| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| The prognostic characteristics of hypertensive left ventricular hypertrophy in a population with low prevalence of hypertension and low plasma cholesterol Chen, D., K. Wu, et al. (1993), Chin Med Sci J 8(4): 197-202. Abstract: One hundred and twenty-six hypertensive patients with ECG left ventricular hypertrophy (HT-LVH) were followed for 10 years to investigate the prognostic characteristics in a population with low prevalence of hypertension (2.93%) and low plasma cholesterol (4.26 +/- 0.91 mmol/L). A cohort of age-, sex-, region- and occupation-matched, randomized hypertensives without ECG-LVH (n = 163) and normotensives (n = 275) served as controls. HT-LVH was found to be associated with an increased risk of overall death, stroke mortality and cardiovascular mortality. The major cause of death in rural hypertensives with ECG-LVH was stroke (56.8%). After adjusting BP and BP stratification, no significant difference of stroke risk was found between patients with and without LVH, while cardiovascular risk persisted in patients with LVH plus ST segment depression. LVH per se did not appear to be an independent factor for stroke death. Higher stroke mortality in patients with LVH may be ascribed to the coexisting higher level of BP. Furthermore, after adjusting for the coexisting hypertension, ECG-LVH in terms of voltage only was not related to the prognosis of stroke and cardiovascular death. The mortality rate of stroke was not affected by plasma cholesterol levels, as the levels seen were in a low range. |
| The prognostic significance of cholesterol determination in the high-density lipoprotein fraction of blood donors Kurashvili, L. V. and A. S. Volkov (1993), Gematol Transfuziol 38(5): 39-40. Abstract: The relationships between concentrations of HDLP cholesterol and total cholesterol (TC), triglycerides in the blood serum; between HDLP cholesterol content and TC have been analyzed in the group of blood donors. Three variants were determined: 1) high TC, normal HDLP cholesterol, low HDLP proportion in TC 2) high TC, high HDLP cholesterol, normal HDLP/TC 3) normal TC, low HDLP cholesterol, low proportion of HDLP in TC. There were no correlations between HDLP cholesterol and triglycerides quantities in the blood serum. |
| The prognostic significance of total serum cholesterol in patients with Hodgkin's disease Muller, C. P., B. Trilling, et al. (1992), Cancer 69(4): 1042-6. Abstract: In the current retrospective study, the authors investigated the prognostic significance of total serum cholesterol values at the time of diagnosis in patients with Hodgkin's disease (n = 179). Cholesterol values were significantly lower in these patients than in age- and sex-matched controls. Subgroups with advanced stages (P less than or equal to 0.01), poor response to therapy (P = 0.04), and relapse after complete response (P = 0.026) (but not with bulky disease) had lower cholesterol values. By univariate analysis (cut-point value, 140 mg/dl), the 5-year survival rate was 2.5 times higher in patients with normal cholesterol values than in hypocholesterolemic patients (P less than 0.00009). Hypocholesterolemia was retained as an adverse, independent prognostic factor by multivariate Cox regression analysis. The authors concluded that total serum cholesterol values at the time of diagnosis may be a parameter with unrecognized significance in Hodgkin's disease. |
| The prognostic value of cholesterol levels in malnourished patients with esophageal carcinoma Faintuch, J., R. Cabraitz, et al. (1993), Nutr Hosp 8(6): 352-7. Abstract: A variety of clinical calculations, including serum cholesterol, have been used as parameters of prognostic value in surgical populations, but there are few studies aimed at patients with esophageal carcinoma. In a set of patients with established esophageal cancer, cholesterol and triglyceride levels were recorded, along with the following parameters: age, sex, body weight, serum albumin, total lymphocytes, and hemoglobin concentration. Manual grip strength was measured, along with delayed cutaneous hypersensitivity response, and the type of surgical treatment was distinguished (palliative versus radical). Total complications and postoperative hospitalisation time are the main indicators used in our study for the surgical results. Patients were divided into two groups: those with serum cholesterol levels over 150 mg/dl (Group I) and those under that figure (Group II). Most nutritional and functional values were lower in Group II patients, for whom the radical surgery rate was also lower, with greater postoperative morbidity. It was concluded that 1): Cholesterol depletion is associated with nutritional and immunological alterations and 2) post-surgical results are poorer in patients with levels below 150 mg/dl. |
| The pronase resistance of cholesterol-nucleating glycoproteins in human bile Zijlstra, A. I., G. D. Offner, et al. (1996), Gastroenterology 110(6): 1926-35. Abstract: BACKGROUND & AIMS: Many putative pronucleating proteins have been isolated from the biliary concanavalin A (con A)-binding fraction. The pronase resistance of the overall nucleating-promoting activity was almost never taken into consideration. The aim of this study was to identify the major pronase-resistant con A-binding glycoproteins. METHODS: Pronase-treated and -untreated con A-binding glycoproteins were separated on a Superose 12 gel permeation column (Pharmacia, Uppsala, Sweden) and tested in a crystal growth assay. Proteins were identified by amino-terminal sequencing. RESULTS: Con A-binding pronucleating activity eluted in two peaks on the Superose column. This activity was unaltered after pronase treatment. Activity peak I contained too little protein to allow amino-terminal sequencing. In activity peak II, the major pronase-resistant con A-binding glycoproteins were identified as alpha 1-antitrypsin and alpha 1-antichymotrypsin. The 130-kilodalton nucleation promoter was identified as aminopeptidase N, but the full pronase resistance of this protein, reported earlier, was not confirmed. Immunoabsorptive removal of alpha 1-antitrypsin and alpha 1-antichymotrypsin and immunopurification showed that only alpha 1-antichymotrypsin had pronucleating activity. CONCLUSIONS: The pronase resistance of the nucleating-promoting activity of the con A-binding glycoprotein fraction was confirmed. An important part of this activity could be attributed to alpha 1-antichymotrypsin. It is an acute-phase protein, as are many other pronucleating proteins, which might indicate a general mechanism of action in gallstone formation. |
| The protective action of ethanolic ginger (Zingiber officinale) extract in cholesterol fed rabbits Bhandari, U., J. N. Sharma, et al. (1998), J Ethnopharmacol 61(2): 167-71. Abstract: The effects of ethanolic extract of ginger (200 mg/kg, p.o.) were studied in cholesterol fed rabbits. The marked rise in serum and tissue cholesterol, serum triglycerides, serum lipoproteins and phospholipids that followed 10 weeks of cholesterol feeding, was significantly reduced by the ethanolic ginger extract and results were compared with gemfibrozil, a standard orally effective hypolipidaemic drug. The severity of aortic atherosclerosis as judged by gross grading was more marked in pathogenic, i.e. the hypercholesterolemic group, while animals receiving ginger extract along with cholesterol showed a lower degree of atherosclerosis. The results indicate that ginger is definitely an antihyperlipidaemic agent. |
| The protective effect of 17 beta-estradiol on vasomotor responses of aorta from cholesterol-fed rabbit is reduced by inhibitors of superoxide dismutase and catalase Ghanam, K., J. Javellaud, et al. (1998), Biochem Biophys Res Commun 249(3): 858-64. Abstract: The involvement of endogenous antioxidant enzymes in the protective effect of 17 beta-estradiol against hypercholesterolemia was evaluated on aorta from cholesterol-fed rabbits treated with estradiol. 17 beta-Estradiol, more potent than alpha-tocopherol, restored the acetylcholine-induced relaxation, which was impaired by cholesterol chow, and enhanced the vasorelaxation induced by sodium nitroprusside. Diethyldithiocarbamate (5 mM), a superoxide dismutase (SOD) inhibitor, reduced relaxation to acetylcholine down to the level obtained in cholesterol-fed rabbits not treated with estrogen. This inhibition was dose-dependently reversed by addition of exogenous SOD. Aminotriazole (5 mM), a catalase inhibitor, reduced slightly this response, which was not reversed by exogenous catalase. A similar concentration of diethyldithiocarbamate prevented the potentiation of response to sodium nitroprusside induced by estrogen, whereas aminotriazole had no effect. These results suggest that, on aorta from cholesterol-fed rabbit, superoxide dismutase and catalase are involved in the protective effect of estrogen on the vasomotor response to acetylcholine, but only superoxide dismutase participates in response to sodium nitroprusside. |
| The protective effects of tetrahydrocurcumin on oxidative stress in cholesterol-fed rabbits Naito, M., X. Wu, et al. (2002), J Atheroscler Thromb 9(5): 243-50. Abstract: Tetrahydrocurcumin (THC) is an antioxidative substance which is derived from curcumin by hydrogenation.Curcumin is the main component of turmeric and is responsible for the yellow color of curried foods.First, LDL derived from a normal human volunteer was incubated in the presence of an antioxidant with 10 microM CuSO(4) at 37 degrees C for 2 hours.All antioxidants tested (THC, curcumin, probucol, and alpha-tocopherol) dose-dependently (1-10 microM) inhibited the oxidative modification of LDL.Probucol was the strongest, followed by THC, alpha-tocopherol, and curcumin.Next, in order to evaluate the antioxidative activity of THC in vivo, we fed rabbits diets containing 1% cholesterol with or without 0.5% THC and examined their effects on oxidative stress and atherosclerosis.Animals were divided into two groups: the control group rabbits (n = 12) were fed a normal chow diet and the experimental group (n = 12) was fed a diet containing 0.5% THC for one week.Then, 1% cholesterol was added to the diets and the animals were allowed to feed further for either 6 (n = 4 for each group) or 12 weeks (n = 8 for each group).Although serum cholesterol levels rapidly increased after starting the high cholesterol diet, no difference was observed between the control and THC groups.TBARS formation in the absence of added copper ion was inhibited in the LDL separated from THC-treated animals compared with that from control animals.THC treatment tended to inhibit the area covered with atherosclerotic lesions compared with the control, although this was not significant (28.8 +/- 17.5% vs. 40.0 +/- 23.7%, p = 0.2).Formation of N(epsilon)-(hexanoyl) lysine, 4-hydroxynonenal and dityrosine in liver and kidney also had a tendency to be inhibited by THC treatment.Although free THC was not detected in serum and liver, THC was detected in samples treated with beta-glucuronidase and sulfatase, suggesting that THC is present as a conjugate with glucuronic acid or sulfate.In conclusion, the present results suggest that curcuminoids, particularly THC, which are contained in turmeric, may be useful as a functional food factor. |
| The quality of cholesterol tests from finger prick blood with physicians' office equipment. The need for rigid quality control and proper interaction Boerma, G. J. (1991), J Int Fed Clin Chem 3(4): 154-9. |
| The questionable wisdom of a low-fat diet and cholesterol reduction Atrens, D. M. (1994), Soc Sci Med 39(3): 433-47. Abstract: The prevalent wisdom that a low-fat diet and cholesterol reduction are essential to good cardiovascular health is coming under increased scrutiny. An examination of the foundations of this view suggests that in many respects it was ill-conceived from the outset and, with the accumulation of new evidence, it is becoming progressively less tenable. Cross-sectional, longitudinal and cross-cultural investigations have variously suggested that the relationship between dietary fat intake and death from heart disease is positive, negative and random. These data are incompatible with the view that dietary fat intake has any causal role in cardiovascular health. Although hypercholesterolemia is associated with increased liability to death from heart disease, it is as frequently associated with increased overall life expectancy as with decreased life expectancy. These findings are incompatible with labelling hypercholesterolemia an overall health hazard. Moreover, it is questionable if the cardiovascular liability associated with hypercholesterolemia is either causal or reversible. The complex relationships between diet, serum cholesterol, atherosclerosis and mortality and their interactions with genetic and environmental factors suggest that the effects of simple dietary prescriptions are unlikely to be predictable, let alone beneficial. These cautions are borne out by numerous studies which have shown that multifactorial primary intervention to lower cholesterol levels is as likely to increase death from cardiovascular causes as to decrease it. Importantly, the only significant overall effect of cholesterol-lowering intervention that has ever been shown is increased mortality. The stress and helplessness associated with misapprehensions as to the dangers of dietary fat and the asceticism inherent in the war on cholesterol have considerable implications for health practices. Recent research in behavioral immunology suggests that stress and helplessness are likely to compromise immunity and promote ill-health. |
| The rabbit 15-lipoxygenase preferentially oxygenates LDL cholesterol esters, and this reaction does not require vitamin E Belkner, J., H. Stender, et al. (1998), J Biol Chem 273(36): 23225-32. Abstract: The oxidation of low density lipoprotein (LDL) by mammalian 15-lipoxygenases (15-LOX) was implicated in early atherogenesis. We investigated the molecular mechanism of 15-LOX/LDL interaction and found that during short term incubations, LDL cholesterol esters are oxygenated preferentially by the enzyme. Even when the LDL particle was loaded with free linoleic acid, cholesteryl linoleate constituted the major LOX substrate. In contrast, only small amounts of free oxygenated fatty acid isomers were detected, and re-esterification of oxidized fatty acids into the LDL ester lipid fraction was ruled out. When LDL was depleted from alpha-tocopherol, specific oxygenation of the cholesterol esters was not prevented, and the product pattern was not altered. Similar results were obtained at low (LDL/LOX ratio of 1:1) and high LOX loading (LDL/LOX ratio of 1:10) of the LDL particle. During long term incubations (up to 24 h), a less specific product pattern was observed. However, when the hydroperoxy lipids formed by the 15-LOX were immediately reduced by the phospholipid hydroperoxide glutathione peroxidase, when the reaction was carried out with vitamin E-depleted LDL, or when the assay sample was diluted, the specific pattern of oxygenation products was retained over a long period of time. These data suggest that mammalian 15-LOX preferentially oxidize LDL cholesterol esters, forming a specific pattern of oxygenation products. During long term incubations, free radical-mediated secondary reactions, which lead to a more unspecific product pattern, may become increasingly important. These secondary reactions appear to be suppressed when the hydroperoxy lipids formed are immediately reduced, when alpha-tocopherol-depleted LDL was used, or when the incubation sample was diluted. It may be concluded that 15-LOX-initiated LDL oxidation constitutes a dual-type oxygenase reaction with an initial enzymatic and a subsequent nonenzymatic phase. The biological relevance of this dual-type reaction for atherogenesis will be discussed. |
| The raft-promoting property of virion-associated cholesterol, but not the presence of virion-associated Brij 98 rafts, is a determinant of human immunodeficiency virus type 1 infectivity Campbell, S., K. Gaus, et al. (2004), J Virol 78(19): 10556-65. Abstract: Lipid rafts are enriched in cholesterol and sphingomyelin and are isolated on the basis of insolubility in detergents, such as Brij 98 and Triton X-100. Recent work by Holm et al. has shown that rafts insoluble in Brig 98 can be found in human immunodeficiency virus type 1 (HIV-1) virus-like particles, although it is not known whether raft-like structures are present in authentic HIV-1 and it is unclear whether a virion-associated raft-like structure is required for HIV replication. Independently, it was previously reported that virion-associated cholesterol is critical for HIV-1 infectivity, although the specific requirement of virion cholesterol in HIV-1 was not examined. In the present study, we have demonstrated that infectious wild-type HIV-1 contains Brij 98 rafts but only minimal amounts of Triton X-100 rafts. To directly assess the functional requirement of virion-associated rafts and various features of cholesterol on HIV-1 replication, we replaced virion cholesterol with exogenous cholesterol analogues that have demonstrated either raft-promoting or -inhibiting capacity in model membranes. We observed that variable concentrations of exogenous analogues are required to replace a defined amount of virion-associated cholesterol, showing that structurally diverse cholesterol analogues have various affinities toward HIV-1. We found that replacement of 50% of virion cholesterol with these exogenous cholesterol analogues did not eliminate the presence of Brij 98 rafts in HIV-1. However, the infectivity levels of the lipid-modified HIV-1s directly correlate with the raft-promoting capacities of these cholesterol analogues. Our data provide the first direct assessment of virion-associated Brij 98 rafts in retroviral replication and illustrate the importance of the raft-promoting property of virion-associated cholesterol in HIV-1 replication. |
| The ras/cholesterol connection: implications for ras oncogenicity Cox, A. D. and C. J. Der (1992), Crit Rev Oncog 3(4): 365-400. Abstract: The frequent detection of mutated ras genes in a variety of cancers (reviewed in Bos, 1988, 1989; Der, 1988) suggests that ras makes a significant contribution to human malignancies (reviewed in Barbacid, 1987; Lacal and Tronick, 1988; Der, 1989). While the role of ras in malignancy is unclear, it is well-established that the association of ras protein with the inner surface of the plasma membrane is critical for triggering ras oncogenicity. The trafficking of ras proteins to the plasma membrane requires a series of three closely linked posttranslational modifications (farnesylation, proteolysis, and carboxymethylation) that are signaled by the consensus C-terminal CAAX motif present on all ras proteins (reviewed in Rine and Kim, 1990; Gibbs, 1991; Der and Cox, 1991). THe recent discovery that an essential intermediate in cholesterol biosynthesis, the isoprenoid farnesol, is attached covalently to ras proteins has stimulated considerable interest and has identified important new directions for studies of ras function. First, understanding the role of farnesol-linked interactions with the plasma membrane may identify the biochemical basis for the oncogenic actions of ras proteins. Second, the enzymes that catalyze the processing steps that trigger membrane association of ras proteins are promising targets for pharmacologic intervention in ras-associated disease. In this review, we summarize our current knowledge of the role of posttranslational processing in ras-membrane interaction and transforming activity. We also provide an update of recent studies addressing the role of isoprenoid modification in the function of ras and of other isoprenoid-modified proteins (reviewed in James and Olson, 1990; Glomset et al., 1990; Maltese, 1990). While this role is likely to be specific for each protein, ras proteins can provide an excellent prototype for understanding the role of isoprenoid modification in protein function. |
| The rate of sphingomyelin synthesis de novo is influenced by the level of cholesterol in cultured human skin fibroblasts Leppimaki, P., R. Kronqvist, et al. (1998), Biochem J 335 (Pt 2): 285-91. Abstract: Plasma membrane sphingomyelin (SM) is known to affect the cellular distribution of cholesterol. The aim of this work was to examine how SM homoeostasis in human skin fibroblasts is affected by alterations in the level of cholesterol in the cell. The cellular cholesterol level was decreased by exposing cells to 2-hydroxypropyl-beta-cyclodextrin, and increased by exposing cells to cholesterol-methyl-beta-cyclodextrin inclusion complexes. A lowering of the cellular unesterified cholesterol content by 20% was shown to increase the incorporation of 14Cpalmitic acid into SM by 70%. Subsequently, the cellular SM mass was shown to be increased (24% increase after a 24 h period). Since l-cycloserine completely abolished the increased incorporation of 14Cpalmitic acid into SM in cholesterol-depleted cells, we concluded that the de novo synthesis of the sphingosine backbone of SM was activated in cholesterol-depleted cells. This conclusion was further verified by performing a cell-free assay of serine C-palmitoyltransferase (SPT) in cholesterol-depleted cells, which showed that the activity of the enzyme was increased by 30% after cholesterol depletion. Most of the newly synthesized SM in cholesterol-depleted cells was susceptible to degradation by sphingomyelinase, indicating that it was transported efficiently to the cell surface. Loading of fibroblasts with cholesterol had essentially the opposite effects on SM homoeostasis to those of cholesterol depletion, i.e. 20-30% decreased incorporation of 14Cpalmitic acid into SM and decreased activity of SPT. The results of this study show that cellular cholesterol levels have marked effects on the homoeostasis of SM. |
| The rate of transbilayer movement of erythrocyte membrane cholesterol is correlated with sodium-lithium countertransport Muriana, F. J., C. Montilla, et al. (1996), Life Sci 59(23): 1945-9. Abstract: Hypertension is associated with some abnormalities in cell membrane structure, including an impaired distribution of cholesterol into the monolayers of erythrocyte membrane. Transbilayer movement of membrane cholesterol modulates the formation of these structural cholesterol domains. We tested whether the rate of cholesterol movement may influence on the erythrocyte Na(+)-Li+ countertransport, that is a marker of human essential hypertension. In single regression analysis, the half-time for the decrease in specific radioactivity of cholestenone (inverse of membrane cholesterol transbilayer movement) was negatively related to the erythrocyte cation flux mediated by Na(+)-Li+ countertransport (r = -0.8983, P < 0.0001 for control subjects; r = -0.8191, P < 0.005 for normocholesterolaemic hypertensive patients; r = -0.7664, P < 0.005 for hypercholesterolaemic hypertensive patients). These data suggest that changes in the transbilayer movement of membrane cholesterol interfere with the main cation transport system which is implicated in the pathophysiology of essential hypertension. This also provides a new link between kinetic cholesterol pools and cell membrane functions. |
| The ratio of non-oxidized/oxidized forms of apolipoprotein A-I can affect cholesterol efflux from human skin fibroblasts mediated by high density lipoprotein Sigalov, A. B., I. E. Petrichenko, et al. (1997), Eur J Clin Chem Clin Biochem 35(5): 395-6. |
| The ratio of waist-to-hip circumference, plasma insulin level, and glucose intolerance as independent predictors of the HDL2 cholesterol level in older adults Ostlund, R. E., Jr., M. Staten, et al. (1990), N Engl J Med 322(4): 229-34. Abstract: High plasma levels of HDL2, a subfraction of high-density lipoprotein (HDL) cholesterol, are associated with a reduced risk of coronary heart disease. To investigate the characteristics related to HDL2 cholesterol levels, we measured lipoprotein levels and several metabolic and anthropometric variables in 146 healthy subjects (77 men and 69 women) in the seventh decade of life. The level of HDL2 cholesterol was inversely correlated with the ratio of the waist-to-hip circumference (r = -0.335 for men; r = -0.370 for women; P less than 0.01) and the plasma insulin level (r = -0.400 for men; r = -0.398 for women; P less than 0.001). In a multiple regression model including both sexes, 41 percent of the variance in the HDL2 level was explained by the combined effect of the waist-to-hip ratio (P less than 0.0001), the plasma insulin level (P = 0.0003), and the degree of glucose tolerance indicated by the integrated area under the plasma glucose curve after an oral glucose-tolerance test (P = 0.05). The body-mass index, total percentage of body fat, maximal oxygen uptake, diet, and sex were not significant predictors of the HDL2 level when added to this model, whereas the original variables remained significant predictors. The HDL2 cholesterol level in subjects at the 25th percentile for waist-to-hip ratio was 153 percent of that in subjects at the 75th percentile. We conclude that HDL2 levels are inversely correlated with truncal fat, plasma insulin levels, and the presence of glucose intolerance and are not independently associated with sex or total body fat. |
| The rationale for lowering serum cholesterol levels in American children Gidding, S. S. (1993), Am J Dis Child 147(4): 386-92. Abstract: The pediatric approach to the primary prevention of coronary artery disease in adults remains controversial. Measurement and intervention to lower serum cholesterol levels have been advocated recently in a selected group of American children by the Expert Panel on Blood Cholesterol Levels in Children and Adolescents of the National Cholesterol Education Program. This article reviews the clinical and scientific data contributing to the controversy surrounding cholesterol in American children. Arguments in favor of and opposed to an aggressive approach to identifying American children with elevated serum cholesterol levels are presented. The rationale for a selective screening approach is demonstrated. |
| The reduction of cardiovascular events after a myocardial infarct in patients with normal cholesterol levels Hartley, H. (1996), Rev Clin Esp 196(4 Monografico): 43-6. |
| The Reflotron Total Cholesterol assay in heparinized venous and capillary blood Boerma, G. J., T. L. Liem, et al. (1990), J Clin Chem Clin Biochem 28(4): 255-8. Abstract: We recently evaluated the Reflotron Total Cholesterol dry chemistry assay by examining the calibration and the accuracy of the assay in serum, whole venous EDTA-blood and capillary EDTA blood. We now describe a study on the analysis in heparinized venous and heparinized finger stick blood. Cholesterol assays in venous serum and plasma, and in finger capillary blood and plasma (all with heparin) were compared. Finger capillary blood was obtained in two ways: 1. in heparinized capillaries; 2. in a Becton Dickinson microtainer that could be centrifuged for separation of the plasma. Venous blood was obtained in plain tubes (for serum) and heparinized tubes to obtain venous whole blood and also venous plasma. We did not, on average, find large differences between the concentrations of cholesterol in the various materials. The regression equations for finger capillary whole blood and venous whole blood however show higher slopes than the others. Inaccuracy due to the sampling technique appears to be no greater for finger capillary samples than for venous samples. |