| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Design and preliminary results of a randomized study on the conversion of treatment with calcineurin inhibitors to mycophenolate mofetil in chronic renal graft failure: effect, on serum cholesterol levels Suwelack, B., U. Gerhardt, et al. (2002), Transplant Proc 34(5): 1803-5. |
| Design and rationale of the ARBITER trial (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol)--a randomized trial comparing the effects of atorvastatin and pravastatin on carotid artery intima-media thickness Markwood, T. T., S. M. Kent, et al. (2001), Am Heart J 141(3): 342-7. Abstract: BACKGROUND: As a class, statins are remarkably effective in reducing low-density lipoprotein (LDL) cholesterol, and several of these drugs have now been shown to reduce coronary heart disease morbidity and mortality. However, several important controversies in the use of statins remain to be answered by clinical trials. For example, it is controversial whether marked cholesterol reduction to levels below 100 mg/dL would further reduce the incidence of coronary heart disease. Furthermore, concerns about differences among statins for nonlipid effects has raised the concern that the assumption of a class effect is premature until head-to-head clinical trials are completed. METHODS: Arterial Biology for the Investigation for the Treatment Effects of Reducing Cholesterol (ARBITER) is a single-center, randomized, active-controlled study comparing the efficacy of high-dose atorvastatin (80 mg/d) and pravastatin (40 mg/d) in patients being treated for either the primary or secondary prevention of coronary heart disease. This trial will enroll up to 200 patients for the primary end point of the mean change in intima-media thickness of the common carotid artery. This effect will be evaluated over a treatment duration of 12 months. Secondary end points include the effects of statin therapy on inflammatory and hemostatic markers (C-reactive protein and fibrinogen). CONCLUSION: ARBITER will provide important data on the role of marked LDL reduction and the "class effect" theory of statin therapy in cardiovascular medicine. |
| Design and synthesis of tricyclic derivatives as high density lipoprotein cholesterol enhancers Elokdah, H., S. Y. Chai, et al. (2001), Bioorg Med Chem Lett 11(3): 339-42. Abstract: A pharmacophore for increasing HDLC was proposed based on common structural features of non-thio-containing compounds with HDLC enhancing properties. A search of the compound database identified various series of these non-thio-containing compounds, including a novel tricyclic imidazoisoquinolone. Preparation of 1-aryl-3-oxo-1,3-dihydro-2-benzofuran-1-carboxamides using a novel and widely applicable one-step process from 2-acyl benzoic acids is reported. Reaction of diamines with 1-aryl-3-oxo-1,3-dihydro-2-benzofuran-1-carboxamides and related aza-analogues proceeded with regio-control to furnish imidazoisoquinolones, pyrimidoisoquinolones, and imidazonaphthyridines. NMR studies and X-ray crystallography confirmed the regiochemistry of the products. Compounds of these series increased concentrations of HDLC in test animals following oral administration. |
| Design of a new class of amphipathic helical peptides for the plasma apolipoproteins that promote cellular cholesterol efflux but do not activate LCAT Labeur, C., L. Lins, et al. (1997), Arterioscler Thromb Vasc Biol 17(3): 580-8. Abstract: Amphipathic helical peptides represent the lipid-binding units of the soluble plasma apolipoproteins. Several synthetic peptide analogues have been designed to mimic such structures and have been used to unravel some of the mechanisms involved in the physiological function of the apolipoproteins, including lipid binding, LCAT activation, and enhancement of cholesterol efflux from lipid-laden cells. A series of novel synthetic peptides, named ID peptides, was modeled on the basis of the structural properties common to the amphipathic helices of apolipoprotein (apo) A-I. In these new peptides, however, the segregation between hydrophobic and hydrophilic faces of the helices is more pronounced than in apoA-I, so that the surface of the hydrophobic and hydrophilic faces of the amphipathic helices is equal. Moreover, there are fewer negatively charged residues in the center of the hydrophilic face of the helical peptides. Most charged amino acids are located along the edge of the helix and are susceptible to forming salt bridges with residues of an antiparallel helix, such as around a discoidal phospholipid/peptide complex. The physicochemical characteristics of these peptides and their complexes with phospholipids were compared with those of the 18A peptide and its lipid/peptide complex. All ID peptides bind dimyristoylphosphatidylcholine vesicles more rapidly than the 18A peptide to yield discoidal peptide/phospholipid complexes of comparable size. The alpha-helical content of the lipid-free ID peptides is close to that of the 18A peptide and increases slightly on lipid binding. The stability of the ID and 18A peptides and of the phospholipid/peptide complexes against guanidinium hydrochloride denaturation is higher than that of lipid-free and lipid-bound apoA-I. LCAT activation by the 18A/phospholipid/cholesterol complexes equals that of apoA-I/ phospholipid/cholesterol complexes, whereas none of the ID peptides tested is able to activate LCAT to a significant extent. Incubation of the peptide/phospholipid complexes with lipid-laden macrophages induces cellular cholesterol efflux and incorporation of cholesterol into the complexes. The cholesterol efflux capacity of the peptide/phospholipid complexes is comparable among the peptides and higher than that of apoprotein/phospholipid complexes. In conclusion, although the amphipathicity of the new peptides is higher than that of the 18A model peptide, the lack of LCAT activation by the ID peptides suggests that an enhanced segregation of the hydrophobic and hydrophilic residues, equal magnitude of hydrophobic and hydrophilic faces of the helix, and the absence of negatively charged residues in the central part of the hydrophilic face might account for the lack of LCAT activity of these peptides. These parameters do not affect the capacity of the peptide/phospholipid complexes to promote cellular cholesterol efflux. |
| Design, synthesis, and biological evaluation of thio-containing compounds with serum HDL-cholesterol-elevating properties Elokdah, H., T. S. Sulkowski, et al. (2004), J Med Chem 47(3): 681-95. Abstract: A novel series of substituted sulfanyldihydroimidazolones (1) that modulates high-density lipoprotein cholesterol (HDL-C) has been reported to have HDL-elevating properties in several animal models. Concerns about the chemical and metabolic stability of 1 directed us to explore the structure-activity relationship (SAR) of a related series of substituted thiohydantoins (2). Expansion of the scope of the thiohydantoin series led to exploration of compounds in related thio-containing ring systems 3-7 and the N-cyanoguanidine derivative 8. Compounds were tested sequentially in three animal models to assess their HDL-C elevating efficacy and safety profiles. Further evaluation of selected compounds in a dose-response paradigm culminated in the identification of compound 2.39 as a candidate compound for advanced preclinical studies. |
| Designing a simpler high blood cholesterol case detection strategy: are the advantages of the NCEP protocol worth the complexity? Hofer, T. and J. Weissfeld (1994), Med Decis Making 14(4): 357-68. Abstract: OBJECTIVE: To determine whether the complex strategy of lipid measurements for the detection of patients with high blood cholesterol levels proposed by the first Expert Panel of the National Cholesterol Education Panel (NCEP) could be simplified without significant loss of accuracy. DESIGN: Decision-analysis-based model of competing case detection strategies as compared with the NCEP strategy. A Markov model was used to estimate numbers of people treated over ten years as a result of the different classification strategies. DATA SOURCES: Conditional probabilities for the decision trees were derived from cholesterol distributions in national population-based surveys. Parameters for the Markov model were from published major epidemiologic studies and clinical trials. MAIN OUTCOME MEASURES: Misclassification to treatment vs non-treatment as a continuous function of the distribution of true low-density lipoprotein (LDL). RESULTS: A simplified strategy was designed that screens high-risk persons with two LDL measurements and low-risk people with one cholesterol measurement followed by two LDL measurements if the initial value is high. This algorithm requires 37% fewer measurements to classify a population. The overall accuracy of classification to treatment based on the NCEP I cutoff points is high, with a positive predictive value of 95% and a negative predictive value of 87% (relative to 97% and 80%, respectively, for the NCEP I protocol). This strategy is very similar to published NCEP II guidelines. A strategy that recommends an LDL determination for everyone, as a recent NIH consensus panel suggested, also significantly reduces the number of measurements required by 48%. The positive predictive value is 93%, vs 97% for the NCEP I protocol. The negative predictive value is 92%, vs 80% for the NCEP I. CONCLUSIONS: The complex measurement strategy initially proposed in the NCEP I guidelines did not improve accuracy of classification over the simpler and more convenient strategies that the authors evaluated and that have been substantially adopted in the NCEP II guidelines. |
| Desirable level of serum cholesterol Nakamura, H. and Y. Hayashi (1991), Rinsho Byori 39(5): 506-7. Abstract: Serum cholesterol level is not only an indicator of nutritional state, and liver functions, but also a parameter of atherosclerotic vascular disease. Based upon the pathognomonic implication of serum cholesterol level, desirable value should be determined by considering the necessity for the individual growth, the maintainance of body activities and the least development of atherosclerosis. Epidemiological studies indicate that serum cholesterol level ever 220 mg/dl is frequently accompanied by the atherosclerotic complications such as coronary heart disease and cerebrovascular accident in Japan. Postmortem examination of Honolulu Heart Study on Japanese descendants also revealed that raised lesions of coronary artery are significantly frequent in the subjects with over 220 mg/dl. These findings suggest that the upper limit of serum cholesterol could be 220 mg/dl at the present conditions. |
| Desirable serum total cholesterol with low HDL cholesterol levels. An undesirable situation in coronary heart disease Sacks, F. M. (1992), Circulation 86(4): 1341-4. |
| Desmosterol may replace cholesterol in lipid membranes Huster, D., H. A. Scheidt, et al. (2005), Biophys J 88(3): 1838-44. Abstract: Recently, knockout mice entirely lacking cholesterol have been described as showing only a mild phenotype. For these animals, synthesis of cholesterol was interrupted at the level of its immediate precursor, desmosterol. Since cholesterol is a major and essential constituent of mammalian cellular membranes, we asked whether cholesterol with its specific impact on membrane properties might be replaced by desmosterol. By employing various approaches of NMR, fluorescence, and EPR spectroscopy, we found that the properties of phospholipid membranes like lipid packing in the presence of cholesterol or desmosterol are very similar. However, for lanosterol, a more distant precursor of cholesterol synthesis, we found significant differences in comparison with cholesterol and desmosterol. Our results show that, from the point of view of membrane biophysics, cholesterol and desmosterol behave identically and, therefore, replacement of cholesterol by desmosterol may not impact organism homeostasis. |
| Desmosterolosis: a new inborn error of cholesterol biosynthesis Clayton, P., K. Mills, et al. (1996), Lancet 348(9024): 404. |
| Despite good compliance, very low fat diet alone does not achieve recommended cholesterol goals in outpatients with coronary heart disease Aquilani, R., R. Tramarin, et al. (1999), Eur Heart J 20(14): 1020-9. Abstract: AIM: A low-saturated, low-cholesterol diet is important in the treatment of hypercholesterolaemia in patients with coronary heart disease. The aim of this study was to investigate the efficacy of a very low fat diet to achieve a targeted serum low density lipoprotein (LDL) cholesterol level (3.37mmol x l-1 were investigated 12-14 weeks after an acute coronary event. After overnight fasting each patient had (a) his resting energy expenditure measured (indirect calorimetry using standard protocol) and (b) venous blood sampled from a forearm vein to determine lipid profile. All the patients were randomly allocated to four groups of treatment: Group A on a very low fat diet (resting energy expenditure-fat diet, where fat intake was |
| Detection and measurement of hypercholesterolaemia in South Africans attending general practitioners in private practice--the cholesterol monitor Steyn, K., J. M. Fourie, et al. (1998), S Afr Med J 88(12): 1569-74. Abstract: BACKGROUND: This paper reports data on the detection and management of hypercholesterolaemia in patients attending general practitioners in private practice in South Africa. METHODS: The frequency of cholesterol testing and the level at which active therapeutic intervention occurred at medical practices were monitored over a 2-year period. A sample of 200 medical practitioners was selected from private practices in major cities. Data on patients seen by the selected doctors during a 5-day monitoring period were recorded on a standardised form. RESULTS: 12,842 patients were seen by the 200 private practice GPs. More men (18.7%) than women (10.4%) had coronary heart disease (CHD), and their mean total cholesterol (TC) levels were 5.9 mmol/l and 6.0 mmol/l, respectively. Only 3.1% of the patients were reported to have familial hypercholesterolaemia (FH) and 12.8% were reported to have a family history of CHD. Reported smoking rates were exceptionally high (77.5% of women and 64.4% of men). The most commonly prescribed group of lipid-lowering agents was HMG-CoA reductase inhibitors. CONCLUSIONS: Inadequate management of hypercholesterolaemia leaves many patients with a high risk of CHD mortality in South Africa. Appropriately investigated patients with hypercholesterolaemia should receive treatment to reduce cardiovascular disease using more effective TC control programmes than are currently used in South Africa. |
| Detection of bacterial DNA from cholesterol gallstones by NP-PCR and its clinical significance Wu, X., L. Xiao, et al. (1997), Zhonghua Wai Ke Za Zhi 35(11): 663-6. Abstract: To search for bacterial DNA sequences in cholesterol gallstones with negative bacterial culture. We used nested primers polymerase chain reaction (NP-PCR) technique to amplify bacterial gene fragments were amplified in vitro from DNA extracted from cholesterol gallstones. Comparative 16S ribosomal RNA sequence analysis was used for elucidation of bacterial identification. The gallbladder gallstones of 30 patients were analyzed. Bacterial DNA was found in the stones of 26 patients. There was no difference either in cholesterol and water content or in harboring bacterial DNA of gallstones. E. coli-related DNA fragments were found in the stones of 8 patients (26.67%). Propionibacteria type DNA was found in the stones of 7 patients (23.33%). Stones of 2 patients (6.67%) harbored bacterial gene fragments with similarity of Streptococcus pyogenes. A more heterogeneous sequence collection was found in 7 patients (23.33%) and could be assigned to the multiple bacterial infections. Another stones of 2 patients (6.67%) had bacterial DNA with lower molecularweight which might be related to some unidentified bacteria. The results suggested that most cholesterol gallstones harbor bacterial DNA. It is important to determine whether these microorganisms are innocent bystanders or active participants in cholesterol gallstone formation. |
| Detection of cholesterol associated with calcium mineral using confocal fluorescence microscopy Sarig, S., T. A. Weiss, et al. (1994), Lab Invest 71(5): 782-7. Abstract: BACKGROUND: Cholesterol and calcium are prominant components within human atherosclerotic lesions. Both accumulate predominantly within the central core region of lesions. Because of similarities in some crystallographic faces of cholesterol monohydrate and calcium apatite, it has been previously proposed that deposition of one may nucleate the deposition of the other. EXPERIMENTAL DESIGN: In this study, we have used the technique of confocal fluorescence microscopy to assess the spatial orientation of cholesterol in association with calcium mineral. Localization of cholesterol within mineral was carried out by staining cholesterol with the fluorescent probe, filipin. RESULTS: With this technique, it was possible to localize cholesterol associated with the surface of hydroxyapatite seeds, cholesterol incorporated within calcium phosphate-cholesterol agglomerates produced in vitro, and cholesterol within apatite isolated from human atherosclerotic lesions. CONCLUSIONS: The presence of cholesterol within the center of calcified granules from atherosclerotic plaque suggests that cholesterol or associated lipids may act to nucleate the deposition of apatite. Confocal fluorescence microscopy should be a useful technique by which to study the relationship of cholesterol associated with calcium minerals that occur not only in atherosclerotic blood vessels, but also in gallstones, and calcified cardiac valves. |
| Detection of free radicals and cholesterol hydroperoxides in blood taken from the coronary sinus of man during percutaneous transluminal coronary angioplasty Coghlan, J. G., W. D. Flitter, et al. (1991), Free Radic Res Commun 14(5-6): 409-17. Abstract: Patients undergoing percutaneous transluminal coronary angioplasty (PTCA) were investigated for the production of free radicals and cholesterol hydroperoxides during reperfusion. Fifteen patients were studied. Ischaemia during balloon inflation was assessed by serial coronary sinus lactate analysis (mean maximal increase in anterior descending artery dilation was 130%), and by the demonstration of reperfusion hyperaemia (mean increase of coronary sinus oxygen saturation 74%). Free radicals were detected by electron spin resonance (ESR) spin trapping using the spin trap PBN (N-t-Butyl-alpha-phenylnitrone). Radical adducts were detected in up to 50% of samples taken during reperfusion after anterior descending lesion angioplasty. No radicals were detected in control samples or during the ischaemic phase. Radical detection was positively correlated with the change in coronary sinus lactate (p less than 0.025). Coronary sinus cholesterol hydroperoxide analysis did not show a significant increase over control during reperfusion, due in part to unexpectedly high pre angioplasty levels. This study provides clear evidence for the production of a burst of free radicals and evidence for lipid peroxidation in the minutes following myocardial reperfusion during angioplasty. A relationship between the severity of the ischaemic insult and the detection of radical adducts has also been found. |
| Detection of high-sensitivity C-reactive protein and total cholesterol/high-density lipoprotein cholesterol ratio for diagnosis of coronary artery disease Jiang, C. X., Z. L. Li, et al. (2004), Di Yi Jun Yi Da Xue Xue Bao 24(5): 576-8. Abstract: OBJECTIVE: To study the value of detecting high-sensitivity C-reactive protein (hs-CRP) combined with determination of total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) in the diagnosis of coronary artery disease (CHD). METHODS: A total of 240 patients with documented CHD and 40 healthy subjects were enrolled in this study for measurement of serum concentrations of hs-CRP, TC and HDL-C. RESULTS: The concentration of hs-CRP and TC/HDL-C ratio was significantly higher in CHD patients than in the control subjects (P<0.01). The positivity rate by detecting both the two markers (0.950) was higher than that of single marker detection of either hs-CRP (0.850) or TC/HDL-C (vs 0.767). CONCLUSION: Detection of hs-CRP combined with determination of TC/HDL-C may facilitate early diagnosis of CHD. |
| Detection of immunoglobulin G antibodies to cholesterol in antisera to mycoplasmas Watanabe, T. and T. Kumazawa (1991), Infect Immun 59(6): 2200-2. Abstract: Antisera were produced by inoculation of mycoplasma cells grown in PPLO broth supplemented with rabbit serum alone or rabbit serum plus Freund complete or incomplete adjuvant. By using an enzyme-linked immunosorbent assay, immunoglobulin G antibodies to cholesterol were detected in antisera to mycoplasmas (Mycoplasma salivarium ATCC 23064, M. orale ATCC 15539, M. buccale IID 802, M. faucium IID 996, and M. hominis IID 801) and rabbit serum. |
| Detection of natural abundance 1H-13C correlations of cholesterol in its membrane environment using a gradient enhanced HSQC experiment under high resolution magic angle spinning Soubias, O., M. Piotto, et al. (2003), J Magn Reson 165(2): 303-8. Abstract: The quality and signal to noise ratio of a J-based HETCOR performed on a standard MAS probe have been compared with a gradient enhanced HSQC performed on a HR-MAS probe at 500 MHz. The sample selected was cholesterol, inserted at 30 mol% in acyl chain deuterated phospholipids (DMPC-d54), at a temperature where the bilayer is in a liquid crystalline phase (310 K). It is representative of any rigid molecule undergoing fast axial diffusion in a bilayer as the main movement. After optimization of the spinning rate and carbon decoupling conditions, it is shown that the ge-HSQC/MAS approach is far superior to the more conventional J-HETCOR/MAS in terms of signal to noise ratio, and that it allows the detection of all the natural abundance cross peaks of cholesterol in a membrane environment. Clear differences between the 1H and 13C chemical shifts of cholesterol in a membrane and in chloroform solution were thus revealed. |
| Detection of unusual lipid mixing in cholesterol-rich phospholipid bilayers: the long and the short of it Tokutake, N., B. Jing, et al. (2003), J Am Chem Soc 125(30): 8994-5. |
| Detergent extraction and enzymatic analysis for fecal long-chain fatty acids, triglycerides, and cholesterol Lee, M. J., T. Crook, et al. (1994), Clin Chem 40(12): 2230-4. Abstract: We report a procedure for determining fecal long-chain fatty acids (LCFA), triglycerides, and cholesterol after detergent extraction with 10 mL/L Triton X-100, 6 mL/L Brij 30, and 0.1 mol/L HCl in isotonic saline by enzymatic analysis of the extraction supernates. Mean recoveries of calibrators ranged from 105% to 117%. Assays of fecal extracts were linear with concentration from 0 to 1000 mumol/L for LCFA, from 10 to 90 mumol/L for triglycerides, and from 0 to 300 mumol/L for cholesterol. Within-run CVs were < 3% for medium and high concentrations, and 3%, 14%, and 28% for low concentrations of LCFA, cholesterol, and triglycerides, respectively. Correlation with gravimetric determination resulted in coefficients (r2) of 0.72 for total fat, 0.63 for neutral fat, and 0.66 for nonesterified fat. Assays of extracts and residues prepared for gravimetric determination indicated that approximately 90% of triglycerides, cholesterol, and LCFA were extracted by organic solvents and that the extracts contain a significant amount of other fats. The proposed method appears accurate, precise, specific, and suitable for routine analysis. |