| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Changes of serum paraoxonase (an HDL-cholesterol-associated lipophilic antioxidant) and arylesterase activities in severe preeclamptic women Kumru, S., S. Aydin, et al. (2004), Eur J Obstet Gynecol Reprod Biol 114(2): 177-81. Abstract: OBJECTIVE: To determine the serum lipid profile, the activity of paraoxonase (PON, the lipophilic antioxidant component of HDL-cholesterol), and alterations of the arylesterase activity in preeclamptic women. STUDY DESIGN: This cross-sectional study included 28 severe preeclamptic, and 24 healthy pregnant women. Fasting venous blood samples were collected during the antepartum period for spectrophotometric determination of the PON and arylesterase activities. RESULTS: In the severe preeclamptic group, the mean levels of total cholesterol, triglycerides, and LDL-cholesterol were 4, 5 and 9.8% higher, respectively, and HDL-cholesterol 9% lower than in the healthy controls. The PON and arylesterase activities were significantly lower in the severe preeclamptic women than in the controls, P<0.001 and P=0.000, respectively. A moderately positive correlation was detected between the serum levels of HDL-cholesterol and PON (r=0.49, P<0.02, n=52) and between HDL-cholesterol and arylesterase (r=0.42, P<0.05, n=52). CONCLUSIONS: Our results suggest that an abnormal lipid profile and decreased PON and arylesterase activities may have a role in pathogenesis of preeclampsia. |
| Changes of serum selenium and serum cholesterol in children during sexual maturation Marano, G., A. Spagnolo, et al. (1991), J Trace Elem Electrolytes Health Dis 5(1): 59-61. Abstract: We investigated the relationship of the degree of sexual maturation to serum selenium and serum cholesterol fractions in a population of Italian children. The following measurements were taken in 109 immature and 108 mature children of both sexes (aged 12 and 13a): serum selenium, total cholesterol, high density lipoprotein cholesterol, height, weight and degree of sexual maturation. Considerable differences were found in the two sexes at the end of maturation, with boys showing a significant decrease in serum selenium, HDL and non-HDL serum cholesterol levels. All variables, except height and weight, remained relatively constant in girls. These data indicate significant changes of serum selenium and serum cholesterol patterns during puberty, at least in boys, suggesting an involvement of sexual hormones in regulating serum selenium levels. |
| Changing physicians' attitudes, knowledge, and self-efficacy regarding cholesterol screening and management Gans, K. M., B. Jack, et al. (1993), Am J Prev Med 9(2): 101-6. Abstract: The National Cholesterol Education Program (NCEP) has identified a need to convey practical approaches for the management of high blood cholesterol (BC) to physicians. Our study was a joint effort between the Pawtucket Heart Health Program and the Brown University Department of Family Medicine to improve family medicine residents' attitudes, knowledge, self-efficacy, and practices regarding cholesterol screening and management. Thirty-six resident physicians received a BC screening and management training program. This program included training in BC screening using the fingerstick method and a desktop analyzer, diet assessment and counseling, and a management protocol for evaluation and treatment of high BC based on NCEP guidelines. The training program also included evaluation of residents' BC screening activity, incentives, chart audits, and biweekly articles in the departmental newsletter. We administered a survey to residents before and one year after the training program began to assess self-reported knowledge, attitudes, self-efficacy, and practices for BC management. Survey results indicated that the residents significantly improved their reported knowledge and attitudes about BC management. In addition, they significantly increased their reported self-efficacy and practices in dietary counseling and patient education. Residents also indicated that the training program was worthwhile, necessary, and practical and that many would use the materials and protocols in their future practices. |
| CHAPSTEROL. A novel cholesterol-based detergent Gehrig-Burger, K., L. Kohout, et al. (2005), Febs J 272(3): 800-12. Abstract: Design, synthesis and characterization of CHAPSTEROL, a novel cholesterol-based detergent developed for functional solubilization of cholesterol-dependent membrane proteins are described. To validate CHAPSTEROL, we employed the oxytocin receptor, a G protein-coupled receptor requiring cholesterol for its high-affinity binding state. Using the photoactivatable cholesterol analogue 3H6,6-azocholestan-3beta-ol3alphaH, we demonstrate that solubilization by CHAPSTEROL leads to an enrichment of cholesterol-binding proteins whereas the widely used bile acid derivative CHAPSO leads to a significant depletion of cholesterol-binding proteins. Similar to Triton X-100 and CHAPS, CHAPSTEROL maintains the localization of caveolin as well as cholesterol and sphingomyelin to lipid rafts, i.e. detergent-insoluble microdomains of the plasma membrane. The data suggest that CHAPSTEROL is an appropriate detergent for the solubilization of cholesterol-dependent membrane proteins and isolation of rafts. |
| Characterisation and selection of probiotic lactobacilli for a preliminary minipig feeding trial and their effect on serum cholesterol levels, faeces pH and faeces moisture content du Toit, M., C. M. Franz, et al. (1998), Int J Food Microbiol 40(1-2): 93-104. Abstract: Three out of 297 Lactobacillus strains isolated from pig faeces were selected for a feeding trial on account of their high bile-salt hydrolase (BSH) activity, bile-salt resistance, low pH tolerance and the production of antimicrobial substances. Two strains were identified as Lactobacillus johnsonii and one as Lactobacillus reuteri by DNA-DNA hybridisation. L. johnsoniii BFE 1061 produced a bacteriocin active against a range of lactic acid bacteria (LAB) and nonrelated bacteria including Clostridium perfringens. Six minipigs were maintained on a high-fat, high-cholesterol ('Western Style') diet for 17 weeks after which the diet was supplemented with the 'probiotic mixture' containing the above mentioned three Lactobacillus strains at 2 x 10(12) CFU per pig per day for five weeks. The mixture was given as a resuspended lyophilisate. During a two week follow-up period the minipigs received only the 'Western-style' diet without probiotic supplementation. A lowering effect on serum cholesterol levels was indicated after three weeks probiotic feeding, concomitant with an increase in the moisture content of the faeces and Lactobacillus cell numbers. Triglycerides, pH and number of lactic acid bacteria in faeces were not significantly influenced by probiotic supplementation. |
| Characteristic effect of soy and rice protein on cholesterol metabolism in rats Yoshida, A., Y. Aoyama, et al. (1990), Monogr Atheroscler 16: 1-10. |
| Characteristic expression of cholesterol sulfate in rabbit endometrium during the implantation period Momoeda, M., Y. Taketani, et al. (1991), Biochem Biophys Res Commun 178(1): 145-50. Abstract: Sialic acids and sulfate residues are the major negative-charged cellular components, which are considered to be crucial in embryonal adhesion to the endometrium. To explore the mechanism of implantation, we examined the change in the amounts of these substances in the rabbit endometrium during the implantation period. Gangliosides and sulfatides were present in very small quantity in the endometrium irrespective of the reproductive stage. Though the content of cholesterol sulfate was relatively low in the nonpregnant endometrium, it abruptly increased at day 5 of pregnancy, i.e. at the beginning of implantation, followed by a gradual decline toward day 9. Cholesterol sulfate level in the inter-implantation sites was about twice as much as that in the implantation sites and was comparable with that in the pseudopregnant endometrium. These results demonstrate that cholesterol sulfate is a major negative-charged lipid in the peri-implantation endometrium in rabbits. We further point to the difference in the concentration of cholesterol sulfate between implantation and interimplantation sites, thus suggesting cholesterol sulfate as a major participant in the process of implantation. |
| Characteristics associated with compliance to cholesterol lowering eating patterns Caggiula, A. W. and J. E. Watson (1992), Patient Educ Couns 19(1): 33-41. Abstract: The achievement of high levels of adherence is the most important objective of nutrition intervention programs. In order to determine characteristics which were most highly related to adherence to a cholesterol lowering eating pattern, a group of 264 men were sampled. Participants had been enrolled for six years in a multi-risk reduction program for cardiovascular disease which included dietary intervention for blood cholesterol. They were asked to respond to 35 statements, each of which was designed to reflect one of seven characteristics: perception of threat of disease, cost-benefit of therapy, quality of care, social support, external environmental media, and internal as well as external health locus of control. There were seven possible responses to each statement, from strongly agree to strongly disagree. Using a reduced rank regression analysis the numerical answers to the items were treated as a set of predictors for the criterion measure, the food record rating (FRR) score which reflected compliance to a cholesterol lowering eating pattern. Overall the seven characteristics accounted for almost half of the variance in the FRR score (multiple R = 0.48). The most highly related characteristics were cost-benefit, quality of care and external environmental media. These results are highly consistent with those obtained in another population, and indicate the importance of minimizing the cost and increasing the benefits of cholesterol lowering programs by providing high quality treatment programs which emphasize tailoring the regimen to the individual. These results also support the importance of public information efforts such as the National Cholesterol Education Program. |
| Characteristics of cholesterol 7 alpha-hydroxylase and 7 alpha-hydroxycholesterol hydroxylase activities of rodent liver Song, W., W. M. Pierce, Jr., et al. (1991), Biochem Pharmacol 41(10): 1439-47. Abstract: A second cholesterol-derived metabolite in addition to 7 alpha-hydroxycholesterol was observed to be produced from endogenous microsomal cholesterol in the presence of hamster liver microsomal fractions and NADPH, when analyzed by HPLC using the method of Ogishima and Okuda (Anal Biochem 158: 228-232, 1986). However, only 7 alpha-hydroxycholesterol was produced in the presence of rat hepatic microsomal protein fractions and NADPH. The second metabolite was facilely produced when endogenous 7 alpha-hydroxycholesterol was incubated with hamster liver microsomes and NADPH, but not with rat liver microsomes. The second metabolite derived from either endogenous cholesterol or exogenous 7 alpha-hydroxycholesterol contained three hydroxyl groups as shown by mass spectrometric analysis. After oxidation of the 3 beta-ol group by cholesterol oxidase, the metabolite comigrated with 7 beta-hydroxycholest-3-one on normal phase HPLC, but was resolved from both 7 alpha- and 7 beta-hydroxycholest-3-one on reverse phase HPLC. The data indicate that the second metabolite is a hydroxylated product of 7 alpha-hydroxycholesterol, possibly cholest-5-ene-3 beta,7 alpha, 12 alpha-triol. Cholestyramine feeding increased production of both 7 alpha-hydroxycholesterol and its metabolite from endogenous cholesterol by 3-fold in hamster liver microsomes in vitro. However, the direct conversion of 7 alpha-hydroxycholesterol to the metabolite by hamster liver microsomes was not increased appreciably after cholestyramine feeding (20-30%). The hydroxylation of 7 alpha-hydroxycholesterol was similar in characteristics to cholesterol 7 alpha-hydroxylase activity in that it was dependent on NADPH, was inhibited by several known P450 inhibitors, and was affected by an inhibitory autobody elicited against rat hepatic NADPH: cytochrome P450 oxidoreductase. 5,6- and 7,8-Benzoflavone were poor inhibitors (IC50 approximately 1 mM) of cholesterol 7 alpha-hydroxylase activity in liver microsomes from cholestyramine-fed rats, but caused a striking enhancement of the 7 alpha-hydroxylase activity of liver microsomes from untreated rats in vitro. In contrast, 7,8-benzoflavone inhibited cholesterol 7 alpha-hydroxylase and 7 alpha-hydroxycholesterol hydroxylase activities of microsomes from normal and cholestyramine-fed hamsters. However, 5,6-benzoflavone stimulated cholesterol 7 alpha-hydroxylase activity in liver microsomes from normal and cholestyramine-fed hamsters, but inhibited 7 alpha-hydroxycholesterol hydroxylase activity by approximately 50%. These results suggest that hepatic cholesterol 7 alpha-hydroxylase and 7 alpha-hydroxycholesterol hydroxylase activities apparently involve multiple forms of cytochrome P450 in untreated and cholestyramine-treated hamsters. |
| Characteristics of mRNA levels of hepatic key enzymes in cholesterol metabolism of genetically gallstone-susceptible mice Xu, G. Q. and L. Zhao (2004), Chin Med J (Engl) 117(8): 1259-61. |
| Characteristics of patients with single versus multiple cholesterol gallstones Diehl, A. K., D. R. Holleman, Jr., et al. (1997), Dig Dis Sci 42(5): 953-4. |
| Characteristics of symptomatic gallbladder disease in patients with either solitary or multiple cholesterol gallstones Juvonen, T., O. Niemela, et al. (1994), Hepatogastroenterology 41(3): 263-6. Abstract: Recent studies have indicated that solitary or multiple gallstones may differ with respect to the conditions favoring their formation, such as nucleation time. We examined the clinical, histological and laboratory characteristics of symptomatic gallstone disease in a series of 125 consecutive patients with either solitary (n = 33) or multiple (n = 92) cholesterol gallstones undergoing cholecystectomy. The nature of biliary pain was found to differ in the two groups. Histological diagnoses of acute cholecystitis and gallbladder cancer was more frequent in the patients with multiple stones, and cholesterolosis in those with solitary stones. Furthermore, the stone cholesterol content was higher in the solitary stone group than in the multiple stone group. Morbid complications such as cholangitis and pancreatitis were rare and occurred only in the multiple stone group. The results support the view that gallbladder disease presents histological evidence of biliary complications more often in patients with multiple cholesterol stones than in those with solitary stones. |
| Characteristics of the cholesterol efflux induced by novel seminal phospholipid-binding proteins Moreau, R. and P. Manjunath (2000), Biochim Biophys Acta 1487(1): 24-32. Abstract: Our recent results indicated that the major proteins of bovine seminal plasma (collectively called BSP proteins) stimulate cholesterol efflux from fibroblasts and that this process shows many differences compared to the efflux induced by apolipoprotein A-I (apoA-I)-containing lipoproteins. The present study was undertaken to investigate the BSP-mediated efflux mechanism. Compared to the slow and constant rate of cholesterol efflux induced by apoA-I-containing lipoproteins, the BSP proteins stimulated a rapid efflux that gradually reached a plateau. The addition of purified BSP proteins after the establishment of the plateau resulted in a further cholesterol efflux indicating that cellular cholesterol was still available for efflux. Incubation of unlabeled fibroblast culture with the spent medium containing BSP-generated lipid ((3)Hcholesterol) particles obtained after the establishment of the plateau did not result in any cholesterol influx. Therefore, the plateau did not correspond to an equilibrium of the radiolabel between the medium and the cells but rather to a saturation of the efflux particles with cholesterol. Numerous studies have indicated that the cholesterol efflux induced by apoA-I-containing lipoproteins involves cell-surface receptor, caveolae and intracellular cholesterol mobilization. Therefore, we investigated these characteristics for the BSP-mediated cholesterol efflux. Binding of BSP proteins to cells (evaluated by immunoblotting) reached saturation rapidly and remained constant thereafter. However, after several washings the cell-bound BSP proteins were unable to promote significant cholesterol efflux. Both results indicate no correlation of cholesterol efflux with cell binding. Moreover, in comparison to apoA-I-mediated cholesterol efflux, BSP-mediated efflux was not abolished at temperatures below 22 degrees C indicating that the BSP-induced cholesterol efflux does not involve intracellular cholesterol mobilization. High-density lipoprotein- and apoA-I-mediated cholesterol efflux was inhibited by preincubating fibroblasts with progesterone, whereas the cholesterol efflux by BSP proteins was not, indicating that cell-surface caveolae do not participate in BSP-mediated cholesterol efflux. Our results indicate that the mechanism of cholesterol efflux by BSP proteins is unidirectional and is strikingly different from that mediated by apoA-I-containing lipoproteins. |
| Characterization and functional studies of lipoproteins, lipid transfer proteins, and lecithin:cholesterol acyltransferase in CSF of normal individuals and patients with Alzheimer's disease Demeester, N., G. Castro, et al. (2000), J Lipid Res 41(6): 963-74. Abstract: We investigated the lipoprotein distribution and composition in cerebrospinal fluid (CSF) in a group of patients with Alzheimer's disease (AD) or affected by other types of dementia in comparison to non-demented controls. We found slightly decreased apolipoprotein (apo)E and cholesterol concentrations in CSF of AD patients and moderately increased apoA-I concentrations, while in patients suffering from other types of dementia the apoA-I CSF concentration was increased. ApoA-IV concentrations varied widely in human CSF, but were not associated with any clinical condition. HDL(2)-like apoE-containing lipoproteins represent the major lipoprotein fraction. In CSF of normal controls, only a minor HDL(3)-like apoA-I-containing lipoprotein fraction was observed; this fraction was more prevalent in AD patients. ApoA-II was recovered mostly in the HDL(3) density range, while apoA-IV was not associated with lipoproteins but appeared in a lipid-free form, co-localizing with LCAT immunoreactivity. Bi-dimensional analysis demonstrated pre-beta and alpha apoA-I-containing particles; apoE and apoA-II were detected only in alpha-migrating particles. ApoA-IV distributed both to pre-beta and gamma-migrating particles; the LCAT signal was co-localized in this gamma-migrating fraction. Enzymatically active LCAT was present in human CSF as well as PLTP activity and mass; no CETP mass was detected. In CSF from AD patients, LCAT activity was 50% lower than in CSF from normal controls. CSF lipoproteins induced a significant cholesterol efflux from cultured rat astrocytes, suggesting that they play an active role in maintaining the cholesterol homeostasis in brain cells. |
| Characterization and properties of cholesterol desaturases from the ciliate Tetrahymena thermophila Nusblat, A. D., L. Munoz, et al. (2005), J Eukaryot Microbiol 52(1): 61-7. Abstract: Live Tetrahymena thermophila transforms exogenous cholesterol into 7,22-bis, dehydrocholesterol (DHC) by desaturation at positions C7(8) and C22(23) of the cholesterol moiety. In this first report on expression, isolation, characterization, and reconstitution of Tetrahymena's cholesterol desaturases in cell-free extracts, we describe conditions for increasing the expression of both desaturases based on the addition of specific sterols to the culture medium. Reactions performed in vitro, with isolated microsomes, yield only the mono-unsaturated derivatives, 7-DHC and/or 22-DHC. However, selectivity towards one product can be improved with the addition of specific compounds: beta-mercaptoethanol inhibited C22(23) desaturase activity completely, while ethanol selectively increased this activity. Detergent-solubilized microsomes showed no desaturase activity, but partial restoration could be achieved with addition of dilauroyl-phosphatidylcholine liposomes (25%). Both cholesterol desaturases require molecular oxygen and cytochrome b(5). NADH or NADPH can serve as reduced cofactors, albeit with different efficiency, delivered by reductases present in the microsomal fraction. Azide and cyanide, but not azole compounds, inhibited these desaturases, suggesting a key role for cytochrome b(5) in these reactions. |
| Characterization of a cholesterol response element (CRE) in the promoter of the cholesteryl ester transfer protein gene: functional role of the transcription factors SREBP-1a, -2, and YY1 Gauthier, B., M. Robb, et al. (1999), J Lipid Res 40(7): 1284-93. Abstract: Cholesteryl ester transfer protein (CETP) is expressed in human adipocytes, where it acts to promote selective uptake of HDL-CE (Benoist, F., M. McDonnell, P. Lau, R. Milne, and R. McPherson. 1997. J. Biol. Chem. 272: 23572;-23577). In contrast to other major sterol-responsive genes such as 3-hydroxy-3-methylglutaryl coenzyme A reductase CETP expression is up-regulated rather than down-regulated in response to cholesterol. To define elements involved in cholesterol-mediated up-regulation of CETP gene expression, deletion derivatives of the CETP promoter were cloned into a luciferase reporter construct and transfected into the human liposarcoma cell line SW872, cultured in the presence or absence of lipoproteins. A fragment associated with a positive cholesterol response was identified between nucleotides -361 and -138 (relative to the initiation site of transcription) of the promoter. This region contains a tandem repeat of a sequence known to mediate sterol dependent regulation of the hamster HMG-CoA reductase gene. We have putatively denoted this region, the cholesterol response element (CRE).Using gel mobility shift assays we demonstrate that both YY1 and SREBP-1 interact with the CRE of CETP. Furthermore, in transient co-transfection experiments, both YY1 and SREBP-1a were found to trans-activate, in a dose-dependent manner, the luciferase activity of constructs harboring the CRE. We also demonstrate that SREBP-2, is able to trans-activate a luciferase construct harboring the CRE although much less effectively as compared to SREBP-1. Finally, functional analysis of the CRE confirms its regulatory role in modulating CETP gene expression through its interaction with YY1 and SREBP-1a. |
| Characterization of a cytosolic heat-shock protein-caveolin chaperone complex. Involvement in cholesterol trafficking Uittenbogaard, A., Y. Ying, et al. (1998), J Biol Chem 273(11): 6525-32. Abstract: Caveolin is a 22-kDa protein that appears to play a critical role in regulating the cholesterol concentration of caveolae. Even though caveolin is thought to be a membrane protein, several reports suggest that this peculiar protein can traffic independently of membrane vesicles. We now present evidence that a cytosolic pool of caveolin is part of a heat-shock protein-immunophilin chaperone complex consisting of caveolin, heat-shock protein 56, cyclophilin 40, cyclophilin A, and cholesterol. Treatment of NIH 3T3 cells with 1 microM cyclosporin A or 100 nM rapamycin disrupted the putative transport complex and prevented rapid (10-20 min) transport of cholesterol to caveolae. The lymphoid cell line, L1210-JF, does not express caveolin, does not form an immunophilin-caveolin complex, and does not transport newly synthesized cholesterol to caveolae. Transfection of caveolin cDNA into L1210-JF cells allowed the assembly of a transport complex identical to that found in NIH 3T3 cells. In addition, newly synthesized cholesterol in transfected cells was rapidly (10-20 min) and specifically transported to caveolae. These data strongly suggest that a caveolin-chaperone complex is a mechanism by which newly synthesized cholesterol is transported from the endoplasmic reticulum through the cytoplasm to caveolae. |
| Characterization of a gadolinium-labeled cholesterol derivative as an organ-specific contrast agent for adrenal MR imaging Muhler, A., J. Platzek, et al. (1995), J Magn Reson Imaging 5(1): 7-10. Abstract: The purpose of the study was to determine if derivatization of cholesterol with a paramagnetic label could result in an organ-specific contrast agent for magnetic resonance imaging of the adrenal glands. Gadolinium-DO3A-labeled cholesterol was synthesized and the relaxivities in water and blood plasma determined at 0.47 T and 40 degrees C. Organ distribution was measured at 2 (n = 2) and 24 (n = 2) hours after intravenous injection of a 50 mumol/kg dose of Gd-DO3A-cholesterol in rats weighing 220-240 g. T1-weighted spin-echo images were acquired at 2 T before and after injection of 50 mumol/kg Gd-DO3A-cholesterol (n = 2) and Gd-DTPA (diethylenetriaminepentaacetic acid)-albumin (n = 2). More than 99% of the Gd-DO3A-cholesterol was found to be protein bound in bovine serum. High T1 and T2 relaxivities were found in water and plasma. High tissue concentrations of Gd-DO3A-cholesterol were found only in adrenal glands and liver. At 24 hours, adrenal gadolinium concentrations were about 10 times higher than in blood. At 2 hours after injection of Gd-DO3A-cholesterol, enhancement was 162% in adrenal glands and 146% in liver. With Gd-DTPA-albumin, enhancement values were 57% and 56%, respectively. |
| Characterization of a small vesicular cholesterol carrier in human gallbladder bile Ahrendt, S. A., M. K. Fox-Talbot, et al. (1994), Ann Surg 220(5): 635-43. Abstract: OBJECTIVE: Cholesterol phospholipid vesicles play an important role in the nucleation of cholesterol in bile. Recent studies have identified an additional vesicle population in human bile. In this study, the role of these small vesicles as cholesterol carriers was examined. METHODS: Gallbladder bile was obtained from 60 patients at cholecystectomy. Large vesicles, small vesicles, lamellae, and mixed micelles were separated using gel filtration chromatography. RESULTS: Small vesicles were present in bile from the majority of patients both with and without cholesterol gallstones, whereas the void volume vesicle fraction was found almost exclusively in bile from patients with cholesterol gallstones. Both large vesicular and small vesicular cholesterol increased as total bile cholesterol concentration increased; however, the cholesterol-phospholipid ratio in the large vesicle fraction from patients with cholesterol stones was significantly greater than the ratio in small vesicles (1.6 +/- 0.3 vs. 1.0 < or = 0.1, p < 0.05). Whole bile cholesterol crystal appearance time was correlated significantly with the percentage of cholesterol transported by large vesicles (r = 0.63, p < 0.001) but not with the percentage of cholesterol present in small vesicles. Finally, large vesicles isolated by gel filtration chromatography formed cholesterol crystals faster than small vesicles (5.3 +/- 2 vs. 17.4 +/- 4 days, p < 0.01). CONCLUSIONS: These data suggest that a heterogenous population of vesicles is present in human gallbladder bile. As bile becomes saturated with cholesterol, it increasingly is solubilized by both small and large vesicles. The small vesicles have relatively less cholesterol and are more stable than the larger variety, from which cholesterol is most likely to precipitate. |
| Characterization of an inclusion complex of cholesterol and hydroxypropyl-beta-cyclodextrin Williams, R. O., 3rd, V. Mahaguna, et al. (1998), Eur J Pharm Biopharm 46(3): 355-60. Abstract: Interactions between endogenous cholesterol and cyclodextrins have been investigated by several researchers, and they found altered skin penetration of some drugs, membrane disruption, and extraction of cholesterol from the large lipoprotein particles or animal fat. In the present study, an inclusion complex composed of cholesterol and hydroxypropyl-beta-cyclodextrin (HPbetaCD) prepared by lyophilization was investigated and characterized in order to confirm these interactions. Five grams of cholesterol were dispersed in 50 ml of 73.2 mM HPbetaCD aqueous solution, mixed for 2 days, and the filtrate lyophilized. A phase solubility study was performed by mixing an excess amount of cholesterol with an aqueous solution containing increasing amounts of HPbetaCD. The amount of cholesterol in solution after mixing for 2 days at 25 degrees C was determined by HPLC. The inclusion complex was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffractometry, and differential scanning calorimetry (DSC). An Ap-type Higuchi phase solubility diagram, DSC, FTIR, and X-ray diffraction demonstrated the formation of an inclusion complex. DSC thermograms indicated that the endothermic peaks of cholesterol and physical mixture of cholesterol with HPbetaCD due to the fusion of drug crystals, were absent in DSC thermograms obtained on the freeze dried inclusion complex. FTIR spectra indicated that some of the absorption peaks in the lyophilized inclusion complex were different from that of the physical mixture of cholesterol and HPbetaCD. X-ray diffraction patterns showed that the pure cholesterol and a physical mixture of cholesterol and HPbetaCD exhibited crystalline characteristics whereas the lyophilized inclusion complex and HPbetaCD displayed amorphous characteristics. The results indicated that the formation of a cholesterol/HPbetaCD inclusion complex is more water soluble than cholesterol alone. |