| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XIII. Relationship of serum cholesterol to retinopathy and hard exudate Klein, B. E., S. E. Moss, et al. (1991), Ophthalmology 98(8): 1261-5. Abstract: Serum total and high-density lipoprotein (HDL) cholesterol were measured in a sample of individuals examined between 1984 and 1986 for the Wisconsin Epidemiologic Study of Diabetic Retinopathy. There was a significant trend for increasing severity of diabetic retinopathy and of retinal hard exudate with increasing cholesterol in insulin-using persons. Cholesterol levels were not related to the severity of either ocular condition in older-onset patients. High-density lipoprotein-cholesterol was unrelated to the severity of either lesion. In multiple logistic regression analyses, cholesterol was not a significant factor in describing the severity of retinopathy in any group but was a significant factor in describing the severity of retinal hard exudate. Glycosylated hemoglobin and diastolic blood pressure were significant descriptors of the severity of retinopathy in younger-onset patients in these multivariate analyses. Diastolic blood pressure added significantly to explaining the severity of hard exudate in older-onset insulin users. These data support the current management strategies for diabetes, which include control of level of glycemia, blood pressure, and blood lipids. |
| The yield of cholesterol screening in an urban black community Russell, N. K., D. M. Becker, et al. (1991), Am J Public Health 81(4): 448-51. Abstract: BACKGROUND: While the distribution of cholesterol levels have been well studied in the general population, little is known about cholesterol and other cardiovascular disease risk factors in screenings held in an urban Black community. This study was designed to determine the yield of cholesterol screening in this community. METHODS: Screening took place in eight community sites. Serum total cholesterol was measured using a rapid capillary technique. Blood pressure was taken according to national guidelines and the average of two to three measurements were used. Standard interviews were used to determine the presence of cardiovascular risk factors by history. RESULTS: Of the 562 individuals screened, 44.9 percent had cholesterol levels requiring referral for follow-up care. Of those with total cholesterol greater than or equal to 6.21 mmol/L, 66.4 percent were previously undetected and more than half also had blood pressure levels greater than or equal to 140/90 mmHg on screening; 45 percent of all participants had blood pressure greater than or equal to 140/90 on screenings. Of those with a history of elevated total cholesterol levels, none had levels below 5.17 mmol/L at the time of screening. CONCLUSIONS: Multiple risk factors are highly prevalent in the urban Black community during cholesterol screening programs. Findings suggest the need for cholesterol programs incorporating blood pressure screening in the urban Black community. |
| Thematic review series: brain Lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal Dietschy, J. M. and S. D. Turley (2004), J Lipid Res 45(8): 1375-97. Abstract: Unesterified cholesterol is an essential structural component of the plasma membrane of every cell. During evolution, this membrane came to play an additional, highly specialized role in the central nervous system (CNS) as the major architectural component of compact myelin. As a consequence, in the human the mean concentration of unesterified cholesterol in the CNS is higher than in any other tissue (approximately 23 mg/g). Furthermore, even though the CNS accounts for only 2.1% of body weight, it contains 23% of the sterol present in the whole body pool. In all animals, most growth and differentiation of the CNS occurs in the first few weeks or years after birth, and the cholesterol required for this growth apparently comes exclusively from de novo synthesis. Currently, there is no evidence for the net transfer of sterol from the blood into the brain or spinal cord. In adults, the rate of synthesis exceeds the need for new structural sterol, so that net movement of cholesterol out of the CNS must take place. At least two pathways are used for this excretory process, one of which involves the formation of 24(S)-hydroxycholesterol. Whether or not changes in the plasma cholesterol concentration alter sterol metabolism in the CNS or whether such changes affect cognitive function in the brain or the incidence of dementia remain uncertain at this time. |
| Thematic review series: the pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy: part I Steinberg, D. (2004), J Lipid Res 45(9): 1583-93. Abstract: This is the first of a series of reviews of the controversy that swirled around the "lipid hypothesis" of atherosclerosis for so many years. Today, in the era of the statins, there is no longer any doubt about the value of decreasing blood cholesterol levels. In fact, "the lower the better" is the position of many clinicians. However, getting to this point has been a long uphill battle marked by heated debate and sometimes violent disagreement. The history of this controversy is worth telling for its own sake and because remembering it may help us avoid similar mistakes in the future. The history of this controversy is worth telling for its own sake and because remembering it may help us avoid similar mistakes in the future. |
| Thematic review series: the pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy: part II: the early evidence linking hypercholesterolemia to coronary disease in humans Steinberg, D. (2005), J Lipid Res 46(2): 179-90. Abstract: The first in this series of historical reviews dealt with the pioneering animal model work of Anitschkow, implicating blood cholesterol in the pathogenesis of atherosclerosis, and the pivotally important work of Gofman, providing evidence that lipoprotein-bound cholesterol was a major factor in the human disease. This second installment reviews the early lines of evidence linking hypercholesterolemia in humans to the progression of atherosclerosis and the risk of coronary heart disease. The argument is made that by 1970, the evidence was already strong enough to justify intervention to lower blood cholesterol levels if all the available lines of evidence had been taken into account. Yet, it would be almost two decades before lowering blood cholesterol levels became a national public health goal. Some of the reasons the "cholesterol controversy" continued in the face of powerful evidence supporting intervention are discussed. |
| Theoretical considerations of what regulates low-density-lipoprotein and high-density-lipoprotein cholesterol Dietschy, J. M. (1997), Am J Clin Nutr 65(5 Suppl): 1581S-1589S. Abstract: The concentration of cholesterol carried in low-density-lipoprotein cholesterol (LDL-C) is predominantly dictated by metabolic events occurring in liver. LDL-C is derived from the intravascular metabolism of very-low-density lipoproteins, and, in every species, this lipoprotein particle is predominantly cleared by liver through receptor-dependent mechanisms. In addition to cholesterol absorbed from the diet, sterol is also synthesized within the body and this synthesis occurs predominantly in extrahepatic organs. When the amount of cholesterol input into the body is increased, there is expansion of the pools of sterol within liver cells and down-regulation of the receptors responsible for clearing LDL-C from the bloodstream. As a consequence, the concentration of LDL-C in plasma increases. When dietary cholesterol intake is kept constant, some long-chain saturated fatty acids further suppress hepatic LDL receptor activity whereas several unsaturated fatty acids have the opposite effect. These regulatory events are apparently articulated through the ability of these fatty acids to shift intracellular cholesterol between a regulatory and a storage pool. High-density lipoproteins, in contrast, function primarily to move excess cholesterol from the extrahepatic organs to liver for excretion. Although the concentration of high-density-lipoprotein cholesterol in the plasma may be influenced by the rate of apolipoprotein A-I production or the activity of cholesterol ester transfer protein, it is less clear whether dietary long-chain fatty acids have any effect on these processes. The regulatory effects of the saturated and unsaturated long-chain fatty acids on LDL-C concentrations can be shown in a variety of experimental animals and also in humans. |
| Theories and problems related to direct determination of lipoprotein cholesterol Sugiuchi, H. (1999), Rinsho Byori Suppl 109: 126-39. |
| Therapeutic abilities of thiol compounds in the restoration of methylmercury-inhibited cholesterol and triglycerides of the rat's central nervous system Sood, P. P. and S. D. Vinay (1991), Arch Environ Contam Toxicol 21(2): 212-7. Abstract: The present study was basically designed to gain an insight into the alterations in the levels of cholesterol and triglycerides in various neuroanatomical areas of the rat under the influence of different doses and durations of methylmercury chloride (MMC), N-acetyl-DL-homocysteine thiolactone (NAHT), and glutathione (GSH) applications. The study showed insignificant alterations in the levels of both the metabolites after two days of drug and antagonist application. The rest of the animal groups exhibited a progressive inhibition of both the metabolites in all the CNS areas with increasing dose and duration of drug treatment. The antagonists, NAHT and GSH, were able to cause a recovery in both the metabolites in most of the groups, yet in no case were absolute control values achieved. It was concluded that antagonists alone are not helpful in mobilizing the mercury as well as producing a recovery in the biochemical lesions induced in the CNS. |
| Therapeutic impact of statin therapy in patients with low HDL cholesterol Gotto, A. M., Jr. (1999), Curr Atheroscler Rep 1(1): 1-2. |
| Therapeutic interventions targeted at the augmentation of reverse cholesterol transport Toth, P. P. and M. H. Davidson (2004), Curr Opin Cardiol 19(4): 374-9. Abstract: PURPOSE OF REVIEW: Serum high-density lipoproteins (HDLs) and reverse cholesterol transport (RCT) are important therapeutic targets in the management of atherosclerotic disease. This review summarizes the pathway of RCT and the currently available means by which investigators are attempting to modulate HDL levels and increase rates of RCT. RECENT FINDINGS: Low levels of HDL are commonly encountered in patients with atherosclerotic disease. HDLs mediate a substantial number of antiatherogenic effects along blood vessel walls. One of the most important of these antiatherogenic mechanisms is RCT, a series of reactions by which HDL is able to facilitate the net translocation of cholesterol from peripheral cells to the liver for excretion. There is scientific evidence supporting the concept of RCT in both animals and humans. To facilitate RCT, it is important that therapeutic effort be made to raise serum levels of HDL. Statins, fibrates, niacin, thiazolidinediones, and various combinations of these drugs all raise HDL levels. However, in many high-risk patients with established atherosclerotic disease, the elevations in HDL achieved with these medications are frequently inadequate. Newer agents designed to raise HDL and promote RCT are currently being developed, including infusible bioengineered HDL, edible HDL composed of D-amino acids, and agents capable of inhibiting cholesterol ester transfer protein, among others. SUMMARY: Established therapies for raising HDL can be effective either as monotherapy or when used in combination. Newer strategies are being developed to exploit more specifically the capacity of HDL to drive RCT and either prevent or reverse the course of atherosclerotic disease. |
| Therapeutic modulation of cellular cholesterol efflux Wang, N. and A. R. Tall (2001), Curr Atheroscler Rep 3(5): 345-7. |
| Therapeutic targets in cardiovascular disease: a case for high-density lipoprotein cholesterol Black, D. M. (2003), Am J Cardiol 91(7A): 40E-43E. |
| Therapy and prevention of coronary heart diseases through lowering of the serum cholesterol levels; third consensus 'Cholesterol'. Consensus Working Group, CBO Simoons, M. L. and A. F. Casparie (1998), Ned Tijdschr Geneeskd 142(38): 2096-101. Abstract: For the second time the consensus text for lipid lowering therapy is revised. In angiographic studies it was shown that a decrease in the total cholesterol as well as the low-density lipoprotein cholesterol level results in a reduction of the progression of vascular disease. Furthermore, intervention trials demonstrated that therapy with cholesterol synthesis inhibitors reduces not only both the cardiovascular and total mortality, but also other manifestations of coronary heart disease (CHD). Hypercholesterolaemia is treated with a low-fat diet and normalisation of the weight. For individuals, this might result in a reduction of the risk for myocardial infarction or death and for the population in a decrease of the mean serum cholesterol concentration and the incidence of CHD. The indication for drug therapy is founded on the expected effectiveness to reduce the incidence of (new manifestations of) CHD, which is related to the level of the absolute risk of vascular disease. In persons without known vascular diseases this risk is calculated from the total and high-density lipoprotein cholesterol ratio, age, sex, blood pressure, diabetes mellitus, and smoking. Treatment with cholesterol synthesis inhibitors must be considered in (a) patients with familial hypercholesterolaemia, (b) all patients with a history of myocardial infarction or other symptomatic vascular disease with a total cholesterol concentration above 5.0 mmol/l and a life expectancy of at least five years; (c) persons with a combination of diabetes mellitus, hypertension, hypercholesterolaemia and high risk for development of CHD, rising from 25% per 10 years at the age of 40 years to 35-40% per 10 years at the age of 70 years, with a life expectancy of at least five years. If these guidelines are followed, the upper limit of the calculated cost-effectiveness is about Dfl. 40,000 per life year gained. The working group judges this reasonable in comparison with other therapeutic interventions in the Netherlands. |
| Thermal history alters cholesterol effect on transition of 1-palmitoyl-2-linoleoyl phosphatidylcholine Morrow, M. R., P. J. Davis, et al. (1996), Biophys J 71(6): 3207-14. Abstract: The effect of cholesterol on the bilayer phase behavior of heteroacid phosphatidylcholines with one unsaturated fatty acid depends on the nature of the unsaturated chain. Previous differential scanning calorimetry (DSC) studies showed that 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine (16:0-18:2 PC) had a broad, weak transition at about -18 degrees C, which was effectively eliminated by less than 15 mol% cholesterol. Phospholipids with greater and lesser degrees of unsaturation displayed stronger phase transitions and less sensitivity to cholesterol. In this work, deuterium nuclear magnetic resonance has been used to examine the phase behavior of 1-perdeuteriopalmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine (16:0-18:2 PC-d31) alone, and with 15 mol % cholesterol. The behavior is found to be sensitive to sample thermal history. Moderately fast cooling (1 degree/h) results in a continuous phase change from a fluid to an ordered phase in the pure lipid. Under similar cooling conditions, the sample containing cholesterol displays increased chain order and a continuous phase change with no apparent isothermal transition. However, when these systems are cooled at a reduced rate (0.3 degree/h), the continuous phase change is pre-empted by a sharp transition into a more ordered phase that gives a deuterium spectrum having intensity at a value of the quadrupole-splitting characteristic of a rigid lattice system. In the pure lipid, this transition effectively coincides with the center of the continuous phase change. Addition of 15 mol % cholesterol lowers the temperature of this sharp transition by about 3 degrees C. These observations provide some insights into the behavior of this system seen using differential scanning calorimetry. Results of deuteron transverse relaxation measurements under these conditions are also reported. |
| Thermal stability of Torpedo californica acetylcholine receptor in a cholesterol lipid environment Perez-Ramirez, B. (1994), Mol Cell Biochem 132(2): 91-9. Abstract: Controlled heating of acetylcholine receptor (AChR) vesicles inactivates the alpha-bungarotoxin (alpha-Bgtx) binding sites with a T50 (temperature at which 50% of the initial capacity to bind alpha-Bgtx remains) of 60 +/- 0.2 degrees C. The same value was obtained for receptor reconstituted in lipid vesicles from Torpedo electroplax where the % mol composition of cholesterol to phospholipid was 30. However, when the reconstitution was carried out in dioleoylphosphatidylcholine (DOPC), dioleoylphosphatidic acid (DOPA) vesicles (3:1 molar ratio), T50 of the curves decreased to 56 +/- 0.2 degrees C and no carbamylcholine stimulated 22Na+ flux was detected. Inclusion of cholesterol in the DOPC-DOPA vesicles increased the toxin binding site stability. The maximal T50 of the toxin binding curves was 63 +/- 0.1 degrees C when the % mol cholesterol/mol DOPC:DOPA in the vesicles was 33. Under these conditions AChR was able to translocate ions, a property that was lost upon heating at 46 degrees C. Preincubation of AChR in the presence of d-tubocurarine, tetracaine or procaine did not affect T50 values of toxin binding. However, a slight increment in thermal stability was found when the receptor was preincubated in the presence of carbamylcholine. The results show that cholesterol requirements for protecting against thermal inactivation of toxin binding and ion gating properties are different and the carbamylcholine-bound receptor may have a different conformation. |
| Thermodynamic characteristics of mixed monolayers of amphotericin B and cholesterol Sykora, J. C., W. C. Neely, et al. (2004), J Colloid Interface Sci 276(1): 60-7. Abstract: Surface-pressure (Pi) and surface-area isotherms as a function of surface area were measured for monolayers of amphotericin B (AmB) and cholesterol mixtures at the air/water interface at 10, 20, and 30 degrees C. When chloroform/methanol was used as a spreading solvent, the Pi-A isotherms of the mixed monolayers exhibited characteristic transitions from the gas to liquid-expanded, then liquid-condensed, and finally the solid state. The expanding effect in monolayers was accompanied by a large Pi-A hysteresis and a positive excess of free energy of mixing at high Pi. At low Pi, a condensing effect was observed with the most significant deviation from ideality occurring at a mole fraction of AmB (XAmB) of 0.67. Free energy calculations revealed a condensing effect at low Pi and an expanding effect at high Pi except at 30 degrees C, where a condensing effect was observed for XAmB around 0.33. In contrast, when 2-propanol/water was used as spreading solvent, the mixed monolayers at 20 degrees C exhibited Pi-A isotherms which obey van der Waals equation of state, with no visible transitions, low hysteresis, a condensing effect, and a negative free energy of mixing. The most stable monolayers were produced from mixtures of AmB and cholesterol with a 2:1 stoichiometry. |
| Thermodynamics and dynamics of phosphatidylcholine-cholesterol mixed model membranes in the liquid crystalline state: effects of water Shin, Y. K., D. E. Budil, et al. (1993), Biophys J 65(3): 1283-94. Abstract: A method for obtaining the thermodynamic activity of each membrane component in phosphatidylcholine (PC)/cholesterol mixtures, that is based upon ESR spin labeling is examined. The thermodynamic activity coefficients, gamma PC and gamma chol, for the PC and cholesterol, respectively, are obtained from the measured orientational order parameters, SPC and S(chol), as a function of cholesterol content for a spin-labeled PC and the sterol-type cholestane spin probe (CSL), respectively, and the effects of water concentration are also considered. At water content of 24 weight%, the thermodynamics of DMPC/cholesterol/water mixtures in the liquid-crystalline state may be treated as a two-component solution ignoring the water, but at lower water content the role of water is important, especially at lower cholesterol concentrations. At lower water content (17 wt%), gamma chol decreases with increasing cholesterol content which implies aggregation. However, at higher water content (24 wt%), gamma chol is found initially to increase as a function of cholesterol content before decreasing at higher cholesterol content. This implies a favorable accommodation for the cholesterol in the membrane at high water and low cholesterol content. Good thermodynamic consistency according to the Gibbs-Duhem equation was obtained for gamma PC and gamma chol at 24 wt% water. The availability of gamma chol (and gamma PC) as a function of cholesterol concentration permits the estimate of the boundary for phase separation. The rotational diffusion coefficients of the labeled PC and of CSL were also obtained from the ESR spectra. A previously proposed universal relation for the perpendicular component of the rotational diffusion tensor, R perpendicular, for CSL in PC/cholesterol mixtures (i.e., R perpendicular = R0 perpendicular exp(-AS2chol/RT)) is confirmed. A change in composition of cholesterol or of water for DMPC/cholesterol/water mixtures affects R perpendicular only through the dependence of S(chol) on the composition. In particular, the amount of water affects the membrane fluidity, monitored by R perpendicular for CSL, solely by the structural changes it induces in the membrane for the compositions studied. Rotational diffusion for the labeled PC is found to be more complex, most likely due to the combined action of the internal modes of motion of the flexible chain and of the overall molecular reorientation. |
| Thermodynamics of transfer of cholesterol from gel to fluid phases of phospholipid bilayers Spink, C. H., S. Manley, et al. (1996), Biochim Biophys Acta 1279(2): 190-6. Abstract: The partitioning of cholesterol between gel and fluid phases of model membrane bilayers has been studied by differential scanning calorimetry. The partition coefficients and thermodynamics of transfer between phases of dimyristoyl-, dipalmitoyl-, distearoyl- and diarachidoylphosphatidylcholines were determined using a regular solution model for the partitioning process. The partition coefficient, which is the ratio of cholesterol in fluid to gel phase lipid, varies from 2.3 to 8.4 as the acyl chain length increases from the C14 to the C20 bilayer and determined at the phase transition temperature. The enthalpies of transfer increase from -46 to +32 kcal/mol as the chain length increases, and there is a compensating increase in the entropy of transfer. The results are interpreted in terms of a disruption of gel phase lipid by the cholesterol, which for the thinner bilayers is increased because the cholesterol molecule spans across the two leafs of the bilayer. At bilayer thicknesses between 18 and 19 carbons, the cholesterol can fit into one-half of the gel phase bilayer, and the enthalpy becomes positive, suggesting less disruption in the gel phase relative to the thinner bilayers. The data support the interpretation that cholesterol does mediate fluidity by acting to disrupt gel domains of lipid. |
| Thermofiltration in hypercholesterolemia treatment: analysis of removal and posttreatment cholesterol recovery Malchesky, P. S., A. Werynski, et al. (1990), J Clin Apher 5(3): 145-50. Abstract: Thermofiltration, a system of membrane plasmapheresis for LDL apheresis, is used to treat patients with refractory hyperlipidemia. In this system, the separated plasma is warmed to or above physiologic temperature, filtered with a membrane filter, and returned to the patient on-line. Plasma infusion products are not required. In this study one calculated plasma volume was treated weekly, biweekly, or monthly in patients classified as type II hypercholesterolemic. Reduction and sieving of lipoproteins were evaluated. The reduction ratios of high-density lipoprotein cholesterol (HDLc) and low-density lipoprotein cholesterol (LDLc) were 0.30 +/- 0.06 and 0.58 +/- 0.05, respectively (mean +/- S.D.). Sieving coefficients of the plasma filter for HDLc and LDLc were 0.62 +/- 0.12 and 0.03 +/- 0.02, respectively (mean +/- S.D. of 31 treatments). To evaluate the posttreatment recovery the apparent fractional catabolic rates (FCRa) for total cholesterol and LDLc were calculated. FCRa was 0.151 +/- 0.06 and 0.148 +/- 0.06 day-1 for total cholesterol and LDLc, respectively. The ratio of the posttreatment concentration on the seventh day to the concentration immediately pretreatment was found to be significantly higher for HDLc than for LDLc, 0.92 +/- 0.8 vs. 0.77 +/- 0.1 (mean +/- S.D.), due to faster HDLc recovery. The ratio of LDLc/HDLc was lowered for up to 2 weeks after the treatments. |
| Thermofiltration in hypercholesterolemia: analysis of removal and posttreatment cholesterol recovery Malchesky, P. S., H. Nomura, et al. (1990), Prog Clin Biol Res 337: 201-4. |