| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Mice overexpressing human lecithin: cholesterol acyltransferase are not protected against diet-induced atherosclerosis Mehlum, A., M. Muri, et al. (1997), Apmis 105(11): 861-8. Abstract: Lecithin: cholesterol acyltransferase (LCAT) (EC 2.3.1.43) is generally assumed to participate in reverse cholesterol transport, i.e., cholesterol transport from peripheral tissues to the liver. LCAT is secreted by the liver and transported in plasma mostly associated with high density lipoprotein. It catalyzes the esterification of cholesterol, mainly high density lipoprotein cholesterol, and produces cholesteryl ester and lysolecithin. Transgenic mice overexpression human LCAT on a C57BL/6 background have elevated high density lipoprotein cholesterol and markedly reduced low and very low density lipoprotein cholesterol and triglyceride levels in plasma, suggesting that such mice may be less susceptible to diet-induced atherosclerosis than isogenic nontransgenic controls. To determine if the apparent anti-atherogenic lipoprotein profile of the LCAT transgenics reduced their susceptibility to atherogenesis, the atherosclerotic lesions developing in transgenic LCAT mice and controls when fed an atherogenic diet were compared by histology and morphometry. Histological examination of the aortas from mice fed a high fat diet for 12, 17 and 22 weeks revealed that the aortic lesions were no smaller or less developed in the transgenic LCAT mice than in the C57BL/6 controls. After 17 weeks there were significantly more "fatty streaks" in the transgenic mice than in the controls. Thus, overexpression of human LCAT in transgenic mice, in spite of their very favourable blood lipoprotein and lipid profile, does not protect against development of atherosclerosis. |
| Micellar aggregation of poloxamer 213 and its interaction with cholesterol derivatives Cheng, H. Y. and W. W. Holl (1990), J Pharm Sci 79(10): 907-12. Abstract: The micellar properties of Poloxamer 213 (1), a Pluronic copolymer shown to affect lipid absorption and serum cholesterol level in experimental animals, are investigated by surface tension measurements, photon correlation spectroscopy (PCS), Reichardt's dye solubilization technique, differential scanning calorimetry (DSC), electron paramagnetic resonance (EPR) spectrometry, and fluorescence spectroscopy. The clear inflection point at 3 x 10(-6) M (25 degrees C) observed in the surface tension-concentration curve may not represent the CMC for the formation of multimolecular aggregates. In the 10(-4) to 10(-2) M concentration range, the temperature-dependent transition (as the concentration of 1 increases) from the larger (hydrodynamic radius, Rh approximately 20-40 nm), highly hydrated aggregates to the contracted (Rh approximately 6-7 nm), less polar form occurs as a discontinuity. This process is endothermic, with an average delta H of 34.5 kcal/mol. At 25 degrees C, both the 25-(NBD-methylamino)-27-norcholesterol (fluorescence probe) and 3-Doxyl-5 alpha-cholestane (EPR spin probe) begin to show significant interaction with 1 in the 10(-3) M range. The sequestration of the fluorescent cholesterol probe by 1 aggregates begins at approximately 2 x 10(-4) M at 35 degrees C. Analysis of EPR and fluorescence data indicates that the cholesterol analogues are in a nonpolar micellar environment of low fluidity. The significance and implication of the data are discussed in the context of the hypothesized cholesterol sequestration by 1 under physiological conditions. |
| Micellar distribution of cholesterol and phytosterols after duodenal plant stanol ester infusion Nissinen, M., H. Gylling, et al. (2002), Am J Physiol Gastrointest Liver Physiol 282(6): G1009-15. Abstract: Properties of the intestinal digestion of the dietary phytosterols, cholesterol and cholestanol, and the mechanisms by which phytosterols inhibit the intestinal absorption of cholesterol in healthy human subjects are poorly known. We have studied the hydrolysis of dietary plant sterol and stanol esters and their subsequent micellar solubilization by determining their concentrations in micellar and oil phases of the jejunal contents. Two liquid formulas with low (formula 1) and high (formula 2) plant stanol concentrations were infused via a nasogastric tube to the descending duodenum of 8 healthy human subjects, and intestinal contents were sampled for gas-liquid chromatographic sterol analysis 60 cm more distally. During the duodenal transit, phytosterol esters were hydrolyzed. This was especially profound for sitostanol, as its esterified fraction per milligram of sitosterol decreased 80% (P < 0.001) in formula 1 and 61% (P < 0.001) in formula 2. Contrary to that, esterified fraction of cholesterol per milligram of sitosterol was increased fourfold (P < 0.001) in formula 1 and almost sixfold (P < 0.001) in formula 2, whereas that of cholestanol remained unchanged. Percentages of esterified sterols and stanols in total intestinal fluid samples were higher after the administration of formula 2 than of formula 1. Esterified cholesterol and stanols accumulated in the oil phase, and free stanols replaced cholesterol in the micellar phase. At high intestinal plant stanol concentrations, cholesterol looses its micellar solubility possibly by replacement of its free fraction in the micellar phase by hydrolyzed plant stanols, which leads to a decreased intestinal absorption of cholesterol. |
| Microalbuminuria in nondiabetic adults: relation of blood pressure, body mass index, plasma cholesterol levels, and smoking: The Gubbio Population Study Cirillo, M., L. Senigalliesi, et al. (1998), Arch Intern Med 158(17): 1933-9. Abstract: BACKGROUND: Evidence exists that cardiovascular risk factors influence progression toward end-stage renal failure. We tested the hypothesis that in nondiabetic middle-aged adults without macroalbuminuria, cardiovascular risk factors are related to urinary albumin excretion and prevalence of microalbuminuria, a sign of early nephropathy. METHODS: Cross-sectional analysis of data for 1567 participants in The Gubbio Population Study (677 men and 890 women), aged 45 to 64 years, without macroalbuminuria, without diabetes mellitus, and with fasting plasma glucose levels of less than 7.8 mmol/L (140 mg/ dL). Data collection included albumin and creatinine excretion in timed overnight urine collection; levels of fasting plasma cholesterol, glucose, triglycerides, creatinine, and uric acid; creatinine clearance; red blood cell sodium-lithium countertransport; blood pressure; weight; height; medical history; smoking status; and alcohol intake. Urinary albumin excretion and prevalence of microalbuminuria were the dependent variables. RESULTS: Blood pressure, plasma cholesterol levels, smoking, and body mass index significantly related to urinary albumin excretion and prevalence of microalbuminuria. In analyses with control for multiple variables, relative risk for microalbuminuria (urinary albumin excretion, 20-199 microg/min) in men and women was 2.51 and 1.62, respectively, with 18 mm Hg higher (1 SD) systolic blood pressure; 2.25 and 2.10, respectively, with 1.0-mmol/L (40 mg/dL) higher plasma cholesterol level; 1.99 and 1.91, respectively, for smokers vs nonsmokers; and 1.83 and 1.33, respectively, with 4 kg/m2 higher body mass index. Findings were similar for microalbuminuria defined as urinary albumin excretion of at least 25 microg/dL glomerular filtration rate. CONCLUSION: Major cardiovascular risk factors are independent correlates of microalbuminuria in nondiabetic middle-aged adults. |
| Microanalysis of cholesterol, phospholipid, and medium- and long-chain fatty acids in biologic materials Wang, H., D. L. Hachey, et al. (1994), Anal Biochem 218(1): 74-9. Abstract: We have developed a procedure for the microanalysis of the cholesterol and phospholipid concentrations and the fatty acid (including medium-chain fatty acids) composition of total lipid and phospholipid. One-milligram lipid samples were extracted from jejunal brush border membranes isolated from rats fed a diet containing 14% medium-chain triglycerides. The samples were analyzed by gas chromatography using an autosampler. We were able to identify 17 fatty acids in the total lipid and in the phospholipid fractions. The cholesterol and phospholipid contents of the membranes were 270 +/- 21 and 298 +/- 35 nmol.mg protein-1, respectively; thus the cholesterol/phospholipid ratio was 0.92 +/- 0.05, a value typically reported for the rat. Medium-chain fatty acids were not detected in the brush border membranes. Therefore, to demonstrate that medium-chain fatty acids were not lost during analysis, we analyzed the rat diet, and brush border membrane samples to which medium-chain triglycerides had been added. Recovery of medium-chain fatty acids from brush border membrane samples was 95.7 +/- 2.6%. The percentage of medium-chain fatty acids detected in the diet was not significantly different from the percentage when the diet was prepared. In summary, our procedure enabled a complete lipid analysis of very small biologic specimens. |
| Microbial ecology in man and animals and cholesterol metabolism. 2. Hypocholesterolemic effect of microorganisms Shenderov, B. A., M. A. Manvelova, et al. (1992), Antibiot Khimioter 37(11): 50-4. |
| Microbial ecology of humans and animals and cholesterol metabolism. 1. Evidence and mechanisms of host microflora participation Shenderov, B. A. and M. A. Manvelova (1992), Antibiot Khimioter 37(11): 46-50. |
| Microbial inhibitors of enzymes of cholesterol biosynthesis and esterification Egorov, N. S., N. A. Baranova, et al. (1999), Antibiot Khimioter 44(5): 38-44. |
| Microbiological production of 3-oxo-bisnorchola-1, 4-dien-22-oic acid from cholesterol by an Arthrobacter 82 Fa, Y. and Q. Su (1992), Wei Sheng Wu Xue Bao 32(1): 17-22. Abstract: Among nineteen strains of Arthrobacter which showed to be able to decompose cholesterol in preliminary experiments, a strain of Arthrobacter 82 was selected for microbiological production of 3-oxo-bisnorchola-1,4-dien-22-oic-acid (BNC) from cholesterol. The yield is over of 50% weight percent concentration of 0.25% in the presence of cobalt sulfate. The main intermediate in such a conversion process is cholestenone. Lower glucose and higher corn steep liquor concentration were favorable for side chain degradation of cholestenone and more BNC could be produced. BNC was crystallized in acidic solution and obtained by centrifugation. The structure and characteristics of BNC has been identified by means of conventional physical, chemical and spectrometric techniques. |
| Microenzymatic fluorescence assay for serum cholesterol Gray, M. C., A. L. Plant, et al. (1995), Anal Biochem 224(1): 286-92. Abstract: An enzymatic assay using fluorometric detection for cholesterol determination in serum is described. Results were compared to a conventional enzymatic colorimetric procedure and to the definitive method, which is based on isotope dilution mass spectrometry. Fluorescence detection enhances sensitivity over current colorimetric methods by approximately two orders of magnitude, and the assay response is linear over three orders of magnitude of cholesterol concentration. The reaction is performed in a single step and can be performed with small sample (1 microliter) and reaction (200 microliters) volumes. The fluorescence intensity is stable after a 30-min sample incubation at room temperature. The sensitivity of this fluorescence assay makes it possible to measure subnanomoles of cholesterol, allowing accurate measurement of total cholesterol in 1 microliter of serum or less. This level of sensitivity will also allow measurement of cholesterol in various isolated lipoprotein fractions. |
| Microimmiscibility and three-dimensional dynamic structures of phosphatidylcholine-cholesterol membranes: translational diffusion of a copper complex in the membrane Subczynski, W. K., W. E. Antholine, et al. (1990), Biochemistry 29(34): 7936-45. Abstract: Saturated and unsaturated phosphatidylcholine (PC)-cholesterol membranes have been studied, with a special attention paid to fluid-phase immiscibility in cis-unsaturated phosphatidylcholine (PC)-cholesterol membranes as previously proposed and to the three-dimensional structure of the membrane. The investigation was carried out with dual probes: a membrane-soluble, square-planar copper complex, (3-ethoxy-2-oxobutyraldehyde bis(N4,N4-dimethylthiosemicarbazonatocopper(II) (CuKTSM2), and one of several nitroxide radical lipid-type spin-labels. Bimolecular collision rates between metal ion and spin-label were determined by measuring the nitroxide spin-lattice relaxation times (T1's) in the presence and absence of CuKTSM2 by use of saturation-recovery ESR techniques, and from these measured rates, translational diffusion coefficients of CuKTSM2 were estimated. Profiles of the collision rate across the membrane bilayer were obtained with Tempocholine phosphatidic acid ester, 5-doxylstearic acid, 16-doxylstearic acid, and cholesterol-type spin-labels as a function of cholesterol mole fraction, length and unsaturation of acyl chains, and temperature. In the liquid-crystalline phase of saturated PC membranes, incorporation of cholesterol decreases the collision rate at all depths in the membrane, and the effect of cholesterol is smallest in the middle of the bilayer. In trans-unsaturated PC membranes, a cholesterol-induced decrease of the collision rate was also observed, except in the head-group regions. In cis-unsaturated PC membranes, virtually no effect of cholesterol was observed on the collision rate, either with phospholipid-type spin-labels or with cholesterol-type spin-labels. This result is in clear contrast with our previous observation, in which the effect of cholesterol in cis-unsaturated PC membranes is small on the alkyl-chain motion of phospholipid-type spin-labels but large on the wobbling rotational diffusion of cholesterol-type spin-labels Pasenkiewicz-Gierula, M., Subczynski, W. K., & Kusumi, A. (1990) Biochemistry 29, 4059-4069. A model is proposed to explain these results in which the fluid-phase immiscibility is prevalent in cis-unsaturated PC-cholesterol membranes, but where cholesterol-rich (cholesterol oligomeric) domains are small (several lipids) and/or of short lifetime (10(-9) s to less than 10(-7) s). It is suggested that this microimmiscibility arises from the structural nonconformability between the rigid cholesterol ring structure and the rigid bend at the cis double bonds in PC alkyl chains.(ABSTRACT TRUNCATED AT 400 WORDS) |
| Micronized fenofibrate and LDL-cholesterol subfractions Soska, V. (1999), Vnitr Lek 45(7): 441-3. Abstract: LDL-cholesterol subfractions have a different atherogenity; the most atherogenic are small LDL3 called small dense LDL. A clear relationship was proved between their concentration and early manifestation of ischaemic heart disease. In some instances they were found to act as an independent risk factor of cardiovascular disease. Their concentration depends to a great extent on the triacyglycerol concentration. They are found most frequently in patients with combined hyperlipidaemia, in associated metabolic syndrome and in patients with type 2 diabetes mellitus. Their plasma concentration can be reduced by non-pharmacological methods (restriction of animal fats, reduction of body weight, physical activity) as well as by pharmacological means (in particular fibrates). Micronized phenofibrate reduces significantly the concentration of small LDL3 and thus contributes to normalization of dyslipoproteinaemia and reduction of the risk of cardiovascular complications. |
| Micronized fenofibrate in dyslipidemia: a focus on plasma high-density lipoprotein cholesterol (HDL-C) levels Sharpe, M., D. Ormrod, et al. (2002), Am J Cardiovasc Drugs 2(2): 125-32; discussion 133-4. Abstract: The prodrug fenofibrate, a synthetic phenoxy-isobutyric acid derivative, is rapidly hydrolyzed in vivo to form fenofibric acid, which alters plasma lipid levels by activating the peroxisome proliferator-activated receptor alpha. The micronized fenofibrate 200 mg capsule formulation, and the recently developed micronized fenofibrate 160 mg tablet formulation, are bioequivalent. Micronized fenofibrate 200 mg/day (capsules) increased high density lipoprotein cholesterol (HDL-C) levels significantly from baseline in up to 7098 patients with various dyslipidemias in noncomparative studies. Micronized fenofibrate 200 mg/day (capsules) produced significantly greater elevations in HDL-C levels than a variety of HMG-CoA reductase inhibitors in small, randomized, double-blind and nonblind studies in patients with dyslipidemia (n = 91 to 227). This formulation of fenofibrate and gemfibrozil produced similar increases in HDL-C levels in a randomized, double-blind study (n = 234). Micronized fenofibrate 160 mg once daily (tablet) increased HDL-C levels significantly from baseline by 10.6 to 14.5% in patients with type IIa or IIb dyslipidemia (n = 353) in two noncomparative studies. Additionally, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and LDL-C to HDL-C and TC to HDL-C ratios were lowered significantly from baseline. The tablet and capsule formulations of fenofibrate were both generally well tolerated in two noncomparative studies in 375 or 9884 patients. In double-blind, placebo-controlled trials in a total of 804 patients, the pooled incidences of individual adverse events were generally similar with fenofibrate and placebo. |
| Micronized fenofibrate, decreased triglyceride levels, total cholesterol and LDL fractions in serum Zaborska, B., J. Klos, et al. (2000), Pol Arch Med Wewn 104(1): 371-5. Abstract: Elevated serum level of triglycerides is a classic indication for fibrates. Micronized fenofibrate is hypolipemic drug with proven safety and efficacy in a view of triglycerides reduction, but according to few papers published so far on the subject is also effective in decreasing elevated total and LDL cholesterol. The aim of study was to confirm results obtained from these few previous studies. Forty seven persons with lipid disturbances (25 males and 22 females, age range 34-71 yrs. mean 48.0) entered the study. Thirty two patients had a history myocardial infarction and fifteen persons without clinical symptoms of heart diseases. All of them were treated with micronized fenofibrate 200 mg daily. Micronized fenofibrate decreased serum concentration of total cholesterol by 13.4% (p < 0.01), LDL cholesterol by 21.2% (p < 0.001) and triglycerides by 39.5% (p < 0.001) in whole group of patients. Most beneficial effects were obtained in persons with mixed hyperlipidemia: reduction of total cholesterol, triglycerides and LDL cholesterol serum levels was 22.4% (p < 0.01), 52.5% (p < 0.0001), 25.4% (p < 0.01), respectively. In individuals with hypercholesterolemia a reduction of total cholesterol by 11% (p < 0.05) and LDL cholesterol by 15.4% (p < 0.05) was observed. In the group with hypertriglyceridemia or mixed hyperlipidemia reduction of serum triglycerides concentration by 33.5% (p < 0.05) was achieved. No significant change in serum HDL cholesterol level in any group was observed. The treatment with micronized fenofibrate was well tolerated. Our study shows that this drug is safe and seems to be effective in some cases with increased serum total and LDL cholesterol level as well. |
| Micronutrients and cholesterol de Villiers, L. S. (1993), S Afr Med J 83(7): 541-2. |
| Microplate methods for determination of serum cholesterol, high density lipoprotein cholesterol, triglyceride and apolipoproteins Shireman, R. B. and J. Durieux (1993), Lipids 28(2): 151-5. Abstract: Microtiter plate methods were developed for the enzymatic determination of serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and triglyceride (TG), and for the turbidometric determination of apolipoproteins. The micromethods resulted in accurate, precise values that were in good agreement with the conventional spectrophotometric assays. The coefficient of variation for TC determinations was 4.5% or less and bias was 5% or less. The lipid micromethod assays are sensitive to 10 mg/dL or less, and the apolipoprotein assay to 1 mg/dL. Less than 100 microL of serum suffices for TC, TG and apoprotein assays; HDL-C requires an additional 100 microL of serum. Advantages of the micromethods include reductions in assay time and in the amount of reagents required. |
| Microquantification of cholesterol and cholesteryl esters in rat peritoneal macrophages by reverse-phase high-performance liquid chromatography Araki, N., S. Horiuchi, et al. (1990), Anal Biochem 185(2): 339-45. Abstract: A simple and rapid method for the microquantification of cholesterol and cholesteryl esters by reverse-phase high performance liquid chromatography has been established. Comparison of elution patterns of authentic cholesterol and cholesteryl esters revealed that a mu Bondasphere reverse-phase C8 (300-A) column was more suitable than a corresponding reverse-phase C4 or C18 column in terms of rapidity and sensitivity. Recovery of cholesterol and cholesteryl esters from a C8 column was greater than 98% when determined either by radioactive cholesterol and cholesteryl oleate or by cholesteryl heptadecanoate. The sensitivity of the quantification ranged from 5 ng to 50 micrograms for both cholesterol and cholesteryl esters. This method was applied to determination of cellular cholesterol and cholesteryl esters of rat peritoneal macrophages. Lipid extracts of these cells were found to contain 38.01 +/- 2.60 micrograms of cholesterol and 3.18 +/- 0.36 micrograms of cholesteryl esters per milligram of cell protein. When the cells were loaded with cholesteryl esters by incubation for 24 h with various concentrations of acetylated low-density lipoprotein, a cellular level of cholesteryl esters showed a dose-dependent increase and reached a maximal level of 106.60 +/- 3.05 micrograms/mg cell protein. Thus, the present method is useful for the microquantification of cholesterol and cholesteryl esters from lipid extracts of biological samples. |
| Microsomal enzyme inducers raise plasma high-density lipoprotein cholesterol levels in healthy control subjects but not in patients with primary hypoalphalipoproteinemia Franceschini, G., J. P. Werba, et al. (1995), Clin Pharmacol Ther 57(4): 434-40. Abstract: In this study we compared the ability of phenytoin, a microsomal enzyme inducer, to raise plasma high-density lipoprotein (HDL) levels in normolipidemic subjects and patients with primary hypoalphalipoproteinemia. In healthy control subjects, phenytoin caused a dose-dependent increase of plasma HDL, HDL2, and HDL3 cholesterol levels, up to 40% to 50%. Minor changes were recorded in the plasma concentrations of apolipoprotein (apo) A-I and apo A-II; the plasma level of the cholesteryl ester transfer protein (CETP) decreased by 42%. In contrast, none of the patients with hypoalphalipoproteinemia had changes in plasma HDL, HDL2, or HDL3 cholesterol, apo A-I, apo A-II, or CETP levels. These findings indicate that microsomal enzyme inducers are unsuitable to increase plasma HDL levels in high-risk patients with primary hypoalphalipoproteinemia, and they disclose a new mechanism, that is, decreased CETP-mediated transfer of cholesterol out of HDL, for the HDL-raising effect of microsomal enzyme inducers in healthy individuals. |
| Microsomal redox systems in brown adipose tissue: high lipid peroxidation, low cholesterol biosynthesis and no detectable cytochrome P-450 Sekhar, B. S., C. K. Kurup, et al. (1990), Mol Cell Biochem 92(2): 147-57. Abstract: The presence of redox systems in microsomes of brown adipose tissue (BAT) in cold exposed rats was investigated and compared with liver. BAT microsomes showed high activity of lipid peroxidation measured both by the formation of malondialdehyde (MDA) and by oxygen uptake. NADH and NADPH dependent cytochrome c reductase activity were present in both BAT and liver microsomes. Aminopyrine demethylase and aniline hydroxylase activities, the characteristic detoxification enzymes in liver microsomes could not be detected in BAT microsomes. BAT minces showed very poor incorporation of 1-14Cacetate and 2-14Cmevalonate in unsaponifiable lipid fraction compared to liver. Biosynthesis of cholesterol and ubiquinone, but not fatty acids, and the activity of 3-hydroxy-3-methyl glutaryl CoA reductase appear to be very low in BAT. Examination of difference spectra showed the presence of only cytochrome b5 in BAT microsomes. In addition to the inability to detect the enzyme activities dependent on cytochrome P-450, a protein with the characteristic spectrum, molecular size in SDS-PAGE and interaction with antibodies in double diffusion test, also could not be detected in BAT microsomes. The high activity of lipid peroxidation in microsomes, being associated with large oxygen uptake and oxidation of NADPH, will also contribute to the energy dissipation as heat in BAT, considered important in thermogenesis. |
| Microsomal triglyceride transfer protein inhibitors: discovery and synthesis of alkyl phosphonates as potent MTP inhibitors and cholesterol lowering agents Magnin, D. R., S. A. Biller, et al. (2003), Bioorg Med Chem Lett 13(7): 1337-40. Abstract: A series of newly synthesized phosphonate esters were evaluated for their effects on microsomal triglyceride transfer protein activity (MTP). The most potent compounds were evaluated for their ability to inhibit lipoprotein secretion in HepG2 cells and to affect VLDL secretion in rats. These inhibitors were also found to lower serum cholesterol levels in a hamster model upon oral dosing. |