| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Behavior of cholesterol and its effect on head group and chain conformations in lipid bilayers: a molecular dynamics study Robinson, A. J., W. G. Richards, et al. (1995), Biophys J 68(1): 164-70. Abstract: Cholesterol molecules were put into a computer-modeled hydrated bilayer of dimyristoyl phosphatidyl choline molecules, and molecular dynamics simulations were run to characterize the effect of this important molecule on membrane structure and dynamics. The effect was judged by observing differences in order parameters, tilt angles, and the fraction of gauche bonds along the hydrocarbon chains between lipids adjacent to cholesterol molecules and comparing them with those further away. It was observed that cholesterol causes an increase in the fraction of trans dihedrals and motional ordering of chains close to the rigid steroid ring system with a decrease in the kink population. The hydrogen-bonding interactions between cholesterol and lipid molecules were determined from radial distribution calculations and showed the cholesterol hydroxyl groups either solvated by water, or forming hydrogen bond contacts with the oxygens of lipid carbonyl and phosphate groups. The dynamics and conformation of the cholesterol molecules were investigated and it was seen that they had a smaller tilt with respect to the bilayer normal than the lipid chains and furthermore that the hydrocarbon tail of the cholesterol was conformationally flexible. |
| Behavior of cholesterol and spin-labeled cholestane in model bile systems studied by electron spin resonance and synchrotron x-ray Somjen, G. J., G. Lipka, et al. (1995), Biophys J 68(6): 2342-9. Abstract: The behavior of mixed bile salt micelles consisting of sodium taurocholate, egg phosphatidylcholine, and cholesterol has been studied by ESR spin labeling and synchrotron x-ray scattering. Consistent with published phase diagrams, pure and mixed bile salt micelles have a limited capacity to incorporate and, hence, solubilize cholesterol. Excess cholesterol crystallizes out, a process that is readily detected both by ESR spin labeling using 3-doxyl-5 alpha-cholestane as a probe for cholesterol and synchrotron x-ray scattering. Both methods yield entirely consistent results. The crystallization of cholesterol from mixed bile salt micelles is indicated by the appearance of a magnetically dilute powder spectrum that is readily detected by visual inspection of the ESR spectra. Both the absence of Heissenberg spin exchange and the observation of a magnetically dilute powder spectrum provide evidence for the spin label co-crystallizing with cholesterol. In mixed bile salt micelles containing egg phosphatidylcholine, the solubility of cholesterol is increased as detected by both methods. With increasing content of phosphatidylcholine and increasing mole ratio cholesterol/phosphatidylcholine, the anisotropy of motion of the spin probe increases. The spin label 3-doxyl-5 alpha-cholestane is a useful substitute for cholesterol provided that it is used in dilute mixtures with excess cholesterol: the cholesterol/spin label mole ratio in these mixtures should be greater than 100. Despite the structural similarity between the two compounds, there are still significant differences in their physico-chemical properties.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Behavior of various cholesterol crystals in bile from patients with gallstones Portincasa, P., K. J. van Erpecum, et al. (1996), Hepatology 23(4): 738-48. Abstract: Besides classical plate-like cholesterol monohydrate crystals, a variety of crystal shapes have recently been described in model biles but their relevance for human gallstone formation is unknown. We therefore studied crystallization behavior in gallbladder bile from cholesterol stone patients (54 untreated, 13 ursodeoxycholate-treated) and 6 pigment stone patients. Bile preparation by ultrafiltration or ultracentrifugation left biliary lipid composition unchanged but plates and their aggregates, and arcs and needles crystallized more extensively while spirals and tubules crystallized less extensively in ultra-centrifuged bile than in ultrafiltered bile. Plates, aggregates, and arcs/needles were seen in 90 percent, 36 percent, and 18 percent of the cases respectively of fresh unfiltered biles of untreated cholesterol stone patients, while spirals and tubules were always absent. In ultrafiltered biles arcs/needles, plates and aggregates progressively developed as persistent forms. Spirals and tubules occurred transiently and were associated with increased deoxycholic acid (+41 percent, P =.039) and with more extensive cholesterol crystallization. Rate/extent of crystallization of all crystal forms was higher (P <.0001) for multiple than solitary cholesterol stone patients. Ursodeoxycholate-treated patients had atypical platelike cholesterol crystals in fresh unfiltered biles that decreased in size at prolonged observation and in 2 cases even dissolved after 15 and 20 days. No crystals ever developed in ultra-filtered bile of ursodeoxycholic acid (UDCA)-treated patients during 21 days. Pigment stone patients seldom developed crystals. Thus, plates, aggregates and arcs/needles are persistent forms with high crystallization rate in multiple cholesterol stone patients. Tubules and spirals are transient forms that are associated with more extensive crystallization. Patients treated with ursodeoxycholate often have atypical crystals in their fresh bile. |
| Behavioral implications of lowering cholesterol levels: a double-blind pilot study Ormiston, T., O. M. Wolkowitz, et al. (2003), Psychosomatics 44(5): 412-4. Abstract: The treatment of hypercholesterolemia may be associated with greater noncardiac mortality. This current pilot study sought to determine which behaviors, if any, are associated with decreases in cholesterol level. Twelve subjects received one of two cholesterol-reducing drugs or placebo. Cholesterol and behavioral ratings were measured at baseline, 4, and 52 weeks with standardized scales. Cholesterol levels markedly declined with concomitant significant increases in impulsivity ratings at 4 weeks. At 52 weeks, the increase in impulsivity ratings was no longer apparent, but depression ratings showed a significant improvement. This pilot study, although limited in size, raises the possibility that cholesterol-lowering drugs are associated with mild, time-limited increases in impulsivity and with mild, time-delayed improvements in depression ratings. |
| Behaviour of phospholipase modified-HDL towards cultured hepatocytes. II. Increased cell cholesterol storage and bile acid synthesis Collet, X., C. Vieu, et al. (1991), Biochim Biophys Acta 1081(2): 211-9. Abstract: Human total HDL (hydrated density 1.070-1.210), HDL2 (1.070-1.125), HDL3 (1.125-1.210) or HDL separated by heparin affinity chromatography were treated with or without purified phospholipase A2 from Crotalus adamanteus. Control and treated HDL were reisolated and were then incubated with cultured hepatocytes. 1. Mass measurements evidenced a time-dependent cholesterol enrichment in hepatocytes cultured in the absence of lipoproteins. Addition of HDL2 still enhanced by 25% the cell cholesterol content and down-regulated endogenous sterol synthesis in similar proportions. Conversely, HDL3 slightly decreased the amount of free cholesterol in hepatocytes (-12%). 2. Incubations with phospholipase A2-treated HDL resulted in a 35%-50% increase of both the cellular cholesterol esterification and the cholesterylester accumulation, when compared to cells cultured in the presence of control-HDL. This effect was observed with HDL2, HDL3 and combining the data with all subfractions. 3. Cultured hepatocytes secreted cholic and beta-muricholic acids as major bile acids and HDL2 showed a tendency to stimulate their secretion. Phospholipase treatment of HDL again induced an increased production by hepatocytes of those two bile acids. Thus, whereas HDL2 and HDL3 display different behaviours with respect to cell cholesterol content, neosynthesis and bile acid secretion, their modifications by phospholipases always orientate the cell sterol metabolism in the same direction: increased cholesterylester accumulation and bile acid production. |
| Behenic acid is a cholesterol-raising saturated fatty acid in humans Cater, N. B. and M. A. Denke (2001), Am J Clin Nutr 73(1): 41-4. Abstract: BACKGROUND: Dietary behenic acid (22:0) is poorly absorbed. Because of its low bioavailability compared with other fatty acids and because of its very long chain length, the effect of dietary behenic acid (behenate) on serum lipid concentrations in humans is assumed to be neutral. OBJECTIVE: The objective was to establish the cholesterol-raising potential of behenic acid by comparing the effects on lipid and lipoprotein concentrations of a specially formulated fat enriched with behenic acid with those of palm oil (rich in palmitic acid; 16:0) and high-oleic acid sunflower oil (rich in cis oleic acid; 18:1). DESIGN: In a randomized, crossover, metabolic-ward study, 7 mildly hypercholesterolemic men were fed 3 natural-food diets supplemented with behenate oil, palm oil, or high-oleic acid sunflower oil. Mean serum lipid and lipoprotein concentrations and plasma triacylglycerol fatty acid composition were determined from fasting blood drawn during the final 4 d of each 3-wk diet period. RESULTS: Behenate oil produced mean concentrations of total cholesterol (5.87+/-0.8 mmol/L) and LDL cholesterol (4.40+/-0.8 mmol/L) not significantly different from those produced by palm oil (5.84+/-0.7 and 4.42+/-0.7 mmol/L, respectively) but significantly higher than those produced by high-oleic acid sunflower oil (5.12+/-0.5 and 3.70+/-0.6 mmol/L, respectively). There were no significant differences in triacylglycerol or HDL-cholesterol concentrations. CONCLUSIONS: Despite its low bioavailability compared with oleic acid, behenic acid is a cholesterol-raising fatty acid in humans and is therefore not a suitable substitute for palmitic acid in manufactured triacylglycerols. |
| Belt-like localisation of caveolin in deep caveolae and its re-distribution after cholesterol depletion Westermann, M., F. Steiniger, et al. (2005), Histochem Cell Biol 123(6): 613-20. Abstract: Caveolae are specialised vesicular microdomains of the plasma membrane. Using freeze-fracture immunogold labelling and stereoscopic imaging, the distribution of labelled caveolin 1 in caveolae of 3T3-L1 mouse fibroblast cells was shown. Immunogold-labelled caveolin structures surrounded the basolateral region of deeply invaginated caveolae like a belt whereas in the apical region distal to the plasma membrane, the caveolin labelling was nearly absent. Shallow caveolar membranes showed a dispersed caveolin labelling. After membrane cholesterol reduction by methyl-beta-cyclodextrin treatment, a dynamic re-distribution of labelled caveolin 1 and a flattening of caveolar structures was found. The highly curved caveolar membrane got totally flat, and the initial belt-like caveolin labelling disintegrated to a ring-like structure and later to a dispersed order. Intramembrane particle-free domains were still observable after cholesterol depletion and caveolin re-distribution. These results indicate that cholesterol interacting with caveolin structures at the basolateral part of caveolae is necessary for the maintenance of the deeply invaginated caveolar membranes. |
| Bending rigidity of SOPC membranes containing cholesterol Song, J. and R. E. Waugh (1993), Biophys J 64(6): 1967-70. Abstract: Bilayer membranes in the fluid state exhibit a large resistance to changes in surface area, negligible resistance to surface shear deformation, and a small but finite resistance to bending. The presence of cholesterol in the membrane is known to increase its resistance to area dilation. In this report, a new method for measuring bilayer membrane bending stiffness has been used to investigate the effect of cholesterol on the bending rigidity of SOPC (1,stearoyl-2,oleoyl-phosphatidylcholine) membranes. The curvature elasticity (kc) for membranes saturated with cholesterol was measured to be 3.3 x 10(-19) J, approximately 3-fold larger than that the modulus for cholesterol-free SOPC membrane. These findings are consistent with previous measurements of bending stiffness based on thermal fluctuations, which showed a similar approximately 3-fold increase in the modulus with cholesterol addition (Evans and Rawicz, 1990, Phys. Rev. Lett. 64:2094) and provide further substantiation of the important contribution that cholesterol makes to membrane cohesion and stability. |
| Beneficial effect of cholesterol-lowering therapy on coronary endothelium-dependent relaxation in hypercholesterolaemic patients Leung, W. H., C. P. Lau, et al. (1993), Lancet 341(8859): 1496-500. Abstract: Since hypercholesterolaemia is associated with impaired endothelium-dependent vasodilation, a study was conducted to find out whether cholesterol reduction will improve endothelial function in patients with hypercholesterolaemia and normal coronary arteries. 25 men (mean age 51 SD 8 years) with total serum cholesterol > 6.2 mmol/L) and angiographically normal coronary arteries had their coronary vasomotor responses to intracoronary acetylcholine and nitroglycerin assessed by computer-assisted quantitative angiography at baseline and after 6 months of cholesterol-reducing diet and cholestyramine. Between baseline and follow-up mean total serum cholesterol level fell by 28.7 (SD 5.6)% (p < 0.001); mean low-density lipoprotein (LDL) cholesterol level by 35.6 (8.7)% (p < 0.001); and mean total cholesterol to high-density lipoprotein (HDL) cholesterol ratio by 29.4 (10.6)% (p < 0.001). Acetylcholine significantly reduced the mean segment diameter at baseline, by 21.7 (14.0)% (p < 0.01), but it increased the diameter at follow-up, by 6.16 (13.3)% (p < 0.01), the difference between the two occasions being significant (p < 0.001). Nitroglycerin significantly increased the mean segment diameter, both at baseline, by 18.7 (11.5)% (p < 0.01), and at follow-up, by 19.3 (12.1)% (p < 0.01), the difference between the two responses being not significant. At baseline total cholesterol and LDL cholesterol did not correlate with acetylcholine response, but they did at follow-up (total cholesterol, r = 0.67, p < 0.01; LDL cholesterol, r = 0.64, p < 0.01). Impairment of endothelium-dependent (acetylcholine-induced) dilation of the epicardial coronary arteries in hypercholesterolaemic patients with angiographically normal coronary arteries is thus reversible by reducing serum cholesterol. In addition, the degree of impairment of acetylcholine-induced vasomotor response is related to the cholesterol concentrations after therapy. |
| Beneficial effects of dietary supplementation in a disorder with defective synthesis of cholesterol. A case report of a girl with Smith-Lemli-Opitz syndrome, polyneuropathy and precocious puberty Starck, L., I. Bjorkhem, et al. (1999), Acta Paediatr 88(7): 729-33. Abstract: In 1993 the Smith-Lemli-Opitz (SLO) syndrome, known as a malformation syndrome characterized by certain stigma, turned out to be a metabolic disease with a defect in the last step of cholesterol biosynthesis. This led to the possibility of identifying affected individuals by biochemical methods and of increasing understanding of pathogenic mechanisms. Hopes of influencing the effects of the metabolic defect by dietary supplementation were raised and reports with some benefits of treatment have been published. This is a report of a 12-y-old girl with the SLO syndrome in an apparently progressive form. In addition to typical signs and well-known symptoms she has a verified polyneuropathy and precocious puberty. She has been treated with cholesterol and bile acids for 3 y, during which time the progressive course has been arrested. A notable effect has been the improvement of her polyneuropathy, verified by measurement of nerve conduction velocities. Possible mechanisms involved in the pathogenesis of her precocious puberty are discussed. |
| Beneficial effects of garlic (Allium sativum Linn) on rats fed with diets containing cholesterol and either of the oil seeds, coconuts or groundnuts Augusti, K. T., A. Narayanan, et al. (2001), Indian J Exp Biol 39(7): 660-7. Abstract: Feeding of 2% cholesterol diet increased lipid parameters in serum and tissues of rats during a period of one month. In addition to the above, lipid peroxidation also increased and activities of certain enzymes were significantly altered in the tissues. Similar changes were also observed to a greater extent with diets containing 40% by weight of coconut kernel or groundnut with and without 2% cholesterol. The enzymes studied were HMGCoA reductase, AST, ALT and ALP in tissues and serum as the case may be. In general the atherogenic effects were observed more with groundnut containing diets than those with coconut. Even though the oil from the former is mostly unsaturated and that from the latter is mostly saturated, these analytical criteria do not relate to their atherogenic effects. When 5% garlic was incorporated with any of the high fat diets, the lipid parameters, their peroxidation and alterations in enzyme activities were significantly decreased. These results show that garlic contains some principles that counteract the atherogenicity of the above oil seeds. |
| Beneficial effects of rosuvastatin alone and in combination with extended-release niacin in patients with a combined hyperlipidemia and low high-density lipoprotein cholesterol levels Capuzzi, D. M., J. M. Morgan, et al. (2003), Am J Cardiol 91(11): 1304-10. Abstract: Patients with combined hyperlipidemia and low high-density lipoprotein (HDL) cholesterol levels may benefit from combination therapy with a statin and niacin; therefore, we assessed the efficacy and safety of rosuvastatin and extended-release (ER) niacin alone and in combination in 270 patients with this atherogenic dyslipidemia. Men and women > or =18 years with fasting total cholesterol levels > or =200 mg/dl, triglycerides 200 to 800 mg/dl, apolipoprotein B > or cf=110 mg/dl, and HDL cholesterol <45 mg/dl were randomized to 1 of 4 treatments in this 24-week, open-label, multicenter trial: rosuvastatin 10 to 40 mg; ER niacin 0.5 to 2 g; rosuvastatin 40 mg/ER niacin 0.5 to 1 g; or rosuvastatin 10 mg/ER niacin 0.5 to 2 g. Percent changes from baseline in low-density lipoprotein (LDL) cholesterol, non-HDL cholesterol, and other lipid measurements at week 24 were determined by analysis of variance, with statistical testing performed separately between the rosuvastatin monotherapy group and each remaining treatment group. Daily doses of rosuvastatin 40 mg reduced LDL and non-HDL cholesterol significantly more than either ER niacin 2 g or rosuvastatin 10 mg/ER niacin 2 g (-48% vs -0.1% and -36% for LDL cholesterol and -49% vs -11% and -38% for non-HDL cholesterol, respectively; p <0.01 for all comparisons); no additional reduction in LDL or non-HDL cholesterol was observed with the combination of rosuvastatin 40 mg/ER niacin 1.0 g (-42% and -47%; p = NS). Triglyceride reductions ranged from -21% (ER niacin monotherapy) to -39% (rosuvastatin 40 mg/ER niacin 1 g), but no observed differences were statistically significant. Compared with rosuvastatin alone, rosuvastatin 10 mg/ER niacin 2 g produced significantly greater increases in HDL cholesterol (11% vs 24%, p <0.001) and apolipoprotein A-I (5% vs 11%, p <0.017). Similar increases in HDL cholesterol and apolipoprotein A-I were noted between the monotherapy groups. Over 24 weeks, rosuvastatin alone was better tolerated than either ER niacin alone or the combinations of rosuvastatin and ER niacin. |
| Beneficial effects of statins in coronary artery disease--beyond lowering cholesterol Sotiriou, C. G. and J. W. Cheng (2000), Ann Pharmacother 34(12): 1432-9. Abstract: OBJECTIVE: To review the benefits of statins in coronary artery disease management beyond their cholesterol-lowering effects. DATA SOURCES: A MEDLINE search (1966-May 2000) was conducted using the following terms: lovastatin, pravastatin, simvastatin, atorvastatin, fluvastatin, cerivastatin, endothelium, plaque stabilization, antithrombotic effects. STUDY SELECTION: English-language human studies and case reports. DATA EXTRACTION: Studies published demonstrating other mechanisms of statins' clinical beneficial effects were evaluated and reviewed. DATA SYNTHESIS: The understanding of the pharmacologic effects of statins has led to the realization that the benefits of these agents extend beyond simply lowering cholesterol. These properties include beneficial effects on vessel endothelial tissue; decreased low-density lipoprotein oxidation and inflammation; ability to stabilize atherosclerotic plaques and perhaps promote regression; proliferative effects on smooth-muscle growths, possibly strengthening atherosclerotic plaques; antithrombotic effects by inhibiting platelet aggregation and stimulation of fibrinolytic factors; and improvement of blood viscosity and flow. With these actions, statins may benefit the situation of long-term atherosclerotic plaque formation and the setting of acute coronary syndrome. CONCLUSIONS: Further large-scale studies are needed to determine the clinical importance and validity of these postulated beneficial effects of statins. |
| Benefit from hypocaloric diet in obese men depends on the extent of weight-loss regarding cholesterol, and on a simultaneous change in body fat distribution regarding insulin sensitivity and glucose tolerance Sonnichsen, A. C., W. O. Richter, et al. (1992), Metabolism 41(9): 1035-9. Abstract: Obesity and an android body fat distribution are related to metabolic disorders. We investigated the interdependences between metabolism, overweight, and body fat distribution in 40 moderately obese men before and after weight-loss. Correlations between metabolic parameters and body mass index (BMI) or waist to hip ratio (WHR) were much weaker in this exclusively obese population than in subjects of all weight categories, but the association between BMI and glucose tolerance (r = -.46, P less than.01) increased significantly after weight-loss. The improvement of metabolic parameters was much stronger in men who achieved normal weight (BMI less than 27 kg/m2) than in those who remained obese (BMI greater than 30 kg/m2, P less than.05). The WHR decreased during the diet (P less than.001), and this decrease and the extent of weight-loss were significantly correlated to an increase in insulin sensitivity (r = -.41, P less than.01) and a decrease in glucose area after an oral glucose load (r =.34, P less than.05). The decrease in apolipoprotein B, total cholesterol, and low-density lipoprotein (LDL) cholesterol was significantly correlated only to the extent of weight-loss (r =.34.31, and.39, respectively; P less than.05). We conclude that it is best to reach normal weight for the normalization of metabolic aberrations. The reduction of cholesterol appears to be dependent on the extent of weight-loss, while the improvement in insulin sensitivity and glucose tolerance apparently is related to both the extent of weight-loss and to a change toward a less android body fat distribution. |
| Benefit of direct determination of LDL-cholesterol (comparison with LDL measurement using calculated estimates Stejskal, D., R. Pastorkova, et al. (1998), Vnitr Lek 44(12): 707-13. Abstract: Treatment of dyslipidemia and its frequently associated complications (manifest atherosclerosis) is very pretentious from the economic aspect. Diagnostic and therapeutic criteria are based mainly on biochemical analyses. Although demands on laboratories are relatively strict (respecting defined laboratory errors, analytical and preanalytical conditions), when defined diagnostic criteria are used, the results of biochemical analyses are not yet satisfactory. A typical example is the stratification of risk patients according to the LDL concentration which in our country is very often preferred, although the LDL concentration is based only on calculation (contrary to investigations from which the majority of recommendations was derived where the LDL concentration was assessed directly). We know from our own experience that a large percentage of results of estimated and assessed LDL differs significantly. Therefore we wanted to know whether the assessed LDL concentration correlates with its estimate according to Friedewald s formula and which analytes have the greatest impact on the LDL concentration. Our objective was also to assess th percentage of incorrectly listed patients (according to the LDL stratification scale). In 1997-1998 we examined a group of 4578 probands, patients of the consultant out-patient departments of the Sternberk hospital. Their mean age was 56 years. On average subjects with as slightly atherogenic phenotype were involved (classification A according to EAS). The values of lipid parameters did not differ significantly in the two sexes. The cholesterol, LDL and triacylglycerol concentrations increased with advancing age. The LDL values obtained by assessment and calculation correlated closely. The LDL value was influenced most by ApoB and total cholesterol. Triacylglycerols correlated with LDL assessment only up to a concentration of.3 mmol/l. HDL, ApoA-1 and higher triacylglycerol concentrations (1.3 mmol/l) did not correlate with the LDL value. The authors provided evidence that in subjects where it was possible to calculate LDL lege artis (2458 probands) were listed according to LDL calculation into a wrong group (stratification according to NCEP) whereby up to an LDL concentration.11 mmol/l this parameter cannot be predicted at all by calculation (error up to 85%). A satisfactory estimate is assumed only at LDL concentrations 5.2 mmol/l. Because the estimated LDL values are in the majority of patients lower than the calculated values, it may be assumed that during stratification of LDL obtained by calculation the patients are treated too aggressively. Assuming pharmacological treatment of all mentioned patients, it may be estimated that by using analyses of direct LDL for stratification of probands the costs of hypolipidaemic treatment will by reduced by about 1/4-1/3 (in the catchment area of the Sternberk hospital this would save more than 10 million crowns). The costs of LDL analyses per year are about 180,000 crowns (in the Sternberk hospital--which amounts to cca 1.5% of the money saved on pharmacotherapy). |
| Benefit on atherosclerosis of adding niacin in patients with low HDL-cholesterol taking a statin Amsterdam, E. A. (2005), Prev Cardiol 8(2): 130. |
| Benefits and risks of lowering serum cholesterol Verschuren, W. M. (1997), Epidemiology 8(2): 120-2. |
| Benefits of atorvastatin in cholesterol lowering Farmer, J. A. (2003), Curr Atheroscler Rep 5(2): 94-5. |
| Benefits of cholesterol reduction Gerdes, L. U. and M. Schroll (1990), Ugeskr Laeger 152(8): 540-4. |
| Benefits of cholesterol screening and therapy for primary prevention of cardiovascular disease: a new paradigm Stein, J. H. and P. E. McBride (1998), J Am Board Fam Pract 11(1): 72-7. |