| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Significance of plasma 7alpha-hydroxy-4-cholesten-3-one and 27-hydroxycholesterol concentrations as markers for hepatic bile acid synthesis in cholesterol-fed rabbits Honda, A., T. Yoshida, et al. (2004), Metabolism 53(1): 42-8. Abstract: Plasma 7alpha-hydroxy-4-cholesten-3-one has been used as an index of hepatic bile acid synthesis. The aim of the current study was to ascertain whether the level of this oxysterol reflects hepatic cholesterol 7alpha-hydroxylase activity when plasma cholesterol concentrations are markedly changed. In addition, the relationship of hepatic sterol 27-hydroxylase activity with plasma concentrations of 27-hydroxycholesterol and 3beta-hydroxy-5-cholestenoic acid was studied. We used New Zealand white rabbits fed 2% cholesterol for 5 or 10 days and/or constructed bile fistula. Feeding cholesterol markedly increased and bile drainage reduced plasma cholesterol concentrations. Initially, in these models there was no correlation between plasma 7alpha-hydroxy-4-cholesten-3-one concentrations and hepatic cholesterol 7alpha-hydroxylase activities (r = -0.24, n = 10). Cholesterol feeding was associated with downregulated 7alpha-hydroxylase activities, while plasma 7alpha-hydroxy-4-cholesten-3-one concentrations were elevated in the presence of increased plasma cholesterol levels. However, this discrepancy was overcome and significant correlation was observed (r = 0.73, P <.05, n = 10) by expressing 7alpha-hydroxy-4-cholesten-3-one levels relative to cholesterol. In contrast, hepatic sterol 27-hydroxylase activities were not significantly correlated with plasma absolute (r = 0.23, difference not significant NS, n = 10) nor cholesterol-related levels of 27-hydroxycholesterol (r = -0.13, NS, n = 10), or 3beta-hydroxy-5-cholestenoic acid concentrations (r = 0.30, NS, n = 10). In conclusion, plasma 7alpha-hydroxy-4-cholesten-3-one concentrations reflected hepatic cholesterol 7alpha-hydroxylase activities when the sterol levels were adjusted to plasma cholesterol concentrations in rabbits with hypercholesterolemia. The results suggest that plasma 7alpha-hydroxy-4-cholesten-3-one relative to cholesterol is a better marker for hepatic cholesterol 7alpha-hydroxylase activity than the absolute concentration when hypercholesterolemia is present. In contrast, 27-hydroxycholesterol and 3beta-hydroxy-5-cholestenoic acid levels in plasma did not reflect hepatic sterol 27-hydroxylase activities even if the levels were adjusted to plasma cholesterol concentrations. |
| Significance of pleural fluid cholesterol and beta-2 microglobulin levels for the differentiation of pleural effusions in childhood Kalayci, A. G., N. Gurses, et al. (1996), Clin Pediatr (Phila) 35(7): 353-8. Abstract: We studied 60 children, ages 3-15 years, with pleural effusions to determine the usefulness of different criteria for the separation of transudates from exudates. Twenty of these effusions were classified as transudates and 40 as exudates. Pleural cholesterol (P chol), pleural/serum cholesterol ratio (P/S chol), and pleural/serum beta 2 microglobulin (P/S beta 2 m) were determined to characterize pleural effusions and were compared with Light's criteria (pleural/serum protein ratio, pleural LDH, pleural/serum LDH ratio). With a threshold of 0.3, the sensitivity and specificity of P/S chol for diagnosis of exudates were 95 and 90%, respectively. With a threshold of 1.3, the sensitivity of P/S beta 2 m was 77.5%, and its specificity was 95%. Our findings indicate that determination of P chol and P/S chol, as well as Light's criteria, is of value for characterizing pleural effusions in childhood, but the measurement of P/S beta 2 m is less sensitive in distinguishing transudates from exudates and it should not be used routinely. |
| Significance of the amino acid composition of dietary protein in the regulation of plasma cholesterol Sugiyama, K. and K. Muramatsu (1990), J Nutr Sci Vitaminol (Tokyo) 36 Suppl 2: S105-10. Abstract: Three approaches were employed to identify the amino acid residue(s) that is responsible for the different effects of dietary proteins on the plasma cholesterol level in rats fed cholesterol-enriched diets. 1) Experiments on the effects of individual amino acids added to a 25% casein diet showed that sulfur-containing amino acids have the most potent effects on the plasma cholesterol level. Under the dietary conditions used, methionine significantly increased the level of plasma cholesterol while cystine decreased it. It was found that glycine can prevent the methionine-induced enhancement of plasma cholesterol. 2) There was a significant negative correlation between cystine content of dietary proteins and plasma cholesterol levels when animals were fed 7 kinds of animal and plant proteins. 3) Experiments with amino acid mixtures varying in methionine, cystine, and glycine content showed that diets high in methionine and low in cystine and glycine content tend to increase the plasma cholesterol level and diets of opposite amino acid content tend to decrease the plasma cholesterol level. From these results, it was suggested that sulfur-containing amino acids and glycine in dietary proteins are responsible, at least in part, for the alteration of plasma cholesterol level by dietary proteins. |
| Significant association between fluctuations in serum urate and high density lipoprotein cholesterol during exhaustive training Yanai, H. and M. Morimoto (2003), Br J Sports Med 37(4): 370. |
| Significant dominance of fibrinogen over immunoglobulins, C-reactive protein, cholesterol and triglycerides in maintaining increased red blood cell adhesiveness/aggregation in the peripheral venous blood: a model in hypercholesterolaemic patients Schechner, V., I. Shapira, et al. (2003), Eur J Clin Invest 33(11): 955-61. Abstract: BACKGROUND: It is not clear what is the relative importance of fibrinogen, immunoglobulins, highly sensitive C-reactive protein (hs-CRP), cholesterol and triglyceride concentrations on the appearance of aggregated red blood cells in the peripheral blood. DESIGN: Six hypercholesterolaemic patients undergoing regular LDL apheresis that were examined repeatedly before and following the procedure. RESULTS: We determined the degree of erythrocyte adhesiveness/aggregation in relation to the concentration of the above-mentioned macromolecules in 80 samples. In a linear logistic regression the respective R2 values for fibrinogen, total cholesterol, triglycerides, hs-CRP, IgG, IgM and IgA were 0.45 (P<0.0001), 0.2 (P<0.0001), 0.02 (P=0.02), 0.001 (P=NS) and 0.002 (P=NS), respectively. We further analyzed the potential of ApoA, ApoB and Lpa to participate in red cell adhesiveness/aggregation and found them to be not significant. CONCLUSIONS: In a milieu of adhesive macromolecules, lipids and inflammation-sensitive proteins including fibrinogen, total cholesterol, triglycerides, hs-CRP and immunoglobins G, M and A, fibrinogen has a dominant role in maintaining the red blood cell adhesiveness/aggregation in the peripheral venous blood. These findings are relevant for the research directed at finding new apheretic modalities to reduce the degree of red blood cell adhesiveness/aggregation in the peripheral blood. |
| Significant increase of high-density lipoprotein2-cholesterol under prolonged simvastatin treatment Neuman, M. P., H. R. Neuman, et al. (1991), Atherosclerosis 91 Suppl: S11-9. Abstract: In a contribution to a prolonged multicenter study 15 patients with primary hypercholesterolemia were treated with simvastatin, a competitive inhibitor of HMG-CoA reductase. The first part of the study was done in a double-blind fashion comparing the effect of this new drug with that of gemfibrozil during 12 weeks, and after this period on open-label treatment was started with the administration to all the patients of simvastatin in doses ranging from 2.5 to 40 mg q.p.m. Persistent and significant reductions (P less than 0.001) were achieved for total serum cholesterol (TC), LDL-cholesterol (LDL-C), apo B and triglycerides: by 38, 49, 44 and 33%, respectively, after 40 weeks of the open-label extension. From week 12, LDL-C levels were maintained at a cut point less than or equal to 140 mg/dl in every patient throughout the study. At week 40, cholesterol values of HDL subfractions showed a significant increase in HDL2-C (28%, P less than 0.01) and a concomitant reduction in HDL3-C (12%, P less than 0.01) in spite of a nonsignificant elevation of total HDL-C (by 6%). The HDL2-C/HDL3-C ratio rose by 47% (P less than 0.001) and the TC/HDL-C ratio was significantly reduced by 43%: from 6.1 +/- 1.2 to 3.5 +/- 0.7 (mean +/- SD, P less than 0.001). No adverse effects were detected. Our results suggest a conversion of HDL3 into HDL2, which could imply a beneficial effect of simvastatin upon the so-called reverse cholesterol transport, in addition to the striking reduction in atherogenic lipoproteins. |
| Significant reduction of the antiatherogenic effect of estrogen by long-term inhibition of nitric oxide synthesis in cholesterol-clamped rabbits Holm, P., N. Korsgaard, et al. (1997), J Clin Invest 100(4): 821-8. Abstract: The purpose of this study was to investigate whether endothelium-derived nitric oxide (NO) is involved in the plasma lipid-independent antiatherogenic effect of estrogen and levormeloxifene, a partial estrogen receptor agonist. 85 rabbits were ovariectomized and balloon-injured in the middle thoracic aorta. The rabbits were fed a cholesterol-enriched diet supplemented with 17beta-estradiol, levormeloxifene, or placebo, either alone, or together with 160 microg/ml NG-nitro- -arginine methyl ester (-NAME), an NO synthase inhibitor, in their drinking water for 12 wk. Plasma cholesterol was maintained at 25-30 mmol/liter by individualized cholesterol feeding. In the undamaged aorta, the extent of atherosclerosis in the estrogen group was only one-third that in the placebo group. Simultaneous administration of -NAME, however, significantly reduced the antiatherogenic effect of estrogen (P < 0.01). There was no significant difference between the placebo group given -NAME and the group treated with placebo alone. At the previously endothelium-denuded site, estrogen had no effect on atherosclerosis development, whereas -NAME combined with estrogen significantly increased atherogenesis (P < 0.05). The effects of levormeloxifene were almost similar to those of estrogen. Active vascular concentrations of -NAME were demonstrated in an additional study, in which maximal aortic/coronary endothelium-dependent relaxation was significantly inhibited in rabbits given -NAME. Thus, in this study a considerable part of the plasma lipid-independent antiatherogenic effect of estrogen was mediated through its effect on endothelial NO in cholesterol-fed rabbits. The results for levormeloxifene suggest a common mechanism of action for estrogen and partial estrogen receptor agonists on atherogenesis. |
| Significant undertreatment of high cholesterol level in ischemic heart disease Berglund, U. and E. Karlsson (2000), Lakartidningen 97(3): 155-7. Abstract: Lipid and lipoprotein analysis was performed in 127 consecutive patients with stable incapaciting angina referred by cardiologists for coronary angiography (mean waiting time, 121 days). Ninety-four per cent of the patients manifested evidence of myocardial ischaemia at exercise testing, or had had earlier myocardial infarction or earlier revascularisation with angioplasty or bypass surgery. Despite the well-known results of the large statin trials in secondary prevention (4S and CARE), only a third of the patients had LDL cholesterol levels in accordance with Swedish and European guidelines, i.e., below 3.0 mmol/L. |
| Significantly high synthetic activities of cholesterol sulfate in the nasal, oral and tracheal mucosae of guinea pigs Higo, R. and M. Iwamori (1995), ORL J Otorhinolaryngol Relat Spec 57(6): 333-7. Abstract: Cholesterol sulfate (CS) is widely distributed in mammalian tissues and various physiological roles for it have been suggested, but the presence of CS in the nasal tissues has not yet been reported. This is the first report in which the CS content and the activity of its regulatory enzymes, cholesterol sulfotransferase (CST) and cholesterol sulfate sulfatase (CSS), in the nasal mucosa of the guinea pig were examined and compared with those in the oral and tracheal mucosae. The highest concentration of CS was detected in the oral mucosa and the second highest in the nasal mucosa. The activity of CST was also highest in the oral mucosa and the second highest in the nasal mucosa. On the other hand, that of CSS was highest in the tracheal mucosa. The accumulation of CS is assumed to be related to squamous differentiation, because the activity of transglutaminase type 1 in the nasal, oral and tracheal mucosae coincided with the order of the concentration of CS in those tissues. These results suggested that the accumulation of CS is correlated with the morphological differences between the oral stratified squamous and the nasal or tracheal pseudostratified epithelium, and furthermore that the nasal epithelium is more susceptible to squamous metaplasia than the tracheal epithelium in the guinea pig. |
| Silver deposition on freeze-dried cells allows subcellular localization of cholesterol with imaging TOF-SIMS Nygren, H. and P. Malmberg (2004), J Microsc 215(Pt 2): 156-61. Abstract: Imaging time-of-flight secondary ion mass spectrometry (TOF-SIMS) was used for characterization and subcellular localization of organic ions in leucocytes adhering to glass surfaces. The cells were fixed by freeze drying in 0.15 m ammonium formate buffer at pH 7.2-7.4. The freeze-dried cells were sputter-coated with silver, and the silver surface was analysed with imaging TOF-SIMS. TOF-SIMS spectra were recorded by scanning the primary ion beam over the analysis area and acquiring positive mass spectra of the ions leaving the surface. The relative brightness of each pixel within the analysis area reflects the signal intensity of a selected ion in that pixel. Data were collected separately at high mass resolution m/delta m > 7000 and at high lateral resolution (= 0.5 micro m). The images were analysed by principal component analysis (PCA). The glass-adhering cells showed a well defined attachment area with a diameter of up to 20 micro m, and an equally well defined cell body, containing the nucleus, with a diameter of 8-10 micro m. On the raw data images, the obtained cholesterol distributions were consistent with a higher cholesterol content of the cell membrane in the attachment area than in the cell body. Using PCA analysis, silver-cationized molecular cholesterol was found localized mainly in the attachment area of the cells. Cholesterol was also seen at higher concentration in circular spots of |
| SIM 6080, a new calcium antagonist, reduces aortic atherosclerosis in cholesterol-fed rabbits Maggi, F. M., F. Bernini, et al. (1993), Pharmacol Res 28(3): 219-27. Abstract: SIM 6080 is a new calcium antagonist, structurally related to diphenylalkylamines, which combines transmembrane and intracellular calcium antagonist activities. In the present study we investigated the effect of SIM 6080 on atherogenesis in cholesterol-fed rabbits. Subcutaneous administration of the compound at 0.33, 1, and 3 mg kg-1/bid for 60 days neither affected plasma lipids nor blood pressure. However at 1 and 3 mg kg-1/bid SIM 6080 reduced in a dose-dependent manner both the area of the aorta covered by plaques and aortic cholesterol content. Determination of SIM 6080 plasma and aortic content indicated that the compound could concentrate up to 10 times in the arterial tissue. In vitro studies demonstrated that at concentrations similar to those observed in the aorta this compound may stimulate rabbit beta VLDL catabolism by smooth muscle cells in an homologous system suggesting that the up-regulation of LDL-receptors in the aorta may contribute to the antiatherosclerotic properties of SIM 6080. |
| Similar serum lipoprotein cholesterol concentrations in healthy subjects on diets enriched with rapeseed and with sunflower oil Nydahl, M., I. B. Gustafsson, et al. (1994), Eur J Clin Nutr 48(2): 128-37. Abstract: A double-blind cross-over study was conducted during two 3-week periods to compare the effects of rapeseed oil and sunflower oil, enriching a normal diet, on the lipoprotein and fatty acid composition in healthy subjects. It was carried out in randomized order at residential schools, comprising 101 persons (mean age 29.2 years). The dietary fats used for cooking and as table margarine were prepared from rapeseed oil during one period and from sunflower oil during the other. No changes were made in the total fat content or other dietary nutrients. During both treatment periods the serum cholesterol (-4%, P < 0.001), LDL cholesterol (-5% to -7%, P < 0.01 and 0.001) and apolipoprotein B (-5%, P < 0.001) concentrations decreased significantly and to the same extent, while serum triglycerides, HDL cholesterol, apolipoprotein A-1 and lipoprotein (a) remained virtually unchanged. The content of 18:2 n-6 serum phospholipids was increased after the sunflower oil-enriched diet, and the contents of oleic acid (18:1 n-9), alpha-linolenic acid (18:3 n-3), and eicosapentaenoic acid (20:5 n-3) were increased after the rapeseed oil-enriched diet. The concentration of alpha-tocopherol increased and gamma-tocopherol decreased after the sunflower oil-enriched diet, less so after the rapeseed oil-enriched diet. It is concluded that substitution of mono- and polyunsaturated fats for saturated fats without any other dietary changes causes a significant improvement of the lipoprotein profile in healthy subjects. The rapeseed oil and sunflower oil fats were equally effective in this respect. The results also indicate that humans have a certain capacity to elongate and desaturate alpha-linolenic acid to 20:5 n-3 in vivo. Dietary fats based on rapeseed oil seem to be attractive alternatives to the more commonly used oils and fats rich in linoleic acid. Financial support from the Swedish Council for Forestry and Agricultural Research and the Swedish Margarine Industrial Association for Nutritional Physiological Research is gratefully acknowledged. |
| Simple and rapid thin-layer chromatographic method for quantitative measurement of free cholesterol in serum Li, K. (1990), J Chromatogr 532(2): 449-52. |
| Simple enzymatic assay for determining cholesterol concentrations in bile Luhman, C. M., S. T. Galloway, et al. (1990), Clin Chem 36(2): 331-3. Abstract: We use bilirubin oxidase (EC 1.3.3.5) to remove interference by bilirubin in the assay of cholesterol concentration in bile by standard enzymatic methods. Samples are treated for 10 min with nonlimiting amounts of bilirubin oxidase to form biliverdin from bilirubin before the reagent for cholesterol is added. The relatively small interference by biliverdin is easily eliminated by use of sample blanks. The method is simple, convenient, and not hampered by the "chromogen oxidase" activity (the inherent ability of bilirubin oxidase to oxidize some chromogens) that plagues other assays of this type. Using this assay, we have accurately and precisely determined the concentration of cholesterol in bile. Such elimination of bilirubin will also be useful in assays of other biliary constituents or constituents of urine or icteric plasma. |
| Simple high-density lipoprotein cholesterol assay based on dry chemistry Yamada, T., S. Nishino, et al. (2002), Clin Chim Acta 320(1-2): 79-88. Abstract: BACKGROUND: Currently, high-density lipoprotein cholesterol (HDL-C), a factor which prevents progression of arteriosclerosis, is measured using laboratory-based chemistry analyzers without a pretreatment step. Because HDL-C is measured with a pretreatment step in many point-of-care testing systems, a direct assay is needed. METHODS: A dry-chemistry-based assay using surfactants has recently been developed in parallel with the development of a dedicated reagent. A simple analyzer that accepts whole blood samples was also developed. RESULTS: The assay demonstrated excellent precision, dilution linearity and intermethod comparison. In an interference test, assay values tended to be lower in the presence of high concentrations of hemoglobin, conjugated or unconjugated bilirubin. Neither ascorbic acid up to 20 mg/dl, nor formazin turbidity up to 2100, had an effect on the assay. CONCLUSIONS: This dry-chemistry assay using only surfactants for specificity in the direct HDL-C method was judged useful for point-of-care instrumentation in terms of equipment compactness, operational simplicity and rapid responsiveness. |
| Simple thin-layer chromatographic purification procedure for the determination of cholesterol ester fatty acid compositions Smuts, C. M. and H. Y. Tichelaar (1991), J Chromatogr 564(1): 272-7. Abstract: A mild procedure for the purification of methyl esters of the fatty acid components of cholesterol esters, from interfering free cholesterol and other contaminating residues, is described. Methyl esters and free cholesterol are formed during the methylation of cholesterol esters. When co-extracted, cholesterol and other contaminating residues interfere with the methyl esters because minute proportions of these residues tend to elute at the same retention times as palmitoleic and stearic acids, to yield unreliable but significantly higher values for palmitoleic (p less than 0.001) and stearic acids (p less than 0.0001), and correspondingly lower values for oleic acid (p less than 0.0001). Purification of methyl esters by thin-layer chromatography eliminates this problem and yields reliable analysis of cholesterol ester fatty acids, without measurable oxidation of unsaturated fatty acids. |
| Simplified gas chromatographic method for the simultaneous determination of phytosterols and cholesterol Tvrzicka, E., P. Mares, et al. (1991), J Chromatogr 563(1): 188-92. |
| Simulation of the early stages of nano-domain formation in mixed bilayers of sphingomyelin, cholesterol, and dioleylphosphatidylcholine Pandit, S. A., E. Jakobsson, et al. (2004), Biophys J 87(5): 3312-22. Abstract: It is known from experimental studies that lipid bilayers composed of unsaturated phospholipids, sphingomyelin, and cholesterol contain microdomains rich in sphingomyelin and cholesterol. These domains are similar to "rafts" isolated from cell membranes, although the latter are much smaller in lateral size. Such domain formation can be a result of very specific and subtle lipid-lipid interactions. To identify and study these interactions, we have performed two molecular dynamics simulations, of 200-ns duration, of dioleylphosphatidylcholine (DOPC), sphingomyelin (SM), and cholesterol (Chol) systems, a 1:1:1 mixture of DOPC/SM/Chol, and a 1:1 mixture of DOPC/SM. The simulations show initial stages of the onset of spontaneous phase-separated domains in the systems. On the simulation timescale cholesterol favors a position at the interface between the ordered SM region and the disordered DOPC region in the ternary system and accelerates the process of domain formation. We find that the smooth alpha-face of Chol preferentially packs next to SM molecules. Based on a comparative analysis of interaction energies, we find that Chol molecules do not show a preference for SM or DOPC. We conclude that Chol molecules assist in the process of domain formation and the process is driven by entropic factors rather than differences in interaction energies. |
| Simultaneous assay of the activities of two key enzymes in cholesterol metabolism by gas chromatography-mass spectrometry Honda, A., J. Shoda, et al. (1991), J Chromatogr 565(1-2): 53-66. Abstract: A very sensitive and specific method for the simultaneous assay of the activities of two key regulatory enzymes in cholesterol metabolism, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (EC 1.1.1.34), and cholesterol 7 alpha-hydroxylase (EC 1.14.13.7), is described. The assay is based on the measurement of 2H3mevalonolactone and 7 alpha-hydroxycholesterol produced by the incubation of 2H3HMG-CoA and endogenous cholesterol with hamster liver microsomes using isotope dilution mass spectrometry. The incubation mixture was purified by means of solid extraction cartridges, and the extract was treated with benzylamine followed by dimethylethylsilyl imidazole. The resulting ether derivatives of the mevalonylbenzylamide and 7 alpha-hydroxycholesterol were quantified by gas chromatography-mass spectrometry with selected-ion monitoring in a high resolution mode. The method made it possible to assay simultaneously the activities of HMG-CoA reductase and cholesterol 7 alpha-hydroxylase in hamster liver microsomes with high sensitivity and accuracy. |
| Simultaneous assessment of cholesterol absorption and synthesis in humans using on-line gas chromatography/ combustion and gas chromatography/pyrolysis/isotope-ratio mass spectrometry Gremaud, G., C. Piguet, et al. (2001), Rapid Commun Mass Spectrom 15(14): 1207-13. Abstract: A number of dietary components and drugs are known to inhibit the absorption of dietary and biliary cholesterol, but at the same time can compensate by increasing cholesterol synthesis. It is, therefore, necessary to have a convenient and accurate method to assess both parameters simultaneously. Hence, we validated such a method in humans using on-line gas chromatography(GC)/combustion and GC/pyrolysis/isotope-ratio mass spectrometry (IRMS). Cholesterol absorption was measured using the ratio of (13)Ccholesterol (injected intravenously) to (18)Ocholesterol (administered orally). Simultaneously, cholesterol synthesis was measured using the deuterium incorporation method. Our methodology was applied to 12 mildly hypercholesterolemic men that were given a diet providing 2685 +/- 178 Kcal/day (mean +/- SD) and 255 +/- 8 mg cholesterol per day. Cholesterol fractional synthesis rates ranged from 5.0 to 10.5% pool/day and averaged 7.36% +/- 1.78% pool/day (668 +/- 133 mg/day). Cholesterol absorption ranged from 36.5-79.9% with an average value of 50.8 +/- 15.4%. These values are in agreement with already known data obtained with mildly hypercholesterolemic Caucasian males placed on a diet similar to the one used for this study. However, our combined IRMS method has the advantage over existing methods that it enables simultaneous measurement of cholesterol absorption and synthesis in humans, and is therefore an important research tool for studying the impact of dietary treatments on cholesterol parameters. |