| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Subcutaneous cholesterol nodules: a case report Kotevoglu, N. and A. Yesilleten (2003), Joint Bone Spine 70(4): 300-2. Abstract: Subcutaneous nodules are important in the diagnosis of some rheumatic and systemic diseases. Subcutaneous cholesterol nodule is a rare occurrence and does not accompany any inflammatory disease. It is generally mistaken for a gouty tophus. We report a case with numerous cholesterol nodules and discuss the clinical presentation and diagnostic procedure. |
| Subcutaneous infusion of r-hirudin does not inhibit neointimal proliferation after angioplasty of the subclavian artery in cholesterol-fed rabbits Hadoke, P. W., R. M. Wadsworth, et al. (1996), Coron Artery Dis 7(8): 599-608. Abstract: BACKGROUND: Thrombin, a potent stimulator of smooth muscle cell proliferation and inhibitor of endothelial cell growth, has been implicated as an important mediator of restenosis after angioplasty. Acute administration of the thrombin inhibitor r-hirudin reduced restenosis in animal models of angioplasty, possibly by inhibiting smooth muscle cell proliferation. Because thrombin-induced proliferation requires prolonged exposure to the agonist, it was hypothesized that a greater reduction in lesion size could be achieved by chronic administration of r-hirudin. OBJECTIVE: To determine whether prolonged treatment with r-hirudin would reduce lesion size and improve vascular function in a rabbit model of neointimal proliferation. METHODS: Male New Zealand white rabbits were fed a high-cholesterol diet for 4 weeks, after which they were subjected to balloon injury of the left subclavian artery. The rabbits were assigned to one of three groups: control (no drug); acute r-hirudin treatment (0.33 mg/kg intravenously plus 0.48 mg/kg per h subcutaneously for 24 h); or chronic r-hirudin treatment (0.33 mg/kg intravenously plus 0.6 mg/kg per h subcutaneously for 28 days). After surgery the rabbits were fed a normal diet and killed 30 days later. Left (angioplastied) and right (control) subclavian arteries were removed for morphological and functional analysis. RESULTS: Angioplasty in control, untreated rabbits produced large neointimal lesions 15.0 +/- 1.8% of the area within the external elastic lamina (EEL), comprised mainly of smooth muscle cells (34 +/- 16 cells/section) and lipid-rich macrophage or foam cells (118 +/- 51 cells/section). Acute r-hirudin treatment neither inhibited smooth muscle cell proliferation (35 +/- 12 cells/section) nor reduced neointimal lesion size (23.5 +/- 4.6% of the area within the EEL). Chronic r-hirudin treatment significantly increased the number of proliferating cells (55 +/- 15 cells/section, P < 0.05) and the size of the lesions (28.5 +/- 5.6% of the area within the EEL, P < 0.05). Further more, treatment with r-hirudin appeared to exacerbate, rather than improve, angioplasty-induced functional alterations. CONCLUSIONS: Prolonged treatment with r-hirudin neither inhibits vascular smooth muscle cell proliferation in rabbits after angioplasty of the left subclavian artery nor reduces the size of neointimal lesions. Furthermore, treatment with r-hirudin might impair endothelial cell function after angioplasty. This suggests that prolonged thrombin inhibition using this r-hirudin regimen is not suitable as an antirestenotic intervention. |
| Subcutaneous tophaceous nodule formation due to deposition of cholesterol crystals Kelley, J. T., 3rd and C. Agudelo (2002), J Rheumatol 29(8): 1798-9. |
| Subfractions of HDL cholesterol in young insulin-dependent diabetic patients Willems, D. and H. Dorchy (1991), Presse Med 20(2): 86. |
| Substance P level is increased in the cholesterol induced anaphylactoid reaction in the pig Kambam, J. R., P. K. Janicki, et al. (1995), Res Exp Med (Berl) 195(6): 327-32. Abstract: The role of substance P (SP) in cholesterol-induced anaphylactoid reaction was investigated in 13 Landrace pigs. Pigs were anesthetized with sodium thiopental and ventilation was controlled with 70% nitrous oxide in oxygen. A Swan-Ganz catheter and a carotid arterial line were placed to monitor the hemodynamic data. Group 1 pigs (control group, n = 5) each received 20 ml of intravenous (IV) colloid infusion solution (Haemaccel) and group 2 pigs (cholesterol group, n = 8) each received an IV injection of pure cholesterol emulsion (12 mg/kg) in 20 ml of Haemaccel. Blood samples for SP and histamine (H) levels were taken just before and for 10 min following the placebo, Haemaccel, and cholesterol injections. Urine samples were also collected just before and at 60 min following the injections for methyl histamine (MH) levels. Group 2 pigs (cholesterol) developed an anaphylactoid reaction as indicated by marked and significant hemodynamic changes. None of the group 1 (placebo) pigs developed an anaphylactoid reaction. Significant increases in blood SP and H levels (P < 0.05), and urine MH levels (P < 0.05) were seen in cholesterol-treated pigs (group 2), whereas no significant changes were seen in control pigs (group 1). Our results suggest that SP is involved in the cholesterol-induced anaphylactoid reaction in pigs. |
| Substrate specificity of cholesterol oxidase from Streptomyces cinnamomeus--a monolayer study Slotte, J. P. (1992), J Steroid Biochem Mol Biol 42(5): 521-6. Abstract: The substrate specificity of cholesterol oxidase from Streptomyces cinnamomeus was examined in oriented sterol monolayers at the air/water interface. Of the cholesterol analogues with structural alterations in the A- or B-ring that were examined, it was observed that 5 alpha-cholestan-3 beta-ol was oxidized almost as fast as cholesterol itself. When the delta-5 double bond in cholesterol was instead at the delta-4 position, the oxidation rate became 3.2-fold slower. A similar reduction in the average oxidation rate was observed when the delta-5 double bond in cholesterol was instead at the delta-7 position (5 alpha-cholest-7-en-3 beta- ol). 5,7-Cholestadien-3 beta-ol was oxidized 5.1-fold slower compared to cholesterol, whereas 3 beta-hydroxy-5-cholesten-7-one and 5 beta-cholestan-3 beta-ol were not substrates of the enzyme (also verified from the lack of H2O2-production). With C(17) side chain analogues of cholesterol, it was observed that the complete lack of the C(17) side chain (5-androsten-3 beta-ol), or the insertion of an unsaturation at delta-24 (desmosterol), or even an ethyl group at C(24)(24b-ethyl-5,22- cholestadien-3 beta-ol) had no appreciable effects on sterol oxidation rate, implying that the enzyme did not recognize the side chain in oriented sterol monolayers. This study has shown that the sterol monolayer system is a good technique to examine sterol/cholesterol oxidase interactions, since both the orientation of the substrate molecules, and the quality of the interface can be mastered. |
| Substrate stimulation of 7 alpha-hydroxylase, an enzyme located in the cholesterol-poor endoplasmic reticulum Straka, M. S., L. H. Junker, et al. (1990), J Biol Chem 265(13): 7145-9. Abstract: We examined the role of cholesterol in altering the activity of the microsomal cytochrome P-450 enzyme, cholesterol-NADPH:oxygen oxidoreductase (cholesterol 7 alpha-hydroxylase). Liposomes were used to deliver cholesterol to hepatic microsomes. Formation of 7 alpha-hydroxycholesterol was quantitated by isotope dilution/gas chromatography-mass spectrometry. As the liposomal cholesterol/phospholipid molar ratio increased, 7 alpha-hydroxylase activity increased, whereas the activity of another microsomal cytochrome P-450 enzyme, ethylmorphine N-demethylase, decreased. To determine if the degree of stimulation was affected by the endogenous activity (without liposomes), microsomes, from rats fed chow alone or chow containing cholestyramine, taurocholate, or cholesterol were challenged with cholesterol-enriched liposomes. The degree of stimulation was dependent upon the endogenous activity: cholestyramine-fed much greater than cholesterol = chow control greater than taurocholate-fed. To determine if cholesterol stimulates 7 alpha-hydroxylase by increasing membrane viscosity, microsomes were incubated with liposomes having the same cholesterol/phospholipid molar ratio as microsomes, but different viscosities. Dipalmitoylphosphatidylcholine (high viscosity) liposomes increased microsomal viscosity and decreased 7 alpha-hydroxylase activity. In contrast, dioleoylphosphatidylcholine (low viscosity) liposomes decreased microsomal viscosity and increased enzyme activity. Since greater viscosity inhibits 7 alpha-hydroxylase, cholesterol cannot stimulate the enzyme by increasing membrane viscosity. The data suggest that cholesterol stimulates production of 7 alpha-hydroxycholesterol by providing substrate. |
| Substrate-based inhibitors of lanosterol 14 alpha-methyl demethylase: I. Assessment of inhibitor structure-activity relationship and cholesterol biosynthesis inhibition properties Trzaskos, J. M., S. S. Ko, et al. (1995), Biochemistry 34(30): 9670-6. Abstract: A series of 15-, 32-, and 15,32-substituted lanost-8-en-3 beta-ols is described which function as inhibitors of cholesterol biosynthesis. These agents inhibit lanosterol 14 alpha-methyl demethylase activity as well as suppress HMG-CoA reduction activity in cultured cells. Several of these agents are extremely potent as both demethylase inhibitors and reductase suppressors, while others are more selective in their activities. Selected regio double bond isomers show preference for demethylase inhibition with the following order: delta 8 > delta 7 > delta 6 = unsaturated sterols. Comparisons also show that 4,4-dimethyl sterols are always more potent demethylase inhibitors and reductase suppressors than their 4,4-bisnomethyl counterparts. However, evaluation of an extensive oxylanosterol series leads us to conclude that demethylase inhibition and reductase suppression are not parallel in the same molecule. In addition, the oxylanosterols, but not the oxycholesterols, are able to disrupt coordinate regulation of HMG-CoA reductase from the LDL receptor. Thus, oxylanosterol treatment at levels which suppress reductase activity enhances LDL receptor activity. These results demonstrate that compounds can be made which (1) are selective reductase suppressors enabling dissection of the dual inhibitor nature of these compounds and (2) maximize reductase suppression and LDL receptor induction without demethylase inhibition which could lead to novel agents for serum cholesterol lowering. |
| Substrate-binding region of cytochrome P-450SCC (P-450 XIA1). Identification and primary structure of the cholesterol binding region in cytochrome P-450SCC Tsujita, M. and Y. Ichikawa (1993), Biochim Biophys Acta 1161(2-3): 124-30. Abstract: Cytochrome P-450SCC (P-450 XIA1) from bovine adrenocortical mitochondria was investigated using a suicide substrate: 14Cmethoxychlor. 14CMethoxychlor irreversibly abolished the activity of the side-chain cleavage enzyme for cholesterol (P-450SCC) and the inactivation was prevented in the presence of cholesterol. The binding of 14Cmethoxychlor and cytochrome P-450SCC occurred in a molar ratio of 1:1 and the cholesterol-induced difference spectrum of cytochrome P-450SCC was similar with the methoxychlor-induced difference spectrum. 14CMethoxychlor-binding peptides were purified from tryptic-digested cytochrome P-450SCC modified with 14Cmethoxychlor. Determination of the sequence of the amino-acid residues of a 14Cmethoxychlor-binding peptide allowed identification of the peptide comprising the amino-terminal amino-acid residues 8 to 28. |
| Subunit Ya-specific glutathione peroxidase activity toward cholesterol 7-hydroperoxides of glutathione S-transferases in cytosols from rat liver and skin Hiratsuka, A., H. Yamane, et al. (1997), J Biol Chem 272(8): 4763-9. Abstract: Dermal 7alpha- and 7beta-hydroperoxycholest-5-en-3beta-ols (cholesterol 7alpha- and 7beta-hydroperoxides), regarded as good aging markers in the rat (Ozawa, N., Yamazaki, S., Chiba, K., Aoyama, H., Tomisawa, H., Tateishi, M., and Watabe, T. (1991) Biochem. Biophys. Res. Commun. 178, 242-247), were reduced in the presence of glutathione (GSH) with concomitant formation of GSSG by cytosol from rat liver in which no detectable level of the hydroperoxides had been demonstrated to occur. The GSH peroxidase (GSH Px) activity toward the toxic steroid hydroperoxides was exerted to almost the same extent by both Alpha-class GSH S-transferases (GSTs), Ya-Ya and Ya-Yc, and by selenium-containing GSH Px (Se-GSH Px) in rat liver cytosol. None of three Mu-class GSTs, Yb1-Yb1, Yb1-Yb2, and Yb2-Yb2, and a Theta-class GST, Yrs-Yrs, from rat liver and a Pi-class GST, Yp-Yp, from rat kidney showed any appreciable GSH Px activity toward the hydroperoxides. The subunit Ya-bearing GSTs and Se-GSH Px purified from rat liver cytosol showed marked differences in apparent specific activity toward the cholesterol hydroperoxides (GSTs Ya-Ya > Ya-Yc >> Se-GSH Px). However, a kinetic study indicated that Se-GSH Px had a higher affinity for steroid hydroperoxides than did the GSTs, so that Se-GSH Px could catalyze the reduction of lower concentrations of cholesterol 7-hydroperoxides with approximately equal Vmax/Km values to those by the GSTs. Rat skin had no GST bearing the subunit Ya but contained only a very low concentration of Se-GSH Px, possibly resulting in the accumulation of cholesterol 7-hydroperoxides in the skin but not in the liver. From rat skin cytosol, GSTs Yc-Yc, Yb1-Yb1, Yb1-Yb2, Yb2-Yb2, and Yp-Yp were isolated, purified to homogeneity, and identified with the corresponding GSTs from liver and kidney. The GSTs accounted for 0.23% of total skin cytosolic protein, and the most abundant isoform of skin GSTs was Yb2-Yb2, followed by Yc-Yc, Yp-Yp, Yb1-Yb1, and Yb1-Yb2 in decreasing order. |
| Successful dissolution of cholesterol gallstone during treatment with pravastatin Smit, J. W., K. J. van Erpecum, et al. (1992), Gastroenterology 103(3): 1068-70. Abstract: This case report describes a 51-year-old hypercholesterolemic male patient who had a large solitary cholesterol gallstone. The patient was treated with the 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor pravastatin, 40 mg/day. After 3 months of therapy, serum cholesterol level normalized (7.7 mmol/L before and 5.2 mmol/L during treatment), and biliary cholesterol saturation index decreased from 1.3 before to 0.8 during treatment. Repeatedly performed ultrasonography showed complete gallstone dissolution. Pravastatin may be valuable in the nonsurgical treatment of cholesterol gallstone disease particularly when there is an additional indication for HMG-CoA reductase inhibitors because of hypercholesterolemia. |
| Successful topical dissolution of cholesterol gallbladder stones using ethyl propionate Hofmann, A. F., A. Amelsberg, et al. (1997), Dig Dis Sci 42(6): 1274-82. Abstract: Topical dissolution of cholesterol gallbladder stones using methyl tert-butyl ether (MTBE) is useful in symptomatic patients judged too ill for surgery. Previous studies showed that ethyl propionate (EP), a C5 ester, dissolves cholesterol gallstones rapidly in vitro, but differs from MTBE in being eliminated so rapidly by the liver that blood levels remain undetectable. Our aim was to test EP as a topical dissolution agent for cholesterol gallbladder stones. Five high-risk patients underwent topical dissolution of gallbladder stones by EP. In three patients, the solvent was instilled via a cholecystostomy tube placed previously to treat acute cholecystitis; in two patients, a percutaneous transhepatic catheter was placed in the gallbladder electively. Gallstone dissolution was assessed by chromatography, by gravimetry, and by catheter cholecystography. Total dissolution of gallstones was obtained in four patients after 6-10 hr of lavage; in the fifth patient, partial gallstone dissolution facilitated basketing of the stones. In two patients, cholesterol dissolution was measured and averaged 30 mg/min. Side effects were limited to one episode of transient hypotension and pain at the infusion site; no patient developed somnolence or nausea. Gallstone elimination was associated with relief of symptoms. EP is an acceptable alternative to MTBE for topical dissolution of cholesterol gallbladder stones in high-risk patients. The lower volatility and rapid hepatic extraction of EP suggest that it may be preferable to MTBE in this investigational procedure. |
| Sucrose in a lipid-rich meal amplifies the postprandial excursion of serum and lipoprotein triglyceride and cholesterol concentrations by decreasing triglyceride clearance Grant, K. I., M. P. Marais, et al. (1994), Am J Clin Nutr 59(4): 853-60. Abstract: Nineteen young male normolipidemic volunteers sequentially consumed three test meals consisting of cream only, sucrose only, or cream with sucrose. These oral fat-tolerance tests showed an amplification of the postprandial excursion of serum triglyceride and cholesterol concentrations when sucrose was included in a lipid-rich meal compared with both the cream-only meal and the sucrose-only meal. The triglyceride concentration increase occurred only in the late postprandial phase whereas the cholesterol concentration was increased for the entire 8 h studied. The increased triglyceride and cholesterol concentrations in the triglyceride-rich lipoprotein (TRL) fraction accounted for most of the increase. The clearance of an intravenous lipid emulsion was measured before and 2 and 4 h after a sucrose meal. The two postprandial clearance rates were 34% slower than the fasting value. These data indicate that sucrose-induced postprandial hypertriglyceridemia may be induced by an inhibition of the clearance of triglyceride. The slower rate of lipolysis may cause the accumulation of cholesterol in TRL. |
| Sucrose-induced vacuolation results in increased expression of cholesterol biosynthesis and lysosomal genes Helip-Wooley, A. and J. G. Thoene (2004), Exp Cell Res 292(1): 89-100. Abstract: Mammalian cells cultured in the presence of high concentrations of sucrose demonstrate large, phase-lucent, osmotically swollen vacuoles. Three normal human fibroblast cell lines exposed to 100 mM of sucrose for 24 h demonstrated increased expression of lysosomal, intracellular vesicle trafficking, cholesterol biosynthesis, and fatty acid metabolism genes. Most steps of the cholesterol biosynthesis pathway were upregulated including HMG CoA reductase, which catalyzes the rate-limiting step of cholesterol biosynthesis. The lysosomal genes neuraminidase, CLN3, and CLCN5 and the small GTP-binding proteins Rab7L1 and Arl7 were also increased. A Rab7L1-GFP fusion protein was overexpressed in human fibroblasts and was demonstrated to localize primarily to the Golgi apparatus, and in some cells to the membranes bounding vesicles in the perinuclear region. Increased levels of the transcription factor C/EBP were found in nuclear extracts from cells exposed to sucrose for 12 h, relative to matched controls suggesting regulation of gene expression following sucrose-induced vacuolation may be coordinated, at least in part, by the transcription factor C/EBP. Sucrose-induced vacuolation is a useful model in which to study the regulation of lysosomal gene expression and biogenesis. |
| Sugar-beet fibre increases cholesterol and reduces bile acid excretion from the small bowel Langkilde, A. M., H. Andersson, et al. (1993), Br J Nutr 70(3): 757-66. Abstract: The effect of addition of sugar-beet fibre to the diet on sterol excretion from the small intestine was studied in nine ileostomy subjects. A constant low-fibre diet was given in two 3 d periods with and without 32 g sugar-beet fibre/d in random order. Care was taken to minimize bacterial alteration of the ileostomy contents. The addition of sugar-beet fibre increased net cholesterol excretion by 52 (SE 9)% (P < 0.01), from 294 (SE 99) to 451 (SE 124) mg/d, and decreased bile acid excretion by 26 (SE 15)% (P < 0.01), from 764 (SE 118) to 567 (SE 96) mg/d. The increased cholesterol and decreased bile acid excretion found with sugar-beet fibre addition is different from the pattern associated with fibre sources such as pectin and oat fibre. The interaction between dietary fibre and sterol metabolism may be mediated, therefore, by different mechanisms depending on the fibre source. |
| Sugar-substituted 2-azetidinone cholesterol absorption inhibitors: enhanced potency by modification of the sugar Vaccaro, W. D. and H. R. Davis, Jr. (1998), Bioorg Med Chem Lett 8(3): 313-8. Abstract: A glucuronide conjugate of the potent 2-azetidinone cholesterol absorption inhibitor Sch 58235 was synthesized to confirm the structure of a metabolite isolated from in vivo sources. A series of 2-azetidinone glycosides was prepared via Schmidt trichloroimidate methodology. Enhanced cholesterol absorption inhibition was achieved by modification of the sugar moiety. |
| Suitability of LLC-PK1 pig kidney cells for the study of drug action on renal cell cholesterol uptake: identification and characterization of low-density lipoprotein receptors Chung, N. S., K. Sachs-Barrable, et al. (2005), J Pharmacol Toxicol Methods 51(2): 139-45. Abstract: INTRODUCTION: The purpose of this study was to identify and characterize the presence of low-density lipoprotein receptors (LDLr) in LLC-PK(1) cells. METHODS: LLC-PK(1) cells were assessed for the presence of LDLr by conducting dose-response, LDL specific binding and competitive studies with DiI-LDL, and Western blot and RT-polymerase chain reaction (PCR) analyses. Assay conditions with IgG-C7, a monoclonal antibody (mAb) to the LDLr, were optimized, including temperature, preincubation time, and concentration in LLC-PK(1) cells. RESULTS: LLC-PK(1) cells express LDL receptors as determined by LDL specific and competitive binding studies and Western blot and RT-PCR analysis (specific binding 0.5 ng DiI-LDL/mug of cellular protein). DISCUSSION: Taken together, these findings confirm the presence of LDL receptors on LLC-PK1 cells and support the appropriateness of using these cells in studies involving renal cell cholesterol uptake and metabolism. |
| Sulfonamide derivatives of benzylamine block cholesterol biosynthesis in HepG2 cells: a new type of potent squalene epoxidase inhibitors Gotteland, J. P., C. Loubat, et al. (1998), Bioorg Med Chem Lett 8(11): 1337-42. Abstract: Sulfonamide derivatives of ene-yne benzylamine 1 have been prepared and identified as a new class of potent SE inhibitors having demonstrated activity in HepG2 cells as cholesterol biosynthesis inhibitors. |
| Sulfonylureas induce cholesterol accumulation in cultured human intimal cells and macrophages Sobenin, I. A., M. A. Maksumova, et al. (1994), Atherosclerosis 105(2): 159-63. Abstract: Using primary cultures of human smooth muscle intimal cells and mouse peritoneal macrophages it was demonstrated that oral hypoglycemic agents, sulfonylurea derivatives, at concentrations 10(-5)-10(-4) mol/l caused significant (by 25%-60%) intracellular total cholesterol accumulation. This in vitro atherogenic effect was confirmed in an ex vivo model. Sera from Type 2 diabetic patients, taken after sulfonylurea administration, acquired the ability to induce cholesterol accumulation in cultured cells. This enhanced atherogenic effect of patients' sera was observed for the next 2-4 h following the treatment and corresponded well to the pharmacokinetic characteristics of the tested drugs. The results suggest that sulfonylureas may exert a direct atherogenic action at the level of arterial cells, by increasing intracellular cholesterol content. |
| Summary of a dissertation. Cholesterol screening Pirich, C. (1990), Wien Klin Wochenschr 102(19): 576-9. |