| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Distribution and correlates of non-high-density lipoprotein cholesterol in children: the Bogalusa Heart Study Srinivasan, S. R., L. Myers, et al. (2002), Pediatrics 110(3): e29. Abstract: OBJECTIVE: Serum non-high-density lipoprotein (HDL) cholesterol (total cholesterol minus HDL cholesterol) is considered a better screening tool than low-density lipoprotein (LDL) cholesterol for the assessment of coronary artery disease (CAD) risk in adults because it includes all classes of atherogenic lipoproteins. Although population frequency distribution and clinically useful cutpoints for this variable in adults have been reported recently, such information is lacking in children. Therefore, this study sought to provide population-based data on the distribution and correlates of non-HDL cholesterol in biracial (black-white) children. METHODS: The study sample consisted of 2843 5- to 17-year-olds (57% white, 50% female) who participated in a cross-sectional screening of cardiovascular risk factors as part of the Bogalusa Heart Study. RESULTS: Non-HDL cholesterol levels were similar in black and white children, and higher in girls than in boys, especially among the younger (5-11 years) age group. Age was inversely related to both non-HDL cholesterol and LDL cholesterol. Body fatness as measured by body mass index and waist circumference was positively associated with non-HDL cholesterol. The magnitude of correlation with triglycerides was relatively higher for non-HDL cholesterol versus LDL cholesterol. Non-HDL cholesterol showed an inverse relation to HDL cholesterol. In a multivariate analysis, body mass index, age, gender, waist circumference, and cigarette smoking accounted for 7.7% of the variance in non-HDL cholesterol. Non-HDL cholesterol levels equivalent to currently recommended LDL cutpoints (110, 130, 160, and 190 mg/dL) for CAD risk assessment were 123, 144, 176, and 207 mg/dL. CONCLUSION: Population-based data on non-HDL cholesterol are now available for children, which may help improve the CAD risk assessment and intervention. |
| Distribution and prevalence of inducible nitric oxide synthase in atherosclerotic vessels of long-term cholesterol-fed rabbits Behr, D., A. Rupin, et al. (1999), Atherosclerosis 142(2): 335-44. Abstract: The expression of inducible nitric oxide synthase (iNOS) as well as its functional activity has recently been reported in atherosclerotic lesions. The aim of the present study was to evaluate the expression of iNOS in various arteries of rabbits fed a long-term but low-level cholesterol-enriched diet which promotes different types of atherosclerotic lesions resembling human diseased vessels. No iNOS expression was revealed in arteries from control rabbits and in fatty streaks found in carotid and femoral arteries from hypercholesterolemic rabbits. In transitional lesions from the thoracic and abdominal aortas, the coronary and pulmonary arteries, a punctiform iNOS staining was detected in the intima. When lesions were more advanced, iNOS expression was found more intense and diffuse and localized in the subendothelial layer as well as in the media. Smooth muscle cell accumulation in intimal layers of the arteries is a marker of the degree of evolution of the atherosclerotic lesion; since we found a correlation between the smooth muscle cell infiltration in the intima and the iNOS expression in the intima and the subendothelial layer, our results suggest a link between the severity of the lesion and the iNOS expression. |
| Distribution and trafficking of MPR300 is normal in cells with cholesterol accumulated in late endocytic compartments: evidence for early endosome-to-TGN trafficking of MPR300 Umeda, A., H. Fujita, et al. (2003), J Lipid Res 44(10): 1821-32. Abstract: It has been reported that an accumulation of cholesterol within late endosomes/lysosomes in Niemann-Pick type C (NPC) fibroblasts and U18666A-treated cells causes impairment of retrograde trafficking of the cation-independent mannose 6-phosphate/IGF-II receptor (MPR300) from late endosomes to the trans-Golgi network (TGN). In apparent conflict with these results, here we show that as in normal fibroblasts, MPR300 localizes exclusively to the TGN in NPC fibroblasts as well as in normal fibroblasts treated with U18666A. This localization can explain why several lysosomal properties and functions, such as intracellular lysosomal enzyme activity and localization, the biosynthesis of cathepsin D, and protein degradation, are all normal in NPC fibroblasts. These results, therefore, suggest that the accumulation of cholesterol in late endosomes/lysosomes does not affect the retrieval of MPR300 from endosomes to the TGN. Furthermore, treatment of normal and NPC fibroblasts with chloroquine, which inhibits membrane traffic from early endosomes to the TGN, resulted in a redistribution of MPR300 to EEA1 and internalized transferrin-positive, but LAMP-2-negative, early-recycling endosomes. We propose that in normal and NPC fibroblasts, MPR300 is exclusively targeted from the TGN to early endosomes, from where it rapidly recycles back to the TGN without being delivered to late endosomes. This notion provides important insights into the definition of late endosomes, as well as the biogenesis of lysosomes. |
| Distribution and transport of cholesterol in Caenorhabditis elegans Matyash, V., C. Geier, et al. (2001), Mol Biol Cell 12(6): 1725-36. Abstract: Cholesterol transport is an essential process in all multicellular organisms. In this study we applied two recently developed approaches to investigate the distribution and molecular mechanisms of cholesterol transport in Caenorhabditis elegans. The distribution of cholesterol in living worms was studied by imaging its fluorescent analog, dehydroergosterol, which we applied to the animals by feeding. Dehydroergosterol accumulates primarily in the pharynx, nerve ring, excretory gland cell, and gut of L1-L3 larvae. Later, the bulk of dehydroergosterol accumulates in oocytes and spermatozoa. Males display exceptionally strong labeling of spermatids, which suggests a possible role for cholesterol in sperm development. In a complementary approach, we used a photoactivatable cholesterol analog to identify cholesterol-binding proteins in C. elegans. Three major and several minor proteins were found specifically cross-linked to photocholesterol after UV irradiation. The major proteins were identified as vitellogenins. rme-2 mutants, which lack the vitellogenin receptor, fail to accumulate dehydroergosterol in oocytes and embryos and instead accumulate dehydroergosterol in the body cavity along with vitellogenin. Thus, uptake of cholesterol by C. elegans oocytes occurs via an endocytotic pathway involving yolk proteins. The pathway is a likely evolutionary ancestor of mammalian cholesterol transport. |
| Distribution and transport of cholesterol-rich membrane domains monitored by a membrane-impermeant fluorescent polyethylene glycol-derivatized cholesterol Sato, S. B., K. Ishii, et al. (2004), J Biol Chem 279(22): 23790-6. Abstract: Cholesterol-rich membrane domains function in various membrane events as diverse as signal transduction and membrane traffic. We studied the interaction of a fluorescein ester of polyethylene glycol-derivatized cholesterol (fPEG-Chol) with cholesterol-rich membranes both in cells and in model membranes. Unlike filipin and other cholesterol probes, this molecule could be applied as an aqueous dispersion to various samples. When added to live cells, fPEG-Chol distributed exclusively in the outer plasma membrane leaflet and was enriched in microdomains that dynamically clustered by the activation of receptor signaling. The surface-bound fPEG-Chol was slowly internalized via clathrin-independent pathway into endosomes together with lipid raft markers. Noteworthy, fPEG-Chol could be microinjected in the living cells in which we found Golgi apparatus as the sole major organelle to be labeled. PEG-Chol, thus, provides a novel, sensitive probe for unraveling the dynamics of cholesterol-rich microdomains in living cells. |
| Distribution of 3Hcholesterol-labelled liposomes with or without praziquantel in mice infected with Mesocestoides corti (Cestoda) tetrathyridia Hrckova, G., S. Velebny, et al. (2000), Comp Biochem Physiol C Toxicol Pharmacol 126(2): 167-74. Abstract: The anthelmintic drug praziquantel (PZQ) has a short half-life in the circulation, necessitating repeated daily administration of PZQ for the therapy of larval stages of cestodes. The effect of incorporation of PZQ into multilamellar liposomes on their biodistribution in Mesocestoides corti (syn. M. vogae) infected mice has been examined using 3Hcholesterol as a liposomal marker. Incorporation of PZQ significantly increased the average size of liposomes with 70.3% of 3Hlip.PZQ particles up to 1.9 microm, whereas higher portion of 3Hliposomes (66.3% of total) were of smaller (up to 1.3 microm). Both liposome preparations were given intraperitoneally to avoid rapid sequestration in the liver. There were significant differences between 3Hliposomes and 3Hlip.PZQ-associated radioactivity in peritoneal adherent cells, liver- and peritoneal larvae, liver, spleen and lymph nodes within 16 days of examination. The highest uptake (about 2-fold more 3Hlip.PZQ than 3Hliposomes from the total dose) was found in peritoneal cells on day 1 post therapy (p.t.) followed by a rapid decline. The kinetic of decline in these cells recovered on day 1 p.t. was studied also in vitro. Disappearance of the marker due to the breakdown of liposomes and efflux of lipids and PZQ from cells was slower for 3Hlip.PZQ in comparison with drug-free liposomes and was not completed after 4 days-incubation. Significantly increased levels of radioactivity, more in 3Hliposomes treated groups, were recorded in the liver- and peritoneal larvae between days 8-16 p.t. indicating re-utilization of cholesterol by the larvae. The data suggest that incorporation of PZQ into liposomes contributes to the enlargement of liposome average size and slows down their degradation in phagocytosing cells. In this respect, these cells could serve as the secondary circulating depots for PZQ releasing it slowly to the circulation. |
| Distribution of apolipoprotein A I and B in the blood according to age and gender, as well as their relation to blood cholesterol levels in the Hungarian blood donor population Csaszar, A., L. Romics, et al. (1991), Orv Hetil 132(33): 1795-800. Abstract: In this study we assessed the plasma CHOL, HDL cholesterol (HDL-C), apoprotein A I, apoprotein B levels and the polymorphic isoforms of apoprotein A I in Hungarian blood donors (n = 202, average age: 37.5 year). The mean values are presented for age and sex groups, and the data are compared to the international measurements. The mean CHOL concentration was 5.7 +/- 1.1 mmol/l. The CHOL level correlated with age and no significant association was observed with sex. The level of HDL-C showed no correlation with the age and--in opposite to the international data--there were no significant sex differences (women: 1.42 +/- 0.45, men: 1.34 +/- 0.44 mmol/l), which may be explained by the relative high HDL-C concentration of Hungarian men. Both apo A I and apo B showed an increase with advancing age. The only difference between the sexes was found in apoprotein A I levels, i. e. it was higher in women than in men (women: 156.3 +/- 23.6, men: 143.8 +/- 26.8 mg/dl). In contrary with the results from other countries, the apoprotein B concentrations in men did not differ from that measured in women (women: 72.1 +/- 17.4, men: 69 +/- 15.8 mg/dl). In relation to the age, in the fifth decade the CHOL, the HDL-C and the apo B levels were higher in women than in men.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Distribution of blood total cholesterol in a national sample of Malaysian adults Lim, T. O., L. M. Ding, et al. (2000), Med J Malaysia 55(1): 78-89. Abstract: We describe the distribution of capillary blood total cholesterol (BC) by age, sex and ethnicity in Malaysian adults. A national sample of 20,041 individuals aged 30 or older had usable data. They were selected by stratified 2-stage cluster sampling. BC was measured using reflectance photometer. Percentile tables and curves by age, sex and ethnicity are presented. The BC distribution was right skewed and showed the expected increase with age. There were ethnic differences. Malay had the highest BC concentration, followed by Indian, Chinese and other indigenous ethnic group. However, for all ethnic groups, BC concentrations were low in comparison those prevailing in Western populations. |
| Distribution of cell replication and apoptosis in atherosclerotic plaques of cholesterol-fed rabbits Kockx, M. M., G. R. De Meyer, et al. (1996), Atherosclerosis 120(1-2): 115-24. Abstract: In human atherosclerosis the development of a cell-poor lipid-rich core is an important feature of atheromatous plaque formation. The core is characterized by extracellular lipid deposition, cholesterol crystals and cell death and is situated in the deep layer of the plaque. The aim of the present study was to localize apoptotic cell death and cell replication in atherosclerotic plaques of cholesterol-fed rabbits in order to examine the hypothesis that core formation is a consequence of an imbalance between cell replication and apoptosis. New Zealand White male rabbits were fed a diet supplemented with 0.3% cholesterol for 16 (n = 5) and 27 weeks (n = 9). Cell replication and cell types were demonstrated by immunohistochemistry and apoptotic cell death was demonstrated by DNA in situ end-labeling (ISEL) and transmission electron microscopy. Quantification was done using a colour image analysis system. The plaques showed a clear distinction between a luminal layer composed of numerous lipid-rich foam cells of macrophage origin and a deep layer which was fibrous, containing extracellular lipid deposits and few smooth muscle cells. Cell replication (expressed as percentage of total number of nuclei) in the superficial layer was higher then in the deep layer at both 16 (5.1 +/- 1.8% vs. 1.2 +/- 0.8%) and 27 weeks (11.3 +/- 2.1% vs. 4.4 +/- 1.0%). This was also the case for the total number of nuclei per 50000 microns2 cross-sectional intimal area (numerical density): 235 +/- 13 vs. 147 +/- 7 at 16 weeks and 130 +/- 10 vs. 89 +/- 11 at 27 weeks. Apoptotic cell death (expressed as percentage of total number of nuclei) was low and there was no difference between the superficial and the deep layers of the plaques (0.8% +/- 0.2% vs. 0.4% +/- 0.2% at 16 weeks and 0.6 +/- 0.2% vs. 1.7% +/- 0.6% at 27 weeks). Our results indicate that the control of cell number in superficial vs. deep regions of the plaque is mainly a consequence of differences in cell replication. This may be due to a gradient of endothelial and plasma-derived growth factors. Cells can disappear by apoptosis, albeit at a relatively low level, throughout the lesion. This process may contribute to the pronounced cell loss in more advanced human atherosclerotic plaques, setting the base for plaque rupture. |
| Distribution of cell-derived cholesterol among plasma lipoproteins: a comparison of three techniques Francone, O. L., C. J. Fielding, et al. (1990), J Lipid Res 31(12): 2195-200. Abstract: Three fractionation procedures (immunoaffinity chromatography, two-dimensional nondenaturing electrophoresis, and heparin-agarose affinity chromatography) have been compared in determining the kinetics of free and ester cholesterol transfer in normolipemic native plasma. Similar results were obtained in each case. Cell-derived free cholesterol is initially enriched in high density lipoproteins (HDL) (mainly HDL without apoE); at longer time periods (greater than 10 min) greater proportions are observed in very low density lipoproteins (VLDL) and low density lipoproteins (LDL). The major part of cholesteryl ester (about 90%) was retained in HDL, while VLDL and LDL, which contained about 75% of total cholesteryl ester mass, received only about 10% of cell-derived cholesteryl ester. Within HDL, almost all cholesteryl ester was in the apoE-free fraction. These data provide evidence that lipoprotein free and esterified cholesterol are not at chemical equilibrium in normal plasma, and that cell-derived cholesterol is preferentially directed to HDL. The techniques used had a comparable effectiveness for the rapid fractionation of labile lipoprotein lipid radioactivity. |
| Distribution of cholesterol among its carriers in the bile of male and female hamsters Mikami, T., B. I. Cohen, et al. (1994), Lipids 29(8): 529-34. Abstract: The distribution of cholesterol among its carriers was studied in the bile of male and female hamsters. Sasco hamsters (Sasco Inc., Omaha, NE) were fed a semipurified diet with 0.0% cholesterol and 4% butterfat (group 1, males; group 4, females); a semipurified diet with 0.3% cholesterol and 1.2% palmitic acid (group 2, males; group 5, females); and a semipurified diet with 0.3% cholesterol and 4% safflower oil (group 3, males; group 6, females). At the end of six weeks, gallstones were found only in male hamsters receiving both cholesterol and dietary fat (fatty acid) (incidence of cholesterol stones: 90% in group 2; 22% in group 3). The biliary cholesterol carriers were separated and isolated from the bile of the hamsters by gel filtration chromatography, using the method of Pattinson Pattinson, N.R., Willis, K.E., and Frampton, C.M. (1991) J. Lipid Res. 32, 205-214. In those male hamsters that formed cholesterol gallstones, significant amounts of cholesterol were present in the void volume which contained large cholesterol phospholipid vesicles (void volume vesicles) (23% in group 2 and 15% in group 3). Smaller cholesterol/phospholipid vesicles were eluted next (fractions 30-45) and contained 15% of biliary cholesterol in group 2 and 21% in group 3. The remainder of the cholesterol was associated with mixed cholesterol/phospholipid/bile salt micelles. The cholesterol/phospholipid ratio was larger in both the void volume vesicles and small vesicles (2.40 and 1.48 in group 2; 2.56 and 1.33 in group 3, respectively) compared to the micelles (about 0.3 in groups 2 and 3).(ABSTRACT TRUNCATED AT 250 WORDS) |
| Distribution of cholesterol between vesicles and micelles in human gallbladder bile: influence of treatment with chenodeoxycholic acid and ursodeoxycholic acid Sahlin, S., P. Thyberg, et al. (1991), Hepatology 13(1): 104-10. Abstract: The present study aimed at determining the relative distribution of cholesterol between the vesicular and micellar phases in gallbladder bile of gallstone patients (n = 23) and gallstone-free subjects (n = 7). Nine of the gallstone patients were treated with chenodeoxycholic acid and seven were treated with ursodeoxycholic acid, 15 mg/kg/day, for 3 wk before cholecystectomy. The vesicular and micellar fractions in bile were separated by sucrose density gradient ultracentrifugation, and a clear separation between the two phases was obtained. The vesicles were further identified by quasielastic light scattering spectroscopy and appeared to be of a uniform size with a mean hydrodynamic radius of 760 A. The proportion of cholesterol in the vesicular fraction was significantly higher in the untreated gallstone group (40% +/- 4%) compared with the gallstone-free (28% +/- 3%), ursodeoxycholic acid (28% +/- 3%) and chenodeoxycholic acid (18% +/- 4%) groups. Despite a low cholesterol saturation of bile in the latter three groups (88% +/- 12%, 51% +/- 9% and 65% +/- 5%, respectively), a considerable part of the biliary cholesterol was carried in the vesicular fraction. The cholesterol/phospholipid ratio in the vesicular fraction averaged between 0.49 and 0.58 in the gallstone, gallstone-free and chenodeoxycholic acid groups, whereas the ursodeoxycholic acid group had a significantly lower ratio of 0.24. The nucleation time of bile from the gallstone group was short (2 +/- 1 days) compared with the gallstone-free, chenodeoxycholic acid and ursodeoxycholic acid groups (23 +/- 3, 24 +/- 6 and 14 +/- 3 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Distribution of cholesterol in Caribbean marine algae Govindan, M., J. D. Hodge, et al. (1993), Steroids 58(4): 178-80. Abstract: Eleven species of Caribbean marine algae (red, green, and brown) were investigated for their cholesterol content. All of them were found to contain this sterol. Consistent with previously reported results, all five red algae contained large quantities of cholesterol. However, the two brown algae and three of the four green algae in our study also contained significant quantities of cholesterol. |
| Distribution of cholesterol in HDL and its subfractions in patients with coronary atherosclerotic heart disease Jayakumari, N., K. Raghu, et al. (1993), Indian Heart J 45(4): 265-8. Abstract: The distribution of HDL-C and its subclasses HDL3-C and HDL2-C and other serum lipids was studied in patients with coronary atherosclerotic heart disease grouped as young males (group 1) and older males (group 2) along with age matched controls. All the patients had significantly higher levels of serum cholesterol, triglycerides, LDL-C and VLDL-C and lower levels of HDL-C. The analysis of HDL - subclasses clearly demonstrated that the low levels of HDL-C was due to the significant decrease of cholesterol in both HDL3 (group 1: 32%; group 2: 30%) and HDL2 subclasses (group 1: 55%; group 2: 48%) compared to the respective control values. Further it has also been observed that this low level of HDL-C is a characteristic feature of patients irrespective of whether the levels of serum cholesterol and triglycerides are high or normal. Although both the HDL subclasses were decreased, the percentage of reduction of cholesterol was greater in the HDL2 than in HDL3 subclass. In addition, the levels of cholesterol either in HDL or any of its subclasses, HDL3 and HDL2 did not show any change in relation to the extent of coronary disease which was assessed by coronary angiography. This study confirms the inverse relation of HDL-C with coronary atherosclerosis and also indicates that, of all the lipid parameters examined, only HDL-C, particularly its subclass HDL2-C, shows independent inverse relation to the incidence of coronary atherosclerotic artery disease in men. |
| Distribution of cholesterol sulfate and its anabolic and catabolic enzymes in various rabbit tissues Cui, Y. and M. Iwamori (1997), Lipids 32(6): 599-604. Abstract: Cholesterol sulfate (CS) recently has been shown to be involved in signal transduction pathway. To evaluate its functional significance, we determined the concentration of CS, and the specific activities of cholesterol sulfotransferase and CS sulfatase in various tissues of rabbit, and compared them with the concentration of sulfoglycolipids in rabbit tissues. CS was present in the epithelia and mucosa, but not in the tunica muscularis, of the digestive tract, trachea, uterine endometrium and uterine cervix. It was also present in lung, spleen, kidney, prostate, skin, hair, and nail at relatively high concentrations. Its concentration in the uterine endometrium was nine times higher in pseudopregnant rabbits than in nonpregnant rabbits because of activation of cholesterol sulfotransferase and inhibition of CS sulfatase in the pseudopregnant rabbits. Sulfoglycolipids were not detected in the uterine endometria of either non-pregnant- or pseudopregnant rabbits. However, sulfoglycolipids were detected at relatively high concentrations in the cerebrum, cerebellum, stomach, duodenum, jejunum, testis, and kidney of rabbits and thus the tissues in which both sulfolipids were detected were the gastrointestinal tract and kidney. In the digestive tract, the concentration of CS decreased in the order esophagus, stomach, duodenum, and jejunum, but that of sulfatide increased in the same order, indicating distribution of CS in the squamous epithelium. In addition, both CS and sulfatide were detected in the serum. On the other hand, CS sulfatase activity was detected in all tissues examined, even in hair, from which the enzyme was liberated by brief sonication, and its highest specific activity was detected in the liver. The specific activity of cholesterol sulfotransferase varied among the tissues examined and was found to be significantly high in the esophageal epithelium and the uterine endometrium of pseudopregnant rabbit, indicating involvement of cholesterol sulfation in the formation of epithelium. |
| Distribution of cholesterol within high density lipoproteins fractionated by immunoaffinity chromatography Pometta, D. and R. W. James (1991), Adv Exp Med Biol 285: 101-7. |
| Distribution of erythrocyte membrane cholesterol in human essential hypertension Muriana, F. J., M. A. Garcia-Donas, et al. (1994), J Hypertens 12(12): 1383-6. Abstract: OBJECTIVE: To determine whether the cholesterol distribution is impaired in erythrocyte membranes of normo- and hypercholesterolaemic patients with untreated essential hypertension. DESIGN: Observational case-control study. METHODS: Erythrocytes were prepared from venous blood samples obtained from normotensive subjects and hypertensive patients. The membrane cholesterol distribution was measured by cholesterol oxidation to cholestenone after continuous cholesterol oxidase treatment. The membrane cholesterol content was determined. The ability of cells to be labelled with 3H-cholesterol was also tested. RESULTS: The cholesterol distribution was asymmetric in erythrocyte membranes of the control subjects, and hypertensive patients. The oxidation rate was faster in normotensive subjects, and no differences were found between normo- and hypercholesterolaemic hypertensive patients. Total cholesterol mass was lower in erythrocyte membranes of hypertensive patients, as indicated by a higher incorporation of radioactive cholesterol. CONCLUSION: These data suggest that the membrane cholesterol distribution is impaired in patients with untreated essential hypertension, and support the presence of cholesterol-rich domains in the erythrocyte membrane inner monolayer. |
| Distribution of ganglioside GM1 in L-alpha-dipalmitoylphosphatidylcholine/cholesterol monolayers: a model for lipid rafts Yuan, C. and L. J. Johnston (2000), Biophys J 79(5): 2768-81. Abstract: The distribution of low concentrations of ganglioside GM1 in L-alpha-dipalmitoylphosphatidylcholine (DPPC) and DPPC/cholesterol monolayers supported on mica has been studied using atomic force microscopy (AFM). The monolayers studied correspond to a pure gel phase and a mixture of liquid-expanded (LE) and liquid-condensed (LC) phases for DPPC and to a single homogeneous liquid-ordered phase for 2:1 DPPC/cholesterol. The addition of 2.5-5% GM1 to phase-separated DPPC monolayers resulted in small round ganglioside-rich microdomains in the center and at the edges of the LC domains. Higher amounts of GM1 (10%) give numerous filaments in the center of the LC domains and larger patches at the edges. A gel phase DPPC monolayer containing GM1 showed large domains containing a network of GM1-rich filaments. The addition of GM1 to a liquid-ordered 2:1 DPPC/cholesterol monolayer gives small, round domains that vary in size from 50 to 150 nm for a range of surface pressures. Larger amounts of GM1 lead to coalescence of the small, round domains to give longer filaments that cover 30-40% of the monolayer surface for 10 mol % GM1. The results indicate that biologically relevant GM1 concentrations lead to submicron-sized domains in a cholesterol-rich liquid-ordered phase that is analogous to that found in detergent-insoluble membrane fractions, and are thought to be important in membrane microdomains or rafts. This demonstrates that AFM studies of model monolayers and bilayers provide a powerful method for the direct detection of microdomains that are too small for study with most other techniques. |
| Distribution of key ions of chloroquine biotransformation and cholesterol uptake in rat liver Achudume, A. C. and T. L. Eno (2000), Int J Food Sci Nutr 51(5): 415-20. Abstract: Oral administration to rats of chloroquine (5 mg/kg) three times per week for 8 weeks was investigated in two nutritionally compounded diets. It was observed that ferrous ion was preferentially retained in the presence of high (25%) protein diet even though all other ions, Ca2+, Mg2+ and K+ had varying uptake. The study shows no effect on the utilization of glucose and acid phosphatase. The difference in the level of lactate dehydrogenase (LDH) in both diets was not statistically significant. However, the level of cholesterol was significantly lower in both high and low protein diets when compared to control, suggesting that chloroquine biotransformation may interact with cholesterol metabolism in an unknown manner. The decrease in total cholesterol content corresponds to a similar decrease in malondialdehyde formation (lipid peroxidation). This result suggests that the biologic effects of chloroquine including its antimalarial action may be directly related to its lysosomotrophism. |
| Distribution of lipid phenotypes in community-living men with coronary heart disease. High prevalence of isolated low levels of high-density lipoprotein cholesterol Rubins, H. B., G. Schectman, et al. (1992), Arch Intern Med 152(12): 2412-6. Abstract: BACKGROUND--Risk factor modification, including treatment of dyslipidemias, has been recommended for the prevention of future coronary events in patients with coronary heart disease (CHD). Since the prevalence of various dyslipidemias among outpatients with CHD has not been well documented, the purpose of this study was to determine the frequency of specific lipid phenotypes among ambulatory men with CHD. METHODS--Lipid profiles were obtained in 255 men (mean age, 65.5 +/- 9.1 years) with CHD in three Veterans Affairs medical centers. Desirable levels of lipids were defined according to National Cholesterol Education Program guidelines as follows: low-density lipoprotein cholesterol (LDL-C) levels less than 3.36 mmol/L (130 mg/dL); high-density lipoprotein cholesterol (HDL-C) levels equal to or greater than 0.90 mmol/L (35 mg/dL); and triglyceride levels less than 2.83 mmol/L. RESULTS--Seventy-six percent of the group had one or more abnormalities on lipid profile: 51% had high LDL-C levels with or without abnormalities of HDL-C and/or triglyceride levels; 22% had low HDL-C levels with desirable levels of LDL-C; and 3% had hypertriglyceridemia without any cholesterol abnormalities. Normal lipid profiles were significantly more prevalent in subjects over the age of 65 years than in younger patients (40% vs 14%). CONCLUSIONS--These data suggest that (1) a high proportion of men with CHD have dyslipidemia, including 50% with LDL-C level elevations. For these men, the potential benefits of therapeutic intervention have been documented in clinical trials, although the cost-efficiency of wide-scale treatment has not been determined; (2) isolated hypertriglyceridemia is rare in this population; and (3) low HDL-C levels in association with desirable LDL-C levels are present in more than one fifth of male patients with CHD. Clinical trials focusing on this large group are urgently needed to determine whether efforts to raise HDL-C levels result in reduced cardiac morbidity and/or mortality. |