| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
| First Page | Previous Page | Next Page | Last Page |
| Sustained reduction of serum cholesterol levels following allo-transplantation of parenchymal hepatocytes in Watanabe rabbits Wang, J., R. Pollak, et al. (1991), Transplant Proc 23(1 Pt 1): 894-5. |
| Sustained suppression of serum LH, FSH and testosterone and increase of high-density lipoprotein cholesterol by daily injections of the GnRH antagonist cetrorelix over 8 days in normal men Behre, H. M., A. Bockers, et al. (1994), Clin Endocrinol (Oxf) 40(2): 241-8. Abstract: OBJECTIVE: Recently we have shown that single dose injections of the new GnRH antagonist cetrorelix (Ac-D-Na(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Cit6, D-AlaGnRH; SB-75) decrease serum LH and testosterone in a dose-dependent manner in normal men. These results prompted us to investigate the effectiveness and safety of multiple daily injections of cetrorelix in normal male volunteers. DESIGN AND VOLUNTEERS: Following two control examinations 16 young men were randomly assigned to four study groups (n = 4/group). Daily doses of 0 (placebo), 2, 5, and 10 mg cetrorelix were injected subcutaneously at 0800 h for 8 days and morning and evening blood samples were obtained for 3 weeks. RESULTS: One day after the first cetrorelix injection, serum LH and testosterone concentrations were significantly suppressed in all treatment groups. Whereas in the 2 and 5-mg dose groups LH and testosterone showed some fluctuations, daily injections of 10 mg cetrorelix consistently suppressed LH and testosterone in all men. In addition, in this group serum FSH concentrations were significantly suppressed to subnormal values 1 day after the first injection and remained in this range up to 5 days after the last injection. A time and dose-dependent increase of high-density lipoprotein cholesterol was observed during cetrorelix-induced testosterone deprivation with a maximal increase of 0.38 +/- 0.13 mmol/l (14.8 +/- 5.1 mg/dl; mean +/- SEM) in the 10-mg dose group. In addition, parallel to suppressed testosterone the volunteers' libido was significantly reduced under the GnRH antagonist. Apart from those symptoms caused by androgen deficiency, the only adverse side-effect observed was a mild painless local erythema at the injection site that disappeared within an hour. CONCLUSIONS: Daily injections of 10 mg cetrorelix effectively and consistently suppress serum LH, FSH and testosterone concentrations, and therefore it has potential for treatment of sex hormone-dependent diseases and for male contraception. |
| Sustained-delivery of an apolipoprotein E-peptidomimetic using multivesicular liposomes lowers serum cholesterol levels Ramprasad, M. P., G. M. Anantharamaiah, et al. (2002), J Control Release 79(1-3): 207-18. Abstract: Receptor-mediated removal of lipoproteins by the liver is predominantly mediated by apolipoproteinE (apoE). Recent data show that a novel dual domain peptide (hE-18A) containing the 10-residue receptor-binding domain of human apoE, and a model class A amphipathic helix (18A), can associate with low density and very low density lipoproteins (LDL and VLDL) and enhance their uptake and degradation by HepG2 cells in vitro, and further, causes a dramatic reduction in plasma cholesterol levels in apoE-null mice. The in vivo cholesterol lowering effect, however, is short-lived because of rapid clearance of the peptide from the circulation. These results indicate that a therapeutic benefit may be achieved by sustained-delivery of this novel peptide as an alternate form of treatment for hypercholesterolemia and hypertriglyceridemia. In this report we describe the encapsulation of this peptide in a multivesicular liposome (MVL) depot-delivery system (DepoFoam). An in vitro plasma release assay showed sustained release of the peptide from the DepoFoam particles and its subsequent association with LDL and VLDL. Furthermore, a single subcutaneous dose of the DepohE-18A formulation in apoE-null mice, yielded a mean, cumulative 18% decrease in serum cholesterol levels after 6 days, and the cholesterol levels remained low at 8 days. Whereas, an equivalent dose of free peptide showed maximal cholesterol decrease by 4 h, followed by a rapid decline in efficacy by 24-48 h. Fractionation of the different lipoprotein fractions from serum showed that the majority of the serum cholesterol decrease was associated with the VLDL fraction, followed by LDL. These results indicate that the apoE peptidomimetic encapsulated in DepoFoam has potential as an alternative therapeutic treatment of hyperlipidemia. |
| Sustained-release niacin for low levels of high-density lipoprotein cholesterol Lavie, C. J. (1993), Mayo Clin Proc 68(2): 201-2. |
| Syndrome of multiple cholesterol embolism after parenteral streptokinase therapy of acute myocardial infarct: description of an autopsy case Matturri, L., C. Varesi, et al. (1991), Cardiologia 36(1): 59-61. Abstract: Syndrome caused by multiple cholesterol embolism can be seen as a complication in patients affected by acute myocardial infarction, treated with streptokinase thrombolytic therapy. Fragments of atheromatous plaques may embolize and occlude arterial vessels in different organs. Only the histological examination can give a reliable diagnosis, because symptomatology changes according to different localization of the emboli. An emblem case of this pathology observed by the Authors is described in this article. |
| Synergetic effect of desialylated and glycated low density lipoproteins on cholesterol accumulation in cultured smooth muscle intimal cells Sobenin, I. A., V. V. Tertov, et al. (1991), Atherosclerosis 89(2-3): 151-4. Abstract: We have studied the combined effect of non-enzymatically glycosylated and desialylated low density lipoproteins (LDL) on the cholesterol content of cells cultured from unaffected human aortic intima. Native LDL did not alter the intracellular cholesterol level while glycated LDL taken in the concentration percent, respectively. The effect of the same concentrations of glycated LDL treated with neuraminidase (desialylated-glycated LDL) was twice as powerful. Desialylated LDL in the concentration of 50 and 100 micrograms/ml raised the cholesterol level by 1.4- and 2.1-fold, respectively. Simultaneous incubation of cells with glycated (50 micrograms/ml) and desialylated (50 micrograms/ml) LDL brought about a 3.4-fold increase in intracellular cholesterol. The obtained data suggest that intensive development of atherosclerosis in diabetes mellitus may be partially explained by synergetic effects of desialylated and glycated lipoproteins as well as LDL with both types of modification. |
| Synergism between the effects of dietary cholesterol and coconut oil on plasma, liver and lipoprotein composition of neonatal chick Castillo, M., J. H. Hortal, et al. (1998), Int J Biochem Cell Biol 30(6): 707-18. Abstract: The nature of the synergism between dietary factors and the development of atherosclerosis has not been fully defined. Our studies showed that simultaneous supplementation of 10% saturated fat rich in 12:0 and 14:0 fatty acids (coconut oil) plus 1% cholesterol to the diet produced a sharp increase of plasma cholesterol, indicating a synergic influence of both dietary constituents. This increase was especially patent in the VLDL fraction, modifying the distribution of other lipid components between the core and the surface of these particles. These changes are consistent with the atherogenic function of VLDL and its responsiveness to dietary manipulation. |
| Synergistic effect between size and cholesterol content in the enhanced hepatic uptake clearance of liposomes through complement activation in rats Harashima, H., T. M. Huong, et al. (1996), Pharm Res 13(11): 1704-9. Abstract: PURPOSE: The effect of liposome size and cholesterol (CH) content on the pharmacokinetics of liposomes was investigated in rats. METHODS: The pharmacokinetics of liposomes was examined using 5(6)-carboxyfluorescein (CF) as an aqueous phase marker. The extent of complement activation (ECA) was also measured by the release of CF from liposomes in serum. RESULTS: Both the size and the CH content influenced the mean residence time, total body clearance, and the hepatic uptake clearance (CLh) of liposomes. The increase of the size of liposomes increased the CLh at each CH content. There was no CH dependency of CLh in small liposomes (200 nm in diameter), although the CLh increased with the increase in the CH content in large (800 nm) and medium (400 nm) liposomes. A significant interaction effect was observed between liposome size and the CH content on CLh according to the analysis of variance. The good correlation between CLh and ECA indicated the role of complements as opsonins in enhancing the hepatic uptake of liposomes. The interaction effect between the size and CH content on CLh was explained principally by the product of the size and CH content. CONCLUSIONS: A synergistic effect was observed between the size and the CH content on CLh. An underlying hypothesis of the synergistic effect was postulated based on the size dependent recognition of liposomes by complement system. |
| Synergistic perturbation of phosphatidylcholine/sphingomyelin bilayers by diacylglycerol and cholesterol Armstrong, D. L., D. B. Borchardt, et al. (2002), Biochem Biophys Res Commun 296(4): 806-12. Abstract: The perturbations induced by second messenger diacylglycerols (DAGs) into bovine brain phosphatidylcholine (BBPC) bilayers in the presence or absence of bovine brain sphingomyelin (SM) and/or cholesterol were studied by (2)H NMR. Addition of 15 mol% DAG to BBPC bilayers did not induce non-bilayer lipid phases in the temperature range 30-60 degrees C. Similar measurements performed in the presence of cholesterol revealed that cholesterol progressively destabilizes PC bilayers with respect to DAG-induced perturbations. Thus, at 40 mol% cholesterol, addition of 15 mol% DAG induced the formation of non-bilayer (isotropic and inverted hexagonal) phases at 60 degrees C. Whereas some lateral separation of the bilayers into domains of different cholesterol contents was observed in BBPC/cholesterol membranes, such a lateral heterogeneity was greatly facilitated by the addition of SM. Since both a tendency to form non-bilayer lipid phases and lateral heterogeneity of the membranes are associated with increased activation of a number of membrane-associated enzymes, our results suggest that SM- and cholesterol-enriched regions of biological membranes (rafts) provide an environment with increased sensitivity to the generation of lipid second messengers and modified transmembrane signal transduction properties. |
| Syntaxin is efficiently excluded from sphingomyelin-enriched domains in supported lipid bilayers containing cholesterol Saslowsky, D. E., J. C. Lawrence, et al. (2003), J Membr Biol 194(3): 153-64. Abstract: Formation of a trans-complex between the three SNARE proteins syntaxin, synaptobrevin and SNAP-25 drives membrane fusion. The structure of the core SNARE complex has been studied extensively. Here we have used atomic force microscopy to study the behavior of recombinant syntaxin 1A both in detergent extracts and in a lipid environment. Full-length syntaxin in detergent extracts had a marked tendency to aggregate, which was countered by addition of munc-18. In contrast, syntaxin lacking its transmembrane region was predominantly monomeric. Syntaxin could be integrated into liposomes, which formed lipid bilayers when deposited on a mica support. Supported bilayers were decorated with lipid vesicles in the presence, but not the absence, of full-length syntaxin, indicating that formation of syntaxin complexes in trans could mediate vesicle docking. Syntaxin complexes remained at the sites of docking following detergent solubilization of the lipids. Raised lipid domains could be seen in bilayers containing sphingomyelin, and these domains were devoid of syntaxin and docked vesicles in the presence, but not the absence, of cholesterol. Our results demonstrate that syntaxin is excluded from sphingomyelin-enriched domains in a cholesterol-dependent manner. |
| Synthesis and absorption markers of cholesterol in serum and lipoproteins during a large dose of statin treatment Miettinen, T. A. and H. Gylling (2003), Eur J Clin Invest 33(11): 976-82. Abstract: BACKGROUND: Serum contains noncholesterol sterols, which are reliable markers of cholesterol metabolism, but their presence and importance in different lipoproteins have been insufficiently studied. MATERIALS AND METHODS: Serum and lipoprotein cholesterol precursors squalene, cholestanol, desmosterol and lathosterol (markers of cholesterol synthesis) and cholestanol and plant sterols (markers of cholesterol absorption), and absorption efficacy and absolute synthesis of cholesterol were studied at baseline and during 6-month atorvastatin (80 mg day(-1)) treatment by the sterol balance technique in men with type 2 diabetes. RESULTS: At baseline, approximately 14% of serum squalene was transported by VLDL, 12% by IDL, 40% by LDL and 30% by HDL. The respective values for the noncholesterol sterols were approximately 8, 4, 61 and 26%. The squalene to cholesterol ratios were highest in VLDL and IDL, those of cholestanol, desmosterol and absorption marker sterols were gradually higher, and that of lathosterol lower from VLDL to HDL. Atorvastatin reduced LDL cholesterol by approximately 50%, decreased the absolute cholesterol synthesis and turnover by approximately 40%, but increased significantly the fractional and mass absorption of cholesterol. In accordance with the fecal data, the ratios of the precursor sterols to cholesterol were reduced (-50%), but those of squalene (+48%) and the absorption sterols increased (e.g. 2.6-fold for sitosterol) similarly in each lipoprotein, but progressively from VLDL to HDL. CONCLUSIONS: Effective lowering of LDL cholesterol by large dose of statin is associated with decreased synthesis and turnover of cholesterol and increased fractional and mass absorption of cholesterol. These changes are detectable by noncholesterol sterols in serum and in different lipoprotein fractions. |
| Synthesis and antifungal activity of cholesterol-hydrazone derivatives Loncle, C., J. M. Brunel, et al. (2004), Eur J Med Chem 39(12): 1067-71. Abstract: A series of hydrazones synthesized from various cholesterol derivatives were evaluated for their in vitro antimicrobial properties against human pathogens. The activity was highly dependent on the structure of the different compounds involved. The best results have been obtained with tosylhydrazone cholesterol derivatives 8 and 9 exhibiting activities against Candida albicans (CIP 1663-80) at a concentration of 1.5 microg/ml. |
| Synthesis and biochemical properties of a new photoactivatable cholesterol analog 7,7-azocholestanol and its linoleate ester in Chinese hamster ovary cell lines Cruz, J. C., M. Thomas, et al. (2002), J Lipid Res 43(8): 1341-7. Abstract: We report the chemical synthesis of a new photoactivatable cholesterol analog 7,7-azocholestanol (AC) and its linoleate ester (ACL). We also examined the biochemical properties of the sterol and its ester by employing several different mutant Chinese hamster ovary (CHO) cell lines with defined abnormalities in cholesterol metabolism as tools. AC mimics cholesterol in supporting the growth of a mutant cell line (M19) that requires cholesterol for growth. In normal cells, tritiated ACL present in low-density lipoprotein (LDL) was hydrolyzed and reesterified in a manner similar to tritiated cholesteryl linoleate (CL) in LDL. Also, in the mutant cell line (AC29) lacking the enzyme acyl-coenzyme A:cholesterol acyltransferase or in the mutant cell line (CT60) defective in the Niemann-Pick type C1 protein, the hydrolysis of ACL in LDL was normal, but the reesterification of the liberated AC was defective. Therefore, the metabolism of ACL in LDL is very similar to that of CL in LDL. Tritium-labeled AC delivered to intact CHO cells as a cyclodextrin complex was shown to photoaffinity label several discrete polypeptides, including caveolin-1. These results demonstrate AC as an effective reagent for studying cholesterol-protein interactions involved in intracellular cholesterol trafficking. |
| Synthesis and blood compatibility evaluation of segmented polyurethanes based on cholesterol and phosphatidylcholine analogous moieties Li, Y. J., T. Yokawa, et al. (1996), Biomaterials 17(22): 2179-89. Abstract: New segmented polyurethanes based on cholesterol and phosphatidylcholine analogous moieties were synthesized. The soft segments used in this study were the poly(butadiene), poly(isoprene) or hydrogenated poly(isoprene) glycols; the hard segments of these segmented polyurethanes were composed of 4,4'-methylenediphenyl diisocyanate, 2-bis(2-hydroxyethyl)methylammonioethyl 5-cholesten-3 beta-yl phosphate and 1,4-butanediol. The blood compatibilities of synthesized segmented polyurethanes were evaluated by platelet-rich plasma contact studies and scanning electron microscopy observation using glass as the reference. The results show that the blood compatibilities of the synthesized segmented polyurethanes have great difference between the glass contact side and air exposed side for the same cast films. Generally, the hydrogenated poly(isoprene)-based segmented polyurethane is the best surface in terms of platelet adhesion, and the morphology of adhered platelets undergoes the lowest degree of variation among the segmented polyurethanes investigated in this study. |
| Synthesis and hypocholesterolemic activity of 6,7-dihydro-4H-pyrazolo1,5-apyrrolo3,4-dpyrimidine-5,8-diones, novel inhibitors of acylCoA:cholesterol O-acyltransferase Larsen, S. D., C. H. Spilman, et al. (1991), J Med Chem 34(5): 1721-7. Abstract: A novel series of 6,7-dihydro-4H-pyrazolo1,5-apyrrolo3,4-dpyrimidine-5,8-dione inhibitors of the enzyme acyl-CoA:cholesterol O-acyltransferase is described. A number of these derivatives were found to be potent modulators of serum lipoprotein levels in cholesterol-fed rats. Further evaluation of one of the most effective analogues confirmed that it was significantly blocking the absorption of cholesterol from the gut. |
| Synthesis and in vitro cholesterol dissolution by 23- and 24-phosphonobile acids Babu, P. and U. Maitra (2005), Steroids 70(10): 681-9. Abstract: A new class of 23- and 24-phosphonobile acids have been synthesized from bile acid and their in vitro cholesterol-dissolving efficiency have been estimated. 24-Phosphonobile salts (PBSs) are slightly more efficient in solubilizing cholesterol than 23-PBSs and natural bile salts. The cholesterol solubilizing power is influenced by the structure of PBSs, and is considerably reduced with an increase in the bulk pH. |
| Synthesis and preliminary in vitro evaluation of antitumor nitrosoureido cholesterol derivatives Elkihel, L., M. Gelin, et al. (1995), Arzneimittelforschung 45(2): 190-4. Abstract: A new class of chloroethyl nitrosourea analogues of cholesterol has been synthetized from the corresponding 7-amino and 7-aminoalkylcholesterol derivatives. Compounds III-V inhibited L1210 cell growth in culture much more effectively than N,N'-bis(2-chloroethyl)-N'-nitrosourea (BCNU) after 48 h incubation. Stability and cytotoxic activity of these prodrugs are promising for brain tumor treatments and as lymphotropic vectors for tumor cells spreading along the lymphatic pathways. |
| Synthesis and secretion of VLDL by rat hepatocytes--modulation by cholesterol and phospholipids Kumar, N. S., R. Abraham, et al. (1992), Indian J Biochem Biophys 29(5): 438-41. Abstract: The synthesis and secretion of apoB, the major protein component of very low density lipoprotein (VLDL) and low density lipoprotein (LDL), were studied using rat hepatocytes maintained in primary culture. Supplementation of hepatocytes with rat serum VLDL and LDL increased the production of apoB while delipidated lipoproteins had no significant effect, suggesting a role for lipids in the production of apoB. Addition of cholesterol to the culture medium also increased the production of apoB in a concentration-dependent manner. Pulse labelling followed by chase in presence of cholesterol indicated enhancement in apoB secretion. Mevinolin which inhibits cholesterol synthesis significantly reduced the secretion of apoB. The presence of phosphatidylcholine and phosphatidylethanolamine in the culture medium also increased the secretion of apoB into the medium. These data suggest that availability of lipids, particularly cholesterol, is an important determinant of apoB synthesis and secretion as VLDL. |
| Synthesis of 2-(p-chlorobenzyl)-3-aryl-6-methoxybenzofurans as selective ligands for antiestrogen-binding sites. Effects on cell proliferation and cholesterol synthesis Teo, C. C., O. L. Kon, et al. (1992), J Med Chem 35(8): 1330-9. Abstract: A series of nonsteroidal compounds, 2-(p-chlorobenzyl)-3-aryl-6- methoxybenzofurans derived from the 2-(p-chlorobenzyl)-6-methoxy-3(2H)-benzofuranones has been synthesized. The key steps in the synthesis were reactions of 2-(p-chlorobenzyl)-6-methoxy-3(2H)-benzofuranones with the arylorganometallic reagents followed by dehydration of the resulting carbinols. The benzofurans are ligands for antiestrogen-binding sites (AEBS) and display no significant interaction with the estrogen receptor (ER). All bind to AEBS with equivalent or greater affinity than tamoxifen. These compounds decrease 3Hthymidine incorporation in AEBS-containing EL4 lymphoid cells and MCF7 breast cancer cells in a concentration-dependent manner between 10(-8) and 10(-6) M and are generally more inhibitory than tamoxifen. In contrast, they have no effect on 3Hthymidine incorporation by an AEBS-deficient variant of the MCF7 cell line, RTx6. The present findings of (1) selective and high affinity binding of the benzofurans to AEBS, (2) their concentration-dependent inhibition of 3Hthymidine incorporation in AEBS-containing cells, and (3) their lack of antiproliferative effect in an AEBS-deficient cell line suggest a functional role for AEBS in mediating the antigrowth effect of these compounds. Two of the more active benzofuran compounds also significantly inhibited de novo cholesterol biosynthesis in EL4 cells which lack ER. This effect could be obtained after 5 h of treatment and preceded significant loss of cell viability. This is the first demonstration that selective ligands of AEBS (other than the known nonsteroidal antiestrogens) interfere with cholesterol biosynthesis-an action that may contribute to their antigrowth effect. |
| Synthesis of 27-hydroxycholesterol in rat liver mitochondria: HPLC assay and marked activation by exogenous cholesterol Petrack, B. and B. J. Latario (1993), J Lipid Res 34(4): 643-9. Abstract: Sterol 27-hydroxylase, the mitochondrial enzyme that catalyzes the first step in oxidation of the sterol side chain in hepatic bile acid synthesis, also catalyzes the synthesis of 27-hydroxycholesterol from cholesterol. We have developed a high performance liquid chromatography (HPLC) assay for this enzyme, using either endogenous or exogenous cholesterol as substrate and cholesterol oxidase to convert 27-hydroxycholesterol to 4-cholesten-27-hydroxy-3-one. The alpha,beta-unsaturated ketone product was separated by normal phase HPLC and quantitated via absorption at 240 nm. Addition of cholesterol dissolved in 2-hydroxypropyl-beta-cyclodextrin to the assay mixture raised the enzyme activity of rat liver mitochondria more than 10-fold. 2-Hydroxypropyl-beta-cyclodextrin itself was partially effective, apparently by making more endogenous cholesterol accessible to the enzyme. Availability of cholesterol to the enzyme limits synthesis of 27-hydroxycholesterol in rat liver. Using our assay to simultaneously determine the activities of cholesterol 7 alpha-hydroxylase and cholesterol 27-hydroxylase in rat liver homogenates, we demonstrated that the two enzymes are separately regulated. |