| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Psychological minimization of cholesterol test results: moderators of appraisal in college students and community residents Croyle, R. T., Y. C. Sun, et al. (1993), Health Psychol 12(6): 503-7. Abstract: College students received randomly assigned desirable or borderline-high cholesterol test results. Borderline-high Ss rated high cholesterol as a less serious threat to health, viewed the test as less accurate, and perceived high cholesterol as more common than did those given desirable readings. High self-esteem or blunting coping style predicted lower distress after borderline-high readings but did not moderate cognitive appraisal. In Study 2, minimization was again observed among participants in a community screening, primarily among those who had never been tested. Although the never-tested group was younger and less knowledgeable about cholesterol, these factors did not account for minimization. The results support the generalizability of laboratory data on risk appraisal and provide new evidence regarding the nature and determinants of threat minimization. |
| Psyllium augments the cholesterol-lowering action of cholestyramine in hamsters by enhancing sterol loss from the liver Turley, S. D., B. P. Daggy, et al. (1994), Gastroenterology 107(2): 444-52. Abstract: BACKGROUND/AIMS: Psyllium hydrophilic mucilloid is a nonabsorbable soluble fiber that lowers plasma cholesterol levels in several species, including humans. However, its mechanism of action has not been fully elucidated. Therefore, using a hamster model, experiments were performed to determine whether psyllium given alone or in combination with a submaximal dose of cholestyramine blocks intestinal cholesterol absorption. METHODS: The efficiency of cholesterol absorption and concentrations of plasma and hepatic total cholesterol were measured in male hamsters fed a cholesterol-enriched chow diet (0.1%) that contained either avicel (cellulose) (7.5%), surfomer (3%), cholestyramine (1% or 3%), or psyllium (7.5%) as single agents or a fixed level of cholestyramine (1%) combined with variable levels of psyllium (2%, 4%, 6%, or 8%). RESULTS: Psyllium, cholestyramine, and surfomer, when given alone, markedly lowered plasma and hepatic cholesterol concentrations. Surfomer, and cholestyramine at the higher dose (3%), blocked cholesterol absorption by 54% and 75%, respectively, whereas psyllium had no effect. Combining psyllium with a submaximal dose of cholestyramine augmented the cholesterol-lowering action of the resin without effecting any marked change in the level of cholesterol absorption, except at the highest dose used. CONCLUSIONS: Psyllium, given either as a single agent or as an adjunct to treatment with cholestyramine, exerts a significant hypocholesterolemic effect by enhancing net negative sterol balance across the liver. |
| Psyllium husk. I: Effect on plasma lipoproteins, cholesterol metabolism, and atherosclerosis in African green monkeys McCall, M. R., T. Mehta, et al. (1992), Am J Clin Nutr 56(2): 376-84. Abstract: Psyllium's effects on plasma and lipoprotein cholesterol concentrations, cholesterol metabolism, and diet-induced atherosclerosis were studied in adult male African green monkeys (Cercopithecus aethiops). Animals were fed for 3.5 y one of three experimental diets: low-cholesterol cellulose (LCC), high-cholesterol cellulose (HCC), or high-cholesterol psyllium (HCP). The LCC and HCP groups had significantly (P less than 0.05) lower plasma cholesterol concentrations (39% lower) at 1 mo than did the HCC group. These responses persisted throughout the study. Plasma cholesterol changes were due to a reduction in intermediate-density and low-density lipoproteins; very-low and high-density-lipoprotein concentrations were similar among groups. Aortic atherosclerosis, evaluated as percent sudanophilia at 3.5 y, was lowest in the LCC group, intermediate in the HCP group, and highest in the HCC group. Cholesterol absorption, neutral steroid and fat excretion, HMGCoA reductase activity (in intestine and liver), and body weight were unrelated to psyllium's hypocholesterolemic effects. |
| Psyllium reduces plasma LDL in guinea pigs by altering hepatic cholesterol homeostasis Fernandez, M. L., L. R. Ruiz, et al. (1995), J Lipid Res 36(5): 1128-38. Abstract: Male Hartley guinea pigs were fed semipurified diets containing various levels of psyllium and cholesterol to determine mechanisms by which psyllium lowers plasma low density lipoprotein (LDL) concentrations. Four diets were tested: control diets with 12.5% (w/w) cellulose, and psyllium diets in which cellulose was partially replaced with 7.5% (w/w) psyllium. Two levels of dietary cholesterol were used, either low (LC, 0.04%, w/w) or high (HC, 0.25%, w/w). Plasma LDL was reduced by 30 and 54% with psyllium intake in the LC and HC groups, respectively (P < 0.001), while plasma very low density lipoprotein (VLDL) was lowered only in the HC group (P < 0.001). Psyllium intake modified LDL composition and size compared to LDL from control animals with a lower proportion of cholesteryl ester and higher proportion of triacylglycerol, lower molecular weight, smaller diameter, and higher peak density (P < 0.001). Plasma VLDL from animals fed the psyllium-HC diet compared to the control-HC contained lower relative proportions of free and esterified cholesterol and a higher proportion of triacylglycerol, compositional characteristics similar to VLDL from animals fed LC diets. Hepatic free and esterified cholesterol concentrations were significantly reduced by psyllium an average of 25 and 55%, respectively, while hepatic HMG-CoA reductase activity was increased in both psyllium groups compared to the respective controls (P < 0.001). In addition, psyllium intake reduced hepatic acyl-CoA:cholesterol acyltransferase (ACAT) activity in both the LC and HC groups (P < 0.001) and increased hepatic membrane apoB/E receptor number (Bmax) by 17 and 52% for animals fed LC and HC diets, respectively (P < 0.005). Significant psyllium-induced increases in cholesterol 7 alpha-hydroxylase of 4- and 1.6-fold were also observed in animals fed the LC and HC diets respectively (P < 0.001). These results indicate that psyllium generates a negative cholesterol balance across the liver which results in induction of cholesterol 7 alpha-hydroxylase and HMG-CoA reductase and suppression of ACAT activities, upregulation of apoB/E receptors, and secretion of smaller VLDL particles, metabolic alterations that contribute to a lowering of plasma LDL cholesterol levels. |
| Psyllium-enriched cereals lower blood total cholesterol and LDL cholesterol, but not HDL cholesterol, in hypercholesterolemic adults: results of a meta-analysis Olson, B. H., S. M. Anderson, et al. (1997), J Nutr 127(10): 1973-80. Abstract: We conducted a meta-analysis to determine the effect of consumption of psyllium-enriched cereal products on blood total cholesterol (TC), LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) levels and to estimate the magnitude of the effect among 404 adults with mild to moderate hypercholesterolemia (TC of 5.17-7.8 mmol/L) who consumed a low fat diet. Studies of psyllium cereals were identified by a computerized search of MEDLINE and Current Contents and by contacting United States-based food companies involved in psyllium research. Published and unpublished studies were reviewed by one author and considered eligible for inclusion in the meta-analysis if they were conducted in humans, were randomized, controlled experiments, and included a control group that ate cereal providing /=50 y) on blood lipids. The meta-analysis showed that subjects who consumed a psyllium cereal had lower TC and LDL-C concentrations differences of 0.31 mmol/L (5%) and 0.35 mmol/L (9%), respectively than subjects who ate a control cereal; HDL-C concentrations were unaffected in subjects eating psyllium cereal. There was no effect of sex, age or menopausal status on blood lipids. Results indicate that consuming a psyllium-enriched cereal as part of a low fat diet improves the blood lipid profile of hypercholesterolemic adults over that which can be achieved with a low fat diet alone. |
| Pterostilbene, a new agonist for the peroxisome proliferator-activated receptor alpha-isoform, lowers plasma lipoproteins and cholesterol in hypercholesterolemic hamsters Rimando, A. M., R. Nagmani, et al. (2005), J Agric Food Chem 53(9): 3403-7. Abstract: Resveratrol, a stilbenoid antioxidant found in grapes, wine, peanuts and other berries, has been reported to have hypolipidemic properties. We investigated whether resveratrol and its three analogues (pterostilbene, piceatannol, and resveratrol trimethyl ether) would activate the peroxisome proliferator-activated receptor alpha (PPARalpha) isoform. This nuclear receptor is proposed to mediate the activity of lipid-lowering drugs such as the fibrates. The four stilbenes were evaluated at 1, 10, 100, and 300 microM along with ciprofibrate (positive control), for the activation of endogenous PPARalpha in H4IIEC3 cells. Cells were transfected with a peroxisome proliferator response element-AB (rat fatty acyl CoA beta-oxidase response element)-luciferase gene reporter construct. Pterostilbene demonstrated the highest induction of PPARalpha showing 8- and 14-fold increases in luciferase activity at 100 and 300 microM, respectively, relative to the control. The maximal luciferase activity responses to pterostilbene were higher than those obtained with the hypolipidemic drug, ciprofibrate (33910 and 19460 relative luciferase units, respectively), at 100 microM. Hypercholesterolemic hamsters fed with pterostilbene at 25 ppm of the diet showed 29% lower plasma low density lipoprotein (LDL) cholesterol, 7% higher plasma high density lipoprotein (HDL) cholesterol, and 14% lower plasma glucose as compared to the control group. The LDL/HDL ratio was also statistically significantly lower for pterostilbene, as compared to results for the control animals, at this diet concentration. Results from in vitro studies showed that pterostilbene acts as a PPARalpha agonist and may be a more effective PPARalpha agonist and hypolipidemic agent than resveratrol. In vivo studies demonstrate that pterostilbene possesses lipid and glucose lowering effects. |
| Puberty-associated differences in total cholesterol and triglyceride levels according to sex in French children aged 10-13 years Bertrais, S., B. Balkau, et al. (2000), Ann Epidemiol 10(5): 316-23. Abstract: PURPOSE: To assess the relationships between lipid levels and sexual maturity, independently of age-related differences, and to investigate possible differences related to sexual maturity across the percentiles of the lipid distributions. METHODS: Fasting serum total cholesterol and triglyceride concentrations were measured in 6577 boys and 6605 girls, aged from 10 to 13 years, with different Tanner stages. The total cholesterol and triglyceride mean and percentile levels were estimated according to age and Tanner stage by ordinary least squares and percentile regression models, separately in both sexes. RESULTS: In boys and girls, total cholesterol levels were significantly associated with pubertal stage after controlling for age. At age 12, the estimated mean levels in boys varied from 4.82 mmol/L for Tanner 1 to 4.41 for Tanner 5. The corresponding values were 5.05 and 4.62 mmol/L in girls, for whom the association with maturity was stronger in the upper than in the lower percentiles (p < 0.0001); between the extreme Tanner stages, the 95th percentiles of total cholesterol differed by 0.80 mmol/L, in comparison to 0.19 mmol/L for the 5th percentiles. Therefore, 1. 8% of girls and 0.7% of boys were classified differently whether Tanner stage was used or not to assess hypercholesterolemia (concentrations in the upper 5% of the distributions). Triglycerides were positively related to sexual maturity independently of age, but the discrepancies between classifications were lower; 1.1% in girls and 0.4% in boys. CONCLUSIONS: Our findings emphasize the importance of sexual maturity, even for a given age, for interpreting lipid levels in children. |
| Public cholesterol screening in the previously diagnosed: misuse of resources or beneficial function? Maiman, L. A., P. Greenland, et al. (1994), Am J Prev Med 10(1): 20-5. Abstract: The attendance of individuals with a previous diagnosis of hyperlipidemia at public cholesterol screenings is often criticized as a misuse of such programs. This study explored the post-screening actions of 811 participants in a cholesterol screening program who had previously been diagnosed with cholesterol elevations and whose blood levels at this screening required further medical referral. We also studied the responses of physicians from whom these subjects sought care. Within five months, 559 of 753 participants completing the survey (74.0%) sought medical follow-up. Physicians retested the blood cholesterol levels of 75.0% of these 559; high-risk screenees were more likely to be retested and to be informed that their levels were elevated than moderate-risk subjects (P <.0001). Physicians increased cholesterol-lowering dietary advice for high-risk subjects (P <.0001) and medication prescriptions for both risk groups (P <.0001). Participants seeking medical care after the screening program had better cholesterol-lowering dietary practices and reported increased regimen compliance (moderate-risk: P =.01; high-risk: P <.0001) than those individuals not obtaining medical follow-up. One year after screening, blood cholesterol levels were 4.5% lower (P =.001) in those complying with referral but were virtually unchanged in noncompliers. Screening program confirmation of high blood cholesterol levels combined with referral appeared to have a positive impact on previously diagnosed screenees. We conclude that there may be merit in including previously diagnosed individuals in cholesterol screening programs. |
| Pulmonary atherosclerosis and pulmonary arterial pressure in cholesterol-fed New Zealand white rabbits Kamimura, R., S. Suzuki, et al. (2001), J Vet Med Sci 63(6): 647-53. Abstract: The lung produces many vasoactive substances originating from its vascular endothelium and plays an important part in various pathose. The present study was carried out to clarify pulmonary atherosclerosis and pulmonary arterial pressure, and to elucidate a part of the pulmonary pathosis in cholesterol-fed rabbits. Atherosclerosis was induced by feeding the animals a cholesterol-rich diet. When the rabbits were fed the cholesterol-enriched diets for 15 weeks, the grade of the atherosclerosis was severer than in 8W-feeding rabbits. The lesions of 8W-feeding rabbits were mainly composed of foam cells and fibrous components, whereas in 15W-feeding rabbits, the aggregation of foam cells beneath the endothelium of the vessel was infiltrating the media and severe stenose of the lumen was observed. In the entire pulmonary arterial system, the severe obstructive vascular lesions were localized and not diffused. The pulmonary arterial pressures of the rabbits increased slightly with time and the mean pressures were 11.3+/-0.9 (control group), 11.8+/-1.0 (8W group) and 13.7+/-1.5 mmHg (15W group) respectively. A significant difference existed in the mean pressure between the control group and 15W-feeding group, but there were no significant differences in the systolic and diastolic pressures among the three groups. In conclusion, we could induce pulmonary atherosclerosis in rabbits by feeding them a hyper-cholesterol diet but not overt pulmonary hypertension. |
| Pulmonary cholesterol granulomas in patients with pulmonary artery hypertension: chest radiographic and CT findings Nolan, R. L., H. P. McAdams, et al. (1999), AJR Am J Roentgenol 172(5): 1317-9. Abstract: OBJECTIVE: We describe the chest radiographic and CT findings of pulmonary cholesterol granulomas in patients with pulmonary artery hypertension. CONCLUSION: Histopathologic evidence of cholesterol granulomas was found in five (25%) of 20 patients with severe pulmonary hypertension. In three of these five patients, the granulomas manifested on chest radiographs and CT as small centrilobular nodules mimicking the appearance of sarcoidosis, bronchiolitis, hypersensitivity pneumonitis, or aspiration. |
| Purification and characterization of a novel cholesterol esterase from Pseudomonas aeruginosa, with its application to cleaning lipid-stained contact lenses Sugihara, A., Y. Shimada, et al. (2002), Biosci Biotechnol Biochem 66(11): 2347-55. Abstract: With the aim of developing a new cholesterol esterase for eliminating lipids on used contact lenses, microorganisms were screened for the enzyme activity. A Pseudomonas aeruginosa isolated from soil was found to produce a desirable enzyme. The enzyme had an isoelectric point of 3.2, and molecular mass of 58 kDa. The optimal temperature was around 53 degrees C at pH 7.0, and the optimal pH was from 5.5 to 9.5. The enzyme was stable between pH 5 and 10 for 19 h at 25 degrees C, and retained its activity up to 53 degrees C on 30 min of incubation at pH 7.0. The rates of hydrolysis of cholesteryl esters of different fatty acids were in the following order: linoleate > oleate > stearate > palmitate > caprylate > myristate > laurate, caprate > caproate > butyrate, acetate. Addition of (tauro)cholate to a final concentration of 100 mM markedly promoted the hydrolysis of triglycerides of short-, medium-, and long-chain fatty acids. When used with taurocholate, the enzyme acted as an effective cleaner for contact lenses stained with lipids consisting of cholesteryl oleate, tripalmitin, and stearyl stearate. |
| Purification and characterization of a novel human 15 kd cholesterol crystallization inhibitor protein in bile Secknus, R., G. Yamashita, et al. (1996), J Lab Clin Med 127(2): 169-78. Abstract: Crystallization-inhibiting proteins can explain longer nucleation times associated with bile from gallstone-free subjects as compared with bile from patients with cholesterol gallstones. We partially characterized and examined the crystallization inhibitory potency of a newly purified 15 kd human biliary protein. Gallbladder bile was passed through an anti-apolipoprotein A-I (apo A-I) immunoaffinity column to extract lipid-associated proteins. The bound fraction was separated by 30 kd ultrafiltration. Sodium dodecyl sulfate-polyacrylamide gel electrophesis (SDS-PAGE) was performed under nonreducing and reducing conditions. Cholesterol crystallization activity was tested in a photometric cholesterol crystal growth assay. Isoelectric focusing was performed by using a standard gel. The purified 15 kd protein was subjected to N-terminal amino acid sequencing. Although the whole apo A-I-bound fraction contained a variety of proteins and lipids, its 30 kd filtrate yielded a nearly pure 15 kd protein with only minor contamination from apo A-1. Amino acid sequencing showed that the protein was unique. Enzymatic deglycosylation revealed no evidence for glycosylation. At a protein concentration of 10 micrograms/ml, crystallization time was delayed as compared with control and apo A-I, and final crystal mass was reduced to 75% of control. Its isoelectric point was 6.1 without isoforms. Under nonreducing conditions, the protein formed a 30 kd dimer and a 60 kd tetramer. We conclude that this protein is a novel potent biliary crystallization inhibitor protein. |
| Purification of cholesterol 7 alpha-hydroxylase from human and rat liver and production of inhibiting polyclonal antibodies Nguyen, L. B., S. Shefer, et al. (1990), J Biol Chem 265(8): 4541-6. Abstract: Cholesterol 7 alpha-hydroxylase, the cytochrome P-450-dependent and rate-controlling enzyme of bile acid synthesis, was purified from rat and human liver microsomes. The purified fractions were assayed in a reconstituted system containing 4-14Ccholesterol, and cholesterol 7 alpha-hydroxylase activities in these fractions increased 500-600-fold relative to whole microsomes. Polyacrylamide gel electrophoresis of rat microsomes followed by immunoblotting with polyclonal rabbit antisera raised against purified cholesterol 7 alpha-hydroxylases revealed two peaks at molecular masses of 47,000 and 49,000 daltons for both rat and human fractions. Increasing amounts of rabbit anti-rat and anti-human antibodies progressively inhibited rat microsomal cholesterol 7 alpha-hydroxylase activity up to 80%. In contrast, monospecific antibodies raised against other purified cytochrome P-450 enzymes (P-450f, P-450g, and P-450j) did not inhibit rat or human cholesterol 7 alpha-hydroxylase activity. Immunoblots of rat microsomes with the rabbit anti-rat cholesterol 7 alpha-hydroxylase antibody demonstrated that the antibody reacted quantitatively with the rat microsomal enzyme. Microsomes from cholesterol-fed rats showed increased cholesterol 7 alpha-hydroxylase mass, whereas treatment with pravastatin, an inhibitor of hydroxy-methylglutaryl-coenzyme A reductase, reduced enzyme mass. Microsomes from starved rats contained slightly less cholesterol 7 alpha-hydroxylase protein than chow-fed control rats. These results indicate a similarity in molecular mass, structure, and antigenicity between rat and human cholesterol 7 alpha-hydroxylases; demonstrate the production of inhibiting anti-cholesterol 7 alpha-hydroxylase antibodies that can be used to measure the change in cholesterol 7 alpha-hydroxylase enzyme mass under various conditions; and emphasize the unique structure of cholesterol 7 alpha-hydroxylase with respect to other cytochrome P-450-dependent hydroxylases. |
| Purification of cholesterol-esterifying enzymes from rat liver cytosol by high-performance liquid chromatography Hradec, J., F. Franek, et al. (1996), J Chromatogr B Biomed Appl 681(1): 55-62. Abstract: Three enzymes esterifying cholesterol with long-chain fatty acids were purified approximately 31,000-fold to apparent homogeneity from the cytosol of normal rat liver. The enzymatic activity was tested by incubation of active fractions with tritiated cholesterol and separation of newly formed esters from non-reacted cholesterol by a passage through silica gel cartridges with subsequent assay for radioactivity by liquid scintillation. For the purification of enzymes, active proteins were precipitated by (NH4)2SO4 to 35% saturation. The bulk of inactive proteins was removed by size-exclusion chromatography on TSK G3000 SW. The active fraction was subsequently separated on Separon HEMA BIO 1000 DEAE in gradients of 0-500 mM KCl into three enzymatic activities differing in their retention and these proteins were finally purified by affinity HPLC on columns of cholesterol immobilized on HEMA BIO 1000 E-H. Final purified enzymes showed the same single band in polyacrylamide gel electrophoresis corresponding to 16.5 kDa. Combination of individual enzymes did not increase the overall yield of cholesteryl esters but the reaction-rate was significantly accelerated. These proteins are apparently subunits of a larger complex (M(r) 65,000) that can be demonstrated by electrophoresis in the absence of 2-mercaptoethanol. Results presented in this paper indicate that because of good and rapid separation of active proteins, HPLC may be a method of choice for enzyme purifications. |
| Purification, characterization and reverse cholesterol transport of human serum apolipoprotein A-IV Hu, Y. (1992), Zhongguo Yi Xue Ke Xue Yuan Xue Bao 14(4): 273-9. Abstract: In order to study the function of apoA-IV, human serum apoA-IV was isolated and purified. LDS was isolated with NaBr density gradient ultracentrifugation and then incubated with intralipid according to the method of Weinberg and Scanu. Protein complex containing apoA-IV was obtained. The apo-IV was purified from protein complex by preparative SDS-PAGE, electroelution and removal of SDS. ApoA-IV thus prepared gave a single band on SDS-PAGE with a MW of 46 kD. Amino acid composition and isoelectric focusing pI (5.27 and 5.47) of apoA-IV were similar to those reported in the literature. The effects of apoA-IV and liposome (apoA-IV: DMPC) on cholesterol efflux from hum skin fibroblast were studied. There was no significant difference (P > 0.5) between apoA-IV and control but a very significant difference (P < 0.001) between liposome (apoA-IV:DMPC) and control, suggesting that liposomes (apoA-IV:DMPC) play a role in reverse cholesterol transport. The results may offer a new approach for the prevention and treatment of atherosclerotic coronary heart disease. |
| Purified outer membranes of Serpulina hyodysenteriae contain cholesterol Plaza, H., T. R. Whelchel, et al. (1997), J Bacteriol 179(17): 5414-21. Abstract: We have isolated outer and inner membranes of Serpulina hyodysenteriae by using discontinuous sucrose density gradients. The outer and inner membrane fractions contained less than 1 and 2%, respectively, of the total NADH oxidase activity (soluble marker) in the cell lysate. Various membrane markers including lipooligosaccharide (LOS), the 16-kDa outer membrane lipoprotein (SmpA), and the C subunit of the F1F0 ATPase indicated that the lowest-density membrane fraction contained outer membranes while the high-density membrane fraction contained inner membranes and that both are essentially free of contamination by the periplasmic flagella, a major contaminant of membranes isolated by other techniques. The outer membrane fractions (rho = 1.10 g/cm3) contained 0.25 mg of protein/mg (dry weight), while the inner membrane samples (rho = 1.16 g/cm3) contained significantly more protein (0.55 mg of protein/mg dry weight). Lipid analysis revealed that the purified outer membranes contained cholesterol as a major component of the membrane lipids. Treatment of intact S. hyodysenteriae with different concentrations of digitonin, a steroid glycoside that interacts with cholesterol, indicated that the outer membrane could be selectively removed at concentrations as low as 0.125%. |
| Purple grape juice improves endothelial function and reduces the susceptibility of LDL cholesterol to oxidation in patients with coronary artery disease Stein, J. H., J. G. Keevil, et al. (1999), Circulation 100(10): 1050-5. Abstract: BACKGROUND: In vitro, the flavonoid components of red wine and purple grape juice are powerful antioxidants that induce endothelium-dependent vasodilation of vascular rings derived from rat aortas and human coronary arteries. Although improved endothelial function and inhibition of LDL oxidation may be potential mechanisms by which red wine and flavonoids reduce cardiovascular risk, the in vivo effects of grape products on endothelial function and LDL oxidation have not been investigated. This study assessed the effects of ingesting purple grape juice on endothelial function and LDL susceptibility to oxidation in patients with coronary artery disease (CAD). METHODS AND RESULTS: Fifteen adults with angiographically documented CAD ingested 7.7+/-1.2 mL. kg(-1). d(-1) of purple grape juice for 14 days. Flow-mediated vasodilation (FMD) was measured using high-resolution brachial artery ultrasonography. Susceptibility of LDL particles to oxidation was determined from the rate of conjugated diene formation after exposure to copper chloride. At baseline, FMD was impaired (2.2+/-2. 9%). After ingestion of grape juice, FMD increased to 6.4+/-4.7% (P=0.003). In a linear regression model that included age, artery diameter, lipid values, and use of lipid-lowering and antioxidant therapies, the effect of grape juice on FMD remained significant (mean change 4.2+/-4.4%, P<0.001). After ingestion of grape juice, lag time increased by 34.5% (P=0.015). CONCLUSIONS: Short-term ingestion of purple grape juice improves FMD and reduces LDL susceptibility to oxidation in CAD patients. Improved endothelium-dependent vasodilation and prevention of LDL oxidation are potential mechanisms by which flavonoids in purple grape products may prevent cardiovascular events, independent of alcohol content. |
| Purple toes and livido reticularis in a patient with cardiovascular disease taking coumadin. Cholesterol emboli associated with coumadin therapy Park, S., A. L. Schroeter, et al. (1993), Arch Dermatol 129(6): 777, 780. |
| Putting medical practice guidelines into practice: the cholesterol model Ammerman, A., A. Caggiula, et al. (1994), Am J Prev Med 10(4): 209-16. Abstract: As more and more medical practice guidelines are developed in the United States, commensurate evaluation efforts should assess their impact on professional practice and patient outcomes. We describe an ongoing research program designed to develop and test practice models for applying the 1988 Adult Treatment Panel Guidelines for the clinical management of high blood cholesterol. Four studies are evaluating different models to assist nonacademic community practices in the detection, evaluation, and treatment of high blood cholesterol. We have designed randomized controlled trials set in solo and small-group primary care practices of family or general practitioners and internists situated in rural, suburban, and urban settings. Patients include adult men and women who represent diverse socioeconomic and ethnic backgrounds. We are measuring rates of cholesterol screening; dietary and drug treatment and follow-up; changes in dietary intake and compliance with drug therapy; changes in quality of life and cost of intervention; and reduction in cholesterol level. Scheduled for completion in 1994, this program will provide insights into practical and effective methods of lipid management. It serves as a model for studying the application of health guidelines in the context of nonacademic primary care practices serving diverse patient populations. |
| PXR and the regulation of apoA1 and HDL-cholesterol in rodents Bachmann, K., H. Patel, et al. (2004), Pharmacol Res 50(3): 237-46. Abstract: Orphan nuclear receptors (ONRs) have been implicated in the regulation of lipids. Several clinical studies conducted either prospectively or epidemiologically have pointed to a link between the regulation of hepatic CYP enzymes and HDL-cholesterol (HDL-C) and/or apolipoprotein A1 (apoA1). The treatment of rats with a series of imidazole inducers of CYP3A yielded correlations between in vitro CYP3A activity measured as erythromycin demethylase activity and plasma HDL-C and hepatic apoA1 mRNA. Similarly, a correlation was established between in vivo CYP3A activity, measured as ethosuximide clearance, and plasma HDL-C and hepatic apoA1 mRNA. The treatment of wild-type (WT) mice with PXR agonists elicited increases in serum HDL-C and serum apoA1 levels. On the other hand, the treatment of PXR-knockout mice (PXR-KOs) with the same PXR agonists failed to elicit increases in either serum HDL-C or serum apoA1 levels. Superposition of the structures of three imidazoles known to be active CYP3A inducers in rats with the human PXR pharmacophore demonstrated a partial fit and predicted EC(50) values typical of weak-moderate hPXR inducers in humans. These imidazoles have been shown to increase apoA1 and HDL-C in rats and mice. Taken together, these data suggest that PXR plays an important role in the regulation of apoA1 and HDL-C in rodents. |