| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| The North Coast Cholesterol Check Campaign. Results of the first three years of a large-scale public screening programme van Beurden, E. K., R. James, et al. (1991), Med J Aust 154(6): 385-91. Abstract: Although cardiovascular disease (CVD) mortality has been declining, CVD is still the major cause of death in Australia and an elevated blood cholesterol level is considered a major contributor. Large-scale community-based screening programmes in other countries have demonstrated that a population approach can be effective in reducing cholesterol levels and the risk of CVD. The North Coast Cholesterol Check Campaign is the largest community-based cholesterol intervention programme in Australia. Since its inception in 1987, 13% of the Region's adult population (over 29,000 persons) have been screened. About half had elevated blood cholesterol levels (greater than or equal to 5.5 mmol/L) and were given dietary counselling to reduce fat intake. Mean blood cholesterol levels were significantly reduced between initial screening and follow-up in all three years. Reductions, after correction for regression, were 8%, 6% and 10%, respectively, in 1987, 1988 and 1989. There was also a consistent and significant 1.5% to 2% reduction in weight. All age/sex cohorts above age 35 were well represented each year although self-referral did bias both initial and follow-up samples towards women and the aged. Nevertheless, the proportion of men and men in their middle age increased during the three years. The proportion of participants with elevated cholesterol levels increased in each successive year while the proportion of participants who complied with referrals to visit their general practitioner and with requests to return for follow-up decreased. Over half of the North Coast adult population has now had a cholesterol test. The rate of increase in testing since the inception of the Campaign has been approximately four times the national rate. North Coast general practitioners have played a major role by catering for the increased community demand for cholesterol testing and by providing an effective referral service for the Campaign. Community-based screening programmes in Australia can detect and beneficially influence large numbers of persons with elevated cholesterol levels. Interventions like the North Coast Cholesterol Check Campaign, when conducted over a number of years, do attract higher risk and less compliant people.(ABSTRACT TRUNCATED AT 250 WORDS) |
| The novel cholesterol-lowering drug SR-12813 inhibits cholesterol synthesis via an increased degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase Berkhout, T. A., H. M. Simon, et al. (1996), J Biol Chem 271(24): 14376-82. Abstract: SR-12813 (tetra-ethyl 2-(3,5-di-tert-butyl-4-hydroxyphenyl)ethenyl-1, 1-bisphosphonate) lowers plasma cholesterol in five species. In this paper we investigate the underlying mechanism using Hep G2 cells. SR-12813 inhibited incorporation of tritiated water into cholesterol with an IC50 of 1.2 microM but had no effect on fatty acid synthesis. Furthermore, SR-12813 reduced cellular 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity with an IC50 of 0.85 microM. The inhibition of HMG-CoA reductase activity was rapid with a T1/2 of 10 min. After a 16-h incubation with SR-12813, mRNA levels of HMG-CoA reductase and low density lipoprotein (LDL) receptor were increased. The increased expression of LDL receptor translated into a higher LDL uptake, which can explain the primary hypocholesterolemic effect of SR-12813 in vivo. Western blot analysis indicated that the amount of HMG-CoA reductase protein rapidly decreased in the presence of SR-12813. Pulse-chase experiments with 35Smethionine showed that the T1/2 of HMG-CoA reductase degradation decreased in the presence of SR-12813 from 90 to 20 min. Pre-incubation with 50 microM of lovastatin did not prevent the effects of SR-12813 on HMG-CoA reductase degradation, indicating that the compound does not need mevalonate-derived regulators for its action. It is concluded that SR-12813 inhibits cholesterol synthesis mainly by an enhanced degradation of HMG-CoA reductase. |
| The novel compound NO-1886 elevates plasma high-density lipoprotein cholesterol levels in hamsters and rabbits by increasing lipoprotein lipase without any effect on cholesteryl ester transfer protein activity Tsutsumi, K., Y. Inoue, et al. (1997), Metabolism 46(3): 257-60. Abstract: Lipoprotein lipase (LPL) and cholesteryl ester transfer protein (CETP) are determinants of high-density lipoprotein (HDL) cholesterol concentrations in plasma. We have previously reported that NO-1886, by increasing LPL activity, causes elevation of HDL cholesterol levels in rats. In the present study, we studied the effect of NO-1886 on CETP activity in experimental animals. Since previous reports suggest that rats may lack CETP, we examined hamsters and rabbits, as well as rats. We found that NO-1886 increased LPL activity, resulting in elevation of plasma HDL cholesterol in all three animals. We confirmed that rats lack CETP and that both hamsters and rabbits have high CETP activity. NO-1886 had no effect on CETP activity in hamsters and rabbits. These results demonstrate that the compound NO-1886 elevates HDL cholesterol in experimental animals by selectively increasing LPL activity without any effect on CETP. Animals with low CETP and high LPL activities appear to be more sensitive to NO-1886 than those with high CETP and low LPL activities. |
| The novel compound NO-1886 increases lipoprotein lipase activity with resulting elevation of high density lipoprotein cholesterol, and long-term administration inhibits atherogenesis in the coronary arteries of rats with experimental atherosclerosis Tsutsumi, K., Y. Inoue, et al. (1993), J Clin Invest 92(1): 411-7. Abstract: We have discovered a novel compound, NO-1886, which possesses a powerful lipoprotein lipase (LPL) activity-increasing action. Administration of NO-1886 increased LPL activity in the postheparin plasma, adipose tissue, and myocardium of rats, and produced a reduction in plasma triglyceride levels with concomitant elevation of HDL cholesterol levels. Administration of NO-1886 increased LPL enzyme mass in postheparin plasma and mRNA activity in epididymal adipose tissue, and it was concluded that the mode of action of this compound is stimulation of tissue LPL synthesis. We also conducted long-term studies to assess the impact of increases in LPL activity and HDL levels on the development of atherosclerotic lesions in rats. Administration of NO-1886 for as long as 90 d significantly decreased the degree of atherosclerotic changes in the coronary arteries of vitamin D2-treated, cholesterol-fed rats. Statistical analysis indicated that increased concentration of HDL is the factor contributing mostly to the prevention of coronary artery sclerosis. In summary, the results of our study indicate that compound NO-1886 increases LPL activity, causing an elevation in HDL levels, and that long-term administration of NO-1886 to rats with experimental atherosclerosis provides significant protection against the development of coronary artery lesions. |
| The N-terminal globular domain and the first class A amphipathic helix of apolipoprotein A-I are important for lecithin:cholesterol acyltransferase activation and the maturation of high density lipoprotein in vivo Scott, B. R., D. C. McManus, et al. (2001), J Biol Chem 276(52): 48716-24. Abstract: To investigate the role of the N terminus of apolipoprotein A-I (apoA-I) in the maturation of high density lipoproteins (HDL), two N-terminal mutants with deletions of residues 1-43 and 1-65 (referred to as Delta 1-43 and Delta 1-65 apoA-I) were studied. In vitro, these deletions had little effect on cellular cholesterol efflux from macrophages but LCAT activation was reduced by 50 and 70% for the Delta 1-43 and Delta 1-65 apoA-I mutants, respectively, relative to wild-type (Wt) apoA-I. To further define the role of the N terminus of apoA-I in HDL maturation, we constructed recombinant adenoviruses containing Wt apoA-I and two similar mutants with deletions of residues 7-43 and 7-65 (referred to as Delta 7-43 and Delta 7-65 apoA-I, respectively). Residues 1-6 were not removed in these mutants to allow proper cleavage of the pro-sequence in vivo. Following injection of these adenoviruses into apoA-I-deficient mice, plasma concentrations of both Delta 7-43 and Delta 7-65 apoA-I were reduced 4-fold relative to Wt apoA-I. The N-terminal deletion mutants, in particular Delta 7-65 apoA-I, were associated with greater proportions of pre beta-HDL and accumulated fewer HDL cholesteryl esters relative to Wt apoA-I. Wt and Delta 7-43 apoA-I formed predominantly alpha-migrating and spherical HDL, whereas Delta 7-65 apoA-I formed only pre beta-HDL of discoidal morphology. This demonstrates that deletion of the first class A amphipathic alpha-helix has a profound additive effect in vivo over the deletion of the globular domain alone (amino acids 1-43) indicating its important role in the production of mature alpha-migrating HDL. In summary, the combined in vitro and in vivo studies demonstrate a role for the N terminus of apoA-I in lecithin:cholesterol acyltransferase activation and the requirement of the first class A amphipathic alpha-helix for the maturation of HDL in vivo. |
| The one-stop coronary cholesterol clinic: a multidisciplinary approach to implementing evidence-based treatment Giles, P. D., S. Ramachandran, et al. (1996), Postgrad Med J 72(854): 744-8. Abstract: We describe a 'one-stop' cholesterol clinic implementing a regime based on the Scandinavian Simvastatin Survival Study (4S) in patients with established coronary heart disease in a district general hospital. The clinic has been established in collaboration with the cardiac rehabilitation centre. It was commissioned as an audit project by the purchasing authority, Walsall Health, a need having been shown in a previous audit. In the new clinic, audit is inbuilt, rather than being carried out as a separate retrospective exercise, and undertaken prospectively for all patients. Central to this is a database, used for routine correspondence and administration, as well as monitoring outcome. This application of information technology has improved clinical practice. Attendance at the clinic has been excellent. Half the consultations have resulted in therapeutic interventions, many of which may otherwise have been missed. Over 50% of patients were eligible for lipid-lowering medication under the protocol. Cholesterol targets based on 4S were achieved but with much lower drug doses, which may have major cost implications. Cholesterol levels measured within 24 hours of admission for myocardial infarction were poor predictors of results obtained after convalescence. After the clinic visit, most patients were taking aspirin plus one or two other secondary prevention treatments. Guidelines have been issued to primary care. Future plans for audit links with general practitioners, integration of the metabolic and cardiological assessment of survivors of myocardial infarction, and for long-term monitoring of clinical events in treated patients are discussed. |
| The optimum serum cholesterol level. Preface Hayashi, Y. and H. Nakamura (1991), Rinsho Byori 39(5): 481-2. Abstract: The purpose of this forum is set to discuss about serum total cholesterol, especially. (1) Which values should be targetted for the start of therapy, drug administration? (2) Which upper and lower limited values are important for prophylactic purpose of coronary insufficiency? (3) Are there any changes seen in long term determined values of Japanese? etc. Various interesting facts motivated us to held this forum such as increase in total cholesterol due to high cholesterol foods in take among Japanese, difference in values, which has been employed as a group reference values in laboratories, and so-called desirable values. Twenty or thirty years ago, normal values of 130-230 mg/dl were decided with an agreement. However, these days, groups with mean values reaching to 250 mg/dl are reported. On the other hand, patients with coronary arteriosclerosis increase steadily and it is required strongly to popularize the desirable values for prophylactic purpose. As all presenters are experts in this field, we expect to get the conclusion around the subjects. |
| The origins and roles of cholesterol and fatty acids in the fetus Woollett, L. A. (2001), Curr Opin Lipidol 12(3): 305-12. Abstract: The fetus grows at a rate that is unparalleled by that at any other stage of life. Significant amounts of cholesterol and fatty acids are required to maintain membrane growth. Recent studies have shown that these lipids are also necessary mediators of processes that are essential for proper development. |
| The oxidation of cholesterol in the yolk of selective traditional Chinese egg products Yang, S. C. and K. H. Chen (2001), Poult Sci 80(3): 370-5. Abstract: The yolks of traditional chicken egg products (Tiedan, Ludan, and Chayedan) and duck egg products (raw and cooked Xiandan, immersed and coated Pidan) were subjected to moisture, lipid, and thiobarbituric acid (TBA) determinations as well as cholesterol and cholesterol oxidation products (COP) analysis. The main COP detected for these egg products included 20-hydroxycholesterol and 7beta-hydroxycholesterol, other types of COP were not detected. The contents of COP formed in traditional egg products varied, depending upon the types of egg products. The cholesterol oxidation ratio for traditional Chinese chicken egg products ranged from 1.14 to 1.75%, whereas that for traditional Chinese duck egg products ranged from 1.18 to 1.90%. Those traditional egg products that required pickling in salt or alkaline, cooking, hot air drying, and exposure to oxygen and heat all produced COP. |
| The oxygenation of cholesterol esters by the reticulocyte lipoxygenase Belkner, J., R. Wiesner, et al. (1991), FEBS Lett 279(1): 110-4. Abstract: The arachidonate 15-lipoxygenase from rabbit reticulocytes oxygenates cholesterol esters containing polyenoic fatty acids. Cholesterol esterified with saturated fatty acids is not oxygenated. The structures of the oxygenation products formed from various cholesterol esters have been identified by high pressure liquid chromatography, UV-spectroscopy and gas chromatography/mass spectroscopy. Oxygenated cholesterol esters have been detected in atherosclerotic plaques of human aortas. |
| The ozonation of cholesterol: separation and identification of 2,4-dinitrophenylhydrazine derivatization products of 3 beta-hydroxy-5-oxo-5,6-secocholestan-6-al Wang, K., E. Bermudez, et al. (1993), Steroids 58(5): 225-9. Abstract: The ozonation products of cholesterol, which are of interest as possible biomarkers of O3 exposure, were studied by derivatization with 2,4-dinitrophenylhydrazine (DNPH). The DNPH derivatization of 3 beta-hydroxy-5-oxo-5,6-secocholestan-6-al (2) produces the expected trans (3b) and cis (3c) derivatives of 3 beta-hydroxy-5-oxo-5,6-secocholestan-6-al, and the unexpected DNPH derivative of 3,5-dihydroxy-B-norcholestane-6-carboxaldehyde (3a). The structures of 3a, 3b, and 3c were identified with 1H nuclear magnetic resonance (NMR), 13C NMR, DEPT, COSY, and H-C correlation two-dimensional NMR techniques, and by comparison with the spectra of known compounds. A possible mechanism involving an enamine functionality is proposed for the formation of 3a. The ratio of 3a/(3b + 3c) depends on the concentration of acid used and the reaction time. |
| The paraoxonase-1 codon 192 polymorphism is associated with fasting total cholesterol and LDL-cholesterol concentrations only in postmenopausal women. The REGICOR study Senti, M., M. Tomas, et al. (2002), Clin Chem Lab Med 40(7): 677-83. Abstract: Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL)-linked enzyme which appears to protect low-density lipoproteins (LDL) from oxidation. PON1 activity is associated with variation at the PON1 gene locus, specifically the common amino acid polymorphism at codon 192, for which the Q192 allele specifies low activity and the R192 allele specifies high activity. We investigated the association between the PON1 codon 192 polymorphism and fasting concentrations of glucose, lipids, lipoproteins and PON1 activity in 1380 subjects (724 men and 656 women). Several anthropometric and environmental factors were assessed in the present study. The PON1 Q192 allele frequency was 0.70 and 0.68 in men and women, respectively. In women, but not in men, significant associations were found between the PON1 codon 192 genotype and both total and LDL-cholesterol (p=0.004 and p=0.008, respectively), and subgroup analysis indicated that this relationship was predominant in postmenopausal women. Specifically, the Q192 allele was associated with increased total and LDL-cholesterol concentrations. Furthermore, these lipoprotein variables were higher among postmenopausal women with Q192/Q192 and Q192/R192 genotypes than in premenopausal women with the same genotypes (p<0.001). The findings suggest a gender-specific lipoprotein-genotype association with PON1 codon 192 genotypes in this study sample. |
| The participation of sterol carrier protein2 in cholesterol esterification in rat adrenal microsomes Oeda, T., A. Hirai, et al. (1990), Endocrinol Jpn 37(2): 285-92. Abstract: The effect of sterol carrier protein2 (SCP2) purified from rat liver on the formation of cholesterol esters by acyl-CoA: cholesterol acyl-transferase (ACAT: EC 2.3.1.26) in rat adrenal microsomes was studied. The rate of incorporation of 1-14Coleoyl-CoA into cholesteryl oleate was determined in the presence or absence of exogenously added cholesterol or SCP2, or both. The addition of SCP2 had no effect on the formation of cholesterol esters from endogenous cholesterol by ACAT in rat adrenal microsomes. In contrast, the formation of cholesterol esters from exogenous cholesterol by ACAT was dose-dependently increased by the addition of SCP2. These experiments showed that SCP2 had an enhancing effect on cholesterol esterification by ACAT in rat adrenal microsomes most likely by modulating the availability of exogenous cholesterol and that SCP2 may participate in the formation of cholesterol esters in the rat adrenal gland. |
| The pathogenesis of cholesterol gallstones a review Strasberg, S. M. (1998), J Gastrointest Surg 2(2): 109-25. |
| The pathogenesis of polychromatic cholesterol crystals in the anterior chamber Kennedy, C. J. (1996), Aust N Z J Ophthalmol 24(3): 267-73. Abstract: PURPOSE: Polychromatic cholesterol crystal of the anterior chamber are an interesting and unusual finding. This paper examines the different pathogenetic mechanisms leading to the formation of these clinically detectable anterior chamber crystals. METHODS: Three aetiologically different cases which exhibited polychromatic crystals in the anterior chamber were reviewed. Aqueous samples were examined by wet field microscopy in all cases and additionally by electron microscopy in one of these. One enucleated globe was available for histopathology. RESULTS: Typical highly refringent cholesterol crystals were identified in the aqueous of all cases. In the first case, the cholesterol crystals developed following the breakdown of vitreous and anterior chamber haemorrhage. In the second case, the cholesterol appeared to derive from the subretinal fluid of a chronic total retinal detachment in the absence of any intraocular haemorrhage. The cholesterol crystals of the final case resulted from phacolysis and were associated with a marked neutrophil response and the presence of proteinaceous crystals consistent with the crystallins. CONCLUSIONS: Anterior chamber cholesterolosis is a secondary phenomenon that always occurs as a result of an ocular disease process. Although the prognosis is dismal for chronically diseased eyes displaying cholesterol crystals in the anterior chamber, the prognosis for eyes with phacolysis may be excellent. |
| The pathway of return of cholesterol Moulin, P. and F. Berthezene (1994), Ann Med Interne (Paris) 145(4): 247-52. |
| The pattern of surfactant cholesterol during vertebrate evolution and development: does ontogeny recapitulate phylogeny? Orgeig, S., C. B. Daniels, et al. (2003), Reprod Fertil Dev 15(1-2): 55-73. Abstract: Pulmonary surfactant is a complex mixture of phospholipids (PLs), neutral lipids and proteins that lines the inner surface of the lung. Here it modulates surface tension, thereby increasing lung compliance and preventing the transudation of fluid. In humans, pulmonary surfactant is comprised of approximately 80% PLs, 12% neutral lipids and 8% protein. In most eutherian (i.e. placental) mammals, cholesterol (Chol) comprises approximately 8-10% by weight or 14-20 mol% of both alveolar and lamellar body surfactant. It is regarded as an integral component of pulmonary surfactant, yet few studies have concentrated on its function or control. The lipid composition is highly conserved within the vertebrates, except that surfactant of teleost fish is dominated by cholesterol, whereas tetrapod pulmonary surfactant contains a high proportion of disaturated phospholipids (DSPs). The primitive Australian dipnoan lungfish Neoceratodus forsterii demonstrates a 'fish-type' surfactant profile, whereas the other derived dipnoans demonstrate a surfactant profile similar to that of tetrapods. Homology of the surfactant proteins within the vertebrates points to a single evolutionary origin for the system and indicates that fish surfactant is a 'protosurfactant'. Among the terrestrial tetrapods, the relative proportions of DSPs and cholesterol vary in response to lung structure, habitat and body temperature (Tb), but not in relation to phylogeny. The cholesterol content of surfactant is elevated in species with simple saccular lungs or in aquatic species or in species with low Tb. The DSP content is highest in complex lungs, particularly of aquatic species or species with high Tb. Cholesterol is controlled separately from the PL component in surfactant. For example, in heterothermic mammals (i.e. mammals that vary their body temperature), the relative amount of cholesterol increases in cold animals. The rapid changes in the Chol to PL ratio in response to various physiological stimuli suggest that these two components have different turnover rates and may be packaged and processed differently. In mammals, the pulmonary surfactant system develops towards the end of gestation and is characterized by an increase in the saturation of PLs in lung washings and the appearance of surfactant proteins in amniotic fluid. In general, the pattern of surfactant development is highly conserved among the amniotes. This conservation of process is demonstrated by an increase in the amount and saturation of the surfactant PLs in the final stages (>75%) of development. Although the ratios of surfactant components (Chol, PL and DSP) are remarkably similar at the time of hatching/birth, the relative timing of the maturation of the lipid profiles differs dramatically between species. The uniformity of composition between species, despite differences in lung morphology, birthing strategy and relationship to each other, implies that the ratios are critical for the onset of pulmonary ventilation. The differences in the timing, on the other hand, appear to relate primarily to birthing strategy and the onset of air breathing. As the amount of cholesterol relative to the phospholipids is highly elevated in immature lungs, the pattern of cholesterol during development and evolution represents an example of ontogeny recapitulating phylogeny. The fact that cholesterol is an important component of respiratory structures that are primitive, when they are not in use or developing in an embryo, demonstrates that this substance has important and exciting roles in surfactant. These roles still remain to be explored. |
| The pediatric part of the National Cholesterol Education Program--one of the important aspects of modern nutrition of children and adolescents Stozicky, F. (1993), Cesk Pediatr 48(11): 678-9. |
| The periodic flashes of E. Brunwald: lowering cholesterol levels in subjects with myocardial infarction and normal cholesterol levels Prati, P. L. (1997), G Ital Cardiol 27(1): 76-8. |
| The permeability and the effect of acyl-chain length for phospholipid bilayers containing cholesterol: theory and experiment Corvera, E., O. G. Mouritsen, et al. (1992), Biochim Biophys Acta 1107(2): 261-70. Abstract: The model of Cruzeiro-Hansson et al. (Biochim. Biophys. Acta (1989) 979, 166-1176) for lipid-cholesterol bilayers at low cholesterol concentrations is used to predict the thermodynamic properties and the passive ion permeability of lipid bilayers as a function of acyl-chain length and cholesterol concentration. Numerical simulations based on the Monte Carlo method are used to determine the equilibrium state of the system near the main gel-fluid phase transition. The permeability is calculated using an ansatz which relates the passive permeability to the amount of interfaces formed in the bilayer when cholesterol is present. The model predicts at low cholesterol contents an increase in the membrane permeability in the transition region both for increasing cholesterol concentration and for decreasing chain length at a given value of the reduced temperature. This is in contrast to the case of lipid bilayers containing high cholesterol concentrations where the cholesterol strongly suppresses the permeability. Experimental results for the Na+ permeability of C15PC and DPPC (C16PC) bilayers containing cholesterol are presented which confirm the theoretical predictions at low cholesterol concentrations. |