| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| The effect of low density lipoprotein composition on the regulation of cellular cholesterol synthesis: a comparison in diabetic and non-diabetic subjects Owens, D., S. McBrinn, et al. (1993), Acta Diabetol 30(4): 214-9. Abstract: This study investigates compositional differences in low density lipoprotein (LDL) subfractions and their relationship to cellular cholesterol synthesis. We examined ten normocholesterolaemic (serum cholesterol < 6.5 mM) non-diabetic subjects (group 1) and compared them with ten normocholesterolaemic (group 2) and ten hypercholesterolaemic (group 3) (serum cholesterol > 6.5 mM) type 2 (non-insulin-dependent) diabetic patients. Serum cholesterol levels for groups 1, 2 and 3 were 5.19 +/- 0.27, 5.20 +/- 0.27 and 7.51 +/- 0.31 mM. LDL (density 1.006-1.028 g/l) and LDL2 (1.028-1.063 g/l) were isolated by density gradient ultracentrifugation. A significantly greater proportion of cholesterol was carried in LDL2 than LDL1 in all groups. There was a significantly lower cholesterol/protein ratio in LDL1 from the hypercholesterolaemic diabetic patients compared with controls. The LDL esterified/free cholesterol ratio was significantly greater in both LDL1 and LDL2 in the hypercholesterolaemic diabetic patients compared with the other two groups. There was a negative correlation between inhibition of cholesterol synthesis and the esterified/free cholesterol ratio of both LDL1 (r = 0.56, P < 0.002) and LDL2 (r = 0.63, P < 0.001). Cellular cholesterol of 41.0 +/- 0.3 microgram/mg cell protein in the hypercholesterolaemic diabetic patients was also significantly higher compared with values of 30.32 +/- 2.0 and 34.1 +/- 4.2 micrograms/mg cell protein for the normocholesterolaemic non-diabetic and diabetic groups. In vitro LDL esterification led to a decrease in LDL receptor-mediated binding and resulted in a 40% reduction in the ability of the LDL to suppress cholesterol synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) |
| The effect of low density lipoproteins, cholesterol, and 25-hydroxycholesterol on apolipoprotein B gene expression in HepG2 cells Dashti, N. (1992), J Biol Chem 267(10): 7160-9. Abstract: The purpose of the present study was to examine the effects of exogenous cholesterol on the apolipoprotein (Apo) B gene expression in HepG2 cells. Pure cholesterol had no significant effect on either the cellular content of cholesteryl esters or the net accumulation of neutral lipids and ApoB in the culture medium. By contrast, addition of 25-hydroxycholesterol increased the net accumulation of cholesteryl esters in cells and medium by 2-3-fold and decreased that of unesterified cholesterol by 50% in both compartments. A 33% reduction in the cellular content of triglycerides was commensurate with a 40% increase in their accumulation in the medium. A significant 3-fold increase in the net accumulation of ApoB in the medium was predominantly due to enhanced secretion of newly synthesized ApoB as established by pulse-chase studies. The stimulation in ApoB secretion was accompanied by a 55% increase in cellular ApoB mRNA. Under these experimental conditions, the low density lipoprotein receptor activity was decreased by only 12-20%. Addition of progesterone prevented the effects of 25-hydroxycholesterol. The changes in the concentration of neutral lipids and ApoB were reflected in the composition of secreted "low-density" lipoproteins. These particles had increased percentage contents of cholesteryl esters and ApoB and a decreased percentage content of unesterified cholesterol in comparison with lipoproteins produced by control cells. The rate of ApoB production was not correlated with the triglyceride mass in the cells but was positively correlated with the cellular and secreted cholesteryl esters and secreted triglycerides. With the exception of unchanged cellular unesterified cholesterol and ApoB mRNA levels, plasma low density lipoprotein had similar, although less pronounced, effects on the production of neutral lipids and ApoB. These results demonstrate that in HepG2 cells the synthesis and secretion of ApoB and cholesteryl esters are tightly coupled and that 25-hydroxycholesterol increased the concentration of ApoB-containing lipoproteins primarily by stimulating their production rather than reducing their catabolism. |
| The effect of low-dose phenytoin on high-density lipoprotein cholesterol McKenney, J. M., K. S. Petrizzi, et al. (1992), Pharmacotherapy 12(3): 183-8. Abstract: We examined whether low doses of phenytoin, which should be associated with few dose-related side effects, may increase the levels of high-density lipoprotein (HDL) cholesterol. Of 35 healthy adult men who consented to participate, 31 completed the study. They took no medications and consumed no alcohol during the study. We used a three-arm, parallel, prospective, randomized, double-blind research design. Subjects took a single-blind placebo capsule once daily at bedtime for 2 weeks and then were randomly assigned to receive identical-appearing capsules containing 30 mg or 100 mg of phenytoin or placebo, once daily at bedtime for 4 weeks. The HDL cholesterol and HDL subfractions were determined from 12-hour fasting blood samples obtained at the beginning and end of the single-blind period and at the end of the third and fourth weeks of the double-blind period. Mean differences between baseline and posttreatment HDL cholesterol levels with placebo, 30 mg phenytoin, and 100 mg phenytoin were 0.010 mmol/L (0.4 mg/dl), 0.005 mmol/L (0.2 mg/dl), and 0.096 mmol/L (3.7 mg/dl), respectively (p = 0.2947); baseline and posttreatment HDL2 and HDL3 levels were not different among the groups. Total cholesterol levels were significantly higher in subjects taking phenytoin 100 mg than in those taking phenytoin 30 mg or placebo. The results suggest that phenytoin in dosages of up to 100 mg daily for 4 weeks has no substantial effect on HDL cholesterol or HDL subfractions. |
| The effect of membrane cholesterol content on ion transport processes in plasma membranes Bastiaanse, E. M., K. M. Hold, et al. (1997), Cardiovasc Res 33(2): 272-83. Abstract: Cholesterol is a prominent component of mammalian plasma membranes and is one of the factors that determine membrane function. In this review the effects of cholesterol content on transport processes in biological membranes are summarized. Membrane cholesterol affects a variety of membrane proteins, including ion channels, transporters, and receptors. Present concepts concerning the mechanistic basis of lipid-induced modulation of transport protein function range between two extremes: modulation by bulk properties or by specific interactions. Interest in bulk properties has been focussed mainly on membrane fluidity. The fluidity of biomembranes is diminished particularly by enrichment with cholesterol. As a change in membrane composition alters the environment in which the proteins are dissolved, any process which depends on membrane protein function may be affected by alterations in membrane composition, such as a change in cholesterol content. This review emphasizes the inhibitory effect of cholesterol enrichment on all membrane ATPases studied, and the stimulating effect of cholesterol enrichment on most other membrane transport proteins. Together with the intriguing feature that the cholesterol content of plasma membranes is considerably higher than that of subcellular membranes, there is ample evidence for a significant role of plasma membrane cholesterol in transmembrane protein function. |
| The effect of membrane cholesterol content on ion transport processes in plasma membranes Lijnen, P. (1997), Cardiovasc Res 35(2): 384-6. |
| The effect of metformin on blood pressure, plasma cholesterol and triglycerides in type 2 diabetes mellitus: a systematic review Wulffele, M. G., A. Kooy, et al. (2004), J Intern Med 256(1): 1-14. Abstract: BACKGROUND: The UKPDS 34 showed that intensive treatment with metformin significantly reduces macrovascular end-points and mortality in individuals with newly diagnosed type 2 diabetes compared with intensive treatment with insulin or sulphonylurea derivatives, despite similar glycaemic control. How this should be explained is as yet unclear. We hypothesized that metformin may have a glucose-lowering independent effect on blood pressure and lipid profile. In order to test this hypothesis we systematically reviewed the literature and pooled the data obtained in a meta-analysis. METHODS: Included were randomized-controlled trials in patients with type 2 diabetes mellitus and metformin treatment lasting at least 6 weeks. To identify all eligible trials we conducted electronic searches using the bibliographic databases Medline and Embase, contacted the manufacturer and checked obtained publications for cross-references. RESULTS: Forty-one studies (3074 patients) provided data on blood pressure and/or lipid profile. When compared with control treatment, metformin associated effects on systolic and diastolic blood pressure and HDL cholesterol were small and statistically not significant -1.09 mmHg 95% confidence interval (-3.01-0.82), P = 0.30; -0.97 (-2.15-0.21) mmHg, P = 0.11 and +0.01 (-0.02-0.03) mmol L(-1), P = 0.50, respectively. Compared with control treatment, however, metformin decreased plasma triglycerides, total cholesterol and LDL cholesterol significantly -0.13 (-0.21--0.04) mmol L(-1), P = 0.003; -0.26 (-0.34--0.18) mmol L(-1), P < 0.0001 and -0.22 (-0.31--0.13) mmol L(-1), P < 0.00001, respectively. We found no indications for publication bias. Of note, glycaemic control as assessed by HbA1c was better with metformin than with control treatment -0.74 (-0.84--0.65) percentage point; P < 0.00001. When studies were subdivided into tertiles according to increasing difference in glycaemic control between metformin and control treatment, it appeared that in case of near similar glycaemic control metformin had no effect versus control treatment on triglycerides, whereas still there was a significant effect on total and LDL cholesterol. CONCLUSIONS: This meta-analysis of randomized-controlled clinical trials suggests that metformin has no intrinsic effect on blood pressure, HDL cholesterol and triglycerides in patients with type 2 diabetes. This drug, however, independent of its effect on glycaemia, reduces total and LDL cholesterol significantly, but the reductions in these variables are relatively small. |
| The effect of milk intake on serum cholesterol in healthy young females. Randomized controlled studies Naito, C. (1990), Ann N Y Acad Sci 598: 482-90. |
| The effect of multiple plasmapheresis on levels of apolipoprotein B, fibrinogen and cholesterol in blood donors Kondera-Anasz, Z., M. Grabinska, et al. (1995), Wiad Lek 48(1-12): 184-9. |
| The effect of natural and synthetic antioxidant polyhydroxynaphthoquinones on cholesterol metabolism in cultured rabbit hepatocytes Lakeev Iu, V., V. A. Kosykh, et al. (1992), Biull Eksp Biol Med 114(11): 477-80. Abstract: Primary cultures of rabbit hepatocytes were used to examine the effect of natural and synthetic antioxidants--polyhydroxynaphthoquinones (PHNQ) and alpha-tocopherol on cholesterol and bile acid synthesis. Histochrome, one of the PHNQ, slightly decreased cholesterol synthesis at concentrations 10-100 microM, whereas alpha-tocopherol stimulated cholesterol synthesis. After administration of histochrome or alpha-tocopherol into culture medium a significant stimulation of bile acid synthesis in dose-dependent manner was observed. The increase of bile acid secretion by histochrome in the presence of physiological concentration of HDL2 was found as well. Since histochrome in contrast to alpha-tocopherol enhanced accumulation of 14C cholesterol of HDL2 in the hepatocytes, it was concluded that histochrome stimulated bile acid synthesis as a result of increased input of HDL2 cholesterol into hepatocytes. These data suggest that histochrome may exhibit a hypocholesterolemic effect by stimulation of bile acid synthesis and inhibition of cholesterol synthesis. |
| The effect of Neoral on plasma cholesterol concentration in renal transplant recipients Konstadinidou, I., J. N. Boletis, et al. (2001), Transplant Proc 33(3): 2393-4. |
| The effect of new synthetic cholesterol derivatives on cholesterol metabolism in cultured rabbit hepatocytes Mambetisaeva, E. T., V. A. Kosykh, et al. (1993), Biokhimiia 58(7): 1126-32. Abstract: The effects of three novel synthetic derivatives of cholesterol with ethoxy (I), aminoethoxy (II), azidoethoxy (III) and toluenesulfonyloxyethoxy (IV) groups in the 3 beta-hydroxy position of cholesterol on cholesterol synthesis as well as on apolipoprotein B and bile acid secretion in cultured rabbit hepatocytes have been studied. 3 beta-(2-hydroxyethoxy)-cholest-5-en (I) was used as a standard. It was found that the inhibiting effect of these compounds on cholesterol synthesis depends on their structure. Compound II (1 microgram/ml), which inhibited acetate incorporation into cholesterol by 30-50%, appeared to be the most effective among the other compounds tested. This derivative had no effect on the production of bile acids. Compound III was less effective, while compound IV had no effect on cholesterol synthesis. All the compounds under study reduced by 20-36% the secretion of the total apolipoprotein B as measured by the enzyme-linked immunosorbent assay (ELISA). None of the synthetic cholesterol derivatives influenced the leucine incorporation into the total protein fraction. The results obtained indicate that 3 beta-(2-aminoethoxy)cholest-5-en, the most effective compound among other cholesterol derivatives tested in the study, can serve as a basis for synthesizing novel cholesterol derivatives able to inhibit cholesterol biosynthesis in liver cells and to decrease the secretion of very low density lipoproteins in cultured rabbit hepatocytes. |
| The effect of okadaic acid and calyculin A on cholesterol esterification in rat hepatocytes Hernandez, M. L., M. Lopez de Heredia, et al. (1995), Biochem Soc Trans 23(4): 580S. |
| The effect of oxidized cholesterol derivatives on the absorption and degradation of very low density beta-lipoproteins by human and rabbit hepatocytes Volgushev, S. A., V. A. Kosykh, et al. (1991), Biull Eksp Biol Med 111(3): 254-6. Abstract: In our study the influence of oxidated cholesterol derivatives (7 alpha, 7 beta-oxicholesterol, 7-ketocholesterol, cholestene-3-one) on binding and degradation of beta-VLDL by human and rabbit hepatocytes was investigated. Cholesterol oxy derivatives inhibit the degradation of beta-VLDL in rabbit hepatocyte culture. There is no such effect with human hepatocytes. However beta-VLDL binding with human hepatocytes is significantly decreased under oxidated cholesterol derivatives influence. |
| The effect of oxidizing cholesterol on gastrointestinal absorption, plasma clearance, tissue distribution, and processing by endothelial cells Krut, L. H., J. W. Yang, et al. (1997), Arterioscler Thromb Vasc Biol 17(4): 778-85. Abstract: Little is known about the absorption or metabolism of oxysterols. Toward better appreciating the metabolic consequences of oxidizing cholesterol, we compared labeled cholesterol with the labeled oxysterols 7 alpha-hydroxycholesterol, 7 beta-hydroxycholesterol, and 7-ketocholesterol prepared from 4-14Ccholesterol, 26,26,26,27,27,27-2H6cholesterol, and 23,24,25,26,27-13C5 cholesterol. Gastrointestinal absorption of oxysterols in rats was 91.5 +/- 0.3% compared with 75 +/- 1.1% for cholesterol, determined by fecal collection (P <.001). When injected intravenously and followed by gas chromatography/mass spectrometry, 7 alpha-hydroxycholesterol was cleared at 23 times the rate of cholesterol. After 5 minutes, only 1.2 +/- 0.2% of 7 alpha-hydroxycholesterol remained in the plasma, whereas 28.0 +/- 1.7% of cholesterol and 40.0 +/- 2.5% of a triglyceride emulsion injected simultaneously were still present. 14C7 alpha-Hydroxycholesterol injected intravenously was also rapidly cleared from plasma, was widely distributed in tissues and organs, and showed evidence of extensive metabolism at 5 minutes. The fractional rate of uptake of radiolabeled oxysterols by cultured endothelial cells was 15.7 times that of cholesterol (P <.001), and the fractional rate of efflux was 3.4 times that of cholesterol (P <.001). Oxysterols passed through endothelial cells grown on transwell membranes at a rate 4.3 times that of cholesterol (P <.001). Fractional oxysterol transport across the endothelial cell monolayer was increased 62 +/- 17% when HDL was added to the medium in the lower chamber (P =.003). Oxysterols were extensively metabolized to even more polar metabolites during endothelial cell transit. These properties of oxysterols potentially provide a mechanism for enhancing transport of cholesterol through tissues and preventing accumulation of cholesterol in those cells that can oxidize it. |
| The effect of oyster mushroom (Pleurotus ostreatus), its ethanolic extract and extraction residues on cholesterol levels in serum, lipoproteins and liver of rat Bobek, P., L. Ozdin, et al. (1995), Nahrung 39(1): 98-9. |
| The effect of palmitic acid on lipoprotein cholesterol levels Clandinin, M. T., S. L. Cook, et al. (2000), Int J Food Sci Nutr 51 Suppl: S61-71. Abstract: The present study assessed the effect of high versus low palmitic acid intakes of plasma lipoprotein cholesterol levels and on rates for endogenous synthesis of cholesterol in normal and hypercholesterolemic subjects. On day 21 of each diet treatment, a fasting blood sample was drawn for lipoprotein determination and to provide a measure of the background level of deuterium. A priming dose of deuterium was consumed and a second blood sample obtained 24 hours after the first sample. Isotope ratio mass spectrometry was used to determine the incorporation of deuterium into the newly synthesized cholesterol molecule and fractional synthetic rates were calculated. Four diets were formulated to provide combinations of two levels of 16:0 at two levels of 18:2n-6. Subjects received each of the four diet treatments for 21 days, followed by washout periods of 21 days. Serum total cholesterol and LDL-cholesterol was not significantly affected by the high level of 16:0 when diets also contained a high level of 18:2n-6. Fractional synthesis rates of cholesterol observed for each diet treatment did not differ significantly, suggesting no relationship between the endogenous synthesis of cholesterol and dietary 16:0 content. The results indicate that 16:0 has no effect on serum lipoprotein profiles in the presence of recommended intakes for 18:2n-6. |
| The effect of palmitic acid on lipoprotein cholesterol levels and endogenous cholesterol synthesis in hyperlipidemic subjects Clandinin, M. T., S. L. Cook, et al. (1999), Lipids 34 Suppl: S121-4. Abstract: The present study assesses the effect of high vs. low palmitic acid intakes on plasma lipoprotein cholesterol levels and on rates for endogenous synthesis of cholesterol in healthy and hyperlipidemic subjects. Four diets were formulated to provide combinations of 16:0 at two levels of 18:2n-6. Subjects received each diet treatment for 21 d, followed by washout periods of 21 d. On day 21 of each diet treatment, a fasting blood sample was drawn for lipoprotein determination and to provide a measure of the background level of deuterium. A priming dose of deuterium was consumed and a second blood sample obtained 24 h after the first sample. Isotope ratio mass spectrometry was used to determine the incorporation of deuterium into the newly synthesized cholesterol molecule, and fractional synthetic rates were calculated. Serum total cholesterol and low density lipoprotein-cholesterol was not significantly affected by the high level of 16:0 when diets also contained a high level of 18:2n-6. There was no effect of dietary 16:0 on high density liproprotein-cholesterol at either the high or low levels of intake. The results indicate that 16:0 has no effect on serum lipoprotein profiles in the presence of recommended intakes for 18:2n-6. |
| The effect of parenterally administered cyclodextrins on cholesterol levels in the rat Frijlink, H. W., A. C. Eissens, et al. (1991), Pharm Res 8(1): 9-16. Abstract: The inclusion complex formation of intravenously administered hydroxypropyl-beta-cyclodextrin and beta-cyclodextrin with endogenous lipids was studied. We tested the hypothesis that complex formation of endogenous cholesterol with cyclodextrins in the bloodstream leads to extraction of cholesterol from the large lipoprotein particles. The relatively small cholesterol-cyclodextrin complexes then leave the bloodstream via capillary pores, and dissociation of the complex in the extravascular compartment finally causes redistribution of cholesterol from blood to tissue. This hypothesis is supported by the following experimental findings. Intravenous administration of cyclodextrins led to a transient decrease in plasma cholesterol levels in a dose-dependent manner, and in vitro cholesterol-cyclodextrin complexes passed dialysis membranes with a molecular weight cutoff of 6000-8000. Further, cyclodextrins increased protein binding of the steroidal drug spironolactone, probably through removal of cholesterol from plasma protein binding sites. Finally, extravascular redistribution was directly demonstrated in histological studies of the kidneys. Glomerular filtration of the cholesterol-cyclodextrin complex is followed by dissociation of the complex in the ultrafiltrate, resulting in cholesterol accumulation in the proximal tubule cells. The cholesterol-beta-cyclodextrin complex has a limited aqueous solubility. Crystallization of this complex in renal tissue might explain the nephrotoxicity of parenterally administered beta-cyclodextrin. The absence of such crystallization might explain the lower nephrotoxicity of hydroxypropyl-beta-cyclodextrin after intravenous administration. |
| The effect of percutaneous oestradiol on atheroma formation in ovariectomized cholesterol-fed rabbits Haines, C. J., A. E. James, et al. (1999), Atherosclerosis 143(2): 369-75. Abstract: OBJECTIVE: The aim of this study was to examine the effect of percutaneous oestradiol on the lipid profile and on atheroma formation using an animal model. METHODS: The study was of 12 weeks duration. Fifty sexually mature female New Zealand White rabbits were divided into five groups of equal size. Two groups acted as controls and received normal rabbit chow. Rabbits in one of these groups were ovariectomized. The remaining three groups were ovariectomized but received 1% cholesterol enriched rabbit chow. One of these cholesterol-fed groups received 0.3 mg/kg percutaneous oestradiol daily whilst another received 0.1 mg/kg oral oestradiol daily. Measurements of concentrations of total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were made at the beginning and end of the study. Aortic atheroma formation was measured using computerized image analysis of uptake of Sudan III staining. RESULTS: After 12 weeks there were significant increases in the mean concentrations of TC in the three cholesterol-fed groups compared with controls (P < 0.001). Changes in HDL-C and TG concentrations were less consistent. The mean area of aortic atheroma formation was significantly less in both the percutaneous oestradiol group (4.9%) and the oral oestradiol group (8.6%) compared with the non-oestrogen-treated cholesterol-fed group (19.5%) (P < 0.001, < 0.01 respectively). CONCLUSION: These results suggest that percutaneous oestradiol has a direct protective effect on atheroma formation independent of serum concentrations of total cholesterol. |
| The effect of pharmacist intervention and patient education on lipid-lowering medication compliance and plasma cholesterol levels Ali, F., M. Y. Laurin, et al. (2003), Can J Clin Pharmacol 10(3): 101-6. Abstract: BACKGROUND: Dyslipidemias are a modifiable risk factor for coronary heart disease. The benefits of cholesterol reduction drug therapies are limited by poor patient compliance with drug regimens. OBJECTIVES: To determine the impact of a community pharmacist pilot disease-management program on patient compliance with lipid-lowering drug therapy and on serum cholesterol levels. METHODS: One hundred forty-nine patients who were nonadherent to prescribed hypolipidemic drug regimens were recruited for this six-month prospective study. Each subject served as their own control. Pharmacists educated these patients on lipid disorders, the benefit of medication compliance and lifestyle modifications that reduce the risk for coronary heart disease. Pharmacists followed up participants by telephone at two-month intervals. Drug renewal rates were monitored throughout the study and plasma lipid levels were measured at study outset and study end. RESULTS: Pharmacist intervention and patient-education programs significantly increased medication compliance, as shown by a 15.3% increase (P<0.05) in the number of compliant patients and an 11 day (P<0.001) reduction in the average number of days to prescription renewal. Concurrently, levels of total cholesterol, triglycerides and low-density lipoprotein (LDL) cholesterol, were reduced by 6%, 16.2%, and 8.5% (P<0.001, 0.01, 0.01), respectively. High density lipoprotein (HDL) cholesterol remained relatively unchanged (+0.7%) so that the LDL to HDL ratio was improved by 17.2% overall (P<0.01). Almost all of the patients (99.2%) were satisfied with the program and expressed a willingness to pay an average $34.50 per 30 min consultation for the pharmacist services offered. CONCLUSION: Pharmacists can contribute significantly to disease management of dyslipidemic individuals. |