| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Gentisic acid, an aspirin metabolite, inhibits oxidation of low-density lipoprotein and the formation of cholesterol ester hydroperoxides in human plasma Ashidate, K., M. Kawamura, et al. (2005), Eur J Pharmacol 513(3): 173-9. Abstract: Gentisic acid, an aspirin metabolite, has an antioxidant effect, although its detailed mechanism remains elusive. The present study was designed to determine whether it inhibits low-density lipoprotein (LDL) oxidation and the formation of lipid hydroperoxides in human plasma. The susceptibility of LDL oxidative modification was investigated by a method using 2,2'-azobis or Cu2+. To study the effect of gentisic acid on free radical-induced damage to plasma lipids, cholesterol ester hydroperoxides generated by incubating human fresh plasma with Cu2+ and gentisic acid was analyzed. Gentisic acid inhibited LDL oxidation in a concentration-dependent manner. It significantly inhibited the formation of cholesterol ester hydroperoxides in plasma, and was consumed after the depletion of ascorbic acid and reduced form of coenzyme Q-10 (CoQH2-10), whereas concentrations of other antioxidants remained unchanged. Gentisic acid had a potent free radical scavenging activity with a minimal chelating effect. The potent antioxidant property of gentisic acid may partly account for the anti-atherogenic effects of aspirin. |
| Geranylgeraniol and beta-ionone inhibit hepatic preneoplastic lesions, cell proliferation, total plasma cholesterol and DNA damage during the initial phases of hepatocarcinogenesis, but only the former inhibits NF-kappaB activation de Moura Espindola, R., R. P. Mazzantini, et al. (2005), Carcinogenesis 26(6): 1091-9. Abstract: Chemopreventive activities of the isoprenoids geranylgeraniol (GGO) and beta-ionone (BI) were evaluated during initial phases of hepatocarcinogenesis. Rats received 8 or 16 mg/100 g body wt GGO (GGO8 and GGO16 groups) or BI (BI8 and BI16 groups), or only corn oil (CO group, controls) daily for 7 weeks. Incidence (%) and the mean number of visible hepatocyte nodules/animal were inhibited in the GGO8 (64% and 21 +/- 40), GGO16 (33% and 3 +/- 5), BI8 (50% and 13 +/- 34) and BI16 (42% and 9 +/- 19) groups compared with the CO group (100% and 34 +/- 51) (P < 0.05, except for the GGO8 group). Number/cm(2) liver section, mean area (mm(2)) and % liver section area occupied by persistent hepatic placental glutathione S-transferase positive preneoplastic lesions (PNL) were reduced in the GGO8 (11 +/- 9; 0.26 +/- 0.35; 2.7 +/- 3.0), GGO16 (6 +/- 6; 0.18 +/- 0.16; 0.9 +/- 0.9), BI8 (9 +/- 5; 0.13 +/- 0.20; 1.1 +/- 1.2) and BI16 (8 +/- 6; 0.08 +/- 0.09; 0.6 +/- 0.4) groups compared with the CO group (26 +/- 18; 0.29 +/- 0.34; 7.0 +/- 5.5) (P < 0.05). GGO16 and BI16 groups showed smaller visible hepatocyte nodules, reduced PNL cell proliferation and total plasma cholesterol levels compared with the CO group (P < 0.05), but did not show any differences (P > 0.05) in PNL apoptosis. DNA damage expressed as comet length (microm) was reduced in the GGO8 (96.7 +/- 1.5), GGO16 (94.2 +/- 1.5), BI8 (97.1 +/- 1.1) and BI16 (95.1 +/- 1.5) groups compared with the CO group (102.1 +/- 1.7) (P < 0.05). In comparison with normal animals, the CO group animals showed increased (P < 0.05) nuclear levels of nuclear factor kappa B (NF-kappaB) p65 subunit in hepatic cells, which were decreased (P < 0.05) in the GGO16 group animals. Anticarcinogenic actions of these isoprenoids seem to follow a dose-response relationship. Results indicate that GGO and BI could be represented as promising chemopreventive agents against hepatocarcinogenesis. Inhibition of cell proliferation and DNA damage seems to be important for the anticarcinogenic actions of isoprenoids, while the inhibition of NF-kappaB activation seems to be specifically related to GGO actions. |
| Gestational age dependency of essential fatty acids in cord plasma cholesterol esters and triglycerides Hoving, E. B., C. M. van Beusekom, et al. (1994), Pediatr Res 35(4 Pt 1): 461-9. Abstract: Plasma cholesterol ester and triglyceride fatty acid compositions of 38 singleton deliveries (23-42 wk), three twins (32, 39, and 40 wk), and their mothers were investigated. No gestational age-dependent changes occurred in maternal fatty acid compositions. Long-chain polyunsaturated fatty acids in fetal cholesterol esters and triglycerides were higher, and their precursors (18:2c,omega 6 and 18:3c,omega 3) were lower than those in corresponding maternal lipid classes. Except for 22:6c,omega 3,20:2c,omega 6, and 22:5c,omega 6, all long-chain polyunsaturated fatty acids in fetal triglycerides increased with advancing gestation. Fetal triglyceride 22:6c,omega 3/22:5c,omega 3 ratio decreased, whereas 22:5c,omega 6/22:4c,omega 6 remained constant. Fetal cholesterol ester and triglyceride 20:3c,omega 9 contents were higher than those of corresponding maternal fractions and did not change with gestation. Triglyceride 18:2c,omega 6 contents of babies with gestational ages of more than 34 wk were linearly related to those of their mothers. The data suggest that increasing triglyceride long-chain polyunsaturated fatty acid content with advancing gestation is partially caused by delta 6- and delta 5-desaturase maturation in the liver. Constancy of 22:6c,omega 3 and 22:5c,omega 6/22:4c,omega 6 and decrease of 22:6c,omega 3/22:5c,omega 3 in triglycerides may point to low hepatic delta 4-desaturation. Transplacental transport of 20:3c,omega 9, following by fetal conservation, should be considered. High 18:2c,omega 6 and low 18:3,omega 3 intakes by the mother may unfavorably influence fetal production of 22:6c,omega 3 in the liver. Because of low hepatic delta 4-desaturation capacity the influence may be small, however. |
| Getting a handle on "good" cholesterol with the high-density lipoprotein receptor Rigotti, A. and M. Krieger (1999), N Engl J Med 341(26): 2011-3. |
| Getting there: statin plus ezetimibe for low-density lipoprotein cholesterol goals Hurley, D. L. and W. L. Isley (2005), Mayo Clin Proc 80(5): 585-6. |
| Getting to the heart of the cholesterol debate Palca, J. (1990), Science 247(4947): 1170-1. |
| Getting to the heart of the problem: women and cholesterol Berlin, B. (1998), N J Med 95(1): 35-7. |
| Ghrelin levels correlate with insulin levels, insulin resistance, and high-density lipoprotein cholesterol, but not with gender, menopausal status, or cortisol levels in humans Purnell, J. Q., D. S. Weigle, et al. (2003), J Clin Endocrinol Metab 88(12): 5747-52. Abstract: The gut peptide, ghrelin, may participate in the control of energy homeostasis and pituitary hormone secretion in humans, stimulating both food intake and, at pharmacological doses, ACTH and cortisol secretion. Meal consumption and weight loss regulate ghrelin levels, but less is known about the relationship of ghrelin to body composition, aging, menopausal status, and lipid metabolism. Therefore, 60 adult men and women of widely varying ages and weights were characterized in terms of body composition and levels of ghrelin, glucose, insulin, lipids, and cortisol. Fasting ghrelin levels correlated positively with age and negatively with BMI and fat cell size, but were not related to fat mass, intraabdominal fat, or lean mass. Fasting ghrelin levels correlated most strongly with insulin levels (r = -0.39; P = 0.002), insulin resistance as determined by the quantitative insulin sensitivity check index (r = 0.38; P = 0.003), and high-density lipoprotein cholesterol levels (r = 0.33; P = 0.009). Meal-induced ghrelin suppression correlated with the postprandial rise in insulin (r = 0.39; P < 0.05). Ghrelin levels were similar in men and women and did not vary by menopausal status or in association with cortisol levels. Our data are consistent with the hypotheses that insulin may negatively regulate ghrelin and that high-density lipoprotein may be a carrier particle for circulating ghrelin. |
| Giant cholesterol cyst of the petrous bone: a case report Gokalp, H. Z., H. Deda, et al. (1995), Neurosurg Rev 18(3): 205-8. Abstract: The giant cholesterol cyst (GCC) is a benign lesion that gradually enlarges and causes progressive bone erosion and serious neurologic deficits of the cranial nerves within the temporal bone and jugular foramen. We report here a lesion located behind the petrous bone and describe the diagnostic evaluation, pathology, and surgical management. |
| Giant cholesterol cysts of the petrous apex Pellet, W., S. Valenzuela, et al. (1992), Neurochirurgie 38(5): 267-80; discussion 280-1. Abstract: In connection with their two own cases, the authors deal about the giant cholesterol cysts of the petrous apex. The lesions which are to be differentiated from epidermoid cysts are cholesterol granulomas. Their petrous apex location explains their characteristic large appearance. As each cholesterol granuloma, they occur when a bony cell is obstructed. This chronic obstruction induces mucosal edema then bleedings which lead to the formation and, by the lack of drainage, to the accumulation of cholesterol crystals. These crystals initiate a non specific reaction to foreign bodies, a granuloma, which also can bleed. Thus, a continuous cycle perpetuates the growth of the lesion. This lesion, when it is localized in the petrous apex, can reach a big size before the appearance of some signs. Usually, these are otologic (sensorineural hearing loss, tinnitus, vertigo) and/or cranial nerve palsies (V, VI, VII). C.T. scan (well defined, sharply marginated bony expansible lesion with isodense to the brain central part) and M.R.I. (central region of increased intensity on both T1 and T2 weighted images and peripheral rim of markedly decreased signal intensity in all instances) features are characteristic enough to allow diagnose with other petrous apex lesions (cholesteatoma, mucocele, epithelial cyst, histiocytosis X.). Surgical treatment must try to evacuate and to aerate the cavity or perhaps to obliterate it with fatty pieces in order to prevent the recurrence. |
| Ginger extract consumption reduces plasma cholesterol, inhibits LDL oxidation and attenuates development of atherosclerosis in atherosclerotic, apolipoprotein E-deficient mice Fuhrman, B., M. Rosenblat, et al. (2000), J Nutr 130(5): 1124-31. Abstract: Oxidative modification of LDL is thought to play a key role in the pathogenesis of atherosclerosis. Consumption of nutrients rich in phenolic antioxidants has been shown to be associated with attenuation of development of atherosclerosis. This study was undertaken to investigate the ex vivo effect of standardized ginger extract on the development of atherosclerosis in apolipoprotein E-deficient (E(0)) mice, in relation to plasma cholesterol levels and the resistance of their LDL to oxidation and aggregation. E(0) mice (n = 60; 6-wk-old) were divided into three groups of 20 and fed for 10 wk via their drinking water with the following: group i) placebo (control group), 1.1% alcohol and water (11 mL of alcohol in 1 L of water); group ii) 25 microg of ginger extract/d in 1.1% alcohol and water and group iii) 250 microg of ginger extract/day in 1.1% alcohol and water. Aortic atherosclerotic lesion areas were reduced 44% (P<0.01) in mice that consumed 250 microg of ginger extract/day. Consumption of 250 microg of ginger extract/day resulted in reductions (P<0.01) in plasma triglycerides and cholesterol (by 27 and 29%, respectively), in VLDL (by 36 and 53%, respectively) and in LDL (by 58 and 33%, respectively). These results were associated with a 76% reduction in cellular cholesterol biosynthesis rate in peritoneal macrophages derived from the E(0) mice that consumed the high dose of ginger extract for 10 wk (P<0.01). Furthermore, peritoneal macrophages harvested from E(0) mice after consumption of 25 or 250 microg of ginger extract/day had a lower (P<0.01) capacity to oxidize LDL (by 45 and by 60%, respectively), and to take up and degrade oxidized LDL (by 43 and 47%, respectively). Consumption of 250 microg of ginger extract/day also reduced (P<0.01) the basal level of LDL-associated lipid peroxides by 62%. In parallel, a 33% inhibition (P<0.01) in LDL aggregation (induced by vortexing) was obtained in mice fed ginger extract. We conclude that dietary consumption of ginger extract by E(0) mice significantly attenuates the development of atherosclerotic lesions. This antiatherogenic effect is associated with a significant reduction in plasma and LDL cholesterol levels and a significant reduction in the LDL basal oxidative state, as well as their susceptibility to oxidation and aggregation. |
| Ginkgo biloba extract (Egb 761) inhibits beta-amyloid production by lowering free cholesterol levels Yao, Z. X., Z. Han, et al. (2004), J Nutr Biochem 15(12): 749-56. Abstract: Ginkgo biloba extract (EGb 761) can improve cognitive function in patients with Alzheimer's disease, but the molecular mechanisms underlying this effect remain undefined. Because free cholesterol may be involved in the production of beta-amyloid precursor protein and amyloid beta-peptide, key events in the development of Alzheimer's disease, we examined EGb 761 in relation to cholesterol and amyloidogenesis. In aging rats, EGb 761 treatment lowered circulating free cholesterol and inhibited the production of brain beta-amyloid precursor protein and amyloid beta-peptide. Exposure of PC12 cells to EGb 761 decreased the processing of beta-amyloid precursor protein and abolished cholesterol-induced overproduction of this protein. Exposure of human NT2 cells to EGb 761 decreased free cholesterol influx and increased free cholesterol efflux. Our findings indicate that free circulating and intracellular cholesterol levels affect the processing of beta-amyloid precursor protein and amyloidogenesis. Our findings also provide the first demonstration that EGb 761 can influence these mechanisms. |
| Glial soluble factors regulate the activity and expression of the neuronal glutamate transporter EAAC1: implication of cholesterol Canolle, B., F. Masmejean, et al. (2004), J Neurochem 88(6): 1521-32. Abstract: A co-ordinated regulation between neurons and astrocytes is essential for the control of extracellular glutamate concentration. Here, we have investigated the influence of astrocytes and glia-derived cholesterol on the regulation of glutamate transport in primary neuronal cultures from rat embryonic cortices. Glutamate uptake rate and expression of the neuronal glutamate transporter EAAC1 were low when neurons were grown without astrocytes and neurons were unable to clear extracellular glutamate. Treatment of the neuronal cultures with glial conditioned medium (GCM) increased glutamate uptake Vmax, EAAC1 expression and restored the capacity of neurons to eliminate extracellular glutamate. Thus, astrocytes up-regulate the activity and expression of EAAC1 in neurons. We further showed that cholesterol, present in GCM, increased glutamate uptake activity when added directly to neurons and had no effect on glutamate transporter expression. Furthermore, part of the GCM-induced effect on glutamate transport activity was lost when cholesterol was removed from GCM (low cholesterol-GCM) and was restored when cholesterol was added to low cholesterol-GCM. This demonstrates that glia-derived cholesterol regulates glutamate transport activity. With these experiments, we provide new evidences for neuronal glutamate transport regulation by astrocytes and identified cholesterol as one of the factors implicated in this regulation. |
| Glibenclamide acts as an inhibitor of acyl-CoA:cholesterol acyltransferase enzyme Ohgami, N., A. Kuniyasu, et al. (2000), Biochem Biophys Res Commun 277(2): 417-22. Abstract: Sulfonylureas are used in the treatment of non-insulin-dependent diabetes mellitus. Little is known, however, about their effects on cholesterol metabolism. We tested in the present study the effects of glibenclamide (GB) on cholesterol esterification (CE) in macrophage-derived cells. GB inhibited intracellular accumulation of CE induced by acetylated LDL or oxidized LDL in J774 cells, but no such effect on total cholesterol, suggesting that the target of GB was acyl-CoA:cholesterol acyltransferase (ACAT). In the cell-free reconstitution ACAT assay, GB inhibited the ACAT activity with an IC(50) value of 20 microM. Furthermore, GB effectively inhibited the ACAT activity of PMA-stimulated THP-1 cells to the undifferentiated level of THP-1. In the whole-cell ACAT assay using CHO cells overexpressed with ACAT-1 or ACAT-2, GB inhibited the activity of both isozymes with similar potency. Our in vitro data suggest that sulfonylurea could be a potential seed for a new generation of ACAT inhibitors. |
| Glibenclamide inhibits cholesterol metabolism in macrophage Nakayama, H., N. Ohgami, et al. (1999), Nippon Yakurigaku Zasshi 114 Suppl 1: 150P-153P. Abstract: Sulfonylureas are generally used in the therapeutic treatment of non-insulin-dependent diabetes mellitus. Little is known, however, whether they also affect the lipid metabolism. Using glibenclamide (GB), a typical sulfonylurea, we have investigated its effects on the lipid metabolism in macrophages, J774 and phorbol ester-treated THP-1 cells. In the whole-cell assay system for cholesteryl ester (CE) accumulation that is induced by addition of chemically modified low-density lipoprotein (LDL), such as Ac-LDL and ox-LDL, GB effectively inhibited the CE accumulation of J774 cells in dose-dependent manners. The inhibition was resulted from increase in free cholesterol but not from change in total cholesterol amount. The results suggest that GB acts on acyl-CoA: cholesterol acyltransferase (ACAT) and inhibits its activity. To confirm the possibility, we then tested GB by another assay system using ACAT that was solubilized from the cells and reconstituted into the liposome composed of phosphatidyl choline- cholesterol. GB inhibition was not so much effective as those by CI-976 and NTE-122, known ACAT inhibitors, but the inhibition was complete in the presence of 100 microM GB. Using cell homogenates of PMA-stimulated THP-1 cells, GB also inhibited the ACAT activity to the level of undifferentiated THP-1 cells. These results indicate that GB acts as ACAT inhibitor but the chemical structure is quite different from the conventional ACAT inhibitors, suggesting it can be a seed to generate potential ACAT inhibitors which do not exhibit toxicity in adrenal gland. |
| Glucocorticoids enhance the cholesterol side-chain cleavage activity of ovine adrenocortical mitochondria Picard-Hagen, N., H. Darbeida, et al. (1995), J Steroid Biochem Mol Biol 55(1): 57-65. Abstract: We have shown previously that a chronic treatment with glucocorticoids enhances cAMP- or ACTH-induced steroidogenesis of cultured ovine adrenocortical cells. This effect appears to involve a greater amount of cholesterol in mitochondria. Hence, the present study aimed to define the role of glucocorticoids in cholesterol metabolism by these cells. 2-day-old cultures were exposed to different hormones or inhibitors (10(-6) M ACTH, 10(-5) M metyrapone) for 28-48 h. At the end of the treatment period, the cells were stimulated for 2 h with 10(-3) M 8Br-cAMP, in the presence of 10(-3) M aminoglutethimide (in order to load mitochondria with cholesterol). Mitochondria were then isolated and incubated without or with 100 microM cholesterol either in the presence or absence of 10(-3) M CaCl2, or with 25 microM 22R-hydroxycholesterol. Mitochondria isolated from dexamethasone-treated cells produced consistently more pregnenolone than mitochondria from control cells, suggesting that at least part of the additional cholesterol present in these mitochondria was available for steroidogenesis. However, similar differences were obtained when mitochondria were incubated in the presence of exogenous cholesterol, both with or without calcium, or in the presence of 22R-hydroxycholesterol. Pregnenolone production under these latter conditions was much higher than when endogenous cholesterol was the only substrate. Conversely, metyrapone treatment of the cells resulted in lower production of pregnenolone from 22R-hydroxycholesterol by their mitochondria. Likewise ACTH treatment enhanced pregnenolone production by isolated mitochondria irrespective of the incubation conditions. These effects of dexamethasone and ACTH were not related to higher amounts of adrenodoxin, adrenodoxin reductase or cytochrome P450scc. These results indicate that exposure of ovine adrenocortical cells to glucocorticoids or ACTH enhances their steroidogenic potency not only by increasing the amount of cholesterol available for steroidogenesis but also by enhancing some step(s) involved in the transformation of cholesterol into pregnenolone. |
| Glucosamine/cholesterol a possible interaction Lassen, E. (2004), Ugeskr Laeger 166(44): 3957; author reply 3957-8. |
| Glucose and cholesterol elevations during thiazide therapy: intention-to-treat versus actual on-therapy experience Elliott, W. J. (1995), Am J Med 99(3): 261-9. Abstract: PURPOSE: This nonrandomized, parallel-group, prospective clinical series in consecutive patients was conducted to determine if the method of analysis of biochemical data collected in long-term treatment trials can explain the controversy regarding the effects of thiazides on plasma glucose or cholesterol. PATIENTS AND METHODS: Fasting serum glucose, potassium, and cholesterol levels were determined before therapy, and yearly thereafter (4.0 +/- 0.1 years) in 634 consecutive patients treated for more than 1 year with antihypertensive monotherapy. RESULTS: When the data were analyzed by the intention-to-treat paradigm (ignoring changes in therapy), glucose and cholesterol levels in the thiazide group were significantly higher (compared to baseline or to the other therapy group) only at year 1. When the data were analyzed by actual on-therapy experience (censoring patients when therapy is altered)--a more traditional way to examine side effects--these differences were significant for all 5 years studied. Even if as few as 8% of patients who changed therapies were included in an intention-to-treat analysis, these differences became nonsignificant. CONCLUSION: These comparisons not only indicate why a dichotomy might exist between clinical practice (analyzed by actual on-therapy experience) and randomized trials (analyzed by intention-to-treat methods), regarding biochemical changes in glucose and cholesterol during thiazide therapy, but also that, for secondary hypotheses, analyzing data by both methods of assignment is important. |
| Glucose and galactose regulate intestinal absorption of cholesterol Play, B., S. Salvini, et al. (2003), Biochem Biophys Res Commun 310(2): 446-51. Abstract: A dose-dependent increase in cholesterol absorption was induced by glucose addition (0-75 mM) to the apical medium of TC7 cells, a well-characterized clone of Caco-2. The uptake into the cells and the secretion rate to the basolateral space were both enhanced by glucose and galactose. This up-regulation was suppressed by SGLT1 inhibition but not by GLUT2 inhibition. Cholesterol cell uptake was significantly decreased by PMA and increased by chelerythrine, with more pronounced changes in the presence of hexoses. Thus, the involvement of a protein kinase C signalling pathway was evidenced in the regulation processes of intestinal cholesterol absorption. In the presence of antibodies directed to hSR-BI cholesterol absorption was reduced by 40% and glucose or galactose no longer enhanced it. We suggest that glucose or galactose, through an interaction with SGLT1, activates a protein kinase C pathway that regulates the activity of one of the intestinal cholesterol transporters, namely hSR-BI. |
| Glucose interaction magnifies atherosclerotic risk from cholesterol. Findings from the PDAY Study Cohen, H. W. and G. D. Sloop (2004), Atherosclerosis 172(1): 115-20. Abstract: OBJECTIVE: To examine whether the atherosclerotic risk from cholesterol is modified by serum glucose level. METHODS: Data from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study of 1530 individuals with complete autopsy data for total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and hemoglobin A1c (HbA1c) were examined with any atherosclerotic raised lesions (RL) >0% of surface area on any of three arterial specimens as the outcome. A TC/HDL-C ratio was categorized into quintiles and HbA1c was dichotomized as the upper quartile versus lower three quartiles. Odds ratios (ORs) were estimated from logistic regression models adjusting for sex, race, age, body mass index, smoking and hypertension. Results: An interaction product term of TC/HDL x HbA1c was statistically significant (P=0.006) despite adjustment for the main effects and other covariates. In models stratified by HbA1c, ORs (3.0, 3.9, 1.9, 3.5) for four upper quintiles of TC/HDL-C in the upper HbA1c stratum were substantially higher than those in the lower HbA1c stratum (0.9, 1.3, 1.4 and 1.1). Strata differences were even more striking in the subset of those > or =25 years old. CONCLUSIONS: These results suggest a synergistic interaction between glucose and cholesterol that magnifies the atherosclerotic risk associated with TC/HDL-C for those with higher HbA1c levels. |