| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Idiopathic pericarditis caused by cholesterol Gallego Page, J. C., M. Hernando Martin, et al. (2001), Rev Esp Cardiol 54(11): 1327. |
| Idoxifene: a novel selective estrogen receptor modulator prevents bone loss and lowers cholesterol levels in ovariectomized rats and decreases uterine weight in intact rats Nuttall, M. E., J. N. Bradbeer, et al. (1998), Endocrinology 139(12): 5224-34. Abstract: Idoxifene, a novel selective estrogen receptor modulator, was tested for its effects on bone loss, serum cholesterol, and uterine wet weight and histology in the ovariectomized (Ovx) rat. Idoxifene (0.5 mg/kg x day) completely prevented loss of both lumbar and proximal tibial bone mineral density (BMD). In an intervention study, idoxifene (0.5 and 2.5 mg/kg x day) completely prevented further loss of both lumbar and proximal tibial BMD during a 2-month treatment period commencing 1 month after surgery, when significant loss of BMD had occurred in the Ovx control group. Idoxifene reduced total serum cholesterol, which was maximal at 0.5 mg/kg x day. Idoxifene alone displayed minimal uterotrophic activity in Ovx rats and inhibited the agonist activity of estrogen in intact rats. Histologically, myometrial and endometrial atrophy were observed in both idoxifene and vehicle-treated Ovx rats. In this report, we also provide molecular-based evidence to support the observations in vivo of a novel selective estrogen receptor modulator (SERM) mechanism of action in bone and endometrial cells. Idoxifene is an agonist through the estrogen response element (ERE) and exhibits similar postreceptor effects to estrogen in bone-forming osteoblasts. Idoxifene also stimulates osteoclast apoptosis, and these pleiotropic effects ultimately could contribute to the maintenance of bone homeostasis. However, idoxifene differs from estrogen in a tissue-specific manner. In human endometrial cells, where estrogen is a potent agonist through the ERE, idoxifene has negligible agonist activity. Moreover, idoxifene was able to block estrogen induced gene expression in endometrial cells, which is in agreement with the observation in the intact rat study. In the uterus, idoxifene has a pharmacologically favorable profile, lacking agonist and therefore growth-promoting activity. Together with its cholesterol lowering effect and lack of uterotrophic activity, these data suggest that idoxifene may be effective in the prevention of osteoporosis and other postmenopausal diseases without producing unwanted estrogenic effects on the endometrium. |
| Ileal bile acid transport regulates bile acid pool, synthesis, and plasma cholesterol levels differently in cholesterol-fed rats and rabbits Xu, G., B. L. Shneider, et al. (2000), J Lipid Res 41(2): 298-304. Abstract: We investigated the effect of ileal bile acid transport on the regulation of classic and alternative bile acid synthesis in cholesterol-fed rats and rabbits. Bile acid pool sizes, fecal bile acid outputs (synthesis rates), and the activities of cholesterol 7alpha-hydroxylase (classic bile acid synthesis) and cholesterol 27-hydroxylase (alternative bile acid synthesis) were related to ileal bile acid transporter expression (ileal apical sodium-dependent bile acid transporter, ASBT). Plasma cholesterol levels rose 2.1-times in rats (98 +/- 19 mg/dl) and 31-times (986 +/- 188 mg/dl) in rabbits. The bile acid pool size remained constant (55 +/- 17 mg vs. 61 +/- 18 mg) in rats but doubled (254 +/- 46 to 533 +/- 53 mg) in rabbits. ASBT protein expression did not change in rats but rose 31% (P < 0.05) in rabbits. Fecal bile acid outputs that reflected bile acid synthesis increased 2- and 2.4-times (P < 0.05) in cholesterol-fed rats and rabbits, respectively. Cholesterol 7alpha-hydroxylase activity rose 33% (24 +/- 2.4 vs. 18 +/- 1.6 pmol/mg/min, P < 0.01) and mRNA levels increased 50% (P < 0.01) in rats but decreased 68% and 79%, respectively, in cholesterol-fed rabbits. Cholesterol 27-hydroxylase activity remained unchanged in rats but rose 62% (P < 0.05) in rabbits. Classic bile acid synthesis (cholesterol 7alpha-hydroxylase) was inhibited in rabbits because an enlarged bile acid pool developed from enhanced ileal bile acid transport. In contrast, in rats, cholesterol 7alpha-hydroxylase was stimulated but the bile acid pool did not enlarge because ASBT did not change. Therefore, although bile acid synthesis was increased via different pathways in rats and rabbits, enhanced ileal bile acid transport was critical for enlarging the bile acid pool size that exerted feedback regulation on cholesterol 7alpha-hydroxylase in rabbits. |
| Ileal pouch-anal anastomosis, conventional ileostomy and ileorectal anastomosis modify cholesterol metabolism Nissinen, M. J., H. Gylling, et al. (2004), Dig Dis Sci 49(9): 1444-53. Abstract: Proctocolectomy modifies the enterohepatic circulation and activity of bacterial enzymes depending on the structure of the stoma and function of the terminal ileum. We evaluated in our comparative study effects of different colectomy constructions on cholesterol metabolism. Levels of lipoprotein cholesterol and triglycerides, noncholesterol sterols, and squalene in serum, fecal fat, and bile acids, cholesterol absorption efficiency, and cholesterol metabolism by sterol balance technique were analyzed in human subjects with ileal pouch-anal anastomosis (n = 34), conventional ileostomy (n = 8), ileorectostomy (n = 6), and controls (n = 29). Malabsorption of bile acids, but not of fat, and low serum levels of total and low-density lipoprotein cholesterol, but high levels of high-density lipoprotein cholesterol and increased cholesterol synthesis were evident in the colectomy groups. In contrast to the ileorectostomy group, expressing high absorption and biliary secretion of cholesterol, a low cholesterol absorption percentage accompanied by elevated serum proportions of cholesterol precursor sterols and phytosterols characterized the ileal pouch-anal anastomosis and conventional ileostomy groups. After colectomy, fecal excretion of secondary bile acids was low, whereas relative proportions of identifiable bile acids remained the same in each study group. Low serum levels of total and low-density lipoprotein cholesterol of colectomized subjects may decrease the risk of premature atherosclerosis. The favorable serum lipid profile was due to enhanced fecal loss of cholesterol as bile acids despite abnormally high cholesterol synthesis. Ileal dysfunction probably diminished cholesterol absorption in subjects with ileal pouch-anal anastomosis and conventional ileostomy, with no explanation for those with ileorectostomy with no clinical gastrointestinal dysfunction. Relative synthesis of identifiable primary bile acids remained unchanged postoperatively, but formation of secondary bile acids was weak due to scarce bacterial flora. |
| Ileorectostomy or cecectomy but not colectomy abolishes the plasma cholesterol-lowering effect of dietary beet fiber in rats Nishimura, N., H. Nishikawa, et al. (1993), J Nutr 123(7): 1260-9. Abstract: Adult male rats were fed a cholesterol-free diet with no added fiber (fiber-free) or with 10% cellulose or beet fiber. After 7 d of feeding, plasma total cholesterol concentrations were significantly lower in rats fed beet fiber than in those fed fiber-free or cellulose diets. This difference was due mainly to lower HDL cholesterol concentrations and remained significant for 28 d. The hypocholesterolemic effect of beet fiber relative to fiber-free disappeared when the cecum and colon were concurrently resected (ileorectostomy). Plasma cholesterol concentrations were the same in colectomized rats as in sham-operated rats fed the same diet and significantly lower in animals fed the beet fiber diet than in those fed the fiber-free diet. In cecectomized rats fed beet fiber, plasma cholesterol concentrations were intermediate between sham-operated rats fed the beet fiber diet and cecectomized or sham-operated rats fed the fiber-free diet. Fecal bile acid excretion was higher in rats fed the beet fiber diet than in those fed the fiber-free diet but did not correlate with plasma total cholesterol concentration. In rats with intact ceca, cecal total and individual short-chain fatty acids correlated negatively with plasma total cholesterol concentration. Dietary beet fiber lowers plasma cholesterol concentrations in rats, and the lower digestive tract, especially the cecum, seems to be necessary for this effect. |
| I'm 56 years old and have total cholesterol of 217 milligrams per deciliter, LDL of 131 mg/dl, HDL of 67 mg/dl, and a total-to-HDL ratio of 3.24. My doctor says that ratio is good for a woman my age, so why does she want me to lower my LDL? Lilly, L. S. (2003), Health News 9(5): 12. |
| Image-guided endoscopic transsphenoidal drainage of select petrous apex cholesterol granulomas DiNardo, L. J., G. W. Pippin, et al. (2003), Otol Neurotol 24(6): 939-41. Abstract: OBJECTIVE: Explore the indications and advantages of image-guided transsphenoidal endoscopic drainage of select petrous apex cholesterol granulomas. STUDY DESIGN: Case report and literature review. SETTING: Tertiary referral center. CONCLUSIONS: Image-guided endoscopic transsphenoidal drainage of cholesterol granulomas is the procedure of choice for petrous apex cholesterol granulomas that abut the sphenoid sinus and are accessible through its posterior wall. |
| Image-guided transphenoidal drainage of a cholesterol granuloma of the petrous apex in a child Michaelson, P. G., B. B. Cable, et al. (2001), Int J Pediatr Otorhinolaryngol 57(2): 165-9. Abstract: Cholesterol granulomas of the petrous apex are well-described lesions that originate from chronic obstruction of the air cells in the petrous pyramid. Intracranial surgery, associated with multiple potential complications, has been the salutary action to treat this entity with only two reports of endoscopic drainage of a cholesterol granuloma of the paranasal sinuses. We present the first pediatric patient to be treated by not only endoscopic drainage, but also by the incorporation of computer-assisted image-guided surgery to minimize risk of injury to structures adjacent to the posterior wall of the sphenoid sinus. |
| Images in clinical medicine. Cholesterol crystals DeMarco, P. J. and R. M. Keating (1995), N Engl J Med 333(20): 1325. |
| Imaging quiz case 1. Cholesterol granuloma cyst of the petrous apex Soliman, A. M., E. E. Smouha, et al. (1998), Arch Otolaryngol Head Neck Surg 124(1): 108,110. |
| Imidazolylbenzopyrane derivatives: a new class of acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors Fancelli, D., A. Chiari, et al. (1994), J Enzyme Inhib 8(3): 159-72. Abstract: Inhibitors of the enzyme Acyl-CoA: Cholesterol Acyltransferase are regarded as potentially useful agents in the treatment of hypercholesterolemia and atherosclerosis. We report here a novel series of 2, 6-disubstituted-3-imidazolylbenzopyrane derivatives with significant in vitro ACAT inhibitory activity (IC50 range 0.05-0.5 microM). Compounds of this series such as 26 are examples of a new, structurally distinct class of potent ACAT inhibitors with high specificity for the aortic subtype of the enzyme. The structure-activity relationships of the 3-imidazolylbenzopyrane ACAT inhibitors were investigated by systematic manipulation of two regions of the parent compound 1 and the inhibitory activity resulted linked to the substituent in position 6 of the benzopyrane ring and modulated by the size of lipophilic substituents in position 2. Investigation of the mechanism of the inhibitory effect leads to the conclusion that these compounds act in a non-competitive fashion. |
| Immediate and sustained reduction in serum cholesterol achieved in 4-week Heart Tune program Groth, K., M. Kirk, et al. (1991), J Am Diet Assoc 91(9): 1100-3. Abstract: Currently, there is limited information about educational models effective in assisting individuals to lower their serum cholesterol. Dietitians and nutritionists involved in cholesterol-reduction programs need to inform other health professionals about programs utilized and the success of those programs. The National Cholesterol Education Program has published guidelines for the detection, evaluation, and treatment of high blood cholesterol in adults. Educational programs should be systematically evaluated to confirm their success in cholesterol reduction. The Heart Tune program is a 4-week class developed by a dietitian to assist clients in cholesterol reduction. An evaluation of the lipoprotein levels of 49 program participants demonstrated that serum total cholesterol levels significantly decreased at the completion of the 4-week class (0.65 mmol/L) and after 1 year (0.80 mmol/L). |
| Immobilization of cholesterol oxidase on cellulose acetate membrane for free cholesterol biosensor development Wang, S., S. Li, et al. (2004), Artif Cells Blood Substit Immobil Biotechnol 32(3): 413-25. Abstract: This article describes the immobilization of cholesterol oxidase on a cellulose acetate (CA) membrane activated by Sodium periodate, ethylenediamine, and glutaraldehyde etc. The properties of the immobilized enzyme membrane were investigated. The factors affecting the activity of immobilized enzyme such as the concentration of glutaraldehyde, the concentration of enzyme used during immobilization, temperature, pH, and immobilizing time etc. were also studied. The immobilized COD membrane has been used to construct fibre-optic fluorescent biosensor. |
| Immobilization of phospholipase A2 on porous glass and its application for lowering serum cholesterol concentration Teke, M., S. Onal, et al. (2003), Artif Cells Blood Substit Immobil Biotechnol 31(4): 467-78. Abstract: Phospholipase A2 (PLA2; EC 3.1.1.4) is a lipolytic enzyme that hydrolysis the ester bond in sn-2 position of phospholipids. In this work, the PLA2 from hog pancreas was covalently coupled to porous glass. The properties of free and immobilized enzyme were also investigated and compared. The optimum pH and temperature were found as 8.5 and 50 degrees C, respectively for both free and immobilized enzyme. The immobilized enzyme had good properties that potential for medical application is considerable. Its use in lowering plasma cholesterol concentrations in blood samples was also demonstrated. |
| Immobilized beta-cyclodextrin as a simple and recyclable method for cholesterol removal in milk Kwak, H. S., S. H. Kim, et al. (2004), Arch Pharm Res 27(8): 873-7. Abstract: This study was designed to determine the optimum conditions of three different factors (mixing time, mixing temperature, and tube size) in reduction of cholesterol in milk using immobilized beta-CD beads. Immobilized beta-CD glass beads were prepared at different conditions of silanization and beta-CD immobilization reactions. In result, the glass beads (diameter 1 mm) at 20 mM 3-isocyanatopropyltriethoxysilane and 30 mM beta-CD without base showed the highest cholesterol removal rate as 41%. Using above immobilized beta-CD glass beads, the cholesterol removal rate was 40.2% with 6 h of mixing time in 7 mm diameter tube at 10 degrees C. After cholesterol removal from milk, the glass beads were washed for cholesterol dissociation and reused. In recycling study, the cholesterol removal rate was 41%, which was mostly same as that using new glass beads. These results indicated that cholesterol removal rate was about 40% with beta-CD immobilized glass beads, however, the recycling efficiency was almost 100%. |
| Immune complexes and IFN-gamma decrease cholesterol 27-hydroxylase in human arterial endothelium and macrophages Reiss, A. B., N. W. Awadallah, et al. (2001), J Lipid Res 42(11): 1913-22. Abstract: The enzyme cholesterol 27-hydroxylase, expressed by arterial endothelium and monocytes/macrophages, is one of the first lines of defense against the development of atherosclerosis. By catalyzing the hydroxylation of cholesterol to 27-hydroxycholesterol, which is more soluble in aqueous medium, the enzyme promotes the removal of cholesterol from the arterial wall. Prior studies have suggested that immune reactants play a role in the pathogenesis of atherosclerosis; we report here that immune reactants, IFN-gamma and immune complexes bound to C1q, but not interleukin-1 and tumor necrosis factor, diminish the expression of cholesterol 27-hydroxylase in human aortic endothelial cells, peripheral blood mononuclear cells, monocyte-derived macrophages, and the human monocytoid cell line THP-1. In addition, our studies demonstrate that immune complexes down-regulate cholesterol 27-hydroxylase only after complement fixation via interaction with the 126-kD C1qRp protein on endothelial cells and THP-1 cells. These results are consistent with the prior demonstration that IFN-gamma contributes to the pathogenesis of atherosclerosis and suggest a role for C1q receptors in the atherogenic process. Moreover, these observations suggest that one mechanism by which immune reactants contribute to the development of atherosclerosis is by down-regulating the expression of the enzymes required to maintain cholesterol homeostasis in the arterial wall. |
| Immunization with bacillus Calmette-Guerin vaccine increases aortic atherosclerosis in the cholesterol-fed rabbit Lamb, D. J., L. J. Eales, et al. (1999), Atherosclerosis 143(1): 105-13. Abstract: New Zealand White rabbits were injected subcutaneously with either a human dose of bacillus Calmette Guerin (BCG) vaccine (n = 7) or saline (n = 7). A further half dose of BCG or saline was injected after a further 4 weeks. The animals were subsequently fed a 0.25-1% cholesterol diet for 10 weeks, 8 weeks after the first injection. The rabbits were killed and perfusion fixed with 4% paraformaldehyde. The integrated plasma cholesterol levels did not differ significantly between the groups (P > 0.05). Plasma levels of anti-mycobacterial antibodies rose following BCG immunization, reaching a peak after 8 weeks (P < 0.05) compared to basal titers and the control group. BCG immunization was also associated with increased peripheral lymphocyte and monocyte activation, as evidenced by increased surface expression of IL-2 receptor (CD25) (P < 0.02) and MAC-I (CD11b) (P < 0.05), respectively. Significantly more mononuclear cells bound to the aortic endothelium of BCG immunized, cholesterol-fed rabbits (1.93+/-0.77 mononuclear cells/1000 endothelial cells) than to that of saline immunized rabbits (0.08+/-0.08 mononuclear cells/1000 endothelial cells; P < 0.01). The aortic intimal:medial ratio was greater in the BCG immunized rabbits (0.19+/-0.08) than those treated with saline (0.04+/-0.03; P < 0.05). This suggests that BCG immunization enhances peripheral leucocyte activation, aortic monocyte recruitment and atherogenesis in the cholesterol-fed rabbit. |
| Immunization with cholesterol-rich liposomes induces anti-cholesterol antibodies and reduces diet-induced hypercholesterolemia and plaque formation Alving, C. R., G. M. Swartz, Jr., et al. (1996), J Lab Clin Med 127(1): 40-9. Abstract: Immunization of rabbits with a protein-free formulation consisting of liposomes containing 71% cholesterol and lipid A as an adjuvant induced anticholesterol antibodies that caused complement-dependent lysis of liposomes lacking lipid A. The antibodies, immunoglobulin G (IgG) and immunoglobulin M (IgM), also recognized nonoxidized crystalline cholesterol as an antigen by enzyme-linked immunosorbent assay (ELISA). The effects of immunization against cholesterol on elevations in serum cholesterol and development of atherosclerosis were examined in rabbits fed a diet containing 0.5% to 1.0% cholesterol. Although the mean serum cholesterol level, mainly in the form of very-low-density lipoprotein cholesterol, rose as much as 60-fold in the nonimmunized rabbits, the elevation was significantly less--as much as 35% lower--in the immunized rabbits. Elevation of serum cholesterol was accompanied by an apparent drop in the level of antibodies on initiating the diet, followed by a rebound on stopping the diet, thus suggesting that the antibodies were adsorbed to cholesterol that was present in circulating lipoproteins. When lipoprotein fractions--composed of either very-low-density and intermediate-density lipoproteins derived from cholesterol-fed nonimmunized rabbits or human low-density lipoproteins--were tested as capture antigens by solid-phase ELISA, reactivity was observed with IgG and IgM antibodies present in the serum of immunized rabbits. Immunization also resulted in a marked decrease in the risk of developing atherosclerosis. Analysis of aortic atherosclerosis by quantitative histologic examination and fatty streaks by automated morphometric probability-of-occurrence mapping showed diminished atherosclerosis in most areas of the aorta in vaccine recipients. It is proposed that immunization with liposomes containing 71% cholesterol and lipid A can reduce diet-induced hypercholesterolemia and atherosclerosis. |
| Immunization with genetic toxoids of the Arcanobacterium pyogenes cholesterol-dependent cytolysin, pyolysin, protects mice against infection Jost, B. H., H. T. Trinh, et al. (2003), Infect Immun 71(5): 2966-9. Abstract: Pyolysin (PLO), a cholesterol-dependent cytolysin expressed by Arcanobacterium pyogenes, is an important host-protective antigen. However, this molecule is toxic and requires inactivation prior to its use as a vaccine. Three genetically toxoided, nonhemolytic PLO molecules, HIS-PLO.F(497), HIS-PLO.Delta P(499), and HIS-PLO.A(522), were found to be nontoxic, and vaccinated mice were protected from infection, indicating the potential of these toxoids as vaccines. Furthermore, in a mouse model of infection, A. pyogenes carrying the F(497) mutation was as attenuated as a PLO-deficient strain, indicating that the cytolytic activity of PLO is important in virulence. |
| Immunoadsorption of cholesterol on protein A oriented beads Yavuz, H. and A. Denizli (2005), Macromol Biosci 5(1): 39-48. Abstract: Anti-low density lipoprotein antibody (anti-LDL) molecules were attached covalently and oriented through Protein A onto poly(2-hydroxyethyl methacrylate-ethylene glycol dimethacrylate) poly(HEMA-EGDMA) beads in order to remove cholesterol specifically from hypercholesterolemic human plasma. Poly(HEMA-EGDMA) beads were produced by suspension polymerization. Blood compatibility tests were performed. All the clotting times were increased when compared with control plasma. Loss of platelets and leukocytes was very low. The maximum anti-LDL attachment was 11.6 mg. g(-1) in the case of random immobilization and 28.3 mg. g(-1) in the case of oriented immobilization. In the latter case, Protein A loading was 8.3 mg. g(-1) at pH 7.5 (borate buffer, 0.15 M NaCl). There was low non-specific cholesterol adsorption onto the poly(HEMA-EGDMA) beads, about 0.83 mg. g(-1). Random and oriented anti-LDL attached beads adsorbed 8.2 mg and 11.7 mg cholesterol per g of bead from hypercholesterolemic human plasma, respectively. Up to 96% of the adsorbed cholesterol was desorbed. The binding-elution cycle was repeated 6 times using the same beads. There was no significant loss of binding capacity. |