Cholesterol Journal Articles

Record 9761 to 9780

Permeabilization of MDCK cells with cholesterol binding agents: dependence on substratum and confluency
Esparis-Ogando, A., C. Zurzolo, et al. (1994), Am J Physiol 267(1 Pt 1): C166-76.
Abstract: We studied systematically the susceptibility of Madin-Darby canine kidney (MDCK) cells to permeabilization by two cholesterol binding agents, digitonin and streptolysin-O (SLO), under different culture conditions. Monolayers grown on polycarbonate filter chambers (Transwells) required twice the concentration of digitonin effective on monolayers grown on glass or plastic (80 vs. 40 micrograms/ml) to allow antibody penetration or the release of 90% of the cytosolic protein lactate dehydrogenase (LDH). Neither the apical nor the basolateral surface showed preferential susceptibility to digitonin. Confluent MDCK cells, cultured either on filters or on impermeable substrates, showed poor antibody permeability after addition of commercial SLOs, even when used at concentrations 100 times higher (20 U/ml) than those effective on nonepithelial Chinese hamster ovary cells. Surprisingly, culture conditions that prevent tight junction formation and the acquisition of a polarized phenotype (< 10 microM Ca2+) increased dramatically the susceptibility to permeabilization by SLO. On restoration of normal Ca2+ levels, susceptibility to SLO quickly decreased. Thus conditions that lead to the full establishment of polarity result in decreased sensitivity to disruption by digitonin and SLO.

Peroxidation of phosphatidylcholine and cholesterol in mixed monolayers
Chasovnikova, L. V., V. E. Formaziuk, et al. (1991), Biofizika 36(4): 589-93.
Abstract: Peroxidation of phosphatidylcholine and cholesterol in mixed monolayers at the air-water surface is studied. It is shown that the rate of phosphatidylcholine peroxidation is abruptly decreased in the presence of cholesterol.

Peroxide-induced damage to high-density lipoproteins and their cholesterol-acceptor function in patients with ischemic heart disease and in healthy people
Plavinskii, S. L. and A. S. Kuznetsov (1997), Fiziol Cheloveka 23(1): 103-7.

Peroxisomal cholesterol synthesis in vivo: accumulation of 4-methyl intermediate sterols after aminotriazole inhibition of cholesterol synthesis
Hashimoto, F. and H. Hayashi (1994), Biochim Biophys Acta 1214(1): 11-9.
Abstract: To clarify the importance and pathway of peroxisomal cholesterol synthesis in vivo, we have examined whether or not 4,4-dimethyl-5 alpha-cholest-8-en-3 beta-ol and 4 alpha-methyl-5 alpha-cholest-7-en-3 beta-ol are accumulated in hepatic peroxisomes of aminotriazole-treated rats (we have shown that these intermediate steroids accumulate in rat liver when cholesterol synthesis is inhibited by aminotriazole: Hashimoto, F. and Hayashi, H. (1991) Biochim. Biophys. Acta 1086, 115). Differential centrifugation and Nycodenz gradient centrifugation showed that these intermediate steroids were localized in peroxisomes and microsomes. Cholestyramine (3-hydroxy-3-methylglutaryl-CoA reductase activator) pretreatment of aminotriazole-treated rats increased the contents of the intermediate steroids in both peroxisomes and microsomes. In peroxisomes, both 4 alpha-methyl-5 alpha-cholest-7-en-3 beta-ol and 4,4-dimethyl-5 alpha-cholest-8-en-3 beta-ol were increased to about 3 times the control (aminotriazole-treated rat), and they were predominantly (about 70%) recovered in the membrane fraction after treatment with 0.05% deoxycholate or 100 mM Na2CO3. Gemfibrozil (peroxisomal proliferator) pretreatment enhanced the contents of 4 alpha-methyl-5 alpha-cholest-7-en-3 beta-ol and 4,4-dimethyl-5 alpha-cholest-8-en-3 beta-ol of peroxisomes to 4.5 times and 37 times the control, respectively. The effects of aminotriazole, cholestyramine and gemfibrozil on the intermediate contents were different between peroxisomes and microsomes. We suggest that peroxisomes in addition to microsomes participate in cholesterol synthesis in vivo, and the biosynthetic pathway includes 4 alpha-methyl-5 alpha-cholest-7-en-3 beta-ol and 4,4-dimethyl-5 alpha-cholest-8-en-3 beta-ol.

Peroxisomal protein targeting and identification of peroxisomal targeting signals in cholesterol biosynthetic enzymes
Olivier, L. M. and S. K. Krisans (2000), Biochim Biophys Acta 1529(1-3): 89-102.
Abstract: At least three different subcellular compartments, including peroxisomes, are involved in cholesterol synthesis. Recently, it has been demonstrated that peroxisomes contain a number of enzymes involved in cholesterol biogenesis that previously were considered to be cytosolic or located in the endoplasmic reticulum. Peroxisomes have been shown to contain acetoacetyl-CoA thiolase, HMG-CoA synthase, HMG-CoA reductase, mevalonate kinase, phosphomevalonate kinase, phosphomevalonate decarboxylase, isopentenyl diphosphate isomerase and FPP synthase. Moreover, the activities of these enzymes are also significantly decreased in liver tissue and fibroblast cells obtained from patients with peroxisomal deficiency diseases. In addition, the cholesterol biosynthetic capacity is severely impaired in cultured skin fibroblasts obtained from patients with peroxisomal deficiency diseases. These findings support the proposal that peroxisomes play an essential role in isoprenoid biosynthesis. This paper presents a review of peroxisomal protein targeting and of recent studies demonstrating the localization of cholesterol biosynthetic enzymes in peroxisomes and the identification of peroxisomal targeting signals in these proteins.

Peroxisome deficiency does not result in deficiency of enzymes involved in cholesterol biosynthesis
Hogenboom, S., G. J. Romeijn, et al. (2003), Adv Exp Med Biol 544: 329-30.

Peroxisome proliferator-activated receptor agonists prevent 25-OH-cholesterol induced c-jun activation and cell death
Chang, J. Y. and L. Z. Liu (2001), BMC Pharmacol 1: 10.
Abstract: BACKGROUND: Cholesterol oxides, the oxygenated derivatives of cholesterol, have been shown to cause programmed cell death in a variety of cell types. Using N9 microglia, this study was designed to investigate the molecular events induced by cholesterol oxides prior to the execution of programmed cell death. RESULTS: Microglia were very sensitive to 25-OH-cholesterol, such that a 2-day treatment of the cells with 5 microM 25-OH-cholesterol reduced cell viability to 5-10% of controls. There was a dose- and time-dependent increase in c-jun and phospho-c-jun levels in microglia prior to this 25-OH-cholesterol induced cell death. In contrast, 7-beta-OH-cholesterol, which was relatively non-toxic to microglia, did not increase phospho-c-jun levels. Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors that have important roles in atherogenesis. Results from this study indicate that PPAR agonists such as 15d-PGJ2, indomethacin and WY14643 can attenuate cholesterol oxide induced c-jun activation and cell death in microglia. CONCLUSIONS: Peroxisome proliferator-activated receptor agonists may be useful in future development of pharmacological agents against cholesterol oxide induced cytotoxicity.

Peroxisome proliferator-activated receptor alpha reduces cholesterol esterification in macrophages
Chinetti, G., S. Lestavel, et al. (2003), Circ Res 92(2): 212-7.
Abstract: Peroxisome proliferator-activated receptor alpha (PPARalpha) is a nuclear receptor activated by fatty acid derivatives and hypolipidemic drugs of the fibrate class. PPARalpha is expressed in monocytes, macrophages, and foam cells, suggesting a role for this receptor in macrophage lipid homeostasis with consequences for atherosclerosis development. Recently, it was shown that PPARalpha activation promotes cholesterol efflux from macrophages via induction of the ABCA1 pathway. In the present study, the influence of PPARalpha activators on intracellular cholesterol homeostasis was investigated. In human macrophages and foam cells, treatment with fibrates, synthetic PPARalpha activators, led to a decrease in the cholesteryl ester (CE):free cholesterol (FC) ratio. In these cells, PPARalpha activation reduced cholesterol esterification rates and Acyl-CoA:cholesterol acyltransferase-1 (ACAT1) activity. However, PPARalpha activation did not alter ACAT1 gene expression, whereas mRNA levels of carnitine palmitoyltransferase type 1 (CPT-1), a key enzyme in mitochondrial fatty acid catabolism, were induced. Finally, PPARalpha activation blocked CE formation induced by TNF-alpha, possibly due to the inhibition of neutral sphingomyelinase activation by TNF-alpha. In conclusion, our results identify a role for PPARalpha in the control of cholesterol esterification in macrophages, resulting in an enhanced availability of FC for efflux through the ABCA1 pathway.

Peroxisome proliferator-activated receptor-gamma agonist increases both low-density lipoprotein cholesterol particle size and small high-density lipoprotein cholesterol in patients with type 2 diabetes independent of diabetic control
Bavirti, S., F. Ghanaat, et al. (2003), Endocr Pract 9(6): 487-93.
Abstract: OBJECTIVE: To ascertain whether troglitazone, independent of control of diabetes, increases low-density lipoprotein (LDL) particle size. METHODS: We administered 600 mg of troglitazone (a peroxisome proliferator-activated receptor-gamma agonist) daily for 8 weeks to 10 patients with type 2 diabetes (8 of whom completed the study). Then troglitazone therapy was discontinued, and alternative medication for diabetic control was used for another 4 weeks. The LDL, very-low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) concentrations and subpopulations, as well as blood glucose and hemoglobin A1c (HbA1c), were determined at weeks 0, 4, 8, and 12 and analyzed statistically. RESULTS: Small, dense LDL cholesterol is commonly seen in patients with diabetes and is thought to be associated with an increased risk for coronary artery disease. After both 4 and 8 weeks of troglitazone therapy, control of diabetes was significantly improved (mean HbA1c values at baseline, week 4, and week 8 were 8.0 +/- 0.7%, 7.4 +/- 0.5%, and 7.0 +/- 0.7%, respectively; P<0.05). HbA1c (6.5 +/- 0.6% at 12 weeks) and blood glucose levels (126 +/- 19 mg/dL at 8 weeks versus 145 +/- 9 mg/dL at 12 weeks) were not significantly different 4 weeks after troglitazone therapy was discontinued. Troglitazone treatment increased the large LDL particle at 4 and 8 weeks, a change that significantly (P<0.05) enlarged the LDL particle size (20.5 +/- 0.3 nm, 21.2 +/- 0.3 nm, and 21.3 +/- 0.2 nm at baseline, week 4, and week 8, respectively). After 8 weeks of troglitazone therapy, VLDL triglycerides were reduced (195 +/- 37 mg/dL versus 136 +/- 28 mg/dL; P<0.05) and HDL was increased (31.6 +/- 2.4 mg/dL versus 35.5 +/- 2.9 mg/dL; P<0.05). This greater HDL value was due to an increase in the small HDL particles. A decrease in the larger VLDL particles (V5 and V6) resulted in a reduction in the mean VLDL particle size (59 +/- 3 nm versus 46 +/- 2 nm; P<0.05). Despite the fact that control of diabetes remained significantly improved after troglitazone therapy was discontinued, the LDL particle size decreased to the baseline value. This change was due to a reduction in the large LDL cholesterol particle (L3). CONCLUSION: This study shows that troglitazone therapy increases LDL particle size, reduces VLDL particle size, and increases small HDL particles. These changes may lower the risk for coronary artery disease.

Peroxisomes and intracellular cholesterol trafficking in adult rat Leydig cells following Luteinizing hormone stimulation
Mendis-Handagama, S. M. (2000), Tissue Cell 32(1): 102-6.
Abstract: The present study was designed to explore the intracellular cholesterol trafficking in Leydig cells of adult rats following Luteinizing hormone (LH) injection. Histochemical techniques were used to demonstrate distribution of free cholesterol in Leydig cells of control and LH-injected rats. Two groups of sexually mature male Sprague Dawley rats (n=4/group) were used. Fifteen min following an injection of 200 microl of either saline (control) or luteinizing hormone (LH, 500 microg in saline) testes of rats were fixed by whole body perfusion using 0.5% glutaraldehyde and 4% paraformaldehyde in 0.1 M cacodylate buffer for 20 min. Fixed testes were cut into 3 mm3 and kept immersed in the fixative for further 15 min. Tissue cubes were then incubated at 37 degrees C in a medium containing cholesterol oxidase, 3,3'-diaminobenzidine tetrahydrochloride, horseradish peroxidase and dimethyl sulfoxide to histochemically localize free cholesterol in Leydig cells and processed for electron microscopy. Thin sections of these tissues were stained with aqueous uranyl acetate and lead citrate and examined with a Philips 201C electron microscope. In Leydig cells of control rats, free cholesterol was detected primarily in lipid droplets and plasma membrane. In the majority of Leydig cells, peroxisomes were unstained for free cholesterol, but occasionally few stained ones were present. Staining was not detected in mitochondria and smooth endoplasmic reticulum (SER) in Leydig cells of control rats. In LH-injected rats, lipid droplets, many peroxisomes, inner and outer mitochondrial membranes and some cisternae of SER in Leydig cells showed staining for free cholesterol. Fusion of Leydig cell peroxisomes with lipid droplets and mitochondria was also observed in the LH treated rats. These findings suggested that peroxisomes in adult rat Leydig cells participate in the intracellular cholesterol trafficking and delivery into mitochondria during LH stimulated steroidogenesis. Lipid droplets are used as one source for cholesterol for this process.

Peroxisomes and sterol carrier protein-2 in luteal cell steroidogenesis: a possible role in cholesterol transport from lipid droplets to mitochondria
Mendis-Handagama, S. M., R. F. Aten, et al. (1995), Tissue Cell 27(5): 483-90.
Abstract: In the present investigation, we have studied peroxisomes and sterol carrier protein-2 (SCP2) in control and luteinizing hormone stimulated rat luteal cells. Superovulated immature rats in mid-luteal phase (8 days after ovulation) were divided into two groups (n = 4/group) and treated with vehicle (0.2 ml saline), or luteinizing hormone (LH, 20 micrograms/rat). In this animal model, LH acutely stimulates steroidogenesis. Thirty minutes later, corpora lutea were fixed by whole body perfusion and processed for (1) electron microscopic immunocytochemistry to localize SCP2 via the protein A gold immunolabeling technique, and for (2) electron microscopic histochemistry to stain peroxisomal catalase via the alkaline 3,3'-diaminobenzidine tetrahydrochloride method. In the steroidogenic, mid-phase luteal cells of vehicle treated rats (controls), SCP2 was highly concentrated in peroxisomes and sparsely scattered on mitochondria, but no labeling was observed in lipid droplets. In the luteal cells of rats acutely stimulated with LH, peroxisomes immunolabeled for SCP2 were observed within the luteal cell lipid droplets and mitochondria, and in union with lipid droplets and mitochondria. Moreover, in contrast to control luteal cells, significant immunolabeling for SCP2 was detected within the lipid droplets and mitochondria in luteal cells of LH-treated rats. As SCP2 binds cholesterol to 1:1 molar ratio and is known to be involved in the intracellular movement of cholesterol, these findings suggest that peroxisomes and SCP2 may possibly be involved in delivering cholesterol from lipid droplets to the mitochondria when luteal cell steroidogenesis is acutely stimulated by LH.

Persistent plasma cholesterol elevations are produced by one or three stressor exposures in rats fed a normal laboratory diet
Servatius, R. J., J. E. Ottenweller, et al. (1993), Physiol Behav 53(6): 1101-4.
Abstract: Typically, stress-related elevations in rat plasma cholesterol (CHOL) require preexposure to diets high in fats or cholesterol and lengthy stressor protocols. We report on two studies in which we measured plasma CHOL 22-h poststressor in rats fed Purina Laboratory Rodent Chow and exposed to 3 (3-day) or 1 (1-day) daily stressor sessions 40, 2 mA tailshocks. In the first study, both the 3-day and 1-day groups exhibited moderately elevated morning plasma CHOL 22-h poststressor compared to nonshocked controls. Along with the groups in the first study, a second study included a restricted food control, rats transferred to the stressor environment, and rats simply transferred to an adjacent room. Neither restricted feeding nor the room transfers had an effect on morning plasma CHOL. However, the 3-day and 1-day groups again exhibited moderately elevated CHOL. Previous reports did not find elevated plasma CHOL in rats given a single stressor exposure when sampled at the end of the stressor session. Thus, the persistently elevated morning CHOL exhibited by the 1-day group may develop over time. The relatively slow development of plasma CHOL elevations may be related to the time course of stressor-induced thyroid suppression.

Perspectives in cholesterol-lowering therapy: the role of ezetimibe, a new selective inhibitor of intestinal cholesterol absorption
Bruckert, E., P. Giral, et al. (2003), Circulation 107(25): 3124-8.

Perspectives on cholesterol screening programs for children
Daniels, S. R., J. A. Morrison, et al. (1991), J Pediatr 119(5): 834-8.

Perspectives on soy protein as a nonpharmacological approach for lowering cholesterol
Goldberg, A. C. (1995), J Nutr 125(3 Suppl): 675S-678S.
Abstract: Dietary therapy is the first step in the treatment of hyperlipidemia. However, some patients are unable to lower their cholesterol concentrations to a desirable range with diet alone. For primary prevention of coronary artery disease, physicians and patients often wish to avoid pharmacologic therapy of elevated cholesterol concentrations. The use of adjuncts to diet such as soluble fibers, garlic and soy protein may allow target lipid concentrations to be reached without the use of drugs. Soy protein incorporated into a low-fat diet can reduce cholesterol and LDL-cholesterol concentrations. The main obstacles to greater use of soy protein in the therapy of hyperlipidemia include lack of knowledge by physicians and patients of its effects and lack of availability of easily used products. Although soy products such as tofu and soymilk are available in many stores, consumers may be unaware of their presence and uses. Without the publication of articles in mainstream medical journals on the cholesterol-lowering effects of soy protein, few physicians are likely to know of possible uses. Readily available packaged products, recipes and cookbooks also will be necessary to make incorporation of soy protein into the American diet a reality.

Perspectives: The significance of measuring non-HDL-cholesterol
Hirsch, G. A., N. Vaid, et al. (2002), Prev Cardiol 5(3): 156-9.
Abstract: The third Adult Treatment Panel of the National Cholesterol Education Program has recently issued revised guidelines for the treatment of cholesterol in adults. Increased attention to the metabolic syndrome and diabetes, including the inaccuracy of the low-density lipoprotein cholesterol (LDL-C) measurement in these patients because of elevated triglycerides is highlighted. To overcome the inaccuracy of the Friedewald equation in calculating LDL-C when the triglycerides are elevated, measuring non-high-density lipoprotein (non-HDL-C) may provide a better means to follow these patients toward their treatment goals. Recently, non-HDL-C was shown to be a better predictor of cardiovascular death than LDL-C, even in patients with triglyceride levels below 200 mg/dL. The authors review the basis for using non-HDL-C as a treatment target for cholesterol, in comparison with other lipoproteins.

Perturbations of triglycerides but not of cholesterol metabolism are prevented by anti-tumour necrosis factor treatment in rats bearing an ascites hepatoma (Yoshida AH-130)
Dessi, S., B. Batetta, et al. (1995), Br J Cancer 72(5): 1138-43.
Abstract: Rats transplanted with the ascites hepatoma Yoshida AH-130 developed a severely progressive cachexia, characterised by marked alterations in protein and lipid metabolism. In particular, high levels of serum triglycerides and free fatty acids were associated with altered levels and distribution of plasma cholesterol, with increased total and very low-density lipoprotein-low-density lipoprotein (VLDL-LDL) cholesterol and reduced high-density lipoprotein (HDL) cholesterol. The tumour cells showed high rates of cholesterol synthesis and elevated content of free and esterified cholesterol, whereas total cholesterol synthesis was reduced in the host liver. To determine whether these perturbations could be related to the elevation of tumour necrosis factor alpha (TNF-alpha) previously shown in the AH-130 bearers (Tessitore L, Costelli P, Baccino FM 1993, Br J Cancer, 67, 15-23), either anti-TNF polyclonal antibodies or non-immune IgGs were injected daily after tumour transplantation. The anti-TNF treatment neither affected tumour growth nor prevented the serum cholesterol changes, while attenuating the hypertriglyceridaemia and the elevated serum free fatty acid levels. These data indicate that TNF does not appear to be directly involved in the altered cholesterol metabolism in AH-130 hosts, thus supporting the view that cholesterol metabolism and lipid metabolism are regulated differently during tumour growth.

Petrous apex cholesterol granulomas: evolution and management
Eisenberg, M. B., G. Haddad, et al. (1997), J Neurosurg 86(5): 822-9.
Abstract: Petrous apex cholesterol granulomas result from obstruction of the normal aeration of the petrous air cells and have traditionally been treated by drainage and stent placement via a transtemporal approach. The immediate results were quite satisfying, but recurrence rates as high as 60% have been reported in some series. The authors present their experience treating 14 patients with petrous apex cholesterol granulomas. An extended middle fossa approach and a petrosal approach were used for eight and two patients, respectively. All underwent complete removal of the granuloma and cyst wall followed by obliteration of the cavity with a pedicled strip of temporalis muscle. No recurrences were seen at a mean follow-up period of 3.8 years. Four patients who did not undergo surgery are being followed clinically and with serial magnetic resonance images. Additionally, the clinical and radiographic findings in this series give new insights into the origin and continued growth of these lesions and confirm what had been described previously only in experimental models. It is concluded that petrous apex cholesterol granulomas feature a continuum of both clinical and radiographic findings and radical removal via an extended middle fossa approach is advocated.

P-glycoprotein retains function when reconstituted into a sphingolipid- and cholesterol-rich environment
Modok, S., C. Heyward, et al. (2004), J Lipid Res 45(10): 1910-8.
Abstract: P-glycoprotein (P-gp) appears to be associated within specialized raftlike membrane microdomains. The activity of P-gp is sensitive to its lipid environment, and a functional association in raft microdomains will require that P-gp retains activity in the microenvironment. Purified hamster P-gp was reconstituted in liposomes comprising sphingomyelin and cholesterol, both highly enriched in membrane microdomains and known to impart a liquid-ordered phase to bilayers. The activity of P-gp was compared with that of proteoliposomes composed of crude egg phosphatidylcholine (unsaturated) or dipalmitoyl phosphatidylcholine (saturated) in the presence or absence of cholesterol. The maximal rate of ATP hydrolysis was not significantly altered by the nature of the lipid species. However, the potencies of nicardipine and XR9576 to modulate the ATPase activity of P-gp were increased in the sphingolipid-based proteoliposomes. The drug-P-gp interaction was investigated by measurement of the rates of (3)HXR9576 association and dissociation from the transporter. The lipid environment of P-gp did not affect these kinetic parameters of drug binding. In summary, P-gp retains function in liquid-ordered cholesterol and sphingolipid model membranes in which the communication between the transmembrane and the nucleotide binding domains after drug binding to the protein is more efficient.

pH gradient loading of anthracyclines into cholesterol-free liposomes: enhancing drug loading rates through use of ethanol
Dos Santos, N., K. A. Cox, et al. (2004), Biochim Biophys Acta 1661(1): 47-60.
Abstract: Application of cholesterol-free liposomes as carriers for anticancer drugs is hampered, in part, because of standard pH gradient based loading methods that rely on incubation temperatures above the phase transition temperature (Tc) of the bulk phospholipid to promote drug loading. In the absence of cholesterol, liposome permeability is enhanced at these temperatures which, in turn, can result in the collapse of the pH gradient and/or unstable loading. Doxorubicin loading studies, for example, indicate that the drug could not be loaded efficiently into cholesterol-free DSPC liposomes. We demonstrated that this problem could be circumvented by the addition of ethanol as a permeability enhancer. Doxorubicin loading rates in cholesterol-free DSPC liposomes were 6.6-fold higher in the presence of ethanol. In addition, greater than 90% of the added doxorubicin was encapsulated within 2 h at 37 degrees C, an efficiency that was 2.3-fold greater than that observed in the absence of ethanol. Optimal ethanol concentrations ranged from 10% to 15% (v/v) and these concentrations did not significantly affect liposome size, retention of an aqueous trap marker (lactose) or, most importantly, the stability of the imposed pH gradient. Cryo-transmission electron micrographs of liposomes exposed to increasing concentrations of ethanol indicated that at 30% (v/v) perturbations to the lipid bilayer were present as evidenced by the appearance of open liposomes and bilayer sheets. Ethanol-induced increased drug loading was temperature-, lipid composition- and lipid concentration-dependent. Collectively, these results suggest that ethanol addition to preformed liposomes is an effective method to achieve efficient pH gradient-dependent loading of cholesterol-free liposomes at temperatures below the Tc of the bulk phospholipid.

Cholesterol Articles and Abstracts

Cholesterol Journal Articles