojtaba

    2010-12-01

    An experiment was conducted to determine the effect of dietary vitamin E and C on serum metabolites, yolk cholesterol, egg quality, and performance of layer hens. One hundred sixty-eight commercial Hy-Line W-36 layer hens were randomly divided into seven groups and six replicates with four hens in each. Dietary treatments were introduced after the pre-experimental period (10 days) to adjust egg production. Treatments were levels of vitamin E or C (100, 200, and 400 mg/kg diet) supplementation to the basal diet for 4 weeks, whereas the control group received no supplementation. Egg production, egg weight, and feed consumption were recorded during the study. Shell thickness, Haugh unit score, yolk color, yolk weight, yolk cholesterol, and blood parameters were measured at the end of experiment. There was no significant effect of dietary vitamin E or C on hen performance. Egg yolk cholesterol concentrations decreased linearly by antioxidant vitamin supplementation (P < 0.01). Egg yolk cholesterol reduction did not have any negative effect on egg production rate. Antioxidants, especially vitamin C, increased serum glucose concentration (P < 0.05). Serum total cholesterol content did not change by vitamin supplementation but cholesterol in high-density lipoprotein (HDL-C) decreased and cholesterol in low-density lipoprotein (LDL-C) increased (P < 0.05), as dietary vitamin E or C supplementation increased in diets. These results are in conflict with the previous hypothesis that antioxidants have a role in LDL-C removal from the blood or increasing HDL-C. Vitamin E was more effective than vitamin C in this case and if these results are confirmed by further studies, they may result to revision in researchers' point of view about antioxidant especially in human medicine. PMID:20127202

  6. Cholesterol as a causative factor in Alzheimer's disease: a debatable hypothesis.

    PubMed

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

    2014-05-01

    High serum/plasma cholesterol levels have been suggested as a risk factor for Alzheimer's 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 (Ab) 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 amyloid precursor protein and Ab. The purpose of this review, therefore, was to examine the above-mentioned issues, discuss the pros and cons of the cholesterol-AD hypothesis, involvement of other lipids in the mevalonate pathway, and consider that AD may impact cholesterol homeostasis. PMID:24329875

  7. Implementation of a pilot school-site cholesterol reduction intervention.

    PubMed

    Resnicow, K; Orlandi, M A; Vaccaro, D; Wynder, E

    1989-02-01

    A school-based cholesterol reduction intervention was offered to primary grade students in two New York City public schools. Subjects were participating in the "Know Your Body" school health program which includes an annual cholesterol screening for all students. Students with total serum cholesterol values greater than 170 mg/dl were eligible for a workshop designed to teach students to identify the amount and type of fat and fiber in various foods and to recognize the negative health consequences of eating a diet high in cholesterol and saturated fat as well as the benefits of eating a diet high in complex carbohydrate and fiber. Thirty-four students completed the five-session behavioral group intervention. Following the workshop, mean total cholesterol for the 34 intervention participants fell 9.0% from baseline (196.9 mg/dl to 179.1 mg/dl). Cholesterol levels decreased 6.6% for a matched sample of comparison subjects (n = 118) participating only in the "Know Your Body" program. While several methodological limitations existed in this pilot study, the results suggest school-site cholesterol reduction interventions for high-risk individuals are feasible, cost-effective, and potentially efficacious. PMID:2538679

  8. Cholesterol Balance in Prion Diseases and Alzheimer’s Disease

    PubMed Central

    Hannaoui, Samia; Shim, Su Yeon; Cheng, Yo Ching; Corda, Erica; Gilch, Sabine

    2014-01-01

    Prion diseases are transmissible and fatal neurodegenerative disorders of humans and animals. They are characterized by the accumulation of PrPSc, an aberrantly folded isoform of the cellular prion protein PrPC, in the brains of affected individuals. PrPC is a cell surface glycoprotein attached to the outer leaflet of the plasma membrane by a glycosyl-phosphatidyl-inositol (GPI) anchor. Specifically, it is associated with lipid rafts, membrane microdomains enriched in cholesterol and sphinoglipids. It has been established that inhibition of endogenous cholesterol synthesis disturbs lipid raft association of PrPC and prevents PrPSc accumulation in neuronal cells. Additionally, prion conversion is reduced upon interference with cellular cholesterol uptake, endosomal export, or complexation at the plasma membrane. Altogether, these results demonstrate on the one hand the importance of cholesterol for prion propagation. On the other hand, growing evidence suggests that prion infection modulates neuronal cholesterol metabolism. Similar results were reported in Alzheimer’s disease (AD): whereas amyloid β peptide formation is influenced by cellular cholesterol, levels of cholesterol in the brains of affected individuals increase during the clinical course of the disease. In this review, we summarize commonalities of alterations in cholesterol homeostasis and discuss consequences for neuronal function and therapy of prion diseases and AD. PMID:25419621

  9. Understand Your Risk for High Cholesterol

    MedlinePlus

    ... or trans fats also increases the amount of LDL cholesterol in your blood. If high blood cholesterol runs ... may not be enough to help lower your LDL blood cholesterol. View an animation of cholesterol . More information: Women ...

  10. Overview of Cholesterol and Lipid Disorders

    MedlinePlus

    ... Cholesterol and Lipid Disorders Dyslipidemia Hypolipidemia Cholesterol and triglycerides are important fats (lipids) in the blood. Cholesterol ... needs, but it also obtains cholesterol from food. Triglycerides, which are contained in fat cells, can be ...

  11. Enteric lactoferrin attenuates the development of high-fat and high-cholesterol diet-induced hypercholesterolemia and atherosclerosis in Microminipigs.

    PubMed

    Morishita, Satoru; Kawaguchi, Hiroaki; Ono, Tomoji; Miura, Naoki; Murakoshi, Michiaki; Sugiyama, Keikichi; Kato, Hisanori; Tanimoto, Akihide; Nishino, Hoyoku

    2016-01-01

    Previously, we found that enteric lactoferrin (eLF) could reduce the visceral fat accumulation known to associate strongly with metabolic syndrome symptoms and consequently with an increased risk of atherosclerosis. In this study, the atherosclerosis-preventive potential of LF was assessed in a high-fat and high-cholesterol diet (HFCD)-induced hypercholesterolemia and atherosclerosis model using Microminipig™. Eight-week orally administered eLF remarkably reduced the HFCD-induced serum total and low-density lipoprotein cholesterol levels but not high-density lipoprotein cholesterol levels. A histological analysis of 15 arteries revealed that eLF systemically inhibited the development of atherosclerotic lesions. Pathway analysis using identified genes that characterized eLF administration in liver revealed significant changes in the steroid biosynthesis pathway (ssc00100) and all affected genes in this pathway were upregulated, suggesting that cholesterol synthesis inhibited by HFCD was recovered by eLF. In summary, eLF could potentially prevent the hypercholesterolemia and atherosclerosis through protecting homeostasis from HFCD-induced dysfunction of cholesterol metabolism. PMID:26549014

  12. A macadamia nut-rich diet reduces total and LDL-cholesterol in mildly hypercholesterolemic men and women.

    PubMed

    Griel, Amy E; Cao, Yumei; Bagshaw, Deborah D; Cifelli, Amy M; Holub, Bruce; Kris-Etherton, Penny M

    2008-04-01

    Epidemiologic studies and clinical trials have demonstrated that the unique fatty acid profile of nuts beneficially affects serum lipids/lipoproteins, reducing cardiovascular disease (CVD) risk. Nuts are low in SFA and high in PUFA and monounsaturated fatty acids (MUFA). Macadamia nuts are a rich source of MUFA. A randomized, crossover, controlled feeding study (5-wk diet periods) compared a Macadamia nut-rich diet [42.5 g (1.5 ounces)/8.79 MJ (2100 kcal)] [MAC; 33% total fat (7% SFA, 18% MUFA, 5% PUFA)] vs. an average American diet [AAD; 33% total fat (13% SFA, 11% MUFA, 5% PUFA)] on the lipid/lipoprotein profile of mildly hypercholesterolemic (n = 25; 15 female, 10 male) subjects. Serum concentrations of total cholesterol (TC) and LDL cholesterol (LDL-C) following the MAC (4.94 +/- 0.17 mmol/L, 3.14 +/- 0.14 mmol/L) were lower than the AAD (5.45 +/- 0.17 mmol/L, 3.44 +/- 0.14 mmol/L; P < 0.05). The serum non-HDL cholesterol (HDL-C) concentration and the ratios of TC:HDL-C and LDL-C:HDL-C were reduced following consumption of the MAC diet (3.83 +/- 0.17, 4.60 +/- 0.24, and 2.91 +/- 0.17, respectively) compared with the AAD (4.26 +/- 0.17, 4.89 +/- 0.24, and 3.09 +/- 0.18, respectively; P < 0.05). There was no change in serum triglyceride concentration. Thus, macadamia nuts can be included in a heart-healthy dietary pattern that reduces lipid/lipoprotein CVD risk factors. Nuts as an isocaloric substitute for high SFA foods increase the proportion of unsaturated fatty acids and decrease SFA, thereby lowering CVD risk. PMID:18356332

  13. Cholesterol modulates open probability and desensitization of NMDA receptors

    PubMed Central

    Korinek, Miloslav; Vyklicky, Vojtech; Borovska, Jirina; Lichnerova, Katarina; Kaniakova, Martina; Krausova, Barbora; Krusek, Jan; Balik, Ales; Smejkalova, Tereza; Horak, Martin; Vyklicky, Ladislav

    2015-01-01

    NMDA receptors (NMDARs) are glutamate-gated ion channels that mediate excitatory neurotransmission in the CNS. Although these receptors are in direct contact with plasma membrane, lipid–NMDAR interactions are little understood. In the present study, we aimed at characterizing the effect of cholesterol on the ionotropic glutamate receptors. Whole-cell current responses induced by fast application of NMDA in cultured rat cerebellar granule cells (CGCs) were almost abolished (reduced to 3%) and the relative degree of receptor desensitization was increased (by seven-fold) after acute cholesterol depletion by methyl-β-cyclodextrin. Both of these effects were fully reversible by cholesterol repletion. By contrast, the responses mediated by AMPA/kainate receptors were not affected by cholesterol depletion. Similar results were obtained in CGCs after chronic inhibition of cholesterol biosynthesis by simvastatin and acute enzymatic cholesterol degradation to 4-cholesten-3-one by cholesterol oxidase. Fluorescence anisotropy measurements showed that membrane fluidity increased after methyl-β-cyclodextrin pretreatment. However, no change in fluidity was observed after cholesterol enzymatic degradation, suggesting that the effect of cholesterol on NMDARs is not mediated by changes in membrane fluidity. Our data show that diminution of NMDAR responses by cholesterol depletion is the result of a reduction of the open probability, whereas the increase in receptor desensitization is the result of an increase in the rate constant of entry into the desensitized state. Surface NMDAR population, agonist affinity, single-channel conductance and open time were not altered in cholesterol-depleted CGCs. The results of our experiments show that cholesterol is a strong endogenous modulator of NMDARs. Key points NMDA receptors (NMDARs) are tetrameric cation channels permeable to calcium; they mediate excitatory synaptic transmission in the CNS and their excessive activation can lead to

  14. Cholesterol binding to ion channels

    PubMed Central

    Levitan, Irena; Singh, Dev K.; Rosenhouse-Dantsker, Avia

    2014-01-01

    Numerous studies demonstrated that membrane cholesterol is a major regulator of ion channel function. The goal of this review is to discuss significant advances that have been recently achieved in elucidating the mechanisms responsible for cholesterol regulation of ion channels. The first major insight that comes from growing number of studies that based on the sterol specificity of cholesterol effects, show that several types of ion channels (nAChR, Kir, BK, TRPV) are regulated by specific sterol-protein interactions. This conclusion is supported by demonstrating direct saturable binding of cholesterol to a bacterial Kir channel. The second major advance in the field is the identification of putative cholesterol binding sites in several types of ion channels. These include sites at locations associated with the well-known cholesterol binding motif CRAC and its reversed form CARC in nAChR, BK, and TRPV, as well as novel cholesterol binding regions in Kir channels. Notably, in the majority of these channels, cholesterol is suggested to interact mainly with hydrophobic residues in non-annular regions of the channels being embedded in between transmembrane protein helices. We also discuss how identification of putative cholesterol binding sites is an essential step to understand the mechanistic basis of cholesterol-induced channel regulation. Clearly, however, these are only the first few steps in obtaining a general understanding of cholesterol-ion channels interactions and their roles in cellular and organ functions. PMID:24616704

  15. Amniotic fluid and maternal serum levels of CA125 in pregnancies affected by Down syndrome: a re-evaluation of the role of CA125 in Down syndrome screening.

    PubMed

    Spencer, K; Muller, F; Aitken, D A

    1997-08-01

    In a study of amniotic fluid from 91 Down syndrome cases and 240 controls, we have shown that the median value of CA125 in pregnancies affected by Down syndrome on the whole reflects those observed in the maternal serum from 106 affected cases and 238 controls. The median MOM for CA125 in amniotic fluid from Down syndrome pregnancies was 1.04 and in maternal serum 1.06, neither value being significantly different from that for the control population. We confirm our previous observation that CA125 is not a marker of Down syndrome and conclude that CA125 has no role to play in Down syndrome screening. PMID:9267892

  16. Cholesterol-Lowering Probiotics as Potential Biotherapeutics for Metabolic Diseases

    PubMed Central

    Kumar, Manoj; Nagpal, Ravinder; Kumar, Rajesh; Hemalatha, R.; Verma, Vinod; Kumar, Ashok; Chakraborty, Chaitali; Singh, Birbal; Marotta, Francesco; Jain, Shalini; Yadav, Hariom

    2012-01-01

    Cardiovascular diseases are one of the major causes of deaths in adults in the western world. Elevated levels of certain blood lipids have been reported to be the principal cause of cardiovascular disease and other disabilities in developed countries. Several animal and clinical trials have shown a positive association between cholesterol levels and the risks of coronary heart disease. Current dietary strategies for the prevention of cardiovascular disease advocate adherence to low-fat/low-saturated-fat diets. Although there is no doubt that, in experimental conditions, low-fat diets offer an effective means of reducing blood cholesterol concentrations on a population basis, these appear to be less effective, largely due to poor compliance, attributed to low palatability and acceptability of these diets to the consumers. Due to the low consumer compliance, attempts have been made to identify other dietary components that can reduce blood cholesterol levels. Supplementation of diet with fermented dairy products or lactic acid bacteria containing dairy products has shown the potential to reduce serum cholesterol levels. Various approaches have been used to alleviate this issue, including the use of probiotics, especially Bifidobacterium spp. and Lactobacillus spp.. Probiotics, the living microorganisms that confer health benefits on the host when administered in adequate amounts, have received much attention on their proclaimed health benefits which include improvement in lactose intolerance, increase in natural resistance to infectious disease in gastrointestinal tract, suppression of cancer, antidiabetic, reduction in serum cholesterol level, and improved digestion. In addition, there are numerous reports on cholesterol removal ability of probiotics and their hypocholesterolemic effects. Several possible mechanisms for cholesterol removal by probiotics are assimilation of cholesterol by growing cells, binding of cholesterol to cellular surface, incorporation of

  17. Cholesterol modulates alkaline phosphatase activity of rat intestinal microvillus membranes.

    PubMed

    Brasitus, T A; Dahiya, R; Dudeja, P K; Bissonnette, B M

    1988-06-25

    Experiments were conducted, using a nonspecific lipid transfer protein, to vary the cholesterol/phospholipid molar ratio of rat proximal small intestinal microvillus membranes in order to assess the possible role of cholesterol in modulating enzymatic activities of this plasma membrane. Cholesterol/phospholipid molar ratios from 0.71 to 1.30 were produced from a normal value of 1.05 by incubation with the transfer protein and an excess of either phosphatidylcholine or cholesterol/phosphatidylcholine liposomes for 60 min at 37 degrees C. Cholesterol loading or depletion of the membranes was accompanied by a decrease or increase, respectively, in their lipid fluidity, as assessed by steady-state fluorescence polarization techniques using the lipid-soluble fluorophore 1,6-diphenyl-1,3,5-hexatriene. Increasing the cholesterol/phospholipid molar ratio also decreased alkaline phosphatase specific activity by approximately 20-30%, whereas decreasing this ratio increased this enzymatic activity by 20-30%. Sucrase, maltase, and lactase specific activities were not affected in these same preparations. Since the changes in alkaline phosphatase activity could be secondary to alterations in fluidity, cholesterol, or both, additional experiments were performed using benzyl alcohol, a known fluidizer. Benzyl alcohol (25 mM) restored the fluidity of cholesterol-enriched preparations to control levels, did not change the cholesterol/phospholipid molar ratio, and failed to alter alkaline phosphatase activity. These findings, therefore, indicate that alterations in the cholesterol content and cholesterol/phospholipid molar ratio of microvillus membranes can modulate alkaline phosphatase but not sucrase, maltase, or lactase activities. Moreover, membrane fluidity does not appear to be an important physiological regulator of these enzymatic activities. PMID:3379034

  18. [Inhibitory action of natural compounds of microbial origin on cholesterol metabolism].

    PubMed

    Fujioka, T

    1997-10-01

    1) Repeated administration of pravastatin significantly increased serum and liver cholesterol in rats. Hepatic LDL receptor activity was not changed and VLDL cholesterol secretion from the liver was increased. Net cholesterol synthesis in rat liver was increased after 7 days of repeated pravastatin administration. These results suggest that for rats, unlike other animals for which serum cholesterol is decreased, induced HMG-CoA reductase activity due to pravastatin treatment might overcome the inhibitory capability of pravastatin. 2) In the course of screening for squalene synthase inhibitors, novel zaragozic acids-F10863A, B, C and D-containing zaragozic acid D3 were isolated. F10863A was most potent and selectively inhibited cholesterol synthesis in freshly isolated rat hepatocytes among several cultured and isolated cells. It also showed in vivo serum cholesterol-lowering effects in hamsters and marmosets. However, the inhibition for squalene synthase proved to cause acidosis due to the accumulation of farnesol-derived dicarboxylic acids in urines. 3) A novel acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor, designated epi-cochlioquinone A, a stereoisomer of cochlioquinone A, which has been previously reported as a nematocidal agent, was isolated from the fermentation broth of Stachybotrys bisbyi. It inhibited in vivo cholesterol absorption in rats by 50% at 75 mg/kg. PMID:9503410

  19. Effects of Jamaican bitter yam (Dioscorea polygonoides) and diosgenin on blood and fecal cholesterol in rats.

    PubMed

    McKoy, Marsha-Lyn; Thomas, Peta-Gaye; Asemota, Helen; Omoruyi, Felix; Simon, Oswald

    2014-11-01

    A sapogenin-rich preparation from Jamaican bitter yam (Dioscorea polygonoides) has been shown to reduce blood cholesterol concentrations in hypercholesterolemic rats and mice. Also, diosgenin supplementation has been reported to have antilipemic effects in several animal species. We investigated potential mechanisms of the lipid-lowering actions of bitter yam and also whether the actions were mediated by diosgenin. Sprague-Dawley rats were fed a hypercholesterolemic diet (4% cholesterol) alone or with 5% bitter yam or 1% diosgenin supplementation for 6 weeks. The control group was fed normal rat chow. The serum lipid profile, fecal cholesterol concentration, and serum lipase activity were assessed at the end of the period. The induction of hypercholesterolemia was inhibited by coadministration of 5% bitter yam or 1% diosgenin in the diet. Serum lipid profiles were similar in rats fed bitter yam or diosgenin. The fecal cholesterol concentration was significantly (P < .01) higher in rats fed diosgenin compared to the cholesterol group. However, there was no corresponding elevation in the group fed bitter yam. Administration of bitter yam or diosgenin supplement significantly increased (P < .01) the serum lipase activity compared to the normal control and cholesterol groups. The cholesterol-supplemented diet inhibited normal gain in body weight over the period. This action was potentiated by diosgenin. The effects of the respective supplements on body weight were not completely explained by food consumption. Supplementation of the diet with Jamaican bitter yam may be therapeutically beneficial in the management of hypercholesterolemia. PMID:25058383

  20. Influence of psyllium preparations on plasma and liver lipids of cholesterol-fed rats.

    PubMed

    Kritchevsky, D; Tepper, S A; Klurfeld, D M

    1995-01-01

    Rats were fed a semi purified diet containing 0.5% cholesterol and 10% fiber (cellulose, pectin, psyllium seed and defatted psyllium husk). One additional group of rats was fed cholesterol (0.5%) as part of a fiber-free diet and another was fed the fiber free diet without cholesterol. Cellulose had virtually no effect on serum or liver lipids. Pectin had a lipid lowering effect. Psyllium seed exerted an effect on total serum cholesterol equal to that of pectin but gave higher levels of HDL-cholesterol. The effects of psyllium seed on liver lipids were more pronounced than those of pectin. Defatted psyllium husk feeding virtually normalized liver size and serum triglyceride levels and produced lower serum total cholesterol levels and higher HDL-cholesterol than observed in normal controls. Defatted psyllium husk feeding also yielded liver lipid values which were in the normal range. Fecal wet and dry weights were significantly higher in rats fed either psyllium preparation. PMID:8833230

  1. Influence of cholesterol and ceramide VI on the structure of multilamellar lipid membranes at water exchange

    SciTech Connect

    Ryabova, N. Yu. Kiselev, M. A.; Balagurov, A. M.

    2010-05-15

    The structural changes in the multilamellar lipid membranes of dipalmitoylphosphatidylcholine (DPPC)/cholesterol and DPPC/ceramide VI binary systems during hydration and dehydration have been studied by neutron diffraction. The effect of cholesterol and ceramide on the kinetics of water exchange in DPPC membranes is characterized. Compared to pure DPPC, membranes of binary systems swell faster during hydration (with a characteristic time of {approx}30 min). Both compounds, ceramide VI and cholesterol, similarly affect the hydration of DPPC membranes, increasing the repeat distance due to the bilayer growth. However, in contrast to cholesterol, ceramide significantly reduces the thickness of the membrane water layer. The introduction of cholesterol into a DPPC membrane slows down the change in the parameters of the bilayer internal structure during dehydration. In the DPPC/ceramide VI/cholesterol ternary system (with a molar cholesterol concentration of 40%), cholesterol is partially released from the lamellar membrane structure into the crystalline phase.

  2. Cholesterol efflux is LXRα isoform-dependent in human macrophages

    PubMed Central

    2014-01-01

    Background The nuclear receptor liver X receptor (LXR) has two isoforms: LXRα and LXRβ. LXR activation promotes cholesterol efflux in macrophages, but the relative importance of each LXR isoform in mediating cholesterol efflux remains elusive. Methods We evaluated the ability of different doses of LXRs agonist T0901317 to affect cholesterol efflux in human macrophages and its relationship with mRNA and protein levels of several well-characterized proteins involved in cholesterol efflux, including ABCA1, ABCG1, SR-BI, LXRβ and LXRα, using quantitative real-time PCR, Western blotting, and siRNA techniques. Results Here we show that LXRα rather than LXRβ sustains baseline cholesterol efflux in human blood-derived macrophages. Treatment of human macrophages with a non-isoform-specific LXR agonist T0901317 substantially increased HDL- and apoA-I-mediated cholesterol efflux, which was associated with increased mRNA and protein expression levels of ABCA1, ABCG1, SR-BI, LXRα and LXRβ. The siRNA- mediated silencing of LXRα, but not LXRβ significantly reduced the protein levels of ABCA1,ABCG1, and SR-BI as wellas HDL- and ApoA1-mediated cholesterol in human macrophages. Conclusions These findings imply that LXRα- rather than LXRβ- specific agonists may promote reverse cholesterol transport in humans. PMID:24996838

  3. High Cholesterol: Cholesterol-Lowering Medicines

    MedlinePlus

    ... is called a "drug-drug interaction." Vitamins and herbal supplements can also affect the way your body processes ... over-the-counter and prescription medicines, vitamins and herbal supplements that you are taking. Also, talk to your ...

  4. Female offspring of rat dams fed low boron diets during pregnancy and lactation exhibit signs of the metabolic syndrome during early adulthood: increased body weight, & serum triglycerides and total cholesterol concentrations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To expand on reports from this laboratory that low dietary boron may affect energy substrate utilization, we determined whether low dietary boron during early development promotes manifestation of the metabolic syndrome in adult offspring. Sprague-Dawley dams were fed either a boron-low (BL; ~0.1 mg...

  5. Female offspring of rat dams fed low boron diets during pregnancy and lactation exhibit signs of the metabolic syndrome during early adulthood: increased body weight, and serum triglycerides and total cholesterol concentratio

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To expand on reports from this laboratory that low dietary boron may affect energy substrate utilization, we determined whether low dietary boron during early development promotes manifestation of the metabolic syndrome in adult offspring. Sprague-Dawley dams were fed either a boron-low (BL;~0.1 mg ...

  6. Novel Replication-Competent Circular DNA Molecules from Healthy Cattle Serum and Milk and Multiple Sclerosis-Affected Human Brain Tissue

    PubMed Central

    Whitley, Corinna; Gunst, Karin; Müller, Hermann; Funk, Mathis; zur Hausen, Harald

    2014-01-01

    Epidemiological data point to the involvement of a cow milk factor in the etiology of multiple sclerosis (MS). Eleven circular DNA molecules closely related to transmissible spongiform encephalopathy (TSE)-associated isolate Sphinx 1.76 were isolated from healthy cattle serum, cow milk, and serum and brain tissue from MS patients. PMID:25169859

  7. Novel replication-competent circular DNA molecules from healthy cattle serum and milk and multiple sclerosis-affected human brain tissue.

    PubMed

    Whitley, Corinna; Gunst, Karin; Müller, Hermann; Funk, Mathis; Zur Hausen, Harald; de Villiers, Ethel-Michele

    2014-01-01

    Epidemiological data point to the involvement of a cow milk factor in the etiology of multiple sclerosis (MS). Eleven circular DNA molecules closely related to transmissible spongiform encephalopathy (TSE)-associated isolate Sphinx 1.76 were isolated from healthy cattle serum, cow milk, and serum and brain tissue from MS patients. PMID:25169859

  8. Comparison of biosensors based on entrapment of cholesterol oxidase and cholesterol esterase in electropolymerized films of polypyrrole and diaminonaphthalene derivatives for amperometric determination of cholesterol.

    PubMed

    Vidal, J C; Garcia-Ruiz, E; Espuelas, J; Aramendia, T; Castillo, J R

    2003-09-01

    Cholesterol amperometric biosensors constructed with enzymes entrapped in electropolymerized layers of polypyrrole and poly-naphthalene derivative polymers are compared. The biosensors are based on entrapment of cholesterol oxidase and/or cholesterol esterase in monolayer or multilayer films electrochemically synthesised from pyrrole, 1,8-diaminonaphthalene (1,8-DAN), and 1,5-diaminonaphthalene (1,5-DAN) monomers. Seven configurations were assayed and compared, and different analytical properties were obtained depending on the kind of polymer and the arrangement of the layers. The selectivity properties were evaluated for the different monolayer and bilayer configurations proposed as a function of the film permeation factor. All the steps involved in the preparation of the biosensors and determination of cholesterol were carried out in a flow system. Sensitivity and selectivity depend greatly on hydrophobicity, permeability, compactness, thickness, and the kind of the polymer used. In some cases a protective outer layer of non-conducting poly( o-phenylenediamine) polymer improves the analytical characteristics of the biosensor. A comparative study was made of the analytical performance of each of the configurations developed. The biosensors were also applied to the flow-injection determination of cholesterol in a synthetic serum. PMID:12923606

  9. Oat Bran as a Cholesterol-Reducing Dietary Adjunct in a Young, Healthy Population

    PubMed Central

    Gold, Kurt V.; Davidson, Dennis M.

    1988-01-01

    In a study to examine the effects of dietary oat bran on serum lipids, subjects who ate two oat bran muffins a day for 28 days showed a 5.3% reduction in serum total cholesterol and an 8.7% reduction in low-density-lipoprotein-cholesterol levels, while no changes were noted in subjects consuming wheat or mixed wheat and oat bran muffins. Similarly, those who ingested oat bran muffins showed an 8.3% reduction in serum triglyceride values as contrasted with an overall increase of 6.4% in the other groups combined. These findings suggest that oat bran taken daily can significantly lower serum cholesterol and triglyceride levels in a young, healthy population. PMID:2834883

  10. Cholesterol-modulating agents kill acute myeloid leukemia cells and sensitize them to therapeutics by blocking adaptive cholesterol responses.

    PubMed

    Li, Henry Y; Appelbaum, Frederick R; Willman, Cheryl L; Zager, Richard A; Banker, Deborah E

    2003-05-01

    The mevalonate pathway produces many critical substances in cells, including sterols essential for membrane structure and isoprenoids vital to the function of many membrane proteins. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is a rate-limiting enzyme in the mevalonate pathway. Because cholesterol is a product of this pathway, HMG-CoA reductase inhibitors (statins) are used to treat hypercholesterolemia. Statins are also toxic to several malignancies, including acute myeloid leukemia (AML). Although this toxicity has been attributed to the inhibition of Ras/Rho isoprenylation, we have previously shown that statin toxicity in primary AML cells (AMLs) does not correlate with Ras isoprenylation or with activating Ras mutations. In other studies, we have shown that hypoxic and oxidant injuries induce cholesterol increments in renal tubule cells and that statins sensitize these cells to injury by blocking protective cholesterol responses. We now demonstrate that exposing particular AMLs to radiochemotherapy induces much greater cellular cholesterol increments than those seen in similarly treated normal bone marrow. Treatment of these AMLs with mevastatin or zaragozic acid (which inhibits cholesterol synthesis but not isoprenoid synthesis) attenuates the cholesterol increments and sensitizes cells to radiochemotherapy. The extent of toxicity is affected by the availability of extracellular lipoproteins, further suggesting that cellular cholesterol is critical to cell survival in particular AMLs. Because zaragozic acid does not inhibit isoprenoid synthesis, these data suggest that cholesterol modulation is an important mechanism whereby statins exert toxic effects on some AMLs and that cholesterol modulators may improve therapeutic ratios in AML by impacting cholesterol-dependent cytoresistance. PMID:12506040

  11. Squalene synthase, a determinant of Raft-associated cholesterol and modulator of cancer cell proliferation.

    PubMed

    Brusselmans, Koen; Timmermans, Leen; Van de Sande, Tine; Van Veldhoven, Paul P; Guan, Guimin; Shechter, Ishaiahu; Claessens, Frank; Verhoeven, Guido; Swinnen, Johannes V

    2007-06-29

    Several cues for cell proliferation, migration, and survival are transmitted through lipid rafts, membrane microdomains enriched in sphingolipids and cholesterol. Cells obtain cholesterol from the circulation but can also synthesize cholesterol de novo through the mevalonate/isoprenoid pathway. This pathway, however, has several branches and also produces non-sterol isoprenoids. Squalene synthase (SQS) is the enzyme that determines the switch toward sterol biosynthesis. Here we demonstrate that in prostate cancer cells SQS expression is enhanced by androgens, channeling intermediates of the mevalonate/isoprenoid pathway toward cholesterol synthesis. Interestingly, the resulting increase in de novo synthesis of cholesterol mainly affects the cholesterol content of lipid rafts, while leaving non-raft cholesterol levels unaffected. Conversely, RNA interference-mediated SQS inhibition results in a decrease of raft-associated cholesterol. These data show that SQS activity and de novo cholesterol synthesis are determinants of membrane microdomain-associated cholesterol in cancer cells. Remarkably, SQS knock down also attenuates proliferation and induces death of prostate cancer cells. Similar effects are observed when cancer cells are treated with the chemical SQS inhibitor zaragozic acid A. Importantly, although the anti-tumor effect of statins has previously been attributed to inhibition of protein isoprenylation, the present study shows that specific inhibition of the cholesterol biosynthesis branch of the mevalonate/isoprenoid pathway also induces cancer cell death. These findings significantly underscore the importance of de novo cholesterol synthesis for cancer cell biology and suggest that SQS is a potential novel target for antineoplastic intervention. PMID:17483544

  12. Modulation of endothelial inward-rectifier K+ current by optical isomers of cholesterol.

    PubMed Central

    Romanenko, Victor G; Rothblat, George H; Levitan, Irena

    2002-01-01

    Membrane potential of aortic endothelial cells under resting conditions is dominated by inward-rectifier K(+) channels belonging to the Kir 2 family. Regulation of endothelial Kir by membrane cholesterol was studied in bovine aortic endothelial cells by altering the sterol composition of the cell membrane. Our results show that enriching the cells with cholesterol decreases the Kir current density, whereas depleting the cells of cholesterol increases the density of the current. The dependence of the Kir current density on the level of cellular cholesterol fits a sigmoid curve with the highest sensitivity of the Kir current at normal physiological levels of cholesterol. To investigate the mechanism of Kir regulation by cholesterol, endogenous cholesterol was substituted by its optical isomer, epicholesterol. Substitution of approximately 50% of cholesterol by epicholesterol results in an early and significant increase in the Kir current density. Furthermore, substitution of cholesterol by epicholesterol has a stronger facilitative effect on the current than cholesterol depletion. Neither single channel properties nor membrane capacitance were significantly affected by the changes in the membrane sterol composition. These results suggest that 1) cholesterol modulates cellular K(+) conductance by changing the number of the active channels and 2) that specific cholesterol-protein interactions are critical for the regulation of endothelial Kir. PMID:12496090

  13. The macrophage and its related cholesterol efflux as a HDL function index in atherosclerosis.

    PubMed

    Yamamoto, Suguru; Narita, Ichiei; Kotani, Kazuhiko

    2016-06-01

    The macrophage and its related cholesterol efflux are considered to be a key player in atherosclerotic formation in relation to the function of high-density lipoprotein (HDL). The HDL function can be evaluated by the reaction between lipid-loaded macrophages and lipid-acceptors in the HDL fraction from the plasma, apolipoprotein B-depleted serum, and/or whole serum/plasma. Recent studies have reported that an impaired cholesterol efflux of HDL is observed in patients with cardiometabolic diseases, such as dyslipidemia, diabetes mellitus, and chronic kidney disease. A population-based cohort study has reported an inverse association between the cholesterol efflux capacity of HDL and the incidence of atherosclerotic disease, regardless of the serum HDL-cholesterol level. Moreover, in this paper, when we summarized several clinical interventional studies of statin treatment that examined cholesterol efflux, a potential increase in the efflux in patients treated with statins was implied. However, the effect was not fully defined in the current situation because of the small sample sizes, lack of a unified protocol for measuring the efflux, and short-term intervention periods without cardiovascular outcomes in available studies. Further investigation is necessary to determine the effect of drugs on cholesterol efflux. With additional advanced studies, cholesterol efflux is a promising laboratory index to understand the HDL function. PMID:27087419

  14. Epigenetic regulation of cholesterol homeostasis

    PubMed Central

    Meaney, Steve

    2014-01-01

    Although best known as a risk factor for cardiovascular disease, cholesterol is a vital component of all mammalian cells. In addition to key structural roles, cholesterol is a vital biochemical precursor for numerous biologically important compounds including oxysterols and bile acids, as well as acting as an activator of critical morphogenic systems (e.g., the Hedgehog system). A variety of sophisticated regulatory mechanisms interact to coordinate the overall level of cholesterol in cells, tissues and the entire organism. Accumulating evidence indicates that in additional to the more “traditional” regulatory schemes, cholesterol homeostasis is also under the control of epigenetic mechanisms such as histone acetylation and DNA methylation. The available evidence supporting a role for these mechanisms in the control of cholesterol synthesis, elimination, transport and storage are the focus of this review. PMID:25309573

  15. Cholesterol - what to ask your doctor

    MedlinePlus

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

  16. What Do My Cholesterol Levels Mean?

    MedlinePlus

    ... Tools & Resources Stroke More What Do My Cholesterol Levels Mean? Updated:Mar 22,2016 High cholesterol can ... a fasting “lipoprotein profile” to measure your cholesterol levels. It assesses several types of fat in the ...

  17. Relation between high density lipoprotein cholesterol and coronary artery disease in asymptomatic men

    SciTech Connect

    Uhl, G.S.; Troxler, R.G.; Hickman, J.R. Jr.; Clark, D.

    1981-11-01

    The well established inverse relation of high density lipoprotein cholesterol (HDL) and the risk of coronary artery disease was tested in a cross-sectional group of 572 asymptomatic aircrew members who were being screened for risk of coronary artery disease. A battery of tests was performed, including determinations of fasting serum cholesterol, HDL cholesterol and triglycerides and performance of a maximal symptom-limited exercise tolerance test. Of the 572 patients, 132 also had an abnormal S-T segment response to exercise testing or were otherwise believed to have an increased risk of organic heart disease and subsequently underwent coronary angiography. Significant coronary artery disease was found in 16 men and minimal or subcritical coronary disease in 14; coronary angiograms were normal in the remaining 102 men. The remaining 440 men, who were believed to have a 1 percent chance of having coronary artery disease by sequential testing of risk factors and treadmill testing, had a mean cholesterol level of 213 mg/100 ml, a mean HDL cholesterol of 51 mg/100 ml and a mean cholesterol/HDL ratio of 4.4. The mean values of cholesterol, HDL cholesterol and cholesterol/HDL cholesterol did not differ significantly in men with normal angiographic finding and those with subcritical coronary disease. However, 14 of 16 men with coronary artery disease had a cholesterol/HDL ratio of 6.0 or more whereas only 4 men with normal coronary arteries had a ratio of 6.0 or more. Of the classical coronary risk factors evaluated, the cholesterol/HDL ratio of 6.0 or more had the highest odds ratio (172:1). It appears that determination of HDL cholesterol level helps to identify asymptomatic persons with a greater risk of having coronary artery disease.

  18. Effects of dietary conjugated linoleic acid on the fatty acid profile and cholesterol content of egg yolks from different breeds of layers.

    PubMed

    Yin, J D; Shang, X G; Li, D F; Wang, F L; Guan, Y F; Wang, Z Y

    2008-02-01

    Brown Dwarf hens and White Leghorn hens were fed corn- and soybean meal-based diets containing 0, 2.5, or 5.0% conjugated linoleic acid (CLA) for 56 d to explore the effects of dietary CLA on the fatty acid profile and cholesterol content of egg yolks from laying hens of different breeds. Four hens were placed in 1 cage, and 3 cages were grouped as 1 replicate, resulting in 6 replicates per treatment. After feeding the experimental diets for 11 d, eggs were collected to determine the fatty acid composition of the egg yolks. From d 54 to 56, eggs were collected to measure the cholesterol content of yolks, and on d 56, a hen was selected randomly from each replicate and bled to determine the cholesterol content in plasma. There was a significant effect of layer breed on layer performance and egg composition. Concentrations of stearic, arachidonic, and docosahexaenoic acids were higher in the yolks of Brown Dwarf hens than in those of White Leghorn hens. Enrichment of cis-11, trans-13 was higher in the yolks of White Leghorns, but cis-10, cis-12 was higher in those of Brown Dwarf hens. In contrast, feed intake and egg weight, as well as yolk weight and its ratio to egg, were decreased by the 5% dietary CLA treatment. Egg production and feed efficiency were not affected by dietary CLA. Concentrations of total CLA and CLA isomers in the yolk lipids increased (P < 0.01) with increasing dietary CLA. Furthermore, yolk cholesterol was increased with increasing dietary CLA (P < 0.01), but this was significantly decreased in Brown Dwarf hens (P < 0.01) by feeding 2.5% CLA. There was no apparent correlation between yolk cholesterol content and serum cholesterol content. In conclusion, Brown Dwarf layers had the breed-specific characteristics of enrichment of CLA isomers and fatty acids in yolk lipids in response to dietary CLA. PMID:18212371

  19. Cholesterol level in non-insertional Achilles tendonopathy.

    PubMed

    Singh, Dishan

    2015-12-01

    Familial hypercholesterolaemia is an autosomal dominant disease, with a prevalence of 1 in 500, where lipid deposits occur in the skin, tendons (particularly Achilles tendon) and arteries. It has a high risk of early coronary artery disease and mortality but is treatable with cholesterol lowering strategies if patients are diagnosed early. Studies in patients attending lipid clinics have shown that half the patients may have suffered from Achilles tendon symptoms 20 years earlier and it has been proposed that all patients presenting with Achilles tendon pain should have a serum cholesterol test. All consecutive patients seen in an adult foot and ankle clinic with non-insertional Achilles tendonopathy between April 2012 and March 2014 had their serum cholesterol measured. Only one patient in 83 (p=0.19) was diagnosed with heterozygous familial hypercholesterolaemia but 3 relatives of the proband patient were also diagnosed by cascade testing. Measurement of cholesterol in all patients presenting with achillodynia does not seem to be justified but the literature suggests that it should probably be considered in patients with bilateral extensive disease or those who give a history of intermittent episodes of severe pain lasting a few days. PMID:26275912

  20. Serum Chemerin Levels Are Associated with Abdominal Visceral Fat in Type 2 Diabetes

    PubMed Central

    Kim, Chei Won

    2016-01-01

    Chemerin is a recently identified adipokine suggested to play a role in obesity and its metabolic complications. The relationship between visceral obesity and serum chemerin levels in type 2 diabetes (T2DM) is unknown and may differ from that of subjects without diabetes. Therefore, we evaluated whether serum chemerin was associated with visceral abdominal obesity in patients with T2DM. A total of 218 Korean patients with T2DM were enrolled and metabolic parameters, abdominal visceral and subcutaneous fat areas, and serum chemerin levels were measured. Serum chemerin level showed positive correlation with fasting insulin, HOMA-IR, serum triglyceride, serum creatinine, urine albumin/creatinine ratio, high-sensitivity C-reactive protein (hsCRP), fibrinogen, abdominal visceral fat area, visceral to subcutaneous fat area ratio, and negatively correlation with high density lipoprotein cholesterol and creatinine clearance (CCr) after adjusting for age, gender and body mass index. Multiple linear stepwise regression analysis showed that abdominal visceral fat area (β = 0.001, P < 0.001), serum triglyceride (β = 0.001, P < 0.001), CCr (β = -0.003, P = 0.001), hsCRP (β = 0.157, P = 0.001), fibrinogen (β = 0.001, P < 0.001) and BMI (β = 0.02, P = 0.008) independently affected log transformed serum chemerin levels. Higher serum chemerin level was associated with higher level of abdominal visceral fat area, serum triglyceride, hsCRP and fibrinogen and lower level of CCr in patients with T2DM. Serum chemerin may be used as a biomarker of visceral adiposity and chemerin may play a role in inflammation, decreased renal function, and increased cardiovascular risk in T2DM. PMID:27247502

  1. Serum Chemerin Levels Are Associated with Abdominal Visceral Fat in Type 2 Diabetes.

    PubMed

    Han, Juyoung; Kim, So Hun; Suh, Young Ju; Lim, Hyun Ae; Shin, Heekyoung; Cho, Soon Gu; Kim, Chei Won; Lee, Seung Youn; Lee, Dae Hyung; Hong, Seongbin; Kim, Yong Seong; Nam, Moon-Suk

    2016-06-01

    Chemerin is a recently identified adipokine suggested to play a role in obesity and its metabolic complications. The relationship between visceral obesity and serum chemerin levels in type 2 diabetes (T2DM) is unknown and may differ from that of subjects without diabetes. Therefore, we evaluated whether serum chemerin was associated with visceral abdominal obesity in patients with T2DM. A total of 218 Korean patients with T2DM were enrolled and metabolic parameters, abdominal visceral and subcutaneous fat areas, and serum chemerin levels were measured. Serum chemerin level showed positive correlation with fasting insulin, HOMA-IR, serum triglyceride, serum creatinine, urine albumin/creatinine ratio, high-sensitivity C-reactive protein (hsCRP), fibrinogen, abdominal visceral fat area, visceral to subcutaneous fat area ratio, and negatively correlation with high density lipoprotein cholesterol and creatinine clearance (CCr) after adjusting for age, gender and body mass index. Multiple linear stepwise regression analysis showed that abdominal visceral fat area (β = 0.001, P < 0.001), serum triglyceride (β = 0.001, P < 0.001), CCr (β = -0.003, P = 0.001), hsCRP (β = 0.157, P = 0.001), fibrinogen (β = 0.001, P < 0.001) and BMI (β = 0.02, P = 0.008) independently affected log transformed serum chemerin levels. Higher serum chemerin level was associated with higher level of abdominal visceral fat area, serum triglyceride, hsCRP and fibrinogen and lower level of CCr in patients with T2DM. Serum chemerin may be used as a biomarker of visceral adiposity and chemerin may play a role in inflammation, decreased renal function, and increased cardiovascular risk in T2DM. PMID:27247502

  2. In vitro determination of the solubility limit of cholesterol in phospholipid bilayers.

    PubMed

    Epand, Richard M; Bach, Diana; Wachtel, Ellen

    2016-09-01

    Cholesterol has limited solubility in phospholipid bilayers. The solubility limit is strongly dependent on the nature of the lipid with which the cholesterol is mixed while properties of the crystals formed can be modified by phospholipid-cholesterol interactions. In this review we summarize the various methods that have been developed to prepare hydrated mixtures of cholesterol and phospholipid. We point out some of the factors that determine the form adopted when cholesterol crystallizes in such mixtures, i.e. two- or three-dimensional, monohydrate or anhydrous. These differences can greatly affect the ability to experimentally detect the presence of these crystals in a membrane. Several methods for detecting cholesterol crystals are discussed and compared including DSC, X-ray and GIXRD diffraction methods, NMR and EPR spectroscopy. The importance of the history of the sample in determining the amount and nature of the cholesterol crystals formed is emphasized. PMID:27370110

  3. Lateral organization of cholesterol molecules in lipid-cholesterol assemblies.

    SciTech Connect

    Singh, Rajiv R. P.; Slepoy, Alexander; Sengupta, Pinaki; Cox, Daniel L.

    2005-05-01

    We present results of an off-lattice simulation of a two-component planar system, as a model for lateral organization of cholesterol molecules in lipid-cholesterol assemblies. We explore the existence of 'superlattice' structures even in fluid systems, in the absence of an underlying translational long-range order, and study their coupling to hexatic or bond-orientational order. We discuss our results in context of geometric superlattice theories and 'condensation complexes' in understanding a variety of experiments in artificial lipid-cholesterol assemblies.

  4. SERUM LIPID PROFILE IN SUICIDE ATTEMPTERS

    PubMed Central

    Verma, Sandeep; Trivedi, J.K.; Singh, H.; Dalal, P.K.; Asthana, O.P.; Srivastava, J.S.; Mishra, Rakesh; Ramakant; Sinha, P.K.

    1999-01-01

    Practical difficulties associated with assessment of central parameters necessitates the development of peripheral markers of suicidal risk. Recent research suggest that serum lipid profile may be a useful indicator of suicidal behaviour. Serum lipid profiles of forty suicide attempters were compared with forty age, sex and BMI matched controls. Total serum cholesterol, serum Triglyceride, LDL levels and HDL levels were found to be lower in suicide attempters but were not statistically significant. Statistically significant negative con-elation was seen between risk-rescue score and above mentioned parameters. No statitically significant difference was observed when various diagnostic break-up groups of patients were compared. PMID:21430801

  5. Reductions in Serum Lipids with a 4-year Decline in Serum Perfluorooctanoic Acid and Perfluorooctanesulfonic Acid

    PubMed Central

    Fitz-Simon, Nicola; Fletcher, Tony; Luster, Michael I.; Steenland, Kyle; Calafat, Antonia M.; Kato, Kayoko; Armstrong, Ben

    2016-01-01

    Background Several epidemiological cross-sectional studies have found positive associations between serum concentrations of lipids and perfluorooctanoic acid (PFOA, or C8). A longitudinal study should be less susceptible to biases from uncontrolled confounding or reverse causality. Methods We investigated the association between within-individual changes in serum PFOA and perfluorooctanesulfonic acid (PFOS) and changes in serum lipid levels (low-density lipoprotein [LDL] cholesterol, high-density lipoprotein cholesterol, total cholesterol, and triglycerides) over a 4.4-year period. The study population consisted of 560 adults living in parts of Ohio and West Virginia where public drinking water had been contaminated with PFOA. They had participated in a cross-sectional study in 2005–2006, and were followed up in 2010, by which time exposure to PFOA had been substantially reduced. Results Overall serum concentrations of PFOA and PFOS fell by half from initial geometric means of 74.8 and 18.5 ng/mL, respectively, with little corresponding change in LDL cholesterol (mean increase 1.8%, standard deviation 26.6%). However, there was a tendency for people with greater declines in serum PFOA or PFOS to have greater LDL decrease. For a person whose serum PFOA fell by half, the predicted fall in LDL cholesterol was 3.6% (95% confidence interval = 1.5–5.7%). The association with a decline in PFOS was even stronger, with a 5% decrease in LDL (2.5–7.4%). Conclusions Our findings from this longitudinal study support previous evidence from cross-sectional studies of positive associations between PFOA and PFOS in serum and LDL cholesterol. PMID:23685825

  6. Serum susceptibility of bovine pasteurellas.

    PubMed Central

    Blau, K A; Ward, A C; Prieur, D J; Corbeil, L B

    1987-01-01

    In this study, the serum sensitivity of 23 P. haemolytica isolates and 18 P. multocida isolates was determined by incubating dilutions of bacteria with equal volumes of fresh or heat-inactivated bovine serum for one, two, or three hours. Clinical isolates of both Pasteurella species were resistant to serum, whereas isolates from asymptomatic cattle varied in serum susceptibility. The classical pathway of complement appeared to be the principal means of complement mediated killing as detected by incubation in the presence or absence of EGTA-MgCl2. Lyzozyme and iron saturation of serum did not greatly affect serum susceptibility with either of the Pasteurella species. PMID:3300919

  7. Sensitivity of cholecystokinin receptors to membrane cholesterol content

    PubMed Central

    Desai, Aditya J.; Miller, Laurence J.

    2012-01-01

    Cholesterol represents a structurally and functionally important component of the eukaryotic cell membrane, where it increases lipid order, affects permeability, and influences the lateral mobility and conformation of membrane proteins. Several G protein-coupled receptors have been shown to be affected by the cholesterol content of the membrane, with functional impact on their ligand binding and signal transduction characteristics. The effects of cholesterol can be mediated directly by specific molecular interactions with the receptor and/or indirectly by altering the physical properties of the membrane. This review focuses on the importance and differential effects of membrane cholesterol on the activity of cholecystokinin (CCK) receptors. The type 1 CCK receptor is quite sensitive to its cholesterol environment, while the type 2 CCK receptor is not. The possible structural basis for this differential impact is explored and the implications of pathological states, such as metabolic syndrome, in which membrane cholesterol may be increased and CCK1R function may be abnormal are discussed. This is believed to have substantial potential importance for the development of drugs targeting the CCK receptor. PMID:23087674

  8. Vitamin D-fortified milk achieves the targeted serum 25-hydroxyvitamin D concentration without affecting that of parathyroid hormone in New Zealand toddlers.

    PubMed

    Houghton, Lisa A; Gray, Andrew R; Szymlek-Gay, Ewa A; Heath, Anne-Louise M; Ferguson, Elaine L

    2011-10-01

    For young children, the level of vitamin D required to ensure that most achieve targeted serum 25-hydroxyvitamin D [25(OH)D] ≥50 nmol/L has not been studied. We aimed to investigate the effect of vitamin D-fortified milk on serum 25(OH)D and parathyroid hormone (PTH) concentrations and to examine the dose-response relationship between vitamin D intake from study milks and serum 25(OH)D concentrations in healthy toddlers aged 12-20 mo living in Dunedin, New Zealand (latitude 46°S). Data from a 20-wk, partially blinded, randomized trial that investigated the effect of providing red meat or fortified toddler milk on the iron, zinc, iodine, and vitamin D status in young New Zealand children (n = 181; mean age 17 mo) were used. Adherence to the intervention was assessed by 7-d weighed diaries at wk 2, 7, 11, 15, and 19. Serum 25(OH)D concentration was measured at baseline and wk 20. Mean vitamin D intake provided by fortified milk was 3.7 μg/d (range, 0-10.4 μg/d). After 20 wk, serum 25(OH)D concentrations but not PTH were significantly different in the milk groups. The prevalence of having a serum 25(OH)D <50 nmol/L remained relatively unchanged at 43% in the meat group, whereas it significantly decreased to between 11 and 15% in those consuming fortified study milk. In New Zealand, vitamin D intake in young children is minimal. Our findings indicate that habitual consumption of vitamin D-fortified milk providing a mean intake of nearly 4 μg/d was effective in achieving adequate year-round serum 25(OH)D for most children. PMID:21832027

  9. Targeting Cholesterol Homeostasis to Fight Hearing Loss: A New Perspective

    PubMed Central

    Malgrange, Brigitte; Varela-Nieto, Isabel; de Medina, Philippe; Paillasse, Michael R.

    2015-01-01

    Sensorineural hearing loss (SNHL) is a major pathology of the inner ear that affects nearly 600 million people worldwide. Despite intensive researches, this major health problem remains without satisfactory solutions. The pathophysiological mechanisms involved in SNHL include oxidative stress, excitotoxicity, inflammation, and ischemia, resulting in synaptic loss, axonal degeneration, and apoptosis of spiral ganglion neurons. The mechanisms associated with SNHL are shared with other neurodegenerative disorders. Cholesterol homeostasis is central to numerous pathologies including neurodegenerative diseases and cholesterol regulates major processes involved in neurons survival and function. The role of cholesterol homeostasis in the physiopathology of inner ear is largely unexplored. In this review, we discuss the findings concerning cholesterol homeostasis in neurodegenerative diseases and whether it should be translated into potential therapeutic strategies for the treatment of SNHL. PMID:25688206

  10. Interactions of dicarboxylic porphyrins with unilamellar lipidic vesicles: drastic effects of pH and cholesterol on kinetics.

    PubMed

    Kuzelová, K; Brault, D

    1995-09-01

    The effect of pH on the transfer of deuteroporphyrin from dimyristoylphosphatidylcholine (DMPC) unilamellar vesicles to human serum albumin is investigated using a stopped-flow with fluorescence detection. The kinetics of this process allows for the determination of the rate constants for the porphyrin exist from the outer vesicle layer to the bulk aqueous medium (koff), and for its movement from the inner to the outer vesicle layer (kto). Both koff and kto are found to strongly depend on the pH. The observed behavior can be described by classical titration curves and is most likely due to protonation equilibria involving the two carboxylic groups of the porphyrin. A pH increase accelerates the exist of the porphyrin. The reverse effect is observed for its movement through the bilayer. The presence of cholesterol in the DMPC bilayer also strongly affects the interactions of the porphyrin with the vesicles. The rate constant kto is dramatically reduced by increasing the cholesterol content. An irregularity is noted around 10-20 mol % cholesterol. The results are discussed in relation to the preferential uptake of porphyrins by tumors, a basis of photodynamic therapy, and to possible pH-mediated relocalization of porphyrins among subcellular structures. PMID:7669783

  11. HDL-Mediated Cellular Cholesterol Efflux Assay Method.

    PubMed

    Hafiane, Anouar; Genest, Jacques

    2015-01-01

    Biomarkers of high-density lipoprotein (HDL) function may provide mechanistic insights and better cardiovascular risk discrimination than HDL-cholesterol mass. The purpose of this work is to describe a simplified experimental protocol that can be used in the determination of cholesterol efflux from macrophages cultured cells and be brought to a medium throughput volume. The cellular cholesterol efflux assay is designed to quantify the rate of cholesterol efflux from cultured cells to an acceptor particle or to plasma. This assay is multi step, cell based assay. Various factors, if not carefully controlled may influence the accuracy and reproducibility of the assay. Attempts were made to address factors influencing this assay and to provide a standardized method that is relatively rapid and scalable. We demonstrate that further centrifugation of the HDL fraction is necessary to avoid apolipoprotein B contamination when using polyethylene glycol (PEG) method. We demonstrate also no effect on cholesterol efflux efficiency when using PEG with plasma or serum. This method has been previously applied in our laboratory in context of cardiovascular research, cardiovascular disease and pharmacologic therapies. PMID:26663796

  12. Inflammatory remodeling of the HDL proteome impairs cholesterol efflux capacity.

    PubMed

    Vaisar, Tomáš; Tang, Chongren; Babenko, Ilona; Hutchins, Patrick; Wimberger, Jake; Suffredini, Anthony F; Heinecke, Jay W

    2015-08-01

    Recent studies demonstrate that HDL's ability to promote cholesterol efflux from macrophages associates strongly with cardioprotection in humans independently of HDL-cholesterol (HDL-C) and apoA-I, HDL's major protein. However, the mechanisms that impair cholesterol efflux capacity during vascular disease are unclear. Inflammation, a well-established risk factor for cardiovascular disease, has been shown to impair HDL's cholesterol efflux capacity. We therefore tested the hypothesis that HDL's impaired efflux capacity is mediated by specific changes of its protein cargo. Humans with acute inflammation induced by low-level endotoxin had unchanged HDL-C levels, but their HDL-C efflux capacity was significantly impaired. Proteomic analyses demonstrated that HDL's cholesterol efflux capacity correlated inversely with HDL content of serum amyloid A (SAA)1 and SAA2. In mice, acute inflammation caused a marked impairment of HDL-C efflux capacity that correlated with a large increase in HDL SAA. In striking contrast, the efflux capacity of mouse inflammatory HDL was preserved with genetic ablation of SAA1 and SAA2. Our observations indicate that the inflammatory impairment of HDL-C efflux capacity is due in part to SAA-mediated remodeling of HDL's protein cargo. PMID:25995210

  13. Membrane plasmalogen composition and cellular cholesterol regulation: a structure activity study

    PubMed Central

    2010-01-01

    Background Disrupted cholesterol regulation leading to increased circulating and membrane cholesterol levels is implicated in many age-related chronic diseases such as cardiovascular disease (CVD), Alzheimer's disease (AD), and cancer. In vitro and ex vivo cellular plasmalogen deficiency models have been shown to exhibit impaired intra- and extra-cellular processing of cholesterol. Furthermore, depleted brain plasmalogens have been implicated in AD and serum plasmalogen deficiencies have been linked to AD, CVD, and cancer. Results Using plasmalogen deficient (NRel-4) and plasmalogen sufficient (HEK293) cells we investigated the effect of species-dependent plasmalogen restoration/augmentation on membrane cholesterol processing. The results of these studies indicate that the esterification of cholesterol is dependent upon the amount of polyunsaturated fatty acid (PUFA)-containing ethanolamine plasmalogen (PlsEtn) present in the membrane. We further elucidate that the concentration-dependent increase in esterified cholesterol observed with PUFA-PlsEtn was due to a concentration-dependent increase in sterol-O-acyltransferase-1 (SOAT1) levels, an observation not reproduced by 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibition. Conclusion The present study describes a novel mechanism of cholesterol regulation that is consistent with clinical and epidemiological studies of cholesterol, aging and disease. Specifically, the present study describes how selective membrane PUFA-PlsEtn enhancement can be achieved using 1-alkyl-2-PUFA glycerols and through this action reduce levels of total and free cholesterol in cells. PMID:20546600

  14. ORMDL orosomucoid-like proteins are degraded by free-cholesterol-loading–induced autophagy

    PubMed Central

    Wang, Shuhui; Robinet, Peggy; Smith, Jonathan D.; Gulshan, Kailash

    2015-01-01

    Eukaryotic cells have evolved robust mechanisms to counter excess cholesterol including redistribution of lipids into different compartments and compensatory up-regulation of phospholipid biosynthesis. We demonstrate here that excess cellular cholesterol increased the activity of the endoplasmic reticulum (ER) enzyme serine palmitoyl-CoA transferase (SPT), the rate-limiting enzyme in sphingomyelin synthesis. This increased SPT activity was not due to altered levels of SPTLC1 or SPTLC2, the major subunits of SPT. Instead, cholesterol loading decreased the levels of ORMDL1, a negative regulator of SPT activity, due to its increased turnover. Several lines of evidence demonstrated that free-cholesterol–induced autophagy, which led to increased turnover of ORMDL1. Cholesterol loading induced ORMDL1 redistribution from the ER to cytoplasmic p62 positive autophagosomes. Coimmunoprecipitation analysis of cholesterol-loaded cells showed increased association between ORMDL1 and p62. The lysosomal inhibitor chloroquine or siRNA knockdown of Atg7 inhibited ORMDL1 degradation by cholesterol, whereas proteasome inhibitors showed no effect. ORMDL1 degradation was specific to free-cholesterol loading as autophagy induced by serum starvation or general ER stress did not lead to ORMDL1 degradation. ORMDL proteins are thus previously unidentified responders to excess cholesterol, exiting the ER to activate SPT and increase sphingomyelin biosynthesis, which may buffer excess cellular cholesterol. PMID:25775599

  15. Cholesterol Perturbs Lipid Bilayers Nonuniversally

    SciTech Connect

    Pan Jianjun; Mills, Thalia T.; Tristram-Nagle, Stephanie; Nagle, John F.

    2008-05-16

    Cholesterol is well known to modulate the physical properties of biomembranes. Using modern x-ray scattering methods, we have studied the effects of cholesterol on the bending modulus K{sub C}, the thickness D{sub HH}, and the orientational order parameter S{sub xray} of lipid bilayers. We find that the effects are different for at least three classes of phospholipids characterized by different numbers of saturated hydrocarbon chains. Most strikingly, cholesterol strongly increases K{sub C} when both chains of the phospholipid are fully saturated but not at all when there are two monounsaturated chains.

  16. Targeting cancer using cholesterol conjugates

    PubMed Central

    Radwan, Awwad A.; Alanazi, Fares K.

    2013-01-01

    Conjugation of cholesterol moiety to active compounds for either cancer treatment or diagnosis is an attractive approach. Cholesterol derivatives are widely studied as cancer diagnostic agents and as anticancer derivatives either in vitro or in vivo using animal models. In largely growing studies, anticancer agents have been chemically conjugated to cholesterol molecules, to enhance their pharmacokinetic behavior, cellular uptake, target specificity, and safety. To efficiently deliver anticancer agents to the target cells and tissues, many different cholesterol–anticancer conjugates were synthesized and characterized, and their anticancer efficiencies were tested in vitro and in vivo. PMID:24493968

  17. Ionic channels and nerve membrane constituents. Tetrodotoxin-like interaction of saxitoxin with cholesterol monolayers.

    PubMed

    Villegas, R; Barnola, F V

    1972-01-01

    Saxitoxin (STX) and tetrodotoxin (TTX) have the same striking property of blocking the Na(+) channels in the axolemma. Experiments with nerve plasma membrane components of the squid Dosidicus gigas have shown that TTX interacts with cholesterol monolayers. Similar experiments were carried out with STX. The effect of STX on the surface pressure-area diagrams of lipid monolayers and on the fluorescence emission spectra of sonicated nerve membranes was studied. The results indicate a TTX-like interaction of STX with cholesterol monolayers. The expansion of the monolayers caused by 10(-6)M STX was 2.2 A(2)/cholesterol molecule at 25 degrees C. From surface pressure measurements at constant cholesterol area (39 A(2)/molecule) in media with various STX concentrations, it was calculated that the STX/cholesterol surface concentration ratio is 0.54. The apparent dissociation constant of the STX-cholesterol monolayer complex is 4.0 x 10(-7)M. The STX/cholesterol ratio and the apparent dissociation constant are similar to those determined for TTX. The presence of other lipids in the monolayers affects the STX-cholesterol association. The interactions of STX and TTX with cholesterol monolayers suggest (a) that cholesterol molecules may be part of the nerve membrane Na(+) channels, or (b) that the toxin receptor at the nerve membrane shares similar chemical features with the cholesterol monolayers. PMID:5007264

  18. Effect of chronic exposure to cadmium on serum lipid, lipoprotein and oxidative stress indices in male rats.

    PubMed

    Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Shabestari, Mahmoud M; Azad, Farahzad Jabbari; Farkhondeh, Tahereh; Bafandeh, Fereshteh

    2015-09-01

    Cadmium (Cd) is an environmental toxic metal implicated in lipid abnormalities. The present study was designed to elucidate the possible association between chronic exposure to Cd concentration and alterations in plasma lipid, lipoprotein, and oxidative stress indices in rats. Sixteen male rats were assigned to 2 groups of 8 rats each (test and control). The Cd-exposed group obtained drinking water containing cadmium chloride (CdCl2) in the concentration of 2.0 mg Cd/L in drinking water for 3 months. At the end of the experimental period, blood samples were obtained to determine the changes of serum triglycerides (TG), total cholesterol (TC), highdensity lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), reduced glutathione (GSH), malondialdehyde (MDA) and also serum Cd contents. The results of the present study indicated that Cd administration significantly increased the serum levels of TG, TC, LDL-C, MDA and Cd with reduction in the HDL-C and GSH levels. In conclusion, evidence is presented that chronic exposure to low Cd concentration can adversely affect the lipid and lipoprotein profile via lipid peroxidation. PMID:27486375

  19. Effect of chronic exposure to cadmium on serum lipid, lipoprotein and oxidative stress indices in male rats

    PubMed Central

    Azimi-Nezhad, Mohsen; Shabestari, Mahmoud M.; Azad, Farahzad Jabbari; Farkhondeh, Tahereh; Bafandeh, Fereshteh

    2015-01-01

    Cadmium (Cd) is an environmental toxic metal implicated in lipid abnormalities. The present study was designed to elucidate the possible association between chronic exposure to Cd concentration and alterations in plasma lipid, lipoprotein, and oxidative stress indices in rats. Sixteen male rats were assigned to 2 groups of 8 rats each (test and control). The Cd-exposed group obtained drinking water containing cadmium chloride (CdCl2) in the concentration of 2.0 mg Cd/L in drinking water for 3 months. At the end of the experimental period, blood samples were obtained to determine the changes of serum triglycerides (TG), total cholesterol (TC), highdensity lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), reduced glutathione (GSH), malondialdehyde (MDA) and also serum Cd contents. The results of the present study indicated that Cd administration significantly increased the serum levels of TG, TC, LDL-C, MDA and Cd with reduction in the HDL-C and GSH levels. In conclusion, evidence is presented that chronic exposure to low Cd concentration can adversely affect the lipid and lipoprotein profile via lipid peroxidation. PMID:27486375

  20. Cholesterol and Breast Cancer Pathophysiology

    PubMed Central

    Nelson, Erik R.; Chang, Ching-yi; McDonnell, Donald P.

    2014-01-01

    Cholesterol is a risk factor for breast cancer although the mechanisms by which this occurs are not well understood. One hypothesis is that dyslipidemia results in increased cholesterol content in cell membranes thus impacting membrane fluidity and subsequent signaling. Additionally, studies demonstrate that the metabolite, 27-hydroxycholesterol (27HC), can function as an estrogen, increasing the proliferation of estrogen receptor positive breast cancer cells. This was unexpected as 27HC and other oxysterols activate the liver X receptors resulting in the reduction of intracellular cholesterol. Resolution of this paradox will require a dissection of the molecular mechanisms by which ER and LXR converge in breast cancer cells. Regardless, the observation that 27HC influences breast cancer provides rationale for strategies that target cholesterol metabolism. PMID:25458418

  1. Cholesterol confusion and statin controversy.

    PubMed

    DuBroff, Robert; de Lorgeril, Michel

    2015-07-26

    The role of blood cholesterol levels in coronary heart disease (CHD) and the true effect of cholesterol-lowering statin drugs are debatable. In particular, whether statins actually decrease cardiac mortality and increase life expectancy is controversial. Concurrently, the Mediterranean diet model has been shown to prolong life and reduce the risk of diabetes, cancer, and CHD. We herein review current data related to both statins and the Mediterranean diet. We conclude that the expectation that CHD could be prevented or eliminated by simply reducing cholesterol appears unfounded. On the contrary, we should acknowledge the inconsistencies of the cholesterol theory and recognize the proven benefits of a healthy lifestyle incorporating a Mediterranean diet to prevent CHD. PMID:26225201

  2. Cholesterol's location in lipid bilayers

    DOE PAGESBeta

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

    2016-04-04

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

  3. Cholesterol confusion and statin controversy

    PubMed Central

    DuBroff, Robert; de Lorgeril, Michel

    2015-01-01

    The role of blood cholesterol levels in coronary heart disease (CHD) and the true effect of cholesterol-lowering statin drugs are debatable. In particular, whether statins actually decrease cardiac mortality and increase life expectancy is controversial. Concurrently, the Mediterranean diet model has been shown to prolong life and reduce the risk of diabetes, cancer, and CHD. We herein review current data related to both statins and the Mediterranean diet. We conclude that the expectation that CHD could be prevented or eliminated by simply reducing cholesterol appears unfounded. On the contrary, we should acknowledge the inconsistencies of the cholesterol theory and recognize the proven benefits of a healthy lifestyle incorporating a Mediterranean diet to prevent CHD. PMID:26225201

  4. Cholesterol's location in lipid bilayers.

    PubMed

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

    2016-09-01

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

  5. [Effects of a low-fat diet including vegetables on total blood cholesterol levels in the aged].

    PubMed

    Pentimone, F; Bertoncini, P; Laghi, G; Del Corso, L; Giuliano, G

    1990-11-30

    High total serum cholesterol and low HDL levels are major risk factors for cardiovascular disease before the age of 65. Currently in older populations their role has not yet been defined. In the elderly a low-cholesterol diet is therefore preferable to pharmacological treatment, in view of the absence of collateral effects. In this study 40 elderly patients with hypercholesterolemia were divided at random into two groups. They were respectively fed their usual diet and a legume-supplemented normal caloric diet for 8 weeks. Total serum cholesterol levels significantly decreased in the latter group from the 2nd week onward. PMID:2150025

  6. Large-Scale Glycomics of Livestock: Discovery of Highly Sensitive Serum Biomarkers Indicating an Environmental Stress Affecting Immune Responses and Productivity of Holstein Dairy Cows.

    PubMed

    Rehan, Ibrahim F; Ueda, Koichiro; Mitani, Tomohiro; Amano, Maho; Hinou, Hiroshi; Ohashi, Tetsu; Kondo, Seiji; Nishimura, Shin-Ichiro

    2015-12-01

    Because various stresses strongly influence the food productivity of livestock, biomarkers to indicate unmeasurable environmental stress in domestic animals are of increasing importance. Thermal comfort is one of the basic principles of dairy cow welfare that enhances productivity. To discover sensitive biomarkers that monitor such environmental stresses in dairy cows, we herein performed, for the first time, large-scale glycomics on 336 lactating Holstein cow serum samples over 9 months between February and October. Glycoblotting combined with MALDI-TOF/MS and DMB/HPLC allowed for comprehensive glycomics of whole serum glycoproteins. The results obtained revealed seasonal alterations in serum N-glycan levels and their structural characteristics, such as an increase in high-mannose type N-glycans in spring, the occurrence of di/triantennary complex type N-glycans terminating with two or three Neu5Gc residues in summer and autumn, and N-glycans in winter dominantly displaying Neu5Ac. A multivariate analysis revealed a correlation between the serum expression levels of these season-specific glycoforms and productivity. PMID:26595672

  7. Disentangling the Association between Statins, Cholesterol, and Colorectal Cancer: A Nested Case-Control Study

    PubMed Central

    Mamtani, Ronac; Lewis, James D.; Scott, Frank I.; Ahmad, Tariq; Goldberg, David S.; Datta, Jashodeep; Yang, Yu-Xiao; Boursi, Ben

    2016-01-01

    Background Several prior studies have found an association between statin use and reduced risk of colorectal cancer. We hypothesized that these findings may be due to systematic bias and examined the independent association of colorectal cancer risk with statin use, serum cholesterol, and change in cholesterol concentration. Methods and Findings 22,163 colorectal cancer cases and 86,538 matched controls between 1995 and 2013 were identified within The Health Improvement Network (THIN) a population-representative database. Conditional logistic regression models estimated colorectal cancer risk with statin use, serum total cholesterol (mmol/L), and change in total cholesterol level. We confirmed a decreased risk of colorectal cancer with statin use (long-term: odds ratio [OR], 0.95; 95% confidence interval [CI], 0.91–0.99; short-term: OR, 0.92; 95% CI, 0.85–0.99). However, to assess whether the observed association may result from indication bias, a subgroup analysis was conducted among patients prescribed a statin. In this subgroup (n = 5,102 cases, n = 19,032 controls), 3.1% of case subjects and 3.1% of controls discontinued therapy. The risk of colorectal cancer was not significantly different among those who continued statin therapy and those who discontinued (OR, 0.98; 95% CI, 0.79–1.22). Increased serum cholesterol was independently associated with decreased risk of colorectal cancer (OR, 0.89 per mmol/L increase; 95% CI, 0.87–0.91); the association was only present if serum cholesterol was measured near the cancer diagnosis (<6 mo: OR, 0.76; 95% CI, 0.47–0.61; >24 mo: OR, 0.98; 95% CI, 0.93–1.03). Decreases in serum total cholesterol >1 mmol/L ≥1 year prior to cancer diagnosis were associated with subsequent colorectal cancer (statin users: OR, 1.25; 95 CI%, 1.03–1.53; nonusers: OR, 2.36; 95 CI%, 1.78–3.12). As an observational study, limitations included incomplete data and residual confounding. Conclusions Although the risk of colorectal

  8. An enzyme thermistor-based assay for total and free cholesterol.

    PubMed

    Raghavan, V; Ramanathan, K; Sundaram, P V; Danielsson, B

    1999-11-01

    A method to evaluate the free (FC) and total cholesterol (TC) in human serum, bile and gallstone extract using an enzyme thermistor (ET)-based flow injection analysis (FIA) is presented. The cholesterol in high-density (HDL-C) and low density lipoprotein (LDL-C) have also been evaluated. A heparin functionalized Sepharose column was employed for the isolation of HDL and LDL fractions from serum. The estimation of cholesterol and its esters was based on their reaction with cholesterol oxidase (CO), cholesterol esterase (CE) and catalase (CAT). Three different enzyme columns, i.e. co-immobilized CO/CAT (column A), only CE (column B) and co-immobilized CO/CE/CAT (column C) were prepared by cross-linking the enzymes on glass beads using glutaraldehyde. Column A was used for estimating FC and column C was used for estimating total cholesterol (cholesterol plus esterified cholesterol). Column B was used as a pre-column which could be switched 'in' or 'out' in conjunction with column A for the estimation of TC or FC, respectively. A calibration between 1.0 and 8.0 mmol/l for FC and 0. 25 and 4.0 mmol/l for TC was obtained. For more than 2000 assays with the ET device a C.V. of less than 4% was obtained. The assay time was approximately 4 min per assay. The cholesterol estimations on the ET correlated well with similar estimations using a commercially available cholesterol diagnostic kit. PMID:10556661

  9. Comparative hypocholesterolemic effects of five animal oils in cholesterol-fed rats.

    PubMed

    Fukushima, M; Ohashi, T; Sekikawa, M; Nakano, M

    1999-01-01

    The hypocholesterolemic efficacy of various animal oils was compared in rats given a cholesterol-enriched diet. After acclimatization for one week, male F344 DuCrj rats (8 weeks of age) that had been fed with a conventional diet were assigned to diets containing 5% of oil from emu (Dromaius), Japanese Sika deer (Cervus nippon yesoensis, Heude), sardine, beef tallow, or lard with 0.5% cholesterol for 6 weeks. After this feeding period, the concentrations of serum total cholesterol and of very-low-density lipoprotein + intermediate-density lipoprotein + low-density lipoprotein-cholesterol in the sardine oil group were significantly lower than those in the other groups. The serum high-density lipoprotein-cholesterol concentration in the Japanese Sika deer oil group was significantly higher than that in the other groups. The atherosclerotic index and liver cholesterol concentration in the sardine oil and Japanese Sika deer oil groups were significantly lower than those in the other groups. The fecal cholesterol excretion by the Japanese Sika deer oil group was significantly higher than that of the other groups, except for the sardine oil group, and the fecal bile acid excretion by the sardine oil group was significantly higher than that of the other groups, except for the lard group. These results suggest that Japanese Sika deer oil reduced the atherosclerotic index and liver cholesterol concentration in the presence of excess cholesterol in the diet as well as sardine oil did by increasing the excretion of cholesterol from the intestines of rats. PMID:10052143

  10. Cholesterol and benign prostate disease.

    PubMed

    Freeman, Michael R; Solomon, Keith R

    2011-01-01

    The origins of benign prostatic diseases, such as benign prostatic hyperplasia (BPH) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), are poorly understood. Patients suffering from benign prostatic symptoms report a substantially reduced quality of life, and the relationship between benign prostate conditions and prostate cancer is uncertain. Epidemiologic data for BPH and CP/CPPS are limited, however an apparent association between BPH symptoms and cardiovascular disease (CVD) has been consistently reported. The prostate synthesizes and stores large amounts of cholesterol and prostate tissues may be particularly sensitive to perturbations in cholesterol metabolism. Hypercholesterolemia, a major risk factor for CVD, is also a risk factor for BPH. Animal model and clinical trial findings suggest that agents that inhibit cholesterol absorption from the intestine, such as the class of compounds known as polyene macrolides, can reduce prostate gland size and improve lower urinary tract symptoms (LUTS). Observational studies indicate that cholesterol-lowering drugs reduce the risk of aggressive prostate cancer, while prostate cancer cell growth and survival pathways depend in part on cholesterol-sensitive biochemical mechanisms. Here we review the evidence that cholesterol metabolism plays a role in the incidence of benign prostate disease and we highlight possible therapeutic approaches based on this concept. PMID:21862201

  11. Olive Leaf Extract Improves the Atherogenic Lipid Profile in Rats Fed a High Cholesterol Diet.

    PubMed

    Olmez, Ercument; Vural, Kamil; Gok, Sule; Ozturk, Zeynep; Kayalar, Husniye; Ayhan, Semin; Var, Ahmet

    2015-10-01

    Coronary heart disease because of atherosclerosis is still the most common cause of mortality. Elevated levels of low-density lipoprotein and total cholesterol are major risk factors for atherosclerotic cardiovascular disease. The aim of this study was to evaluate the effects of the olive leaf extract on serum lipid profile, early changes of atherosclerosis and endothelium-dependent relaxations in cholesterol-fed rats. For this purpose, rats were fed by 2% cholesterol-enriched or standard chow for 8 weeks. Some rats in each group were also fed orally by olive leaf extract at doses of 50 or 100 mg/kg/day. Atorvastatin at dose of 20 mg/kg of body weight daily was also given as positive control. After 8 weeks, lipid profiles of rat serums were analyzed. Antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase) and degree of lipid peroxidation (malondialdehyde levels) were also measured in the hearts isolated from rats. In addition, expression of adhesion molecules and endothelium-dependent relaxations of isolated thoracic aortas of rats were evaluated. Total cholesterol and LDL-cholesterol levels were found to be increased in cholesterol-fed rats, and both doses of olive leaf extract and atorvastatin significantly decreased those levels. In conclusion, because the olive leaf extract attenuates the increased cholesterol levels, it may have beneficial effects on atherosclerosis. PMID:26328503

  12. Jeremiah Metzger Lecture: Cholesterol, Inflammation and Atherosclerotic Cardiovascular Disease: Is It All LDL?

    PubMed Central

    Gotto, Antonio M.

    2011-01-01

    Scientific investigation of the relationship between atherosclerosis, inflammation, and lipoprotein metabolism originated in the mid-19th century and has increased exponentially over the past 50 years. Basic research that characterized the lipoproteins and their metabolism was followed by clinical and epidemiologic studies that began to link elevated levels of cholesterol in the blood to the development of atherosclerosis and increased risk for cardiovascular disease. The link between elevated serum cholesterol levels and cardiovascular disease, known as the “lipid hypothesis,” was confirmed with the discoveries of the low-density lipoprotein (LDL) receptor and of the statins. Subsequent results of multiple clinical trials, particularly with statins, have established that reductions in LDL cholesterol are associated with reduced risk for coronary heart disease (CHD). A growing body of evidence suggests that measures of inflammation, such as C-reactive protein (CRP), may enhance cardiovascular risk assessment and help guide clinical decision-making. Reductions in CRP in individuals with low serum levels of LDL cholesterol have been shown to reduce cardiovascular events. A variety of agents designed to further reduce LDL cholesterol, increase high-density lipoprotein (HDL) cholesterol, and target inflammation are currently in development. Future research can help clarify the roles of emerging biomarkers and lipid fractions other than LDL cholesterol in the prevention, diagnosis, and treatment of cardiovascular disease. PMID:21686232

  13. Facts about...Blood Cholesterol. Revised.

    ERIC Educational Resources Information Center

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

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

  14. Current Views on Genetics and Epigenetics of Cholesterol Gallstone Disease

    PubMed Central

    Di Ciaula, Agostino; Wang, David Q.-H.; Bonfrate, Leonilde; Portincasa, Piero

    2013-01-01

    Cholesterol gallstone disease, one of the commonest digestive diseases in western countries, is induced by an imbalance in cholesterol metabolism, which involves intestinal absorption, hepatic biosynthesis, and biliary output of cholesterol, and its conversion to bile acids. Several components of the metabolic syndrome (e.g., obesity, type 2 diabetes, dyslipidemia, and hyperinsulinemia) are also well-known risk factors for gallstones, suggesting the existence of interplay between common pathophysiological pathways influenced by insulin resistance, genetic, epigenetic, and environmental factors. Cholesterol gallstones may be enhanced, at least in part, by the abnormal expression of a set of the genes that affect cholesterol homeostasis and lead to insulin resistance. Additionally, epigenetic mechanisms (mainly DNA methylation, histone acetylation/deacetylation, and noncoding microRNAs) may modify gene expression in the absence of an altered DNA sequence, in response to different lithogenic environmental stimuli, such as diet, lifestyle, pollutants, also occurring in utero before birth. In this review, we will comment on various steps of the pathogenesis of cholesterol gallstones and interaction between environmental and genetic factors. The epigenomic approach may offer new options for therapy of gallstones and better possibilities for primary prevention in subjects at risk. PMID:23691293

  15. Cholesterol in the rod outer segment: A complex role in a "simple" system.

    PubMed

    Albert, Arlene; Alexander, Desiree; Boesze-Battaglia, Kathleen

    2016-09-01

    The rod outer segment (ROS) of retinal photoreceptor cells consists of disk membranes surrounded by the plasma membrane. It is a relatively uncomplicated system in which to investigate cholesterol distribution and its functional consequences in biologically relevant membranes. The light sensitive protein, rhodopsin is the major protein in both membranes, but the lipid compositions are significantly different in the disk and plasma membranes. Cholesterol is high in the ROS plasma membrane. Disk membranes are synthesized at the base of the ROS and are also high in cholesterol. However, cholesterol is rapidly depleted as the disks are apically displaced. During this apical displacement the disk phospholipid fatty acyl chains become progressively more unsaturated, which creates an environment unfavorable to cholesterol. Membrane cholesterol has functional consequences. The high cholesterol found in the plasma membrane and in newly synthesized disks inhibits the activation of rhodopsin. As disks are apically displaced and cholesterol is depleted rhodopsin becomes more responsive to light. This effect of cholesterol on rhodopsin activation has been shown in both native and reconstituted membranes. The modulation of activity can be at least partially explained by the effect of cholesterol on bulk lipid properties. Cholesterol decreases the partial free volume of the hydrocarbon region of the bilayer and thereby inhibits rhodopsin conformational changes required for activation. However, cholesterol binds to rhodopsin and may directly affect the protein also. Furthermore, cholesterol stabilizes rhodopsin to thermal denaturation. The membrane must provide an environment that allows rhodopsin conformational changes required for activation while also stabilizing the protein to thermal denaturation. Cholesterol thus plays a complex role in modulating the activity and stability of rhodopsin, which have implications for other G-protein coupled receptors. PMID:27216754

  16. Intestinal nuclear receptors in HDL cholesterol metabolism

    PubMed Central

    Degirolamo, Chiara; Sabbà, Carlo; Moschetta, Antonio

    2015-01-01

    The intestine plays a pivotal role in cholesterol homeostasis by functioning as an absorptive and secretory organ in the reverse cholesterol transport pathway. Enterocytes control cholesterol absorption, apoAI synthesis, HDL biogenesis, and nonbiliary cholesterol fecal disposal. Thus, intestine-based therapeutic interventions may hold promise in the management of diseases driven by cholesterol overload. Lipid-sensing nuclear receptors (NRs) are highly expressed in the intestinal epithelium and regulate transcriptionally the handling of cholesterol by the enterocytes. Here, we discuss the NR regulation of cholesterol fluxes across the enterocytes with special emphasis on NR exploitation as a bona fide novel HDL-raising strategy. PMID:25070952

  17. Intestinal nuclear receptors in HDL cholesterol metabolism.

    PubMed

    Degirolamo, Chiara; Sabbà, Carlo; Moschetta, Antonio

    2015-07-01

    The intestine plays a pivotal role in cholesterol homeostasis by functioning as an absorptive and secretory organ in the reverse cholesterol transport pathway. Enterocytes control cholesterol absorption, apoAI synthesis, HDL biogenesis, and nonbiliary cholesterol fecal disposal. Thus, intestine-based therapeutic interventions may hold promise in the management of diseases driven by cholesterol overload. Lipid-sensing nuclear receptors (NRs) are highly expressed in the intestinal epithelium and regulate transcriptionally the handling of cholesterol by the enterocytes. Here, we discuss the NR regulation of cholesterol fluxes across the enterocytes with special emphasis on NR exploitation as a bona fide novel HDL-raising strategy. PMID:25070952

  18. Phosphatidylcholine: Greasing the Cholesterol Transport Machinery

    PubMed Central

    Lagace, Thomas A.

    2015-01-01

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

  19. Cholesterol starvation induces differentiation of human leukemia HL-60 cells.

    PubMed

    Sánchez-Martín, Carolina C; Dávalos, Alberto; Martín-Sánchez, Covadonga; de la Peña, Gema; Fernández-Hernando, Carlos; Lasunción, Miguel A

    2007-04-01

    Cholesterol metabolism is particularly active in malignant, proliferative cells, whereas cholesterol starvation has been shown to inhibit cell proliferation. Inhibition of enzymes involved in cholesterol biosynthesis at steps before the formation of 7-dehydrocholesterol has been shown to selectively affect cell cycle progression from G(2) phase in human promyelocytic HL-60 cells. In the present work, we explored whether cholesterol starvation by culture in cholesterol-free medium and treatment with different distal cholesterol biosynthesis inhibitors induces differentiation of HL-60 cells. Treatment with SKF 104976, an inhibitor of lanosterol 14-alpha demethylase, or with zaragozic acid, which inhibits squalene synthase, caused morphologic changes alongside respiratory burst activity and expression of cluster of differentiation antigen 11c (CD11c) but not cluster of differentiation antigen 14. These effects were comparable to those produced by all-trans retinoic acid, which induces HL-60 cells to differentiate following a granulocyte lineage. In contrast, they differed from those produced by vitamin D(3), which promotes monocyte differentiation. The specificity of the response was confirmed by addition of cholesterol to the culture medium. Treatment with PD 98059, an inhibitor of extracellular signal-regulated kinase, abolished both the activation of NADPH oxidase and the expression of the CD11c marker. In sharp contrast, BM 15766, which inhibits sterol Delta(7)-reductase, failed to induce differentiation or arrest cell proliferation. These results show that changes in the sterol composition may trigger a differentiation response and highlight the potential of cholesterol pathway inhibition as a possible tool for use in cancer therapy. PMID:17409448

  20. Cholesterol stabilizes fluid phosphoinositide domains

    PubMed Central

    Jiang, Zhiping; Redfern, Roberta E.; Isler, Yasmin; Ross, Alonzo H.

    2014-01-01

    Local accumulation of phosphoinositides (PIPs) is an important factor for a broad range of cellular events including membrane trafficking and cell signaling. The negatively charged phosphoinositide headgroups can interact with cations or cationic proteins and this electrostatic interaction has been identified as the main phosphoinositide clustering mechanism. However, an increasing number of reports show that phosphoinositide-mediated signaling events are at least in some cases cholesterol dependent, suggesting other possible contributors to the segregation of phosphoinositides. Using fluorescence microscopy on giant unilamellar vesicles and monolayers at the air/water interface, we present data showing that cholesterol stabilizes fluid phosphoinositide-enriched phases. The interaction with cholesterol is observed for all investigated phosphoinositides (PI(4)P, PI(3,4)P2, PI(3,5)P2, PI(4,5)P2 and PI(3,4,5)P3) as well as phosphatidylinositol. We find that cholesterol is present in the phosphoinositide-enriched phase and that the resulting phase is fluid. Cholesterol derivatives modified at the hydroxyl group (cholestenone, cholesteryl ethyl ether) do not promote formation of phosphoinositide domains, suggesting an instrumental role of the cholesterol hydroxyl group in the observed cholesterol/phosphoinositide interaction. This leads to the hypothesis that cholesterol participates in an intermolecular hydrogen bond network formed among the phosphoinositide lipids. We had previously reported that the intra- and intermolecular hydrogen bond network between the phosphoinositide lipids leads to a reduction of the charge density at the phosphoinositide phosphomonoester groups (Kooijman et al. Biochemistry 48, (2009) 9360). We believe that cholesterol acts as a spacer between the phosphoinositide lipids, thereby reducing the electrostatic repulsion, while participating in the hydrogen bond network, leading to its further stabilization. To illustrate the effect of

  1. Effects of peach palm oil on performance, serum lipoproteins and haemostasis in broilers.

    PubMed

    Baldizán, G; Oviedo, M; Michelangeli, C; Vargas, R E

    2010-12-01

    1. An experiment was conducted to study the comparative effects of peach palm oil (PPO, Bactris gasipaes H.B.K), crude palm oil (CPO, Elaeis guinenesis), maize oil (MO) and beef tallow (BT) on serum total and lipoprotein cholesterol levels and haemostatic factors in broiler chickens. 2. Four experimental diets were formulated to be isocaloric (14·2 MJ AME(N)/kg) and isonitrogenous (230 g CP/kg). PPO was extracted from the whole dry fruit with hexane. Each fat was added to the diet in an amount equivalent to 25% of total dietary calories. Six replicate groups of eight male broiler chicks were assigned randomly to each dietary treatment. Diets were fed on ad libitum basis. The experiment lasted 42 d. 3. At 42 d, birds were fasted overnight and three chickens/dietary treatment were utilised to draw blood for lipoprotein separation. Various haemostatic factors were determined in thrombocyte-poor plasma. Thrombocyte aggregation was assayed in whole blood. 4. No significant differences were detected in body-weight gain or feed efficiency between the chickens fed on the PPO diet and those receiving the CPO, MO or BT diets. Total serum cholesterol (TC), very low density lipoprotein cholesterol and low density lipoprotein cholesterol (LDL(C)) were not significantly affected after consuming the PPO, CPO and MO diets. Serum high density lipoprotein cholesterol (HDL(C)) was reduced only by the MO diet. Birds fed on the PPO diet had a significantly lower [corrected] LDLC/HDLC ratio compared with other dietary treatments 5. Thrombocyte count and thrombin time were not significantly affected by the experimental diets. Dietary oils significantly affected prothrombin time, fibrinogen concentration and thrombocyte aggregation. PPO and MO diets elicited the lowest fibrinogen levels compared to the CPO and BT diets. Thrombocyte aggregation in broilers fed on the PPO diet was similar to that of the CPO, MO and BT diets. 6. The results suggest that PPO might efficiently provide up to

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

    PubMed

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

    2016-08-01

    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 investigated the effects on cholesterol metabolism in mice in detail. Surprisingly, direct measurement of whole body cholesterol synthesis revealed that cholesterol synthesis was robustly increased in statin-treated mice. Measurement of organ-specific cholesterol synthesis demonstrated that the liver is predominantly responsible for the increase in cholesterol synthesis. Excess synthesized cholesterol did not accumulate in the plasma, as plasma cholesterol decreased. However, statin treatment led to an increase in cholesterol removal via the feces. Interestingly, enhanced cholesterol excretion in response to rosuvastatin and lovastatin treatment was mainly mediated via biliary cholesterol secretion, whereas atorvastatin mainly stimulated cholesterol removal via the transintestinal cholesterol excretion pathway. Moreover, we show that plasma cholesterol precursor levels do not reflect cholesterol synthesis rates during statin treatment in mice. In conclusion, cholesterol synthesis is paradoxically increased upon statin treatment in mice. However, statins potently stimulate the excretion of cholesterol from the body, which sheds new light on possible mechanisms underlying the cholesterol-lowering effects of statins. PMID:27313057

  3. Maternal serum hyperglycosylated human chorionic gonadotrophin (HhCG) in the first trimester of pregnancies affected by Down syndrome, using a sialic acid-specific lectin immunoassay.

    PubMed

    Spencer, K; Talbot, J A; Abushoufa, R A

    2002-08-01

    In a series of 54 cases of pregnancies complicated by Down syndrome and 224 unaffected pregnancies we examined maternal serum levels of hyperglycosylated human chorionic gonadotrophin (HhCG) in samples collected in the first trimester (11-13 weeks) using a sialic acid-specific lectin immunoassay. We compared these levels with those of other potential first trimester serum markers [free beta-hCG, pregnancy-associated plasma protein A (PAPP-A) and total hCG (ThCG)] and modeled detection rates and false-positive rates of various biochemical markers in conjunction with fetal nuchal translucency (NT) and maternal age using an maternal age standardized population. Maternal serum HhCG in cases of Down syndrome were significantly elevated (median MoM 1.97) with 24/54 (44%) of cases above the 95th centile for unaffected pregnancies. Free beta-hCG was also elevated (median MoM 2.09) with 33% of cases above the 95th centile. PAPP-A levels were reduced (median MoM 0.47) with 38% below the 5th centile. ThCG levels, whilst elevated (median MoM 1.34), had only 20% of cases above the 95th centile. Maternal serum HhCG levels were not correlated with fetal NT but showed significant correlation with ThCG and free beta-hCG and with PAPP-A in the Down syndrome group (r=0.536). Maternal serum HhCG levels in cases with Down syndrome had a significant correlation with gestational age, increasing as the gestation increased. When HhCG was combined together with fetal NT, PAPP-A and maternal age, at a 5% false-positive rate the modeled detection rate was 83%, some 6% lower than when free beta-hCG was used and some 4% better than when ThCG was used. Maternal serum HhCG is unlikely to be of additional value when screening for Down syndrome in the first trimester. PMID:12210572

  4. Serum lipid and antioxidant responses in hypercholesterolemic men and women receiving plant sterol esters vary by apolipoprotein E genotype

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant sterol esters reduce serum total cholesterol (TC) and LDL cholesterol (LDL-C), but with striking inter-individual variability. In this randomized, double-blind, controlled study, serum lipid, plant sterol, fat-soluble vitamin, and carotenoid responses to plant sterols were studied according to...

  5. Serum Lipid Levels in Patients with Eating Disorders.

    PubMed

    Nakai, Yoshikatsu; Noma, Shun'ichi; Fukusima, Mitsuo; Taniguchi, Ataru; Teramukai, Satoshi

    2016-01-01

    Objective To evaluate some risk factors for cardiovascular diseases in feeding and eating disorders, the degree of lipid abnormalities was investigated in a large Japanese cohort of different groups of feeding and eating disorders, according to the Japan Atherosclerosis Society Guidelines for the Prevention of Atherosclerotic Cardiovascular Diseases 2012 (JAS Guidelines 2012). Methods Participants in the current study included 732 women divided into four groups of feeding and eating disorders: anorexia nervosa, restricting type (AN-R); anorexia nervosa, binge-eating/purging type; bulimia nervosa (BN); and binge-eating disorder (BED). We measured the serum levels of total cholesterol, high-density-lipoprotein (HDL) cholesterol, and triglyceride in these participants. Low-density-lipoprotein (LDL) cholesterol and non-HDL cholesterol levels were also calculated. Results The concentrations of LDL cholesterol and non-HDL cholesterol were widely distributed in all groups. When the LDL cholesterol risk was defined as ≥120 mg/dL and the non-HDL cholesterol risk as ≥150 mg/dL, according to the JAS Guidelines 2012, the proportion of LDL cholesterol risk ranged from 29.6% (BN) to 38.6% (AN-R), and the proportion of non-HDL cholesterol risk ranged from 17.8% (BN) to 30.1% (BED). Conclusion The present findings suggest the existence of LDL cholesterol risk and non-HDL cholesterol risk in all groups of eating disorders. Given the chronicity of this condition, the development of elevated concentrations of LDL cholesterol and non-HDL cholesterol at an early age may increase the risk of cardiovascular diseases. PMID:27432092

  6. Physiological performance of quails that underwent dietary and pharmacological manipulation of cholesterol.

    PubMed

    Botelho, G G; Falbo, M K; Ost, P R; Czekoski, Z M; Raviolo, A E; Giotto, F M; Goldoni, E C; Morais, R N

    2015-06-01

    The present work evaluated whether dietary and pharmacological interference on cholesterol synthesis were capable of inducing alterations in blood and yolk cholesterol levels and the secretion of corticosterone metabolites. Forty-five 40-day-old quails were divided into three experimental groups: vegetal fat diet, 2% beef fat (tallow) diet and vegetal fat diet with simvastatin administration (3.13 mg/kg/day). During all experiments, the animal weights and food consumption were recorded and blood and faecal samples (days 0, 15, 30, 45 and 60), as well as eggs (days 30, 45 and 60), were collected. Analysis of serum and yolk cholesterol was performed and faecal corticosterone levels were measured. No differences were observed on blood cholesterol or faecal corticosterone between all treatments, despite a tendency of increased cholesterol in the group with the animal fat diet. However, quails submitted to an animal fat diet displayed an increase in yolk cholesterol at day 30 of the treatment and the egg yolks of quails treated with simvastatin exhibited a decrease in cholesterol content by the end of the treatment at 60 days. These results improved the knowledge regarding the physiology of quails and offered support to other studies concerning the consequences of the pharmacological treatment and the dietary manipulation of cholesterol levels. PMID:25272016

  7. The costs and effects of a nutritional education program following work-site cholesterol screening.

    PubMed Central

    Byers, T; Mullis, R; Anderson, J; Dusenbury, L; Gorsky, R; Kimber, C; Krueger, K; Kuester, S; Mokdad, A; Perry, G

    1995-01-01

    OBJECTIVES. The purpose of this study was to assess the costs and impact of a nutrition education program following a cholesterol screening. METHODS. Forty work-sites were randomly assigned to one of two educational interventions: a "usual" intervention of 5 minutes of counseling, or a "special" intervention of 2 hours of behaviorally based education on dietary changes to lower serum cholesterol. Costs were monitored, and cholesterol levels were retested 6 and 12 months later. RESULTS. The total per-person cost for screening and the educational intervention was about $50. Cholesterol levels differed little between the two intervention groups 6 months after screening, but after 12 months those in the special intervention worksites showed a 6.5% drop in cholesterol, whereas those at the usual intervention worksites showed a drop of only 3.0%. Hence a 3.5% cholesterol reduction was attributable to the special intervention. CONCLUSIONS. A behaviorally based nutrition education program following cholesterol screening can have a meaningful impact on long-term cholesterol levels at a low cost. Nutrition education in work-sites may therefore be a useful way to lower the risk of heart disease in communities. PMID:7733424

  8. Revisiting Human Cholesterol Synthesis and Absorption: The Reciprocity Paradigm and its Key Regulators.

    PubMed

    Alphonse, Peter A S; Jones, Peter J H

    2016-05-01

    Hypercholesterolemia is a major risk factor for cardiovascular disease. Cholesterol homeostasis in the body is governed by the interplay between absorption, synthesis, and excretion or conversion of cholesterol into bile acids. A reciprocal relationship between cholesterol synthesis and absorption is known to regulate circulating cholesterol in response to dietary or therapeutic interventions. However, the degree to which these factors affect synthesis and absorption and the extent to which one vector shifts in response to the other are not thoroughly understood. Also, huge inter-individual variability exists in the manner in which the two systems act in response to any cholesterol-lowering treatment. Various factors are known to account for this variability and in light of recent experimental advances new players such as gene-gene interactions, gene-environmental effects, and gut microbiome hold immense potential in offering an explanation to the complex traits of inter-individual variability in human cholesterol metabolism. In this context, the objective of the present review is to provide an overview on cholesterol metabolism and discuss the role of potential factors such as genetics, epigenetics, epistasis, and gut microbiome, as well as other regulators in modulating cholesterol metabolism, especially emphasizing the reciprocal relationship between cholesterol synthesis and absorption. Furthermore, an evaluation of the implications of this push-pull mechanism on cholesterol-lowering strategies is presented. PMID:26620375

  9. Effects of sphingomyelin and phosphatidylcholine degradation on cyclodextrin-mediated cholesterol efflux in cultured fibroblasts.

    PubMed

    Ohvo, H; Olsio, C; Slotte, J P

    1997-11-15

    The hydrolysis of plasma membrane sphingomyelin is known to dramatically alter cellular cholesterol homeostasis in different ways, whereas the degradation of plasma membrane phosphatidylcholine has much less or no effects on cell cholesterol homeostasis [Pörn, Ares, Slotte, J. Lipid Res. 34 (1993) 1385-1392]. In this study, we used an efficient extracellular cholesterol acceptor (cyclodextrin) and determined the extent of cholesterol efflux from cultured fibroblasts in which plasma membrane sphingomyelin or phosphatidylcholine was degraded. Treatment of cells with sphingomyelinase reduced the cell sphingomyelin content by about 76% (about 13 nmol SM degraded), and dramatically increased the desorption of [3H]cholesterol from the plasma membrane to 2-hydroxypropyl-beta-cyclodextrin. The corresponding hydrolysis of cell surface phosphatidylcholine (about 12% reduction of the cellular phosphatidylcholine content, corresponding to about 12 nmol degraded PC) had almost no effect on cell [3H]cholesterol efflux. The stimulatory effect of sphingomyelin degradation on cell [3H]cholesterol efflux was reversible, since rates of [3H]cholesterol efflux dropped back to control levels when cells (in this case baby hamster kidney cells) were allowed to restore their sphingomyelin content by re-synthesis in the absence of sphingomyelinase. The findings of this study clearly demonstrate that plasma membrane sphingomyelin markedly affected the rate of cholesterol transfer between cells and an extracellular acceptor (i.e., cyclodextrin), whereas the effect of phosphatidylcholine on cholesterol efflux was much smaller. PMID:9421186

  10. Cholesterol diet counteracts repeated anesthesia/infusion-induced cognitive deficits in male Brown Norway rats

    PubMed Central

    Hohsfield, Lindsay A.; Ehrlich, Daniela; Humpel, Christian

    2015-01-01

    A variety of cardiovascular and cerebrovascular diseases are associated with alterations in cholesterol levels and metabolism. Moreover, convincing evidence shows that high cholesterol diet can lead to learning and memory impairments. On the other hand, a significant body of research has also demonstrated that learning is improved by elevated dietary cholesterol. Despite these conflicting findings, it is clear that cholesterol plays an important role in these cognitive properties. However, it remains unclear how this blood-brain barrier (BBB)-impenetrable molecule affects the brain and under what circumstances it provides either detrimental or beneficial effects to learning and memory. The aim of this study was to characterize the effects of 5% cholesterol diet on six-month-old inbred Brown Norway rats. More important, we sought to examine the role that cholesterol can play when repeated anesthesia and intravenous infusion disrupts cognitive function. This present study supports previous work showing that enriched cholesterol diet leads to significant alterations in neuroinflammation and BBB disruption. Following repeated anesthesia and intravenous infusion of saline we observe that animals under normal diet conditions exhibit significant deficiencies in spatial learning and cholinergic neuron populations compared to animals under enriched cholesterol diet, which do not show such deficiencies. These findings indicate that cholesterol diet can protect against or counteract anesthesia/infusion-induced cognitive deficits. Ultimately, these results suggest that cholesterol homeostasis serves an important functional role in the brain and that altering this homeostasis can either exert positive or negative effects on cognitive properties. PMID:23973449

  11. Cholesterol Metabolism and Body Composition in Women: The Effects of Moderate Weight Loss

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective was to determine how moderate weight loss protocol through diet and exercise may affect changes in body composition, to determine the effects of weight loss on cholesterol metabolism, and to examine the relationship between cholesterol metabolism and changes in body composition. Thirt...

  12. Identification of Novel Cholesterol-binding Regions in Kir2 Channels*

    PubMed Central

    Rosenhouse-Dantsker, Avia; Noskov, Sergei; Durdagi, Serdar; Logothetis, Diomedes E.; Levitan, Irena

    2013-01-01

    Inwardly rectifying potassium (Kir) channels play an important role in setting the resting membrane potential and modulating membrane excitability. We have recently shown that cholesterol regulates representative members of the Kir family and that in the majority of the cases, cholesterol suppresses channel function. Furthermore, recent data indicate that cholesterol regulates Kir channels by specific sterol-protein interactions, yet the location of the cholesterol binding site in Kir channels is unknown. Using a combined computational-experimental approach, we show that cholesterol may bind to two nonanular hydrophobic regions in the transmembrane domain of Kir2.1 located between adjacent subunits of the channel. The location of the binding regions suggests that cholesterol modulates channel function by affecting the hinging motion at the center of the pore-lining transmembrane helix that underlies channel gating either directly or through the interface between the N and C termini of the channel. PMID:24019518

  13. Sphingolipid domains in the plasma membranes of fibroblasts are not enriched with cholesterol

    DOE PAGESBeta

    Frisz, Jessica F.; Klitzing, Haley A.; Lou, Kaiyan; Hutcheon, Ian D.; Weber, Peter K.; Zimmerberg, Joshua; Kraft, Mary L.

    2013-04-22

    The plasma membranes of mammalian cells are widely expected to contain domains that are enriched with cholesterol and sphingolipids. In this work, we have used high-resolution secondary ion mass spectrometry to directly map the distributions of isotope-labeled cholesterol and sphingolipids in the plasma membranes of intact fibroblast cells. Although acute cholesterol depletion reduced sphingolipid domain abundance, cholesterol was evenly distributed throughout the plasma membrane and was not enriched within the sphingolipid domains. As a result, we rule out favorable cholesterol-sphingolipid interactions as dictating plasma membrane organization in fibroblast cells. Because the sphingolipid domains are disrupted by drugs that depolymerize themore » cells actin cytoskeleton, cholesterol must instead affect the sphingolipid organization via an indirect mechanism that involves the cytoskeleton.« less

  14. Sphingolipid domains in the plasma membranes of fibroblasts are not enriched with cholesterol

    SciTech Connect

    Frisz, Jessica F.; Klitzing, Haley A.; Lou, Kaiyan; Hutcheon, Ian D.; Weber, Peter K.; Zimmerberg, Joshua; Kraft, Mary L.

    2013-04-22

    The plasma membranes of mammalian cells are widely expected to contain domains that are enriched with cholesterol and sphingolipids. In this work, we have used high-resolution secondary ion mass spectrometry to directly map the distributions of isotope-labeled cholesterol and sphingolipids in the plasma membranes of intact fibroblast cells. Although acute cholesterol depletion reduced sphingolipid domain abundance, cholesterol was evenly distributed throughout the plasma membrane and was not enriched within the sphingolipid domains. As a result, we rule out favorable cholesterol-sphingolipid interactions as dictating plasma membrane organization in fibroblast cells. Because the sphingolipid domains are disrupted by drugs that depolymerize the cells actin cytoskeleton, cholesterol must instead affect the sphingolipid organization via an indirect mechanism that involves the cytoskeleton.

  15. Dietary cholesterol modulates the excitability of rabbit hippocampal CA1 pyramidal neurons

    PubMed Central

    Wang, Desheng; Schreurs, Bernard G.

    2010-01-01

    Previous work has shown high dietary cholesterol can affect learning and memory including rabbit eyeblink conditioning and this effect may be due to increased membrane cholesterol and enhanced hippocampal amyloid beta production. This study investigated whether dietary cholesterol modulates rabbit hippocampal CA1 neuron membrane properties known to be involved in rabbit eyeblink conditioning. Whole-cell current clamp recordings in hippocampal neurons from rabbits fed 2% cholesterol or normal chow for 8 weeks revealed changes including decreased after-hyperpolarization amplitudes (AHPs) – an index of membrane excitability shown to be important for rabbit eyeblink conditioning. This index was reversed by adding copper to drinking water – a dietary manipulation that can retard rabbit eyeblink conditioning. Evidence of cholesterol effects on membrane excitability was provided by application of methyl-β-cyclodextrin, a compound that reduces membrane cholesterol, which increased the excitability of hippocampal CA1 neurons. PMID:20639007

  16. Sphingolipid Domains in the Plasma Membranes of Fibroblasts Are Not Enriched with Cholesterol*

    PubMed Central

    Frisz, Jessica F.; Klitzing, Haley A.; Lou, Kaiyan; Hutcheon, Ian D.; Weber, Peter K.; Zimmerberg, Joshua; Kraft, Mary L.

    2013-01-01

    The plasma membranes of mammalian cells are widely expected to contain domains that are enriched with cholesterol and sphingolipids. In this work, we have used high-resolution secondary ion mass spectrometry to directly map the distributions of isotope-labeled cholesterol and sphingolipids in the plasma membranes of intact fibroblast cells. Although acute cholesterol depletion reduced sphingolipid domain abundance, cholesterol was evenly distributed throughout the plasma membrane and was not enriched within the sphingolipid domains. Thus, we rule out favorable cholesterol-sphingolipid interactions as dictating plasma membrane organization in fibroblast cells. Because the sphingolipid domains are disrupted by drugs that depolymerize the cells actin cytoskeleton, cholesterol must instead affect the sphingolipid organization via an indirect mechanism that involves the cytoskeleton. PMID:23609440

  17. Pleural Fluid Cholesterol in Differentiating Exudative and Transudative Pleural Effusion

    PubMed Central

    Hamal, A. B.; Yogi, K. N.; Bam, N.; Das, S. K.; Karn, R.

    2013-01-01

    Objectives. To study the diagnostic value of pleural fluid cholesterol in differentiating transudative and exudative pleural effusion. To compare pleural fluid cholesterol level for exudates with Light's criteria. Design. Cross sectional descriptive study. Settings. Medical wards of Tribhuvan University Teaching Hospital. Methods. Sixty two cases of pleural effusion with definite clinical diagnosis admitted in TUTH were taken and classified as transudates (19) and exudates (43). The parameters pleural fluid protein/serum protein ratio (pfP/sP), pleural fluid LDH/ serum LDH ratio, pleural fluid LDH (pfLDH) and pleural fluid cholesterol (pCHOL) were compared with clinical diagnosis with regard to their usefulness for distinguishing between pleural exudates and transudates. Results. The pCHOL values determined were 1.92 ± 0.75 for exudates, 0.53 ± 0.28 for transudates, the differences between the transudates and others are statistically significant (P < 0.0001). It is seen that pfP/sP ratio has a sensitivity of 81.4% and specificity of 82.6%; pfLDH/sLDH ratio has a sensitivity of 86% and specificity of 94.7% and pCHOL with sensitivity of 97.7% and specificity of 100% for differentiating exudative and transudative PE. Conclusion. The determination of pCHOL is of great value for distinguishing between pleural exudates and transudates and should be included in routine laboratory analysis of pleural effusion. PMID:23365740

  18. Bias between enzymatic methods and the reference method for cholesterol.

    PubMed

    Kroll, M H; Lindsey, H; Greene, J; Sliva, C; Hainline, A; Elin, R J

    1988-01-01

    Assaying 312 serum samples, we compared four enzymatic methods for serum cholesterol with the Reference Method (modified Abell-Kendall) of the Centers for Disease Control (CDC). The means for the aca, TDx, and SMAC methods (2.27, 2.27, and 2.24 g/L, respectively) were significantly higher (P less than 0.05) than those of the Reference Method and the RA-1000 method (2.19 and 2.18 g/L, respectively). The biased methods had positive proportional and (or) systematic biases. Results with these methods were 2.6% to 4.9% higher than with the Reference Method. The assigned concentrations of cholesterol in the calibration materials for the SMAC and aca agreed with those obtained by the Reference Method, but were lower for the TDx and higher for the RA-1000. These findings document positive biases for cholesterol with three enzymatic methods and suggest that misassignment of calibrators is not primarily responsible for the biases found with the aca and SMAC. It may, however, to be a significant factor for the TDx. PMID:3338142

  19. Very low levels of high density lipoprotein cholesterol in four sibs of a family with non-neuropathic Niemann-Pick disease and sea-blue histiocytosis.

    PubMed Central

    Viana, M B; Giugliani, R; Leite, V H; Barth, M L; Lekhwani, C; Slade, C M; Fensom, A

    1990-01-01

    Very low serum levels of high density lipoprotein cholesterol ranging from 8.6 to 13.9 mg/dl were detected in four out of 12 sibs of a Brazilian kindred with the non-neuropathic form of Niemann-Pick disease. Hepatosplenomegaly, interstitial infiltration of the lungs, absence of neurological signs, sea-blue histiocytes in the bone marrow and liver, and high values for serum acid phosphatase (18 to 32 U/l) were common to all affected children. Leucocyte acid sphingomyelinase activity ranged from 3.6 to 6.5% of mean control values, and fibroblast activity from 9 to 13% of mean controls. The parents had low-normal levels. The relationship between these findings is unclear and deserves further investigation. Images PMID:2120445

  20. The Effect of Residing Altitude on Levels of High-Density Lipoprotein Cholesterol: A Pilot Study From the Omani Arab Population.

    PubMed

    Al Riyami, Nafila B; Banerjee, Yajnavalka; Al-Waili, Khalid; Rizvi, Syed G; Al-Yahyaee, Said; Hassan, Mohammed O; Albarwani, Sulayma; Al-Rasadi, Khalid; Bayoumi, Riad A

    2015-07-01

    Lower mortality rates from coronary heart disease and higher levels of serum high-density lipoprotein cholesterol (HDL-C) have been observed in populations residing at high altitude. However, this effect has not been investigated in Arab populations, which exhibit considerable genetic homogeneity. We assessed the relationship between residing altitude and HDL-C in 2 genetically similar Omani Arab populations residing at different altitudes. The association between the levels of HDL-C and other metabolic parameters was also investigated. The levels of HDL-C were significantly higher in the high-altitude group compared with the low-altitude group. Stepwise regression analysis showed that altitude was the most significant factor affecting HDL-C, followed by gender, serum triglycerides, and finally the 2-hour postprandial plasma glucose. This finding is consistent with previously published studies from other populations and should be taken into consideration when comparing cardiovascular risk factors in populations residing at different altitudes. PMID:25078070

  1. Ethanol enhances de novo synthesis of high density lipoprotein cholesterol

    SciTech Connect

    Cluette, J.E.; Mulligan, J.J.; Noring, R.; Doyle, K.; Hojnacki, J.

    1984-05-01

    Male squirrel monkeys fed ethanol at variable doses were used to assess whether alcohol enhances de novo synthesis of high density lipoprotein (HDL) cholesterol in vivo. Monkeys were divided into three groups: 1) controls fed isocaloric liquid diet; 2) low ethanol monkeys fed liquid diet with vodka substituted isocalorically for carbohydrate at 12% of calories; and 3) High Ethanol animals fed diet plus vodka at 24% of calories. High Ethanol primates had significantly higher levels of HDL nonesterified cholesterol than Control and Low Ethanol animals while serum glutamate oxaloacetate transaminase was similar for the three treatments. There were no significant differences between the groups in HDL cholesteryl ester mass or specific activity following intravenous injection of labeled mevalonolactone. By contrast, High Ethanol monkeys had significantly greater HDL nonesterified cholesterol specific activity with approximately 60% of the radioactivity distributed in the HDL/sub 3/ subfraction. This report provides the first experimental evidence that ethanol at 24% of calories induces elevations in HDL cholesterol in primates through enhanced de novo synthesis without adverse effects on liver function.

  2. Zymosan-mediated inflammation impairs in vivo reverse cholesterol transport.

    PubMed

    Malik, Priya; Berisha, Stela Z; Santore, Jennifer; Agatisa-Boyle, Colin; Brubaker, Gregory; Smith, Jonathan D

    2011-05-01

    Inflammation has been proposed to impair HDL function and reverse cholesterol transport (RCT). We investigated the effects of inflammation mediated by zymosan, a yeast glucan, on multiple steps along the RCT pathway in vivo and ex vivo. Acute inflammation with 70 mg/kg zymosan impaired RCT to plasma, liver, and feces similarly by 17-22% (P < 0.05), with no additional block at the liver. Hepatic gene expression further demonstrated no change in ABCG5, ABCB4, and ABCB11 expression but a decline in ABCG8 mRNA (32% P < 0.05). Plasma from zymosan-treated mice had a 21% decrease in cholesterol acceptor ability (P < 0.01) and a 35% decrease in ABCA1-specific efflux capacity (P < 0.01) in vitro. Zymosan treatment also decreased HDL levels and led to HDL remodeling with increased incorporation of serum amyloid A. In addition, cholesterol efflux from cultured macrophages declined with zymosan treatment in a dose dependent manner. Taken together, our results suggest that zymosan impairs in vivo RCT primarily by decreasing macrophage-derived cholesterol entering the plasma, with minimal additional blocks downstream. Our study supports the notion that RCT impairment is one of the mechanisms for the increased atherosclerotic burden observed in inflammatory conditions. PMID:21335620

  3. Evaluation of the effects of various factors on the serum triglyceride level in young adults.

    PubMed

    Yamasaki, R; Miyoshi, T; Imaki, M; Nakamura, T

    1994-06-01

    The life style of young adults has been receiving attention with a view to its improvement to preventing coronary heart diseases (CHD) in later life. In this study, for determining the influence of different life styles on the serum triglyceride level, we carried out surveys and laboratory studies on the relationships of the nutritional intake, physical activity, and cigarette smoking and alcohol consumption of young adults with their serum triglyceride levels. The nutritional survey indicated a significant correlation between the serum triglyceride level and carbohydrate intake (p < 0.01). In the survey of physical activity, a significant inverse correlation was found between the energy expenditure per kg body weight and the serum triglyceride level (p < 0.05). No significant relationship was found of smoking or drinking with the serum triglyceride level. The body mass index was found to have effects on both the serum triglyceride and total cholesterol levels. Of the factors examined, carbohydrate intake and energy expenditure per kg body weight had the greatest effects on the serum triglyceride level. Considering the trend for young people to consume large quantities of carbonated drinks, in which most of carbohydrate is sucrose, we tested the affect of a high carbohydrate diet on one group of subjects and found that it caused a significant increase in the serum triglyceride level (p < 0.05). Another group for whom a mild exercise regimen was prescribed showed slight, but not significant decrease in the serum triglyceride level. These results suggest that at least optimal nutrition and physical activity including weight control during adolescence are important for preventing CHD. PMID:7940529

  4. Tenuous dose-response correlations for common disease states: case study of cholesterol and perfluorooctanoate/sulfonate (PFOA/PFOS) in the C8 Health Project.

    PubMed

    Kerger, Brent D; Copeland, Teri L; DeCaprio, Anthony P

    2011-10-01

    Persistent organic chemicals, such as perfluorooctanoic acid (PFOA), perfluorooctanesulfonate (PFOS), dioxins, and polychlorinated biphenyls, pose investigative challenges because they are found in virtually everyone (there is no unexposed control group). To overcome this problem, outcome data in some studies are sorted by chemical dose level and findings in low-end dose groups are compared to sequential higher dose groups. An example is the C8 Health Project that evaluated serum PFOA/PFOS (C8) and total cholesterol among 46,294 West Virginia residents who lived, worked, or went to school for at least 1 year in a C8 contaminated drinking-water district and were over age 18 in 2005-2006. The risk for high total cholesterol (>240 mg/dL) measured via odds ratios (ORs) in logistic regression models showed sequential OR increases with PFOA quartile, in comparison to the lowest quartile (OR = 1.00), that were each significantly elevated (OR = 1.21, 1.33, and 1.40, respectively), but age, sex, and body mass index were stronger correlates. Importantly, the magnitude of cholesterol increase was small (12 mg/dL from lowest to highest exposure deciles) and comparison to similar statistics for the general U.S. population showed the C8 cohort had lower rates of high cholesterol. This suggests that inadvertent selection bias may have affected the lowest exposure quartile (control group), making tenuous the dose-response relationship between PFOA/PFOS and risk of high cholesterol. This case illustrates the substantial difficulties in assigning toxicological importance to statistical comparisons for common disease states that utilize subgroups with low exposures as an effective control group. PMID:21770727

  5. Targeting mitochondrial 18 kDa translocator protein (TSPO) regulates macrophage cholesterol efflux and lipid phenotype.

    PubMed

    Taylor, Janice M W; Allen, Anne-Marie; Graham, Annette

    2014-11-01

    The aim of the present study was to establish mitochondrial cholesterol trafficking 18 kDa translocator protein (TSPO) as a potential therapeutic target, capable of increasing macrophage cholesterol efflux to (apo)lipoprotein acceptors. Expression and activity of TSPO in human (THP-1) macrophages were manipulated genetically and by the use of selective TSPO ligands. Cellular responses were analysed by quantitative PCR (Q-PCR), immunoblotting and radiolabelling, including [3H]cholesterol efflux to (apo)lipoprotein A-I (apoA-I), high-density lipoprotein (HDL) and human serum. Induction of macrophage cholesterol deposition by acetylated low-density lipoprotein (AcLDL) increased expression of TSPO mRNA and protein, reflecting findings in human carotid atherosclerosis. Transient overexpression of TSPO enhanced efflux (E%) of [3H]cholesterol to apoA-I, HDL and human serum compared with empty vector (EV) controls, whereas gene knockdown of TSPO achieved the converse. Ligation of TSPO (using PK11195, FGIN-1-27 and flunitrazepam) triggered increases in [3H]cholesterol efflux, an effect that was amplified in TSPO-overexpressing macrophages. Overexpression of TSPO induced the expression of genes [PPARA (peroxisome-proliferator-activated receptor α), NR1H3 (nuclear receptor 1H3/liver X receptor α), ABCA1 (ATP-binding cassette A1), ABCG4 (ATP-binding cassette G4) and APOE (apolipoprotein E)] and proteins (ABCA1 and PPARα) involved in cholesterol efflux, reduced macrophage neutral lipid mass and lipogenesis and limited cholesterol esterification following exposure to AcLDL. Thus, targeting TSPO reduces macrophage lipid content and prevents macrophage foam cell formation, via enhanced cholesterol efflux to (apo)lipoprotein acceptors. PMID:24814875

  6. Identification of liver CYP51 as a gene responsive to circulating cholesterol in a hamster model.

    PubMed

    Huang, Haiqiu; Xie, Zhuohong; Yokoyama, Wallace; Yu, Liangli; Wang, Thomas T Y

    2016-01-01

    Hypercholesterolaemia is a risk factor for CVD, which is a leading cause of death in industrialised societies. The biosynthetic pathways for cholesterol metabolism are well understood; however, the regulation of circulating cholesterol by diet is still not fully elucidated. The present study aimed to gain more comprehensive understanding of the relationship between circulating cholesterol levels and molecular effects in target tissues using the hamster model. Male golden Syrian hamsters were fed with chow or diets containing 36 % energy from fat with or without 1 % cholesteyramine (CA) as a modulator of circulating cholesterol levels for 35 d. It was revealed that the expression of lanosterol 14α-demethylase (CYP51) instead of 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase mRNA expression was responsive to circulating cholesterol in hamsters fed hypercholesterolaemic diets. The high-fat diet increased circulating cholesterol and down-regulated CYP51, but not HMG-CoA reductase. The CA diet decreased cholesterol and increased CYP51 expression, but HMG-CoA reductase expression was not affected. The high-fat diet and CA diet altered the expression level of cholesterol, bile acids and lipid metabolism-associated genes (LDL receptor, cholesterol 7α-hydroxylase (CYP7A1), liver X receptor (LXR) α, and ATP-binding cassette subfamily G member 5/8 (ABCG5/8)) in the liver, which were significantly correlated with circulating cholesterol levels. Correlation analysis also showed that circulating cholesterol levels were regulated by LXR/retinoid X receptor and PPAR pathways in the liver. Using the hamster model, the present study provided additional molecular insights into the influence of circulating cholesterol on hepatic cholesterol metabolism pathways during hypercholesterolaemia. PMID:27110359

  7. Effect of dietary fenugreek seeds on biliary proteins that influence nucleation of cholesterol crystals in bile.

    PubMed

    Reddy, Raghunatha R L; Srinivasan, Krishnapura

    2011-04-01

    Formation of cholesterol gallstones in gallbladder is controlled by procrystallising and anticrystallising factors present in bile. Dietary fenugreek seed has been recently observed to possess anti-lithogenic potential in experimental mice. In the current animal study, we evaluated the effect of dietary fenugreek on the compositional changes in the bile, particularly its effect on glycoproteins, low-molecular-weight (LMW) and high-molecular-weight (HMW) proteins, cholesterol nucleation time and cholesterol crystal growth. Groups of Wistar rats were fed for 10 weeks with diets: (1) basal control (C), (2) C+fenugreek (12%), (3) high cholesterol diet (HCD) and (4) HCD+fenugreek (12%). Feeding of HCD containing 0.5% cholesterol for 10 weeks rendered the bile lithogenic. Incorporation of fenugreek into HCD decreased the cholesterol content (70.5%), total protein (58.3%), glycoprotein (27.5%), lipid peroxides (13.6%) and cholesterol saturation index (from 1.98 to 0.75) in bile, increased the bile flow rate (19.5%), prolonged the cholesterol nucleation time and reduced the vesicular form of cholesterol (65%), which was accompanied with an increase in smaller vesicular form (94%). There was an increase in biliary phospholipid (33%) and total bile acid (49%) contents in the HCD+fenugreek group as compared with the HCD group. Electrophoretic separation of biliary LMW proteins showed the presence of a high concentration of 28-kDa protein, which might be responsible for the prolongation of cholesterol nucleation time in the fenugreek-fed groups. These findings indicate that the beneficial anti-lithogenic effect of dietary fenugreek, which primarily is due to reduction in the cholesterol content in bile, was additionally affected through a modulation of the nucleating and anti-nucleating proteins, which, in turn, affect cholesterol crystallisation. PMID:21215764

  8. Trans Fatty Acid Derived Phospholipids Show Increased Membrane Cholesterol and Reduced Receptor Activation as Compared to Their Cis Analogs

    PubMed Central

    Niu, Shui-Lin; Mitchell, Drake C.; Litman, Burton J.

    2005-01-01

    The consumption of trans fatty acid (TFA) is linked to the elevation of LDL cholesterol and is considered to be a major health risk factor for coronary heart disease. Despite several decades of extensive research on this subject, the underlying mechanism of how TFA modulates serum cholesterol levels remains elusive. In this study, we examined the molecular interaction of TFA-derived phospholipid with cholesterol and the membrane receptor rhodopsin in model membranes. Rhodopsin is a prototypical member of the G-protein coupled receptor family. It has a well-characterized structure and function and serves as a model membrane receptor in this study. Phospholipid–cholesterol affinity was quantified by measuring cholesterol partition coefficients. Phospholipid–receptor interactions were probed by measuring the level of rhodopsin activation. Our study shows that phospholipid derived from TFA had a higher membrane cholesterol affinity than their cis analogues. TFA phospholipid membranes also exhibited a higher acyl chain packing order, which was indicated by the lower acyl chain packing free volume as determined by DPH fluorescence and the higher transition temperature for rhodopsin thermal denaturation. The level of rhodopsin activation was diminished in TFA phospholipids. Since membrane cholesterol level and membrane receptors are involved in the regulation of cholesterol homeostasis, the combination of higher cholesterol content and reduced receptor activation associated with the presence of TFA–phospholipid could be factors contributing to the elevation of LDL cholesterol. PMID:15766276

  9. Cigarette smoking and serum lipid and lipoprotein concentrations: an analysis of published data.

    PubMed Central

    Craig, W. Y.; Palomaki, G. E.; Haddow, J. E.

    1989-01-01

    To examine the association between cigarette smoking in adults and serum lipid and lipoprotein concentrations the results of 54 published studies were analysed. Overall, smokers had significantly higher serum concentrations of cholesterol (3.0%), triglycerides (9.1%), very low density lipoprotein cholesterol (10.4%), and low density lipoprotein cholesterol (1.7%) and lower serum concentrations of high density lipoprotein cholesterol (-5.7%) and apolipoprotein AI (-4.2%) compared with nonsmokers. Among non-smokers and light, moderate, and heavy smokers a significant dose response effect was present for cholesterol (0, 1.8, 4.3, and 4.5% respectively), triglycerides (0, 10.7, 11.5, and 18.0%), very low density lipoprotein cholesterol (0, 7.2, 44.4, and 39.0%), low density lipoprotein cholesterol (0, -1.1, 1.4, and 11.0%), high density lipoprotein cholesterol (0, -4.6, -6.3, and -8.9%), and apolipoprotein AI (0, -3.7 and -5.7% in non-smokers and light and heavy smokers). These dose response effects may provide new evidence for a causal relation between exposure to cigarette smoke and changes in serum lipid and lipoprotein concentrations whether as a direct result of physiological changes or of dietary changes induced by smoking. Adequate prospective data to estimate the excess risk of coronary artery disease existed only for cholesterol concentration. When that information was combined with data from the present study, and given that smokers as a group face an average overall excess risk of coronary artery disease of 70%, it was estimated that the observed increased serum cholesterol concentration in smokers may account for at least 9% of that excess risk. Furthermore, the dose response effect of smoking on serum cholesterol concentration suggests a gradient of increased absolute risk of coronary artery disease between light and heavy smokers. PMID:2496857

  10. Polarizable multipolar electrostatics for cholesterol

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

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

  11. Orally delivered microencapsulated live probiotic formulation lowers serum lipids in hypercholesterolemic hamsters.

    PubMed

    Bhathena, Jasmine; Martoni, Christopher; Kulamarva, Arun; Urbanska, Aleksandra M; Malhotra, Meenakshi; Prakash, Satya

    2009-04-01

    Elevated serum cholesterol is a major risk factor for coronary artery disease. Nutritional therapies such as probiotics have been suggested to manage elevated cholesterol. This study investigates the cholesterol and triglyceride lowering potential of a microencapsulated feruloyl esterase-producing Lactobacillus fermentum 11976 (LF11976) probiotic formulation. Male Bio F(1)B hamsters were assigned to two groups to receive either the microcapsule probiotic formulation (containing LF11976 cells at 12.51 log colony-forming units/mL) or placebo formulation (empty) microcapsules, twice daily, by oral gavage for 18 weeks. For the duration of the study, animals were fed a hypercholesterolemic diet. Serum total cholesterol, low-density lipoprotein (LDL) cholesterol, and the atherogenic index were 21.36%, 31.43%, and 32.59% lower in the group gavaged with the microencapsulated probiotic formulation than in the placebo control group after 18 weeks (P < .05). Histology studies showed reduced progression of atherosclerotic lesions in animals treated with microencapsulated LF11976 as compared to control animals. Treatment with microencapsulated LF11976 formulation produces significant reductions in serum total cholesterol, LDL cholesterol, and serum triglyceride levels in diet-induced hypercholesterolemic hamsters. Findings suggest the potential of the oral microencapsulated probiotic cell formulation as a functional nutritional alternative for managing excessive serum cholesterol and triglyceride levels. PMID:19459731

  12. Cholesterol regulatory effects and antioxidant activities of protein hydrolysates from zebra blenny (Salaria basilisca) in cholesterol-fed rats.

    PubMed

    Ktari, Naourez; Belguith-Hadriche, Olfa; Ben Amara, Ibtissem; Ben Hadj, Aïda; Turki, Mouna; Makni-Ayedi, Fatma; Boudaouara, Tahia; El Feki, Abdelfattah; Boualga, Ahmed; Ben Salah, Riadh; Nasri, Moncef

    2015-07-01

    This study aims to explore the hypocholesterolemic effects and antioxidative activities of zebra blenny protein hydrolysates (ZBPHs) in rats fed with a hypercholesterolemic diet. The rats were fed during eight weeks a standard laboratory diet (normal rats), a high-cholesterol diet (HCD) (1%) or a HCD and orally treated with ZBPHs or undigested zebra blenny proteins (UZBPs) (400 mg per kg per day). Results showed that a hypercholesterolemic diet induced the increase of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C). Treatment with ZBPHs increased the level of high-density lipoprotein cholesterol (HDL-C) and decreased significantly the levels of TC, TG, and LDL-C. In addition, ZBPH treatment showed significant normalization of thiobarbituric acid-reactive substance (TBARS) levels as well as catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities in renal and hepatic tissues. Furthermore, ZBPHs may also exert significant protective effects on liver and kidney functions, evidenced by a marked decrease in the level of serum urea, uric acid, creatinine, alkaline phosphatase (ALP), and alanine aminotransferase (ALAT). Histological studies confirmed that ZBPHs effectively protected the livers and kidneys against hypercholesterolemia-mediated oxidative damage. Therefore, the study strengthens the hypothesis that ZBPHs can be used as novel antioxidants and hypocholesterolemic compounds against hyperlipidemia induced atherosclerosis. PMID:26065510

  13. Effectiveness of different corticosterone administration methods to elevate corticosterone serum levels, induce depressive-like behavior, and affect neurogenesis levels in female rats.

    PubMed

    Kott, J M; Mooney-Leber, S M; Shoubah, F A; Brummelte, S

    2016-01-15

    High levels of chronic stress or stress hormones are associated with depressive-like behavior in animal models. However, slight elevations in corticosterone (CORT) - the major stress hormone in rodents - have also been associated with improved performances, albeit in a sex-dependent manner. Some of the discrepancies in the literature regarding the effects of high CORT levels may be due to different administrations methods. The current study aims to compare the effects of ∼40mg/kg given either via subcutaneous injection, through an implanted pellet, or in the drinking water, for ∼21days on CORT serum levels, depressive-like behavior in the forced swim test (FST), and neurogenesis levels in the dentate gyrus (DG) in adult female rats. We found that animals exposed to the daily injections showed elevated CORT levels throughout the administration period, while the pellet animals showed only a transient increase, and drinking water animals revealed no elevation in CORT in serum. In addition, only the injection group exhibited higher levels of immobility in the FST. Interestingly, animals receiving CORT via injection or drinking water had lower numbers of doublecortin-positive cells in the ventral DG one week after the last CORT administration compared to animals implanted with a CORT pellet. These results will contribute to the growing literature on the effects of chronic CORT exposure and may help to clarify some of the discrepancies among previous studies, particularly in females. PMID:26556064

  14. Cholesterol gallstone disease: focusing on the role of gallbladder.

    PubMed

    Chen, Yongsheng; Kong, Jing; Wu, Shuodong

    2015-02-01

    Gallstone disease (GSD) is one of the most common biliary tract diseases worldwide in which both genetic and environmental factors have roles in its pathogenesis. Biliary cholesterol supersaturation from metabolic defects in the liver is traditionally seen as the main pathogenic factor. Recently, there have been renewed investigative interests in the downstream events that occur in gallbladder lithogenesis. This article focuses on the role of the gallbladder in the pathogenesis of cholesterol GSD (CGD). Various conditions affecting the crystallization process are discussed, such as gallbladder motility, concentrating function, lipid transport, and an imbalance between pro-nucleating and nucleation inhibiting proteins. PMID:25502177

  15. HDL cholesterol and bone mineral density: Is there a genetic link?

    PubMed Central

    Ackert-Bicknell, Cheryl L.

    2011-01-01

    Overwhelming evidence has linked cardiovascular disease and osteoporosis, but the shared root cause of these two diseases of the elderly remains unknown. Low levels of high-density lipoprotein cholesterol (HDL) and bone mineral density (BMD) are risk factors for cardiovascular disease and osteoporosis respectively. A number of correlation studies have attempted to determine if there is a relationship between serum HDL and BMD but these studies are confounded by a number of variables including age, diet, genetic background, gender and hormonal status. Collectively, these data suggest that there is a relationship between these two phenotypes, but that the nature of this relationship is context specific. Studies in mice plainly demonstrate that genetic loci for BMD and HDL co-map and transgenic mouse models have been used to show that a single gene can affect both serum HDL and BMD. Work completed to date has demonstrated that HDL can interact directly with both osteoblasts and osteoclasts, but no direct evidence links bone back to the regulation of HDL levels. Understanding the genetic relationship between BMD and HDL has huge implications for understanding the clinical relationship between CVD and osteoporosis and for the development of safe treatment options for both diseases. PMID:21810493

  16. Feedback modulation of cholesterol metabolism by the lipid-responsive non-coding RNA LeXis.

    PubMed

    Sallam, Tamer; Jones, Marius C; Gilliland, Thomas; Zhang, Li; Wu, Xiaohui; Eskin, Ascia; Sandhu, Jaspreet; Casero, David; Vallim, Thomas Q de Aguiar; Hong, Cynthia; Katz, Melanie; Lee, Richard; Whitelegge, Julian; Tontonoz, Peter

    2016-06-01

    Liver X receptors (LXRs) are transcriptional regulators of cellular and systemic cholesterol homeostasis. Under conditions of excess cholesterol, LXR activation induces the expression of several genes involved in cholesterol efflux, facilitates cholesterol esterification by promoting fatty acid synthesis, and inhibits cholesterol uptake by the low-density lipoprotein receptor. The fact that sterol content is maintained in a narrow range in most cell types and in the organism as a whole suggests that extensive crosstalk between regulatory pathways must exist. However, the molecular mechanisms that integrate LXRs with other lipid metabolic pathways are incompletely understood. Here we show that ligand activation of LXRs in mouse liver not only promotes cholesterol efflux, but also simultaneously inhibits cholesterol biosynthesis. We further identify the long non-coding RNA LeXis as a mediator of this effect. Hepatic LeXis expression is robustly induced in response to a Western diet (high in fat and cholesterol) or to pharmacological LXR activation. Raising or lowering LeXis levels in the liver affects the expression of genes involved in cholesterol biosynthesis and alters the cholesterol levels in the liver and plasma. LeXis interacts with and affects the DNA interactions of RALY, a heterogeneous ribonucleoprotein that acts as a transcriptional cofactor for cholesterol biosynthetic genes in the mouse liver. These findings outline a regulatory role for a non-coding RNA in lipid metabolism and advance our understanding of the mechanisms that coordinate sterol homeostasis. PMID:27251289

  17. Cholesterol Lowering Effect of Plant Stanol Ester Yoghurt Drinks with Added Camelina Oil

    PubMed Central

    Salo, Pia; Kuusisto, Päivi

    2016-01-01

    The aim of this study was to investigate the effects of yoghurt minidrinks containing two doses of plant stanol ester either with or without added camelina oil on the serum cholesterol levels in moderately hypercholesterolemic subjects. In this randomised, double-blind, parallel group study, 143 subjects consumed a 65 mL minidrink together with a meal daily for four weeks. The minidrink contained 1.6 or 2.0 grams of plant stanols with or without 2 grams of alpha-linolenic acid-rich camelina oil. The placebo minidrink did not contain plant stanols or camelina oil. All plant stanol treated groups showed statistically significant total, LDL, and non-HDL cholesterol lowering relative to baseline and relative to placebo. Compared to placebo, LDL cholesterol was lowered by 9.4% (p < 0.01) and 8.1% (p < 0.01) with 1.6 g and 2 g plant stanols, respectively. With addition of Camelina oil, 1.6 g plant stanols resulted in 11.0% (p < 0.01) and 2 g plant stanols in 8.4% (p < 0.01) reduction in LDL cholesterol compared to placebo. In conclusion, yoghurt minidrinks with plant stanol ester reduced serum LDL cholesterol significantly and addition of a small amount of camelina oil did not significantly enhance the cholesterol lowering effect. This trial was registered with ClinicalTrials.gov NCT02628990. PMID:26998355

  18. HDL-apolipoprotein A-I exchange is independently associated with cholesterol efflux capacity.

    PubMed

    Borja, Mark S; Ng, Kit F; Irwin, Angela; Hong, Jaekyoung; Wu, Xing; Isquith, Daniel; Zhao, Xue-Qiao; Prazen, Bryan; Gildengorin, Virginia; Oda, Michael N; Vaisar, Tomáš

    2015-10-01

    HDL is the primary mediator of cholesterol mobilization from the periphery to the liver via reverse cholesterol transport (RCT). A critical first step in this process is the uptake of cholesterol from lipid-loaded macrophages by HDL, a function of HDL inversely associated with prevalent and incident cardiovascular disease. We hypothesized that the dynamic ability of HDL to undergo remodeling and exchange of apoA-I is an important and potentially rate-limiting aspect of RCT. In this study, we investigated the relationship between HDL-apoA-I exchange (HAE) and serum HDL cholesterol (HDL-C) efflux capacity. We compared HAE to the total and ABCA1-specific cholesterol efflux capacity of 77 subjects. We found that HAE was highly correlated with both total (r = 0.69, P < 0.0001) and ABCA1-specific (r = 0.47, P < 0.0001) efflux, and this relationship remained significant after adjustment for HDL-C or apoA-I. Multivariate models of sterol efflux capacity indicated that HAE accounted for approximately 25% of the model variance for both total and ABCA1-specific efflux. We conclude that the ability of HDL to exchange apoA-I and remodel, as measured by HAE, is a significant contributor to serum HDL efflux capacity, independent of HDL-C and apoA-I, indicating that HDL dynamics are an important factor in cholesterol efflux capacity and likely RCT. PMID:26254308

  19. Cholesterol Lowering Effect of Plant Stanol Ester Yoghurt Drinks with Added Camelina Oil.

    PubMed

    Salo, Pia; Kuusisto, Päivi

    2016-01-01

    The aim of this study was to investigate the effects of yoghurt minidrinks containing two doses of plant stanol ester either with or without added camelina oil on the serum cholesterol levels in moderately hypercholesterolemic subjects. In this randomised, double-blind, parallel group study, 143 subjects consumed a 65 mL minidrink together with a meal daily for four weeks. The minidrink contained 1.6 or 2.0 grams of plant stanols with or without 2 grams of alpha-linolenic acid-rich camelina oil. The placebo minidrink did not contain plant stanols or camelina oil. All plant stanol treated groups showed statistically significant total, LDL, and non-HDL cholesterol lowering relative to baseline and relative to placebo. Compared to placebo, LDL cholesterol was lowered by 9.4% (p < 0.01) and 8.1% (p < 0.01) with 1.6 g and 2 g plant stanols, respectively. With addition of Camelina oil, 1.6 g plant stanols resulted in 11.0% (p < 0.01) and 2 g plant stanols in 8.4% (p < 0.01) reduction in LDL cholesterol compared to placebo. In conclusion, yoghurt minidrinks with plant stanol ester reduced serum LDL cholesterol significantly and addition of a small amount of camelina oil did not significantly enhance the cholesterol lowering effect. This trial was registered with ClinicalTrials.gov NCT02628990. PMID:26998355

  20. ABCC6- a new player in cellular cholesterol and lipoprotein metabolism?

    PubMed Central

    2014-01-01

    Background Dysregulations in cholesterol and lipid metabolism have been linked to human diseases like hypercholesterolemia, atherosclerosis or the metabolic syndrome. Many ABC transporters are involved in trafficking of metabolites derived from these pathways. Pseudoxanthoma elasticum (PXE), an autosomal-recessive disease caused by ABCC6 mutations, is characterized by atherogenesis and soft tissue calcification. Methods In this study we investigated the regulation of cholesterol biosynthesis in human dermal fibroblasts from PXE patients and healthy controls. Results Gene expression analysis of 84 targets indicated dysregulations in cholesterol metabolism in PXE fibroblasts. Transcript levels of ABCC6 were strongly increased in lipoprotein-deficient serum (LPDS) and under serum starvation in healthy controls. For the first time, increased HMG CoA reductase activities were found in PXE fibroblasts. We further observed strongly elevated transcript and protein levels for the proprotein convertase subtilisin/kexin type 9 (PCSK9), as well as a significant reduction in APOE mRNA expression in PXE. Conclusion Increased cholesterol biosynthesis, elevated PCSK9 levels and reduced APOE mRNA expression newly found i