| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Mammalian acyl-CoA:cholesterol acyltransferases Buhman, K. F., M. Accad, et al. (2000), Biochim Biophys Acta 1529(1-3): 142-54. Abstract: Cholesterol, the chief sterol found in vertebrates, exists both as a free sterol and as a component of cholesterol esters, which are synthesized by acyl-CoA:cholesterol acyltransferase (ACAT) enzymes. Considerable knowledge concerning cholesterol ester metabolism has accumulated during the past century. However, rapid advances have occurred in the past 7 years since the cloning of an ACAT gene, including the discovery that two ACATs function in mammalian biology. A clearer picture of the functions of ACAT enzymes in cellular cholesterol metabolism and physiologic processes is now emerging. These insights may have relevance for the development of ACAT inhibitors for treating hypercholesterolemia or atherosclerosis in humans. |
| Mammalian bufadienolide is synthesized from cholesterol in the adrenal cortex by a pathway that Is independent of cholesterol side-chain cleavage Dmitrieva, R. I., A. Y. Bagrov, et al. (2000), Hypertension 36(3): 442-8. Abstract: An increasing body of evidence suggests that an endogenous mammalian bufadienolide (BD) may be involved in the regulation of Na(+),K(+)-ATPase activity and the pathogenesis of arterial hypertension. We developed a purification scheme for marinobufagenin (MBG), an amphibian cardiotonic BD, and applied it to purify and characterize material in human plasma, culture medium conditioned by Y-1 adrenocortical cells, and rat adrenal tissue. MBG immunoreactivity purified from plasma and measured by ELISA showed important similarities (chromatography and antibody cross-reactivity) to material secreted into cell culture medium by Y-1 cells. This observation indicates that circulating mammalian BD may have an adrenocortical origin. Release of mammalian BD from adrenocortical cells grown in the absence of exogenous cholesterol was reduced by treatment of cultures with mevastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Supplementation of the serum and cholesterol-free cell culture medium with the LDL fraction of human plasma increased the production of MBG material in the presence of mevastatin, supporting its origin from cholesterol. We used Y-1 cell lines transfected with genes shown to inhibit steroidogenesis through cholesterol side-chain cleavage (Y-1/DAX and Y-1/RIAB) to investigate the dependence of MBG biosynthesis on side-chain cleavage. Our results indicate that the mammalian BD is synthesized in the adrenal cortex from cholesterol and shares important similarities with the amphibian BD MBG, that its biosynthesis is independent of transfer of cholesterol to the side-chain cleavage enzyme complex mediated by steroidogenic acute regulatory protein, and that neither cAMP nor protein kinase A appears to be a critical component of the pathway controlling its biosynthesis. |
| Management of cholesterol gallstones--are there alternatives to cholecystectomy? Halevy, J. (1990), J Intern Med 228(1): 5-8. |
| Management of cholesterol granulomas of the petrous apex based on clinical and radiologic evaluation Mosnier, I., F. Cyna-Gorse, et al. (2002), Otol Neurotol 23(4): 522-8. Abstract: OBJECTIVE: The purpose of this study was to analyze the imaging characteristics of 12 cholesterol granulomas as a function of their clinical symptoms. The results of the different surgical approaches and the management of these lesions are discussed. STUDY DESIGN: Retrospective case review. SETTING: Five tertiary referral centers. PATIENTS: Twelve patients managed for a cholesterol granuloma of the petrous apex. INTERVENTIONS: All patients were evaluated via computed tomography and magnetic resonance imaging. Eight patients required surgical drainage: through a conservative approach in seven patients (infralabyrinthine, n = 5; infracochlear, n = 2) and a transotic approach in one patient. Clinical and radiologic follow-up without surgery was the mode of treatment for four patients. The mean follow-up period was 18 months for patients who underwent operations and ranged from 6 months to 10 years for patients without operations. RESULTS: Four patterns of clinical symptoms were noted: retrocochlear signs by an involvement of the internal auditory meatus (n = 8), headaches by a traction of the dura (n = 4), serous otitis media by a compression of the eustachian tube (n = 2), and asymptomatic lesions with no involvement of the adjacent structures (n = 2). Hearing and facial functions were preserved in all the cases treated by a noninvasive procedure. No recurrence or complication was reported in the patients who underwent operations. None of the noninvasively treated patients with cholesterol granulomas showed significant enlargement on follow-up imaging. CONCLUSION: Clinical manifestations of cholesterol granulomas depend on their anatomic location and the involvement of the adjacent structures. Aggressive lesions in patients with residual hearing can be drained via an infralabyrinthine or an infracochlear approach with minimal morbidity. Follow-up must be preferred for patients with nonaggressive lesions. Although magnetic resonance imaging provides a specific diagnosis tool for cholesterol granulomas, computed tomography is essential for an accurate evaluation of the location of the cyst and choice of the surgical procedure. |
| Management of high blood cholesterol Smith, M. D. and W. F. McGhan (1996), Bus Health 14(4): 67-8, 70, 72-4. |
| Management of high blood cholesterol by primary care physicians: diffusion of the National Cholesterol Education Program Adult Treatment Panel guidelines Shea, S., D. H. Gemson, et al. (1990), J Gen Intern Med 5(4): 327-34. Abstract: OBJECTIVE: To study knowledge of and adherence to National Cholesterol Education Program Adult Treatment Panel (ATP) guidelines among primary care physicians. DESIGN: Cross-sectional telephone survey. SETTING: New York State primary care practitioners; survey conducted November 1988-January 1989. PARTICIPANTS: Physicians in general practice, family practice, internal medicine without subspecialty, and cardiology who reported greater than or equal to 10 hours/week of clinical practice (n = 329; response rate = 63%). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: While 84% of physicians had heard of the ATP guidelines, gaps in knowledge and inconsistencies between ATP recommendations and clinical practices were found. Although the ATP guidelines recommend six months of dietary therapy before starting drug treatment, 41% of physicians would initiate drug treatment for a healthy 40-year-old man with total cholesterol of 7.8 mmol/L (300 mg/dl) either at the initial visit or after one month of lipid-lowering diet. Multivariate analysis of a 24-item knowledge scale revealed that less knowledgeable physicians were more likely to be older, lack board certification, and have a specialty other than cardiology (p less than 0.01). Less knowledgeable physicians were also more likely to consider drug company literature and drug company representatives very useful sources of information about cholesterol (p = 0.02). CONCLUSION: This study suggests that hard-to-reach physician groups may require special efforts to communicate consensus guidelines of major importance to clinical practice. |
| Management of low HDL cholesterol Barter, P. J. (1995), Aust Fam Physician 24(11): 2066-9, 2072, 2074. Abstract: A low concentration of high density lipoprotein (HDL) cholesterol is a powerful predictor of premature coronary heart disease (CHD). This paper presents an overview of the function of HDLs and their relationship with CHD. It summarises conditions in which HDL cholesterol levels are low and discusses the evidence that increasing HDL cholesterol levels may be beneficial. It outlines measures which raise the level of HDL cholesterol and concludes with some practical suggestions for the management of low HDL states. |
| Management of multiple cholesterol embolization syndrome--a case report Kawakami, Y., K. Hirose, et al. (1990), Angiology 41(3): 248-52. Abstract: A sixty-two-year-old man who underwent coronary angiography and received acute thrombolytic and anticoagulant therapy for acute myocardial infarction developed multisystemic injury, including renal insufficiency and cutaneous manifestations. Fundoscopic examination and skin biopsy specimen led to the diagnosis of multiple cholesterol embolization syndrome (MCES). Discontinuation of anticoagulants and administration of hemostatic (carbazochrome, tranexamic acid, reptilase, and vitamin K) and antihyperlipidemic (cholestyramine and probucol) drugs resulted in temporary improvement of cutaneous and renal disorders and extended survival for about one year. Besides severe aortic atherosclerosis, postmortem examination revealed numerous cholesterol emboli to multiple organs. MCES is a rare but serious complication of left heart catheterization and anticoagulant therapy, and the optimal treatment remains to be established. The authors suggest here that the above-mentioned therapy might be effective for management of MCES. |
| Management of persons with high risk of coronary heart disease but low serum low-density lipoprotein cholesterol Case, C. C., T. A. Jacobson, et al. (2003), Am J Cardiol 91(9): 1134-6. |
| Management of selected lipid abnormalities. Hypertriglyceridemia, low HDL cholesterol, lipoprotein(a), in thyroid and renal diseases, and post-transplantation Rader, D. J. and S. Rosas (2000), Med Clin North Am 84(1): 43-61. Abstract: Although the focus in treating lipid disorders is on reducing LDL cholesterol levels, triglycerides, HDL cholesterol, and Lp(a) are all independent risk factors that can be used clinically to assess cardiovascular risk. Decisions to initiate drug therapy for LDL cholesterol reduction may be influenced by levels of these other lipoprotein fractions. Data supporting intervention to modify these factors is less abundant than for LDL cholesterol reduction, but in certain circumstances drug therapy targeted at triglycerides or HDL cholesterol may be appropriate. Patients with nephrotic syndrome and end-stage renal disease are at particularly high risk for the development of cardiovascular disease and should be treated aggressively for lipid disorders. Finally, solid organ transplant recipients are almost always hyperlipidemic, and appropriate therapy could reduce cardiovascular events. |
| Management of selected lipid abnormalities: hypertriglyceridemia, isolated low HDL-cholesterol, lipoprotein(a), and lipid abnormalities in renal diseases and following solid organ transplantation Rosas, S., P. Szapary, et al. (2003), Cardiol Clin 21(3): 377-92. Abstract: Although the focus in treating lipid disorders is on reducing LDL-C levels, additional lipid-related independent risk factors, such as TG, HDL-C, and Lp(a) levels, should be used clinically to assess cardiovascular risk. Decisions to initiate drug therapy for LDL-C reduction may be influenced by levels of these other lipoprotein fractions. Data supporting intervention to modify these factors are less abundant than for LDL-C reduction, but in certain circumstances. drug therapy targeted at TGs or HDL-C may be appropriate. Patients who have nephrotic syndrome and end-stage renal disease are at particularly high risk for the development of CVD and should be treated aggressively for their lipid disorders. Finally, solid organ transplant recipients are almost always hyperlipidemic and appropriate therapy could reduce cardiovascular events. |
| Management of the patient with a low HDL-cholesterol Leighton, R. F. (1990), Clin Cardiol 13(8): 521-32. Abstract: While there is epidemiologic evidence linking a low high-density lipoprotein (HDL) cholesterol level with coronary disease events, and interventions that raise HDL while lowering low-density lipoprotein (LDL) cholesterol levels have been shown to reduce subsequent coronary events, there are no studies showing benefit from raising HDL when a low HDL level is the sole lipid abnormality. HDL is thought to play a key role in reverse cholesterol transport, removing lipids from peripheral cells, but the precise role of HDL in cholesterol metabolism is not understood. The measurement of HDL levels has not been well standardized. Reliance on ratios relating HDL to LDL or to total cholesterol may be misleading in the management of patients. It has not been shown that measuring HDL subfractions or apolipoprotein levels is superior to measuring total HDL levels in predicting coronary risk. HDL levels may be raised by hygienic measures such as smoking cessation and exercise, but a considerable amount of exercise over a long period of time is required. Alcohol consumption and weight loss through dieting inconsistently raise HDL. Estrogen therapy raises and progestational agents lower HDL. Certain beta-blocking drugs lower HDL levels. For the patient with an isolated low HDL level the hygienic measures may be advised, but drug therapy such as nicotinic acid or gem-fibrozil should be prescribed only when low HDL is accompanied by elevated LDL levels that are unresponsive to diet and hygienic measures. |
| Managing cholesterol in children and adolescents Saizow, R. B. (1991), J Okla State Med Assoc 84(4): 153-9. Abstract: Reduction of elevated cholesterol in adults decreases risk of coronary heart disease. Despite evidence of atherosclerosis development at early ages and studies confirming cholesterol tracking from childhood into adulthood, many physicians are reluctant to screen for hypercholesterolemia in children and adolescents. Targeting screening only to children of high-risk families fails to identify as many as two-thirds of at-risk children. Dietary modification and medical therapy appears safe and effective in this age group. Recommendations for screening of all children by age 5 are made, with guidelines for managing elevated cholesterol. |
| Managing cholesterol with plant stanol esters Fulayter, J. (2002), J Ren Nutr 12(3): E1-2. |
| Managing dyslipidemia in Turkey: suggested guidelines for a population characterized by low levels of high density lipoprotein cholesterol Bersot, T. P., K. E. Palaoglu, et al. (2002), Anadolu Kardiyol Derg 2(4): 315-22. Abstract: Based on data from the Turkish Society of Cardiology and others, it is established that Turks have a high prevalence of coronary heart disease (CHD). Several risk factors are prominent in Turks: dyslipidemia, cigarette smoking, and hypertension. The dyslipidemia is unique in that very low levels of HDL-C and typically "normal" LDL-C levels characterize the Turkish population. The low HDL-C levels appear to be genetic in origin and are largely independent of high triglyceride levels (73% of Turkish men and 94% of women with HDL-C <40 mg/dl have triglyceride levels <150 mg/dl; only 15% of men and 3% of women with HDL-C <40 mg/dl have triglyceride levels >200 mg/dl). HDL-C levels are 10-15% mg/dl lower in Turks than seen in the United States or western Europe. Low HDL-C is a major risk factor; CHD risk increases 2-4% for every 1 mg/dl decrease in HDL-C levels. Existing treatment guidelines focus on plasma LDL-C levels and fail to take into account the continuous increase in CHD risk that occurs as HDL-C levels decrease. However, several studies show that patients with CHD or free of CHD but with multiple risk factors, who have low HDL-C and near optimal LDL-C, benefit very significantly from lipid-lowering therapy. Many of these patients with low HDL-C levels do not qualify for drug therapy based on existing guidelines. Therefore, we believe that unique guidelines must be developed to guide the treatment of low HDL-C Turkish patients. We suggest that treatment based on both the LDL-C level and the total cholesterol/HDL-C (TC/HDL-C) ratio is the best way to address treatment of patients with low HDL-C levels. The most effective drug treatment available presently in Turkey relies on lowering LDL-C levels to optimize the TC/HDL-C ratio. |
| Manganese-bilirubin effect on cholesterol accumulation in rat bile canalicular membranes Duguay, A. B., I. M. Yousef, et al. (2000), Toxicol Sci 53(1): 150-5. Abstract: Manganese-bilirubin (Mn-BR)-induced cholestasis in rats is associated with altered lipid composition of various hepatic subcellular fractions. Increased bile canalicular (BCM) cholesterol content in Mn-BR cholestasis and the intracellular source of the accumulating cholesterol were investigated. To label the total hepatic cholesterol pool, male Sprague-Dawley rats were given ip 3H-cholesterol, followed 18 h later by 2-14C-mevalonic acid (a precursor of cholesterol synthesis). To induce cholestasis, manganese (Mn, 4.5 mg/kg) and bilirubin (BR, 25 mg/kg) were injected iv; animals were killed 30 min after BR injection; canalicular and sinusoidal membranes, microsomes, mitochondria, and cytosol were isolated. Total cholesterol content of each fraction was determined by spectrophotometric techniques as well as radiolabeled techniques. In Mn-BR cholestasis, the total cholesterol concentrations of BCM and cytosol were significantly increased. Also, the contribution of 14C-labeled cholesterol (newly synthesized cholesterol) was enhanced in all isolated cellular fractions. The results are consistent with the hypothesis that accumulation of newly synthesized cholesterol in BCM is involved in Mn-BR cholestasis. An enhanced rate of synthesis of cholesterol, however, does not appear to be the causal event, as the activity of HMG-CoA reductase (rate-limiting enzyme in cholesterol synthesis), assessed in vitro, was decreased following Mn-BR treatment. Treatment with the Mn-BR combination may affect other aspects of intracellular cholesterol dynamics. |
| Mania and lower serum cholesterol levels Swartz, C. M. (1995), J Clin Psychopharmacol 15(4): 295. |
| Manidipine inhibits the progression of hypertension and atherosclerosis in endothelium-injured and cholesterol-fed Goldblatt 2K1C rats Sasaki, S., T. Kuwabara, et al. (1992), Blood Press Suppl 3: 36-40. Abstract: In the present study, arteriosclerotic change of the aorta was induced in rats. The effects of manidipine hydrochloride on the resulting hypertension and arteriosclerotic change were studied. In endothelium-injured cholesterol-fed Goldblatt 2K1C rats, moderate elevation of blood pressure was noted at 3, 4, and 5 weeks. Laboratory studies performed at the end of 6 weeks also showed hypercholesterolemia, accompanied by a reduction of triglycerides and HDL cholesterol. Regular doses of manidipine (200 or 500 mg/kg) resulted in a dose dependent inhibition of the blood pressure elevation and a reduction of HDL cholesterol, but had no effect on cholesterol or triglyceride levels. Morphological studies in endothelium-injured rats afflicted with hypercholesterolemia and hypertension, showed medial thickening and intimal hyperplasia. Hyperplasia of the intima was a result of excessive proliferation of the smooth muscle cells. These cells showed an unusually large number of fat droplets and were considered indicative of atheromatous plaque formation. In rats treated with manidipine, hyperplasia of the media was completely suppressed while hyperplasia of the intima was reduced by a minimum of 50%. This study demonstrated that hypercholesterolemia and hypertension produced arteriosclerotic change in endothelium-injured rats, which was inhibited by manidipine. It is not known whether antiarteriosclerotic action was involved in the antihypertensive effect of manidipine. |
| Manipulating intestinal cholesterol absorption and hepatic cholesterol and bile acid metabolism by activation of deorphanized nuclear receptors Rigotti, A. and M. W. Freeman (2001), Gastroenterology 120(4): 1054-5. |
| Manipulation of cholesterol and cholesteryl ester synthesis has multiple effects on the metabolism of apolipoprotein B and the secretion of very-low-density lipoprotein by primary hepatocyte cultures Brown, A., D. Wiggins, et al. (1999), Biochim Biophys Acta 1440(2-3): 253-65. Abstract: Inhibition of esterified and non-esterified cholesterol synthesis by lovastatin in primary rat hepatocytes suppressed the net synthesis and very-low-density lipoprotein (VLDL) secretion of apolipoprotein B (apoB)-48 and apoB-100. Lovastatin did not alter the rates of apoB-48 and apoB-100 post-translational degradation. 25-Hydroxycholesterol, which inhibited non-esterified cholesterol synthesis but increased the synthesis of cholesteryl ester, showed differential effects on the metabolism of apoB-48 and apoB-100. Whereas the secretion of apoB-48 VLDL was suppressed there was no effect on the secretion of apoB-100 VLDL. The post-translational degradation of apoB-48, but not of apoB-100, was enhanced by 25-hydroxycholesterol. The net synthesis rates of apoB-48 and apoB-100 were unaffected by 25-hydroxycholesterol. The inhibitory effect of lovastatin alone on the net synthesis of apoB-48 and apoB-100 was reversed by the simultaneous presence of 25-hydroxycholesterol, suggesting a role for newly synthesised cholesteryl ester. Prevention of the reversal effect by the acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor YM 17E supported this interpretation. In the presence of lovastatin, restoration of the net synthesis of apoB by 25-hydroxycholesterol was not accompanied by an increased VLDL output of apoB-48 and apoB-100. However, under these conditions there was an increased post-translational degradation of apoB-48 and apoB-100. These results suggest that interference with intracellular cholesterol and cholesteryl ester metabolism interrupts VLDL assembly at sites of both apoB net synthesis and post-translational degradation. |