| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Effects of apolipoprotein E phenotype on serum cholesterol level and cholesterol response to diet therapy in patients with hypercholesterolemia Honda, K. and T. Murase (1997), Endocr J 44(3): 425-9. Abstract: We investigated the association of the apolipoprotein (apo) E isoform phenotype with the basal serum cholesterol level and cholesterol response to diet therapy in outpatients with primary hypercholesterolemia. The basal levels of serum cholesterol, triglyceride and HDL-cholesterol in the 132 subjects were 286 +/- 26 mg/dl, 154 +/- 83 mg/dl and 54 +/- 14 mg/dl, respectively. The frequencies of apo E 3/2, 3/3, 4/2, 4/3 and 4/4 were 1, 104, 2, 24 and 1, respectively. There were no differences in serum lipids between subjects with the two most common apo E phenotypes, i.e., apoE 3/3 (n = 104) and apoE 4/3 (n = 24). The serum cholesterol response to diet therapy was evaluated by measuring the serum lipids of 52 participants before and 2-3 months after diet therapy. After dietary counselling, serum cholesterol values were reduced significantly from 293 +/- 27 to 256 +/- 36 mg/dl (P < 0.01) in the total group of study subjects. There was no significant difference in serum cholesterol reduction in response to diet therapy between subjects with apoE4 (E4/2, E4/3 and E4/4, n = 12) and without apoE4 (E3/3 and E3/2, n = 40). Following dietary counselling, patients who lost a large amount of body weight (BM I > or = 1.0) exhibited a greater reduction in serum cholesterol than those who showed less weight loss. In conclusion, the results of our study demonstrated the primary importance of diet therapy in the treatment of hypercholesterolemia, although other investigators have suggested that apo E phenotypes influence the response of serum cholesterol to dietary changes. |
| Effects of apolipoprotein E, beta-very low density lipoproteins, and cholesterol on the extension of neurites by rabbit dorsal root ganglion neurons in vitro Handelmann, G. E., J. K. Boyles, et al. (1992), J Lipid Res 33(11): 1677-88. Abstract: Previous studies suggest that during nerve regeneration apoE acts as a lipid transport protein that assists in the rapid initial extension of axons and then in their myelination. To determine whether apoE and/or apoE-containing lipoproteins can modulate axon growth, we assessed their effect on the out-growth of neurites from neurons in mixed cultures of fetal rabbit dorsal root ganglion cells in vitro. Incubation with beta-very low density lipoprotein (beta-VLDL) particles, which are rich in apoE and cholesterol, increased neurite outgrowth and branching. Unesterified cholesterol added to the cultures had a similar, but less pronounced, effect. These data suggest that cholesterol might be the component responsible for the enhanced neurite growth. In contrast, purified, lipid-free apoE added to the cultures reduced neurite branching. Neurite branching was also reduced when purified apoE was added along with beta-VLDL or cholesterol; however, the striking finding was that under these conditions the neurites extended farther from the neuronal cell body. Dorsal root ganglion cells were examined for the presence of receptors for native and apoE-enriched beta-VLDL. Immunocytochemistry, ligand blots, 45Ca2+ blots, and studies of the interaction of the cells with fluorescent lipoproteins provided evidence of two types of receptors for apoE-containing lipoproteins on neurons: the low density lipoprotein (LDL) receptor, which binds native beta-VLDL, and the LDL receptor-related protein, which binds apoE-enriched beta-VLDL. These findings indicate that apoE may play two complementary roles in neurite outgrowth. When complexed with lipoproteins, apoE stimulates neurite growth by the receptor-mediated delivery of cholesterol and perhaps other components necessary for neurite outgrowth. When apoE as a free protein is added together with apoE-containing lipoproteins, apoE decreases neurite branching and promotes neurite extension away from the cell body. These actions, which would be complementary in promoting target-directed nerve growth in vivo, provide the first direct evidence that apoE and apoE-containing lipoproteins can modulate the outgrowth of neuronal processes. |
| Effects of apolipoproteins on the kinetics of cholesterol exchange Letizia, J. Y. and M. C. Phillips (1991), Biochemistry 30(3): 866-73. Abstract: The effects of apolipoproteins on the kinetics of cholesterol exchange have been investigated by monitoring the transfer of 14Ccholesterol from donor phospholipid/cholesterol complexes containing human apolipoproteins A, B, or C. Negatively charged discoidal and vesicular particles containing purified apolipoproteins complexed with lipid (75 mol % egg PC, 15 mol % dicetyl phosphate, and 10 mol % cholesterol) and a trace of 14Ccholesterol were incubated with a 10-fold excess of neural, acceptor, small unilamellar vesicles (SUV; 90 mol % egg PC and 10 mol % cholesterol). The donor and acceptor particles were separated by chromatography on DEAE-Sepharose, and the rate of movement of labeled cholesterol was analyzed as a first-order exchange process. The kinetics of exchange of cholesterol from both vesicular and discoidal complexes that contain apoproteins are consistent with an aqueous diffusion mechanism, as has been established previously for PC/cholesterol SUV. The addition of 2-3 molecules of apo A-I to a donor SUV does not significantly alter the half-time (t1/2), which is 80 +/- 9 min at 37 degrees C. However, addition of 5-12 apo A-I molecules progressively decreases t1/2 from 65 +/- 2 to 45 +/- 4 min. This enhancement in the rate of desorption of cholesterol molecules is presumed to arise from the creation of packing defects at boundaries around the apoprotein molecules, which are intercalated among the phospholipid and cholesterol molecules in the surface of the donor SUV.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Effects of arsenic (V)-chromium (III) interaction on plasma glucose and cholesterol levels in growing rats Aguilar, M. V., M. C. Martinez-Para, et al. (1997), Ann Nutr Metab 41(3): 189-95. Abstract: Recent studies have demonstrated interaction between arsenic (As) and chromium (Cr) affecting absorption and/or protein catabolism. In the present study the possible effects of As(V)/Cr(III) interaction on growth rate, organ weight, and the two main organic functions of Cr, i.e., regulation of plasma glucose levels and total plasma cholesterol levels, was examined in weaned male Wistar rats. The diet of 20 rats was supplemented with 5 micrograms of As(V) and/or Cr(III) per gram of food for 10 weeks. As/Cr interaction did not significantly affect growth rates on organ weight:body weight ratios but did decrease total plasma cholesterol levels, though the decrease was not as pronounced as in the group supplemented with Cr alone (p < 0.1). Since supplementation with As(V) produced the opposite effect (96.83 vs. 47.27) (p < 0.01), the combined use of As and Cr may prove beneficial in cases of chronic As(V) intoxication. Supplementation treatment with As(V) and Cr(III) combined had no significant effect on glucose levels, because though As(V) affects Cr tissue levels and thus alters the effect of Cr on plasma cholesterol levels, individual effects of As(V) and Cr(III) are similar, and hence basal glucose levels are unaffected. |
| Effects of atorvastatin (and blood pressure lowering comparing amlodipide-based therapy with beta-blocker-based therapy) on serum variables of cholesterol synthesis and absorption, thrombogenicity and on low-density lipoprotein oxidation in vivo Nieminen, M. S., J. Viikari, et al. (2001), J Hum Hypertens 15 Suppl 1: S27-9. |
| Effects of atorvastatin on low-density lipoprotein cholesterol phenotype and C-reactive protein levels in patients undergoing long-term dialysis Dornbrook-Lavender, K. A., M. S. Joy, et al. (2005), Pharmacotherapy 25(3): 335-44. Abstract: STUDY OBJECTIVES: To determine the effects of atorvastatin on low-density lipoprotein cholesterol (LDL) particle size and C-reactive protein (CRP) concentrations in patients undergoing long-term hemodialysis. Another objective was to compare the effects of atorvastatin on lipoprotein profiles as determined by direct versus indirect assessment of lipoprotein composition. DESIGN: Randomized, parallel-group substudy. SETTING: Two university-affiliated outpatient hemodialysis centers. PATIENTS: Nineteen patients with LDL levels above 100 mg/dl and with at least two cardiovascular risk factors. INTERVENTION: Patients were randomized in a 1:1 ratio to atorvastatin 10 mg/day or no treatment (control) for 20 weeks. MEASUREMENTS AND MAIN RESULTS: We compared the differences between LDL particle size and CRP levels at baseline and 20 weeks in the atorvastatin versus control groups. Baseline demographic characteristics were similar between the two groups. Atorvastatin therapy was associated with no change in mean LDL particle size (p=0.23) and with a 90% decrease in mean CRP level (p=0.52). When evaluated by standard chemical analysis, atorvastatin therapy reduced total cholesterol levels by 29% (p=0.025) and resulted in nonsignificant reductions in LDL, high-density lipoprotein cholesterol, and triglyceride levels. Treatment with atorvastatin was not associated with significant changes in lipoprotein profile as determined by nuclear magnetic resonance (NMR) spectroscopy. CONCLUSION: Treatment with atorvastatin did not affect LDL particle size but was associated with a sizable, yet nonsignificant, reduction in CRP concentrations. The drug had variable effects on lipoprotein concentrations as determined by chemical and NMR analytical methods. A larger study is necessary to provide definitive information on the effects of atorvastatin on LDL phenotype and CRP in patients with kidney disease. |
| Effects of atorvastatin on stroke in patients with unstable angina or non-Q-wave myocardial infarction: a Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) substudy Waters, D. D., G. G. Schwartz, et al. (2002), Circulation 106(13): 1690-5. Abstract: BACKGROUND: This report describes the effect of intensive cholesterol lowering with atorvastatin on the incidence of nonfatal stroke, a secondary end point, in a randomized, placebo-controlled trial of patients with unstable angina or non-Q-wave myocardial infarction. The primary end point, a composite of death, nonfatal myocardial infarction, resuscitated cardiac arrest, or recurrent symptomatic myocardial ischemia with objective evidence requiring emergency rehospitalization, was reduced from 17.4% in the placebo group to 14.8% in the atorvastatin group over the 16 weeks of the trial (P=0.048). METHODS AND RESULTS: Strokes were adjudicated by a blinded end-point committee using standard clinical and imaging criteria. The outcomes of nonfatal stroke and fatal plus nonfatal stroke were analyzed by time to first occurrence during the 16-week trial. Of 38 events (in 36 patients) adjudicated as fatal or nonfatal strokes, 3 were classified as hemorrhagic, one as embolic, and 29 as thrombotic or embolic; 5 could not be categorized. Nonfatal stroke occurred in 9 patients in the atorvastatin group and 22 in the placebo group (relative risk, 0.40; 95% confidence intervals, 0.19 to 0.88; P=0.02). Fatal or nonfatal stroke occurred in 12 atorvastatin patients and 24 placebo patients (relative risk, 0.49; 95% confidence intervals, 0.24 to 0.98; P=0.04). All 3 hemorrhagic strokes occurred in the placebo group. CONCLUSION: Intensive cholesterol lowering with atorvastatin over 16 weeks in patients with acute coronary syndromes reduced the overall stroke rate by half and did not cause hemorrhagic stroke. These findings need to be confirmed in future trials. |
| Effects of atorvastatin therapy on the low-density lipoprotein subfraction, remnant-like particles cholesterol, and oxidized low-density lipoprotein within 2 weeks in hypercholesterolemic patients Sakabe, K., N. Fukuda, et al. (2003), Circ J 67(10): 866-70. Abstract: The short- and intermediate-term pleiotropic effects of atorvastatin were investigated in 18 hypercholesterolemic patients, as well as the temporal differences in these pleiotropic effects. Atorvastatin was given for 3 months and fasting lipid concentrations, thiobarbituric acid reactive substances (TBARS), fibrinolytic parameters, and flow-mediated dilation of the brachial artery (FMD) were measured at baseline and after 2 weeks and 3 months of therapy. Atorvastatin reduced the total cholesterol (273+/-34 vs 188+/-31 mg/dl, p<0.0001), low-density lipoprotein-cholesterol (LDL-C: 174+/-28 vs 111+/-23 mg/dl, p<0.0001), small, dense LDL-C (34+/-22 vs 18+/-20%, p<0.01), remnant-like particles cholesterol (RLP-C: 8.8+/-6.0 vs 5.1+/-2.6 mg/ml, p<0.01), and TBARS (3.3+/-1.0 vs 3.1+/-0.9 nmol/ml, p<0.05) after 2 weeks. Atorvastatin decreased the concentration of small, dense LDL-C again after 3 months (8+/-13%, p<0.0001). The plasma concentrations of the fibrinolytic parameters did not change significantly after 3 months of atorvastatin therapy. FMD increased significantly after 2 weeks (5.6+/-2.1 vs 6.3+/-2.0%, p<0.01) and additionally increased after 3 months of therapy (8.3+/-1.9%, p<0.0001). There were no correlations between the pleiotropic effects and the improvement in the lipid profile. The results indicate some short-term pleiotropic effects of atorvastatin therapy within 2 weeks, which may be important with respect to the early benefits of statin therapy. |
| Effects of Bacillus polyfermenticus SCD on lipid and antioxidant metabolisms in rats fed a high-fat and high-cholesterol diet Paik, H. D., J. S. Park, et al. (2005), Biol Pharm Bull 28(7): 1270-4. Abstract: Bacillus polyfermenticus SCD, commonly referred to as Bispan strain, is used as a host in bioindustry and has been shown to have several human health benefits. In a recent in vitro study, we discovered that B. polyfermenticus SCD exerts cholesterol-lowering and antioxidant effects. Here, we evaluate the effects of B. polyfermenticus SCD on the lipid and antioxidant metabolisms of hypercholesterolemic rats. Twenty male Sprague-Dawley rats were divided into two groups after a 1-week adaptation period and were fed for 6 weeks on either a high fat-high cholesterol diet, or a high fat-high cholesterol diet supplemented with B. polyfermenticus SCD (3.1x10(6) cfu/d). B. polyfermenticus SCD significantly reduced plasma low-density-lipoprotein cholesterol, hepatic total cholesterol, and triglycerides, while increasing the fecal excretion rates of total cholesterol and triglycerides. In addition, B. polyfermenticus SCD might reduce the risk of atherosclerosis, as the ratio of high-density-lipoprotein cholesterol to total cholesterol was significantly higher than in the control group. B. polyfermenticus SCD led to an increase in total radical trapping antioxidant potential (TRAP) and a decrease in conjugated dienes in plasma. The erythrocytic glutathione peroxidase (GSH-Px) activity in the B. polyfermenticus group was significantly lower than that in the control group. Plasma TRAP levels exhibited a highly significant negative correlation with hepatic total cholesterol and a marginally significant negative correlation with total plasma cholesterol, while a significant positive correlation was detected between fecal total cholesterol and plasma TRAP. These results suggest that B. polyfermenticus SCD exerts significant health benefits through the modulation of physiologic functions including a variety of atherogenic lipid profiles and antioxidants in hypercholesterolemia. |
| Effects of bezafibrate on biosynthesis of cholesterol and on degradation of native and acetylated low-density lipoproteins in incubated human monocytes Cosentini, R., F. Blasi, et al. (1992), Drugs Exp Clin Res 18(6): 245-50. Abstract: The effects of bezafibrate on 14C-acetate incorporation into non-saponifiable lipids and on degradation of native and acetylated 125I low-density lipoproteins (LDL) in cultured human monocytes has been evaluated. The presence of bezafibrate in the incubation medium resulted in a decrease of labelled acetate incorporation into non-saponifiable lipids. In parallel with the decrease in sterol synthesis, bezafibrate produced an increase in total and specific degradation of native low-density lipoproteins, whereas the degradation of acetylated low-density lipoproteins was not affected by the drug. These data, though obtained with concentrations of bezafibrate in the incubation medium greater than those encountered in ordinary therapeutic conditions, support the hypothesis that bezafibrate inhibits cholesterol biosynthesis and increases removal of low-density lipoproteins by activating the specific receptor pathway. |
| Effects of bezafibrate on hepatic cholesterol metabolism Stahlberg, D., E. Reihner, et al. (1991), Eur J Clin Pharmacol 40 Suppl 1: S33-6. Abstract: The influence of bezafibrate treatment on hepatic cholesterol metabolism was studied in rats and in humans. The activities of the three key enzymes involved in cholesterol metabolism 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, cholesterol 7 alpha-hydroxylase, and acyl-coenzyme A: cholesterol acyltransferase (ACAT) were suppressed by bezafibrate treatment in rats, but only the ACAT activity was significantly decreased when the activity was related to total liver weight. In humans, HMG-CoA reductase activity was increased about twice in the treated normolipidemic gallstone patients. In contrast, the concentration of lathosterol in serum decreased, indicating depression of the cholesterol synthesis. The increase in HMG-CoA reductase activity may be a compensatory effect of an inhibition of some other enzymes in the synthesis of cholesterol, as in vitro study on liver microsomes excluded a direct inhibitory effect of bezafibrate on HMG-CoA reductase. The ACAT activity was not significantly changed, and the cholesterol 7 alpha-hydroxylase activity was decreased by 55-60% compared with controls. The LDL-receptor-binding activity was unaffected by bezafibrate treatment. |
| Effects of bezafibrate therapy on subfractions of plasma low-density lipoprotein and high-density lipoprotein, and on activities of lecithin:cholesterol acyltransferase and cholesteryl ester transfer protein in patients with hyperlipoproteinemia Homma, Y., H. Ozawa, et al. (1994), Atherosclerosis 106(2): 191-201. Abstract: We investigated the effects of 12 weeks of bezafibrate treatment on plasma lipoprotein subfraction levels and on activities of LCAT and CETP in 25 patients with hyperlipoproteinemia. Bezafibrate reduced plasma levels of VLDL-TC and VLDL-TG by 69% and 66% (P < 0.001) and plasma levels of IDL-TC and IDL-TG were decreased by 37% and 31% (P < 0.01). Bezafibrate had no significant effects on plasma levels of LDL1 (1.019 < d < 1.045)-TC and LDL1-TG in the study population as a whole but significantly increased the plasma level of LDL1-TC in the subgroup of 9 patients with type IV hyperlipoproteinemia. Bezafibrate reduced plasma levels of LDL2 (1.045 < d < 1.063)-TC, LDL2-TG by 48% and 44% (P < 0.001) in both type II and type IV hyperlipoproteinemic patients. Gradient polyacrylamide gel electrophoresis revealed a decrease in small LDL particles. Bezafibrate did not affect the plasma level of HDL2-TC but reduced the HDL2-TG concentration significantly (P < 0.001). Bezafibrate increased the plasma level of HDL3-TC by 37% and reduced the HDL3-TG level significantly by 20% (P < 0.001). Gradient polyacrylamide gel electrophoresis revealed an increase in HDL3a and a decrease in HDL2a. Bezafibrate suppressed the activities of LCAT and CETP by 21% (P < 0.001) and 17% (P < 0.01), respectively. The bezafibrate-induced decrease in plasma levels of small, heavy LDL might be related to its inhibition of LCAT and CETP activities which resulted in suppression of heteroexchange of HDL-EC with triglyceride in large, light LDL. The bezafibrate-induced increase in large HDL3 (HDL3a) could not be explained solely by its suppression of LCAT and CETP activities. The decrease of plasma small, heavy LDL as well as TG-rich lipoproteins by bezafibrate seems to be beneficial for prevention of atherosclerotic diseases. |
| Effects of bile acid pool composition on hepatic metabolism of cholesterol in man Carulli, N., P. Loria, et al. (1990), Ital J Gastroenterol 22(2): 88-96. Abstract: This work reviews the evidence concerning the role of the bile acid pool composition in the regulation of the overall hepatic metabolism of cholesterol in man. It has been known that bile acids regulate bile secretion, biliary lipid transport and hepatic cholesterol metabolism. However, the intimate mechanisms of these regulatory functions are not well understood. Current thinking attributes most of this regulation to the size of the bile acid pool. A typical example is represented by the negative feed-back mechanism by which bile acids returning to the liver control their own synthesis. Recent evidence however tend to suggest that not only the size but also the composition contributes to the regulatory activity of the bile acid pool. Specifically the hydrophobic-hydrophilic balance of the pool, as resulting from the characteristics and the proportions of the individual bile acids present within the pool, seems to dictate most of the effects of bile acids on hepatic cholesterol metabolism. Thus abundance within the pool of hydrophobic bile acids, such as deoxycholic or chenodeoxycholic acid, seems to induce a greater biliary lipid secretion and to exert inhibition of cholesterol and bile acid synthesis whereas hydrophilic bile acids such as ursodeoxycholic acid seem to be uneffective. It follows that by changing the composition of the bile acid pool it is possible to influence the hepatic metabolism of cholesterol. |
| Effects of bile salt hydrophobicity on crystallization of cholesterol in model bile Van Erpecum, K. J., P. Portincasa, et al. (1996), Eur J Clin Invest 26(7): 602-8. Abstract: Precipitation of cholesterol crystals is an essential step in gallstone formation. In the present study we found much faster and more extensive precipitation of various cholesterol crystal shapes in whole model biles containing the hydrophobic bile salt taurodeoxycholate than in biles containing the relatively hydrophilic taurocholate. Addition of taurodeoxycholate to isolated cholesterol-phospholipid vesicles also induced more crystallization than taurocholate. Crystallization behaviour in whole model biles and in vesicles after addition of corresponding bile salts was very similar. The very hydrophilic bile salts tauroursodeoxycholate and taurohyodeoxycholate never induced crystallization from vesicles, and crystallization in corresponding whole model biles did not occur. These bile salts also reduced crystallization dose dependently after addition of taurodeoxycholate to vesicles. Ultracentrifugation experiments suggested a higher vesicular cholesterol-phospholipid bile salts. These findings indicate that bile salt hydrophobicity influences shape of cholesterol crystals and extent of crystallization, possibly by modulating the vesicular cholesterol-phospholipid ratio. |
| Effects of bile salts on rat hepatic acyl CoA:cholesterol acyltransferase Erickson, S. K. and P. E. Van Zuiden (1995), Lipids 30(10): 911-5. Abstract: Acyl CoA:cholesterol acyltransferase (EC2.3.1.26, ACAT), responsible for intracellular esterification of cholesterol, may play an important role in cholesterol trafficking within the cell, and thus, in maintenance of cellular cholesterol homeostasis. Bile acids are potential regulators of cholesterol trafficking in the liver. Therefore, the effect of bile salts on hepatic ACAT activity was studied in the perfused rat liver. ACAT activity was increased after liver perfusion with either taurocholate or taurochenodeoxycholate. However, addition of these bile salts at physiological concentrations in vitro had little effect on microsomal ACAT activity. The increase in hepatic ACAT activity due to perfusion with bile salts was accompanied by reduced accumulation of very low density lipoprotein cholesterol in the perfusate, but there was no effect on 3-hydroxy-3-methylglutaryl-CoA reductase activity. Hepatic ACAT activity was decreased after bile diversion for four hours in the intact animal. This treatment had no statistically significant effect on 3-hydroxy-3-methylglutaryl-CoA reductase activity. These data suggest that bile salts induce changes in hepatic compartmentation and traffic of cholesterol within the hepatocyte accompanied by response of ACAT activity to maintain cellular cholesterol homeostasis. |
| Effects of body mass index, plasma glucose and cholesterol levels on isolated systolic hypertension Ko, G. T., C. S. Cockram, et al. (2005), Int J Cardiol 101(3): 429-33. Abstract: Despite the high cardiovascular risk of diabetic patients, there is a paucity of data on isolated systolic hypertension (ISH) in diabetic patients. In this cross-sectional study, we examined the risk of ISH and its associated factors in Chinese type 2 diabetic patients. Isolated systolic hypertension was defined as systolic blood pressure (SBP) > or =140 mm Hg and diastolic blood pressure (DBP) <90 mm Hg. The mean value of two BP measurements taken 1 min apart was used. There were 1048 type 2 diabetic patients recruited from the Prince of Wales Hospital Diabetes Clinic. Another 1043 age- and sex-matched non-diabetic subjects were recruited from the community. The mean age of the 2091 subjects was 40.6 +/- 7.6 years (median: 40 years, range: 16-69 years). Diabetic patients had an increased risk of ISH compared to non-diabetic subjects (7.6% vs. 3.4%, p < 0.001) with an odd ratio of 2.38. On multivariate analysis, age, body mass index, total cholesterol and duration of diabetes in diabetic subjects while age and waist-hip ratio (WHR) in non-diabetic subjects were independently associated with ISH. In conclusion, Chinese type 2 diabetic patients had increased risk to develop ISH than non-diabetic subjects. Age, obesity, lipid and duration of diabetes were independent associated with ISH. These findings suggest that control of body weight and metabolic profile might have beneficial effects on ISH. |
| Effects of cannabinoids in membrane bilayers containing cholesterol Mavromoustakos, T. and I. Daliani (1999), Biochim Biophys Acta 1420(1-2): 252-65. Abstract: The thermotropic and dynamic properties of the biologically active Delta(8)-tetrahydrocannabinol (Delta(8)-THC) and its inactive congener O-methyl-Delta(8)-tetrahydrocannabinol (Me-Delta(8)-THC) in DPPC/cholesterol (CHOL) bilayers have been studied using a combination of DSC and solid-state NMR spectroscopy. The obtained results showed differential effects of the two cannabinoids under study. These are summarized as follows: (a) the presence of the active compound fluidizes more significantly the DPPC/CHOL bilayers than the inactive analog as it is revealed by DSC and NMR spectroscopy results; (b) cholesterol seems to play a significant role in the way cannabinoids act in membrane bilayers; (c) the observed additional peaks in (13)C/MAS-NMR spectra which were cannabinoid specific offer an evidence of their different dynamic properties in membranes. In particular, the aromatic part of the inactive cannabinoid appears more mobile than that of the active one. This finding is in agreement with previously obtained X-ray data which locate the inactive cannabinoid in the hydrophobic core of the bilayer while the active one in the polar region; and (d) the observed downfield shift of C-1 carbon in the preparation containing the active cannabinoid is a strong evidence that Delta(8)-THC resides nearby the polar region where also cholesterol is well known to locate itself. Such downfield shift is absent when Me-Delta(8)-THC is resided in the membrane bilayer. These differential effects of the two cannabinoids propose that the phospholipid/cholesterol core of the membrane may play an important role in the mode of cannabinoid action by regulating their thermotropic and dynamic properties. |
| Effects of canola, corn, and olive oils on fasting and postprandial plasma lipoproteins in humans as part of a National Cholesterol Education Program Step 2 diet Lichtenstein, A. H., L. M. Ausman, et al. (1993), Arterioscler Thromb 13(10): 1533-42. Abstract: The most stringent dietary recommendations of the National Cholesterol Education Program (NCEP) are to limit fat intake to < 30% of calories, saturated fat intake to < 7% of calories, and cholesterol intake to < 200 mg/d (Step 2 diet). There is debate as to whether the remaining fat in the diet should be relatively high in monounsaturated or polyunsaturated fatty acids. We examined this issue by testing the effects of diets meeting the aforementioned guidelines that were enriched in three different vegetable oils on plasma lipids in the fasting and postprandial states in a clinically relevant population. Female and male subjects (n = 15, mean age, 61 years) with low-density lipoprotein cholesterol (LDL-C) concentrations > 130 mg/dL were studied under strictly controlled conditions. Subjects were first placed on a diet similar to that currently consumed in the United States to stabilize plasma lipids with respect to identical fat and cholesterol intakes. The subjects then received diets meeting NCEP Step 2 criteria in which two thirds of the fat calories were given either as canola, corn, or olive oil in a randomized, double-blinded fashion for 32 days each. Plasma cholesterol concentrations declined after consumption of diets enriched in all the test oils; however, the declines were significantly greater for the canola (12%) and corn (13%) than for the olive (7%) oil-enriched diet. Mean plasma LDL-C concentrations declined after consumption of diets enriched in all the test oils (16%, 17%, and 13% for canola, corn, and olive oil, respectively), and the magnitude of the declines was statistically indistinguishable among the test oils. Mean plasma high-density lipoprotein cholesterol (HDL-C) concentrations declined after consumption of the baseline diet, and these declines were significant for the canola (7%) and corn (9%) oil-enriched diets. Changes in LDL apolipoprotein (apo)B concentrations paralleled those of LDL-C. Switching from the baseline to the vegetable oil--enriched diets had no significant effect on plasma triglyceride, apoA-I, and lipoprotein(a) concentrations or the total cholesterol to HDL-C ratio. LDL apoB to apoA-I ratios were significantly reduced when the subjects consumed the vegetable oil--enriched diets. Differences similar to those observed in the fasting state were observed in the postprandial state.(ABSTRACT TRUNCATED AT 400 WORDS) |
| Effects of carbohydrate modification of Quillaja saponaria Molina QH-B fraction on adjuvant activity, cholesterol-binding capacity and toxicity Ronnberg, B., M. Fekadu, et al. (1997), Vaccine 15(17-18): 1820-6. Abstract: The iscom is an efficient antigen-presenting system for various antigens inducing both MHC class I and class II restricted immune responses. Protective immunity has been evoked against a variety of infectious agents. The saponin adjuvant Quil A, which was originally used to form iscoms, is composed of a mixture of structurally similar triterpenoids from Quillaja saponaria Molina having different biological activities. A purified, toxic Quillaja triterpenoid fraction with strong adjuvant activity, designated QH-B, was used to study whether modification of the carbohydrate moiety with sodium periodate would alter the toxicity without harming adjuvant activity and cholesterol-binding capacity. Most sugars, and in particular Api, Gal and Xyl, were modified by periodate treatment with only minor changes of the molecular weights indicating no loss of sugar residues. The adjuvant activity of QH-B was reduced in a dose-related manner, and at a concentration of 25 mM sodium periodate a significant reduction in toxicity was observed. The differences in both toxicity and adjuvant activity of the periodate-treated QH-B could be derived from alterations in the structure of the sugars Gal and Xyl, while modification of Api may influence adjuvant activity but not toxicity in vivo. The cholesterol-binding capacity, a prerequisite for iscom formation, was not affected by periodate oxidation at the doses tested. However, the use of modified QH-B as described in the present study for iscom-matrix formation resulted in "saponin-lipid complexes" which, to a various degree or totally, deviated from the characteristic iscom morphology. |
| Effects of carboxy-terminal truncation on human lecithin:cholesterol acyltransferase activity Francone, O. L., L. Evangelista, et al. (1996), J Lipid Res 37(7): 1609-15. Abstract: Mutagenesis was carried out in human lecithin:cholesterol acyltransferase (LCAT) to generate mutants with stop codons at positions corresponding to amino acids 315, 341, 359, 375, 388, 394, and 398 of the 416-amino acid sequence of the mature enzyme protein. Deletion of the 18 terminal amino acids of the protein was without effect on LCAT phospholipase or acyltransferase activity, or the stability of the protein to denaturation at 37 degrees C. Further deletion led to loss of most of the activity, associated with a 10-fold increase in the rate of denaturation at 37 degrees C. These data indicate that the proline-rich C-terminus of LCAT is not required for effective enzyme activity. The loss of activity that accompanied deletion of residues 394-398 suggests a structural role for these residues, part of a series of predicted beta-sheet sequences in the C-terminal third of the LCAT primary sequence. |