| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Determining success in the cholesterol crusade Wielgosz, A. T. (1992), Cmaj 146(12): 2196. |
| Deuterium uptake and plasma cholesterol precursor levels correspond as methods for measurement of endogenous cholesterol synthesis in hypercholesterolemic women Matthan, N. R., M. Raeini-Sarjaz, et al. (2000), Lipids 35(9): 1037-44. Abstract: To assess the validity of two techniques used to measure human cholesterol synthesis, the rate of uptake of deuterium (D) into plasma free cholesterol (FC), and plasma cholesterol precursor (squalene, lanosterol, desmosterol and lathosterol) levels were compared in 14 women 65-71 yr with low density lipoprotein-cholesterol (LDL-C) > or = 3.36 mmol x L(-1). Subjects consumed each of six diets for 5-wk periods according to a randomized crossover design. The experimental diets included a baseline diet (39% energy as fat, 164 mg chol x 4.2 MJ(-1)) and five reduced-fat diets (30% of energy as fat), where two-thirds of the fat was either soybean oil; squeeze, tub or stick margarines; or butter. Fractional and absolute synthesis rates (FSR and ASR) of FC were determined using the deuterium incorporation (DI) method, while cholesterol precursor levels were measured using gas-liquid chromatography. Data were pooled across diets for each variable and correlation coefficients were calculated to determine if associations were present. There was good agreement among levels of the various cholesterol precursors. In addition, FSR in pools/d (p x d(-1)) and ASR in grams/d (g x d(-1)) were strongly associated with lathosterol (r= 0.72 and 0.71, P= 0.0001), desmosterol (r= 0.75 and 0.75, P = 0.0001), lanosterol (r = 0.67 and 0.67), and squalene (r = 0.69 and 0.68) when levels of the precursors were expressed as micromol x mmol(-1) C. Significant but lower correlations were observed between the D uptake and plasma cholesterol precursor levels when the latter were expressed in absolute amounts (micromol x L(-1)). The wide range of fatty acid profiles of the experimental diets did not influence the degree of association between methods. In conclusion, the DI method and levels of some cholesterol precursors correspond as methods for shortterm measurement of cholesterol synthesis. |
| Deuteron nuclear magnetic resonance study of the dynamic organization of phospholipid/cholesterol bilayer membranes: molecular properties and viscoelastic behavior Weisz, K., G. Grobner, et al. (1992), Biochemistry 31(4): 1100-12. Abstract: The influence of cholesterol on the dynamic organization of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers was studied by deuteron nuclear magnetic resonance (2H NMR) using unoriented and macroscopically aligned samples. Analysis of the various temperature- and orientation-dependent experiments were performed using a comprehensive NMR model based on the stochastic Liouville equation. Computer simulations of the relaxation data obtained from phospholipids deuterated at the 6-, 13- and 14-position of the sn-2 chain and cholesterol labeled at the 3 alpha-position of the rigid steroid ring system allowed the unambiguous assignment of the various motional modes and types of molecular order present in the system. Above the phospholipid gel-to-liquid-crystalline phase transition, TM, 40 mol % cholesterol was found to significantly increase the orientational and conformational order of the phospholipid with substantially increased trans populations even at the terminal sn-2 acyl chain segments. Lowering the temperature continuously increases both inter- and intramolecular ordering, yet indicates less ordered chains than found for the pure phospholipid in its paracrystalline gel phase. Trans-gauche isomerization rates on all phospholipid alkyl chain segments are slowed down by incorporated cholesterol to values characteristic of gel-state lipid. However, intermolecular dynamics remain fast on the NMR time scale up to 30 K below TM, with rotational correlation times tau R parallel for DMPC ranging from 10 to 100 ns and an activation energy of ER = 35 kJ/mol. Below 273 K a continuous noncooperative condensation of both phospholipid and cholesterol is observed in the mixed membranes, and at about 253 K only a motionally restricted component is left, exhibiting slow fluctuations with correlation times of tau R perpendicular greater than 1 microsecond. In the high-temperature region (T greater than TM), order director fluctuations are found to constitute the dominant transverse relaxation process. Analysis of these collective lipid motions provides the viscoelastic parameters of the membranes. The results (T = 318 K) show that cholesterol significantly reduces the density of the cooperative motions by increasing the average elastic constant of the membrane from K = 1 x 10(-11) N for the pure phospholipid bilayers to K = 3.5 x 10(-11) N for the mixed system. |
| Developing a clinical strategy for cholesterol management in an era of unanswered questions Ansell, B. J. (2001), Am J Cardiol 88(4A): 25F-30F. Abstract: Recent clinical trials have supported the use of cholesterol-lowering therapies to reduce cardiovascular events. Despite these results, a number of unanswered questions remain, including the appropriate intensity of lipid-lowering therapy and the role of high-density lipoprotein cholesterol and/or triglycerides in cardiovascular risk assessment and reduction. In addition, the optimal treatment strategies for women, the elderly, and patients with diabetes are more difficult to determine, as these groups have comprised a minority of subjects in prior trials. Studies in progress will provide guidance toward effective treatment of these populations, the appropriate degree of lipid-lowering therapy, and the role of estrogen replacement therapy in postmenopausal women. In the interim, a clinical strategy incorporating the lessons of recent clinical evidence is suggested. |
| Development and assessment of antiatherosclerotic therapies beyond low-density lipoprotein cholesterol and blood pressure Ballantyne, C. M. (2000), Curr Atheroscler Rep 2(4): 281-3. |
| Development and initial evaluation of a culturally sensitive cholesterol-lowering diet program for Mexican and African American patients with systemic lupus erythematosus Shah, M., Y. Coyle, et al. (2000), Arthritis Care Res 13(4): 205-12. Abstract: OBJECTIVE: To develop and evaluate acceptability of an intensive and ethnic-specific cholesterol-lowering diet program with a strong behavioral component in patients with systemic lupus erythematosus (SLE). METHOD: A comprehensive program with a behavioral component and culturally sensitive menus was developed in an effort to alter dietary behavior in patients with SLE. Four SLE patients, 2 African American and 2 Mexican American, enrolled in this program. Data on food intake (3-day food record), acceptability of the program (subjective response), and physiologic variables were collected at baseline, 6 weeks, and 12 weeks. RESULTS: The program was highly rated by all patients and found to be informative, easy to understand, ethnically sensitive, and to contain useful behavioral maintenance strategies. All 4 patients surpassed or were close to their diet goals at both 6 and 12 weeks. In this small group of patients, there was a statistically significant reduction in low-density lipoprotein cholesterol (P = 0.04) and body weight (P = 0.001), as assessed by repeated measures analysis of variance. CONCLUSION: The culturally specific cholesterol-reducing diet program was highly rated and appeared to be effective in changing the diet of this small group of SLE patients, as determined by their food records and body weight. The impact of this program, including the individual components on cardiovascular disease risk factors, needs to be evaluated in a larger multiple-arm study with a lengthier intervention. |
| Development and validation of a quantitative assay for cholesterol crystal growth in human gallbladder bile Ginanni Corradini, S., A. Cantafora, et al. (1994), Biochim Biophys Acta 1214(1): 63-72. Abstract: Crystal observation time is a rough estimate of the first microscopic appearance of cholesterol monohydrate crystals in an isotropic bile, and does not provide information on crystal growth kinetics. We have developed a method for quantitating cholesterol crystal growth in gallbladder bile. Crystals were separated from other biliary particles by ultracentrifugation on a discontinuous NaBr gradient, after bile density adjustment to d = 1.060 g/ml. More than 95% of crystals, both of native or synthetic source, floated in the density range 1.045-1.055. This density fraction was collected and crystal mass was measured by photometric turbidity, after calibration with suspensions of different-sized cholesterol crystals. The recovery of crystals added to original bile samples averaged 96.0 +/- 2.8%. Contamination with vesicles, which may potentially interfere with the turbidimetric assay, was excluded by gel-chromatography. The method was sequentially applied, until the 20th day of incubation, to biles obtained at surgery from patients with (A, n = 6) or without cholesterol gallstone (B, n = 4), and from gallstone patients pretreated for 1 week with oral ursodeoxycholic acid (C, n = 5). Crystal growth curves greatly differed, being much steeper in group A and almost flat in patients receiving ursodeoxycholic acid. The mean percent mass of biliary cholesterol in crystalline form at the 20th day was 19.2 +/- 13.5%, 1.2 +/- 0.8% and 2.7 +/- 1.1% in A, B and C, respectively (A vs. B: P = 0.014; A vs. C: P = 0.008). We conclude that the method allows a precise estimate of cholesterol crystal growth and can be usefully applied to human gallbladder biles. |
| Development and validation of a short food list to assess the intake of total fat, saturated, mono-unsaturated, polyunsaturated fatty acids and cholesterol Rohrmann, S. and G. Klein (2003), Eur J Public Health 13(3): 262-8. Abstract: BACKGROUND: The aim of this study was the development and validation of a short list of food items to assess the intake of total fat, saturated, mono-unsaturated, polyunsaturated fatty acids, and cholesterol. The short list should be able to correctly classify persons according to their intake. METHODS: A short list of 20 food items was selected out of 1009 seven-day food records by means of the variance-based method Max_r. This list was validated using data from a further 479 persons who completed seven-day food records (validation sample 1, VS1) as well as a food frequency questionnaire (validation sample 2, VS2). The intake of total fat, different fatty acids, and cholesterol from the complete VS1 (VS1(complete)) and from the complete VS2 (VS2(complete)), respectively, was computed. Further, the intake in VS1 (VS1(short)) as well as in VS2 (VS2(short)) using only the 20 food items on the short list were calculated. RESULTS: Pearson correlation coefficients between the intake calculated from the items on the short list and the nutrient intake calculated from the full instrument in VS1 and VS2, respectively, were r = 0.81-0.91. In a quartile's cross-classification 53.4-64.1% of the participants were assigned to the same quartile. When comparing VS1(complete) with VS2(short), neither correlation coefficients nor the cross-classification differ much from the comparison of VS1(complete) with VS2(complete). CONCLUSIONS: The short list shows good results in both validation samples. Thus, the short list can assess the variability of fat intake and classify persons according to their intake. |
| Development and validation of the Cholesterol-Saturated Fat Index (CSI) Scorecard: a dietary self-monitoring tool Mitchell, D. T., M. K. Korslund, et al. (1996), J Am Diet Assoc 96(2): 132-6. Abstract: OBJECTIVE: The Cholesterol-Saturated Fat Index (CSI) Scorecard was developed and tested as a self-monitoring tool for patients consuming a cholesterol-lowering diet. SUBJECTS/DESIGN: Twelve nutritionists used the CSI Scorecard to estimate the CSI score of the same five food records. Subsequently, using a revised tool, 12 subjects with hypercholesterolemia estimated the CSI score of their 4-day food records and 11 participated in evaluation meetings. STATISTICAL ANALYSES: Two-tailed, one-sample t tests and the Spearman rho correlation test were used, respectively, to compare CSI Scorecard estimates of nutritionists and participants to CSI scores obtained from computer calculations. RESULTS: The CSI scores estimated by the nutritionists were close to the computed scores at the 25th and 75th food record percentiles. The correlation of the estimated CSI scores of participants to the computed scores was rs =.8 (P <.05). APPLICATION: The CSI Scorecard is a new, simple, quick, and accurate dietary self-monitoring tool patients can use in research centers and primary care settings. By numerically illustrating the saturated fat and cholesterol content of foods, the CSI Scorecard facilitates dietary self-monitoring and, thus, self-efficacy in the adoption and maintenance of a cholesterol-lowering dietary pattern. |
| Development of a platinized and ferrocene-mediated cholesterol amperometric biosensor based on electropolymerization of polypyrrole in a flow system Vidal, J. C., E. Garcia, et al. (2002), Anal Sci 18(5): 537-42. Abstract: The preparation of a cholesterol amperometric biosensor using a platinized Pt electrode as a support for the electropolymerization of a polypyrrole film, in which cholesterol oxidase and ferrocene monocarboxylic acid (electron-transfer mediator) were co-entrapped, is described. All the biosensor preparation steps (platinization and electropolymerization) and the cholesterol determination take place in the same flow system. The presence of the mediator enhances the sensitivity and selectivity of the platinized biosensor without modifying the dynamic parameters of the response, and the platinized layer improves the operational lifetime of the mediated sensor. The sensitivity obtained was 88.51 nA mM(-1) and the limit of detection was 12.4 microM of cholesterol. The analytical properties of the biosensor for the flow-injection determination of cholesterol were studied and compared with those of other more simple amperometric biosensor configurations. |
| Development of a technique of immunoadsorption of LDL-cholesterol Regnault, V., C. Rivat, et al. (1990), Ann Med Interne (Paris) 141(7): 604-7. Abstract: An immunoadsorption system for lowering plasma cholesterol was optimized. Several polyclonal and monoclonal antibodies were compared and the best results were obtained with goat polyclonal antibodies. The optimum quantity of antibodies to be immobilized on the gel was 5 mg/ml. Taking into account two variables, i.e., 1) that the regeneration must be as complete as possible and, 2) that immunoadsorbents must be used several times without a loss of adsorption capacity, desorption was achieved with 0.3 M glycine adjusted to pH 2.8. Antibody release from the immunoadsorbent was determined and can be minimized by glutaraldehyde treatment of the immunoadsorbent. Each phase, adsorption and desorption, respectively, was well-defined and synchronized, so that two columns could be used in parallel in an automated procedure. The kinetics of plasma protein removal demonstrated the efficiency and the specificity of the procedure. |
| Development of an integrated procedure for the detection of central nervous tissue in meat products using cholesterol and neuron-specific enolase as markers Lucker, E., E. Eigenbrodt, et al. (1999), J Food Prot 62(3): 268-76. Abstract: The emergence of a new variant of Creutzfeldt-Jakob disease during the bovine spongiform encephalopathy epidemic has focused attention on the use of tissue from the central nervous system (CNS) in food. So far, the banning of CNS tissue could not be effectively controlled because procedures for detection were missing. With regard to preventive health protection and labeling law enforcement, we have developed an integrated procedure for the detection of CNS tissue in meat products. Herein, we show that antigenic characteristics of neuron-specific enolase (NSE) quantitatively survive technological treatment including severe homogenization and pressure heating. Using both poly- and monoclonal antibodies against NSE in the Western blot, bovine and porcine brain could be detected in sausages, albeit with varying sensitivity (1 to 4%). Sensitivity was increased after reduction of fat content (30 to 40%) of the samples by means of a soxhlet extraction. This made possible the detection of brain addition as low as 0.25% when using monoclonal antibodies. Immunohistology showed distribution of CNS tissue in heat-treated meat products to be homogeneous. Immunoreaction was not found to be bound to morphologically intact histological or cytological structures; however, it proved to be highly specific. The quantification of cholesterol provides a low-cost screening method for the rapid identification of meat products, suspicious with regard to CNS tissue addition. Cholesterol content increased by 26 mg per 100 g of fresh substance for each percentage of brain added to internally produced reference material. Using three different approaches (internal reference material, raw material, and field samples), a provisional cutoff point of normal cholesterol content was calculated for emulsion-type cooked sausages to be 115 mg/100 g (P < 0.05). |
| Development of atherosclerotic lesions in cholesterol-loaded rabbits Kamimura, R., S. Suzuki, et al. (1999), Exp Anim 48(1): 1-7. Abstract: To examine both of the target vessels and the optimal time of their endothelial denudation to study vascular restenosis after balloon injury in cholesterol-loaded rabbits, we made 36 atherosclerotic rabbits by feeding a hypercholesterol diet, and histologically examined the onset time and the development of atherosclerosis. Atheromatous changes were observed first after the 5th week in the thoracic aorta from the start of the diet, and then extended to the abdominal aorta, coronary artery with time. The atherosclerotic lesions in the thoracic aorta and the proximal portion of the coronary artery showed high-grade concentric intimal thickening with luminal stenosis. The abdominal aortic lesion mildly progressed. In the renal, carotid and femoral arteries, in contrast, slight atheroscleromatous changes developed during the diet period. These results suggest that the thoracic and abdominal aortas and the coronary artery would be suitable as target vessels to study vascular restenosis after balloon injury, and the endothelial denudation of these vessels should be performed between the 8th and 15th week in this diet protocol for an accurate analysis. |
| Development of cardiovascular risk factors from ages 8 to 18 in Project HeartBeat! Study design and patterns of change in plasma total cholesterol concentration Labarthe, D. R., M. Z. Nichaman, et al. (1997), Circulation 95(12): 2636-42. Abstract: BACKGROUND: Project HeartBeat! is a longitudinal study of the development of cardiovascular risk factors as growth processes. Patterns of serial change, or trajectories, from ages 8 to 18 years for plasma total cholesterol concentration (TC) and percent body fat illustrate the design and synthetic cohort approach of the study. METHODS AND RESULTS: Six hundred seventy-eight children (49.1% female, 20.1% black) entered the study at ages 8, 11, and 14 years and were followed up with examinations every 4 months for < or = 4 years. Multilevel analysis demonstrated trajectories for population mean values of TC and percent body fat in sex-specific synthetic cohorts from ages 8 to 18 years. Polyphasic patterns of change in TC were confirmed, with notable sex differences in age patterns and with minimum mean values of TC of 3.85 mmol/L for females and 3.59 for males. As illustrated by data for males, the approximate 75th percentile values of mean TC ranged from 4.78 mmol/L at its early peak to 4.06 at its late-teen nadir. Percent body fat exhibited a trajectory closely parallel with that for TC only for males and appeared to be unrelated for females. CONCLUSIONS: The polyphasic trajectory for TC from ages 8 to 18 years differs between females and males, indicates marked age variation in 75th percentile values and, in males only, closely parallels the trajectory for percent body fat. These and other results indicate the value of both follow-up every 4 months across age intervals to detect rapid risk factor change and the synthetic cohort approach for gaining new insights into the dynamics and possible determinants of this change from ages 8 to 18 years. |
| Development of cholesterol embolization syndrome after intravenous streptokinase for acute myocardial infarction Queen, M., H. J. Biem, et al. (1990), Am J Cardiol 65(15): 1042-3. |
| Development of cholesterol homeostatic memory in the rat is influenced by maternal diets Brown, S. A., L. K. Rogers, et al. (1990), Metabolism 39(5): 468-73. Abstract: The hypothesis that dietary factors in early life modify the extent of adaptive responses in adult life was tested in rats. During the gestational and lactational periods, pregnant rats were fed either a high-fat (HF) or low-fat (LF) diet (corn oil, 15% or 2%, wt/wt) until 30 days postpartum. The offspring were maintained on standard chow for an additional 100 days and fed a HF diet for 1, 3, 7, or 21 days. Upon challenge for 3 days, rats born to dams fed the HF diet showed a more rapid hypercholesterolemic response when compared with rats born to dams fed a LF diet (mean +/- S.D., 151 +/- 14 mg/dL v 122 +/- 6 mg/dL; P less than.001). Higher levels of cholesterol were associated with elevated levels of apolipoprotein (apo) B (24.0 +/- 4 mg/dL v 15.8 +/- 3 mg/dL; P less than.05) and apo E (31.0 +/- 4 mg/dL v 24.7 +/- 3 mg/dL; P less than.05). Further comparison of the hypercholesterolemic response between the two groups of animals showed increases in cholesterol in all major lipoprotein classes, cholesterol enrichment at the expense of triglyceride (TG) in very-low-density lipoprotein (VLDL), and elevation of apo E-containing high-density lipoprotein (HDL). Examination at longer time periods of HF challenge showed that apo E levels of the HF-exposed animals remained elevated compared with similarly challenged rats born to dams fed the LF diet (35 +/- 3.8 mg/dL v 26 +/- 2.7 mg/dL; P less than.05).(ABSTRACT TRUNCATED AT 250 WORDS) |
| Development of cholesterol metabolism: the effect of diet composition at weaning Hahn, P. and L. Srubiski (1990), Biol Neonate 58(1): 1-7. Abstract: Wistar rats were weaned on day 18 to a high fat (HF), high carbohydrate (HG) or high cholesterol (HCO 2%) diet. The activities of 3-hydroxy-3-methylglutaryl-CoA-reductase (HMGR), 7 alpha-hydroxylase (7-OHase) and acyl-CoA-cholesterol-acyltransferase (ACAT) were assayed in the liver and small intestinal mucosa on days 21, 25 and 30 and in adult animals. An HF diet raises hepatic ACAT and HMGR activities in young rats but has the opposite effect in the gut. The cholesterol diet also raises hepatic ACAT activity, but less so than the HF diet. In the gut, however, the HCO diet invokes the greatest rise in ACAT of all the diets tested. Except in adult rats, the HG diet always raises hepatic ACAT activity more than the HCO diet or the Purina Chow. In the gut, however, activity is very low for the HG diet, much lower than for the HCO diet. Early feeding of the HCO diet for 12 days (from day 18 to 30) and refeeding the same diet from day 48 to 50 resulted in a subsequent response to the HCO diet. It is concluded that early weaning results in changes in enzyme activities that depend on the composition of the diet fed at weaning and that this may also effect the later response to the same and perhaps other diets. |
| Development of hepatic microsomal activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and cholesterol 7 alpha-hydroxylase in the young chick Inarrea, P., E. Villareal, et al. (1992), Comp Biochem Physiol Comp Physiol 103(2): 417-20. Abstract: 1. The 3-hydroxy-3-methylglutaryl-CoA reductase activity increased from 1 to 4 weeks of age, but decreased from 4 to 8 weeks of age. 2. Cholesterol 7 alpha-hydroxylase activity increased from 1 to 4 weeks, decreased from 4 to 6 weeks, and increased again from 6 to 8 weeks of age. 3. Serum total and free cholesterol concentrations decreased from 1 to 6 weeks of age, but increased from 6 to 8 weeks of age. |
| Development of progressive pulmonary interstitial and intra-alveolar cholesterol granulomas (PICG) associated with therapy-resistant chronic systemic juvenile arthritis (CJA) Schultz, R., J. Mattila, et al. (2001), Pediatr Pulmonol 32(5): 397-402. Abstract: A girl aged 5 years with therapy-resistant chronic systemic juvenile arthritis (CJA) developed progressive fibrosing lung disease. Histology of an open lung biopsy revealed pulmonary interstitial and intra-alveolar cholesterol granulomas (PICG). Since treatment with steroids and immunosuppressive drugs did not prevent progression of lung fibrosis, an experimental treatment with a tumor necrosis factor alpha (TNF alpha) antagonist etanercept was started. Although development of chronic changes in the lung parenchyma could not be prevented, this treatment brought considerable relief and markedly improved the child's physical capacity. By ruling out other causes for development of PICG, we concluded that the primary disease had caused the development of cholesterol granulomata by macrophage activation. We suggest, therefore, that a trial with etanercept in children with otherwise therapy-resistant CJA should be considered, especially if pulmonary complications have developed. |
| Development of serum cholesterol and frequency of hypercholesterolemia in children and adolescents: results of the Berlin-Pankow cohort study Eisenblatter, D., I. Martin-Bothig, et al. (1990), Soz Praventivmed 35(6): 201-5. Abstract: The age-related evolution of serum cholesterol has been studied in a cohort of 475 boys and girls born in 1964, living in Berlin-Pankow district; they have been followed up from age 13-14 to 20-21 (response rate after eight years: 66%). At age 13-14, mean total cholesterol was higher among boys (183 +/- 34 mg/dl) as well as among girls (187 +/- 33 mg/dl) as compared with those observed in other populations. About one third of the subjects at this age had values greater than 200 mn/dl. There was a marked decrease in mean total cholesterol around age 14 in both sexes, inversely related to the degree of sexual maturity. Between age 15 and 20 the serum cholesterol rose continuously. After puberty girls had higher mean values than boys. The evolution of serum cholesterol changes during adolescence should be taken into account when assessing preventive measures in children and young people. |