| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Ask the doctor. I take medicine to lower my cholesterol. My doctor says that I've reached my target (my LDL is just under 100 mg/dL), but I wonder whether I should try to get my cholesterol even lower. I haven't heard that you'll get hurt by taking too much of these drugs, so why shouldn't I increase my dose? Lee, T. H. (2001), Harv Heart Lett 11(9): 7-8. |
| Ask the doctor. Just two years ago, my total cholesterol was 175 mg/dL, and my LDL cholesterol was 128 mg/dL. This week my doctor told me that my cholesterol was 240 and my LDL was 170. I haven't gained any weight or changed my diet--what's going on? Lee, T. H. (2000), Harv Heart Lett 11(2): 8. |
| Ask the doctor. My cholesterol profile is pretty good, except that my HDL level is only 32 mg/dL, and I know the normal range is 40 or more. My LDL cholesterol is 110 mg/dL and my triglycerides are in the normal range. I don't have a history of heart disease and I've never had any symptoms (or diagnosis) of heart disease. Should I be taking a drug to raise my HDL? Lee, T. H. (2001), Harv Heart Lett 11(11): 7. |
| Ask the doctor. My total cholesterol level is well below 200. My LDL is low, my HDL high, and my triglycerides and homocysteine are both in the "desirable" range. The one thing out of whack is that my lipoprotein(a) level is more than double the "normal" limit. My cardiologist wants me to take niacin to bring it down. I can't find any information on how serious a problem this is, especially in the context of otherwise good cholesterol levels and a healthy lifestyle. (I exercise 5 days a week; eat a low-fat, high-fiber diet; and am not overweight.) Lee, T. H. (2002), Harv Heart Lett 12(10): 8. |
| Ask the doctor. Taking a cholesterol-lowering statin has brought down my bad cholesterol (LDL) to only 37 mg/dL. My liver and muscles are fine. The very low LDL worries my doctor. Should I change my regimen? Lee, T. H. (2002), Harv Heart Lett 13(2): 8. |
| Ask the Doctor: I am a woman, age 48, in generally good health, although I've gained about 10 pounds over the past two years. My LDL cholesterol us 142 mg/dL and my HDL cholesterol is 58 mg/dL. I looked at the news reports on the new cholesterol guidelines and was extremely unhappy to see that my LDL is "borderline high". My doctor says I don't need drug therapy. What do you think? Lee, T. H. (2001), Harv Heart Lett 12(1): 8. |
| Aspen Bile Acid/Cholesterol Conference 1991. Report of a conference Steinberg, D. (1992), J Lipid Res 33(6): 937-42. |
| Aspen Hepatic Cholesterol and Lipoprotein Conference 1989. Report of a conference Grundy, S. M. and G. Getz (1990), J Lipid Res 31(7): 1327-33. |
| Aspergillus oryzae produces compounds inhibiting cholesterol biosynthesis downstream of dihydrolanosterol Hajjaj, H., P. Duboc, et al. (2005), FEMS Microbiol Lett 242(1): 155-9. Abstract: The formation of cholesterol synthesis inhibiting molecules by five different strains of the koji mold Aspergillus oryzae was studied. After growing these strains on a complex liquid medium we found in crude organic phase extracts and specific fractions there from compounds inhibiting cholesterol synthesis in human hepatic T9A4 cells in vitro at enzyme sites downstream of dihydrolanosterol. This was evidenced by using different radioactively labeled precursors, namely acetate, mevalonate, 24,25-dihydro-24,25-(3)H2-lanosterol or 3-(3)H-lathosterol. |
| Aspirin attenuates the initiation but not the progression of atherosclerosis in apolipoprotein E-deficient mice fed a high-fat, high-cholesterol diet Tous, M., N. Ferre, et al. (2004), Basic Clin Pharmacol Toxicol 95(1): 15-9. Abstract: Aspirin has potent antiinflammatory properties and attenuates atherosclerosis in apolipoprotein-E-deficient mice fed a high-fat, high-cholesterol diet. In an attempt to clarify the contradictory results obtained with normal chow, we studied the effect of aspirin for a prolonged period of time. The mice were fed a commercial chow until the experiment began at 8 weeks of age. Blood samples were then obtained and several mice (n=8) were sacrificed. The diet of the remaining 48 animals was supplemented with 200 g/kg palm fat and 1 g/kg cholesterol. They were then randomly divided into 2 groups, one of which received 0.5 mg/day of aspirin. The aspirin had a time-dependent effect. First, the extent of lesion decreased; then the effect was neutral; and, finally, after longer periods of being fed the atherogenic diet and receiving aspirin, the extent of the lesion increased. The transitory effect of aspirin should be elucidated in the absence of high dietary lipids. |
| Aspirin does not inhibit cholesterol cholelithiasis in two established animal models Cohen, B. I., E. H. Mosbach, et al. (1991), Gastroenterology 101(4): 1109-16. Abstract: The effect of aspirin on cholesterol cholelithiasis was examined in the hamster and the prairie dog. In the prairie dog, diets were composed of semipurified components of chow, plus cholesterol (1.2%), with and without aspirin. Animals were studied for either 2 weeks or 4 weeks. Cholesterol gallstones were present in all groups at the end of each period; aspirin did not alter the incidence of cholelithiasis. All animals studied had cholesterol crystals in the bile when they were killed. Liver cholesterol levels in prairie dogs with and without aspirin tended to be lower in animals fed chow than in animals fed semipurified diets. There were no significant differences in cholesterol levels in the plasma or bile. The cholesterol saturation index of all biles approached unity when animals were fed chow with aspirin; animals fed the semipurified diets had cholesterol saturation indices of less than 1.0. The prairie dogs fed aspirin plus cholesterol in the semipurified diet showed increased levels of biliary chenodeoxycholic acid amidates and concomitant decreased levels of cholic acid amidates compared with animals fed the same diet without aspirin. Hamsters fed aspirin plus cholesterol in a semipurified diet tended to have a greater incidence of gallstones than animals given no aspirin (80% vs. 55%). Liver and bile cholesterol levels were similar with and without aspirin; plasma cholesterol levels increased significantly with aspirin 14.20 vs. 7.80 mmol/L (549 vs. 301 mg/dL). Lithogenic indices in all hamsters were above unity; biliary lipids, total lipid concentration, and biliary bile acid composition were similar. These results show that the addition of aspirin to a lithogenic diet does not reduce the incidence of cholelithiasis. |
| Aspirin reduces blood cholesterol in copper-deficient rats: a potential antioxidant agent? Fields, M., C. G. Lewis, et al. (2001), Metabolism 50(5): 558-61. Abstract: The purpose of this study was to examine whether the hypocholesterolemic effect of aspirin is to due to its antioxidant properties. Oxidative stress was induced in rats by feeding them a copper-deficient diet. Copper deficiency reduced the activity of the enzyme superoxide dismutase (SOD) and lowered liver copper concentration but elevated liver iron. The combination of reduced SOD activity, high liver iron, and low liver copper resulted in an oxidative stress assessed by increased liver lipid peroxidation compared with copper-adequate controls. In addition, copper-deficient rats exhibited elevation of blood cholesterol. The administration of aspirin lowered both liver lipid peroxidation and blood cholesterol. It is suggested that the hypocholesterolemic properties of aspirin could be due to its ability to reduce oxidative stress. |
| Assay instrument-dependent matrix effects in standardization of cholesterol measurements Waymack, P. P., W. G. Miller, et al. (1993), Clin Chem 39(10): 2058-62. Abstract: Human serum-based frozen reference materials have been used by the Centers for Disease Control and Prevention (CDC)-National Heart, Lung and Blood Institute Lipid Standardization Program to improve the precision and accuracy of blood cholesterol measurements. Occasionally, laboratories in the program have had problems obtaining results for patients' fresh serum samples equivalent to those obtained with frozen CDC standardization pools. This incompatibility of sample, reagent, instrument, and assay characteristics has been labeled broadly as a "matrix effect," which usually is attributed to unknown characteristics of the processed pool material. In this study we showed that a large negative bias obtained with CDC pools was attributable to use of the sample blank mode on the Cobas-Bio analyzer. However, under the same conditions, fresh patients' serum samples were analyzed accurately. The use of a blank absorbance immediately after mixing sample and reagents (the "autoblank" mode) allowed the instrument to accurately analyze both fresh serum samples and CDC standardization pools and thus allowed the documentation of traceability of the cholesterol measurements to the National Reference System for Cholesterol. |
| Assays of lecithin cholesterol acyltransferase (LCAT) Dobiasova, M. and J. J. Frohlich (1998), Methods Mol Biol 110: 217-30. |
| Assembly and topography of the prepore complex in cholesterol-dependent cytolysins Heuck, A. P., R. K. Tweten, et al. (2003), J Biol Chem 278(33): 31218-25. Abstract: Cholesterol-dependent cytolysins are a family of poreforming proteins that have been shown to be virulence factors for a large number of pathogenic bacteria. The mechanism of pore formation for these toxins involves a complex series of events that are known to include binding, oligomerization, and insertion of a transmembrane beta-barrel. Several features of this mechanism remain poorly understood and controversial. Whereas a prepore mechanism has been proposed for perfringolysin O, a very different mechanism has been proposed for the homologous member of the family, streptolysin O. To distinguish between the two models, a novel approach that directly measures the dimension of transmembranes pores was used. Pore formation itself was examined for both cytolysins by encapsulating fluorescein-labeled peptides and proteins of different sizes into liposomes. When these liposomes were re-suspended in a solution containing anti-fluorescein antibodies, toxin-mediated pore formation was monitored directly by the quenching of fluorescein emission as the encapsulated molecules were released, and the dyes were bound by the antibodies. The analysis of pore formation determined using this approach reveals that only large pores are produced by perfringolysin O and streptolysin O during insertion (and not small pores that grow in size). These results are consistent only with the formation of a prepore complex intermediate prior to insertion of the transmembrane beta-barrel into the bilayer. Fluorescence quenching experiments also revealed that PFO in the prepore complex contacts the membrane via domain 4, and that the individual transmembrane beta-hairpins in domain 3 are not exposed to the nonpolar core of the bilayer at this intermediate stage. |
| Assembly of myelin by association of proteolipid protein with cholesterol- and galactosylceramide-rich membrane domains Simons, M., E. M. Kramer, et al. (2000), J Cell Biol 151(1): 143-54. Abstract: Myelin is a specialized membrane enriched in glycosphingolipids and cholesterol that contains a limited spectrum of proteins. We investigated the assembly of myelin components by oligodendrocytes and analyzed the role of lipid-protein interactions in this process. Proteolipid protein (PLP), the major myelin protein, was recovered from cultured oligodendrocytes from a low-density CHAPS-insoluble membrane fraction (CIMF) enriched in myelin lipids. PLP associated with the CIMF after leaving the endoplasmic reticulum but before exiting the Golgi apparatus, suggesting that myelin lipid and protein components assemble in the Golgi complex. The specific association of PLP with myelin lipids in CIMF was supported by the finding that it was efficiently cross-linked to photoactivable cholesterol, but not to phosphatidylcholine, which is underrepresented in both myelin and CIMF. Furthermore, depletion of cholesterol or inhibition of sphingolipid synthesis in oligodendrocytes abolished the association of PLP with CIMF. Thus, PLP may be recruited to myelin rafts, represented by CIMF, via lipid-protein interactions. In contrast to oligodendrocytes, after transfection in BHK cells, PLP is absent from isolated CIMF, suggesting that PLP requires specific lipids for raft association. In mice deficient in the enzyme ceramide galactosyl transferase, which cannot synthesize the main myelin glycosphingolipids, a large fraction of PLP no longer associates with rafts. Formation of a cholesterol- and galactosylceramide-rich membrane domain (myelin rafts) may be critical for the sorting of PLP and assembly of myelin in oligodendrocytes. |
| Assessing heart disease risk in primary care. Cholesterol lowering should be just one part of a multiple risk factor intervention Fahey, T. (1998), Bmj 317(7166): 1093-4. |
| Assessing hypercholesterolemias by total and non-high-density lipoprotein cholesterol Lippi, U., M. S. Graziani, et al. (1990), Clin Chem 36(7): 1391. |
| Assessing low levels of high-density lipoprotein cholesterol as a risk factor in coronary heart disease: a working group report and update Gotto, A. M., Jr. and E. A. Brinton (2004), J Am Coll Cardiol 43(5): 717-24. Abstract: Clinical data show that a 1% increase in serum concentrations of high-density lipoprotein cholesterol (HDL-C) can decrease cardiovascular risk by 2% to 3%. Therefore, mechanisms affecting the level and functionality of high-density lipoprotein (HDL) and its constituents are being investigated as targets for the rational development of drugs to prevent or treat cardiovascular disease. High-density lipoprotein-related research may also increase our understanding of the link between atherosclerosis and metabolic disorders. This report and update of the HDL Working Group discusses HDL metabolism and reverse cholesterol transport, impaired HDL as a marker and a cause of proatherogenic states, and experimental and current approaches to HDL-related therapy. |
| Assessing plasma pharmacokinetics of cholesterol following oral coadministration with a novel vegetable stanol mixture to fasting rats Wasan, K. M., L. Holtorf, et al. (2001), J Pharm Sci 90(1): 23-8. Abstract: The purpose of this project was to assess the plasma pharmacokinetics of (3)Hcholesterol following coadministration of a novel vegetable stanol mixture composed of sitostanol and campestanol (FCP-3P4) to fasting rats. Following an overnight fast (12-16 h) and 48 h post-surgery, adult male Sprague Dawley rats were divided into six treatment groups and received a single-dose oral gavage at 0700 h of either: (3)Hcholesterol (25 microCi/mL), FCP-3P4 (5 mg/kg) + (3)Hcholesterol (25 microCi/mL), FCP-3P4 (12.5 mg/kg) + (3)Hcholesterol (25 microCi/mL), FCP-3P4 (25 mg/kg) + (3)Hcholesterol (25 microCi/mL), FCP-3P4 (50 mg/kg) + (3)Hcholesterol (25 microCi/mL), or FCP-3P4 (100 mg/kg) + (3)Hcholesterol (25 microCi/mL). Intralipid (10%) was the vehicle used to solubilize and coadminister (3)Hcholesterol and FCP-3P4. Liquid chromatography-mass spectrometry analysis confirmed minimal cholesterol and vegetable stanol content within 10% Intralipid. Analysis of plasma pharmacokinetics was initiated by sampling 0.5 mL of blood prior to and 0.25, 0.5 1.0, 2.0, 4.0, 6.0, 8.0, 10, 24, 28, 32, and 48 h post-oral gavage. Plasma samples were obtained by centrifugation of the blood samples and analyzed for (3)Hcholesterol radioactivity. Pharmacokinetics analysis was performed by standard noncompartmental methods using statistical moment theory. Thin-layer chromatography was used to confirm that the majority of radioactivity measured in plasma was cholesterol (in the form of esterified or unesterified cholesterol). Greater than 90% of the radioactivity measured in all plasma samples was cholesterol-associated (in the form of either esterified or unesterified cholesterol). The coadministration of FCP-3P4 significantly decreased the area under the curve of (3)Hcholesterol concentration versus time from 0 to 48 h (AUC(0-48h)) and maximum concentration (C(max)) in a dose-dependent manner. However, coadministration of FCP-3P4 at 25, 50, and 100 mg/kg resulted in a significant increase in apparent total body clearance (CL/F, where F is the bioavailability constant), apparent volume of distribution (V(d)/F), and oral absorption rate constant (k(a)) of (3)Hcholesterol compared with controls. These findings suggest that the novel vegetable stanol mixture, FCP-3P4, modifies the plasma pharmacokinetics of (3)Hcholesterol in fasting rats on oral coadministration. |