| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Controlled comparison of effects of exercise and alcohol on blood pressure and serum high density lipoprotein cholesterol in sedentary males Cox, K. L., I. B. Puddey, et al. (1990), Clin Exp Pharmacol Physiol 17(4): 251-5. Abstract: 1. Seventy-two sedentary male drinkers, aged 20-45 years, and with mean blood pressure (BP) at entry of 132 +/- 1.2/73 +/- 0.9 mmHg, completed a 4 week study during which they were assigned randomly to either drink a low alcohol beer (effectively reducing their weekly alcohol intake from 481 +/- 47 mL to 52 +/- 5 mL) or to continue their normal drinking habits. 2. Within these two groups subjects were further assigned to either a moderate exercise programme of three 30 min sessions per week of stationary cycling at 60-70% maximum workload or to a control light exercise programme where they pedalled against zero or minimal resistance. 3. Both alcohol restriction and moderate exercise were associated with mean falls in bodyweight of 0.5 kg. After adjustment for bodyweight a significant main effect of alcohol restriction on systolic BP (-4.1 +/- 1.7 mmHg, P less than 0.05) and diastolic BP (-1.6 +/- 0.8 mmHg, P = 0.05) was demonstrated. There was no significant main effect of moderate exercise on systolic or diastolic blood pressure despite a significant improvement in physical fitness (maximal oxygen uptake increasing from 33.2 +/- 0.8 mL/kg per min to 35.5 +/- 0.1 mL/kg per min). 4. Significant falls in high density lipoprotein cholesterol (HDLC) and triglyceride levels seen with alcohol restriction were unaffected by the increase in fitness, the magnitude of the fall being similar in both the moderate and light exercise groups.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Controlling membrane cholesterol content. A role for polyunsaturated (docosahexaenoate) phospholipids Brzustowicz, M. R., V. Cherezov, et al. (2002), Biochemistry 41(41): 12509-19. Abstract: The molecular organization of cholesterol in 1,2-didocosahexaenoylphosphatidylcholine (22:6-22:6PC) and 1-stearoyl-2-docosahexaenoylphosphatidylcholine (18:0-22:6PC) bilayers was investigated. Using low- and wide-angle X-ray diffraction (XRD), we determined that the solubility of the sterol at 20 degrees C was 11 +/- 3 mol % in 22:6-22:6PC vs 55 +/- 3 mol % in 18:0-22:6PC bilayers. Solubility in the dipolyunsaturated membrane rose to 17 +/- 3 mol % at 40 degrees C, while in the saturated-polyunsaturated membrane there was no change within experimental uncertainty. We compared the molecular orientation of 3alpha-(2)H(1)cholesterol incorporated into 22:6-22:6PC bilayers to its solubility limit and into 18:0-22:6PC bilayers to a comparable concentration (10 mol %) in solid-state (2)H NMR experiments. The sterol possessed a tilt angle alpha(0) = 24 degrees +/- 1 degrees in 22:6-22:6PC that was independent of temperature over a range from 20 to 40 degrees C. In contrast, the value was alpha(0) = 21 degrees +/- 1 degrees in 18:0-22:6 bilayers at 20 degrees C and increased to alpha(0) = 24 degrees +/- 1 degrees at 40 degrees C. We attribute the low solubility of cholesterol in 22:6-22:6PC membranes to steric incompatibility between the rigid steroid moiety and the highly disordered docosahexaenoic acid (DHA) chain, which has the potential to promote lateral heterogeneity within DHA-rich membranes. Considering 22:6-22:6PC to be the most unsaturated phospholipid found in vivo, this model membrane study provides a point of reference for elucidating the role of sterol-lipid interactions in controlling local compositional organization. Our results form the basis for a model that is consistent with cholesterol's ability to modulate the activity of certain neural transmembrane proteins. |
| Controversies in meta-analysis: the case of the trials of serum cholesterol reduction Thompson, S. G. (1993), Stat Methods Med Res 2(2): 173-92. Abstract: There has recently been disagreement in the literature on the results and interpretation of meta-analyses of the trials of serum cholesterol reduction, both in terms of the quantification of the effect on ischaemic heart disease and as regards the evidence of any adverse effect on other causes of death. This paper describes statistical aspects of a recent meta-analysis of these trials, and draws some more general conclusions about the methods used in meta-analysis. Tests of an overall null hypothesis are shown to have a basis clearly distinct from the more extensive assumptions needed to provide an overall estimate of effect. The fixed effect approach to estimation relies on the implausible assumption of homogeneity of treatment effects across the trials, and is therefore likely to yield confidence intervals which are too narrow and conclusions which are too dogmatic. However the conventional random effects method relies on its own set of unrealistic assumptions, and cannot be regarded as a robust solution to the problem of statistical heterogeneity. The random effects method is more usefully regarded as a type of sensitivity analysis in which the weights allocated to each study in estimating the overall effect are modified. However, rather than using a statistical model for the 'unexplained' heterogeneity, greater insight and scientific understanding of the results of a set of trials may be obtained by a careful exploration of potential sources of heterogeneity. In the context of the cholesterol trials, the heterogeneity according to the extent and duration of cholesterol reduction are of prime concern and are investigated using logistic regression. It is concluded that the long-term benefits of serum cholesterol reduction on the risk of heart disease have been seriously underestimated in some previous meta-analyses, while the evidence for adverse effects on other causes of death have been misleadingly exaggerated. |
| Convergence of atherosclerosis and Alzheimer's disease: inflammation, cholesterol, and misfolded proteins Casserly, I. and E. Topol (2004), Lancet 363(9415): 1139-46. Abstract: Late-onset sporadic Alzheimer's disease is a heterogeneous disorder. In elderly patients, increasing evidence suggests a link between this neurodegenerative disease, and vascular risk factors and atherosclerosis. The nature of this link remains speculative. Some investigators have suggested that the disease arises as a secondary event related to atherosclerosis of extracranial or intracranial vessels. A toxic effect of vascular factors on the microvasculature of susceptible brain regions has also been argued. An alternative explanation is that atherosclerosis and Alzheimer's disease are independent but convergent disease processes. This hypothesis is lent support by observations of shared epidemiology, pathophysiological elements, and response to treatment in both disorders. It provides a potential framework for an improved understanding of the pathogenesis of Alzheimer's disease, especially in elderly patients with vascular risk factors, and offers some promise toward the search for preventive and therapeutic treatments. |
| Conversion from cyclosporin A to tacrolimus is safe and decreases blood pressure, cholesterol levels and TGF-beta 1 type I receptor expression Baan, C. C., I. C. van Riemsdijk-van Overbeeke, et al. (2001), Clin Transplant 15(4): 276-83. Abstract: To determine whether conversion from cyclosporin A (CsA) to tacrolimus (TAC)-based immunosuppressive therapy is safe and might lead to improvement in the clinical side effect profile we studied 55 cardiac allograft recipients. Ten stable patients were electively converted (0.2-1.5 yr after transplantation; group I) and 45 patients were converted on indication (0.5-14 yr after transplantation; group II). We studied blood pressure, cholesterol level and renal function in all patients. To unravel the mechanisms by which CsA may exert its toxic effects and to evaluate whether conversion is associated with immune activation, we analyzed the transforming growth factor (TGF)-beta 1 system and intragraft interleukin (IL)-2 and IL-15 mRNA expression by real-time reverse transcription-polymerase chain reaction (RT-PCR) and quantitative flow cytometry in the selectively converted patients (group I). Conversion did not result in immune activation as no clinical, histological or molecular signs of immune activation (increased intragraft IL-2 and IL-15 messenger RNA (mRNA) expression) leading to rejection were found. It did not improve renal function neither in patient group I nor in patient group II. However, after conversion the blood pressure decreased (group I: systolic 154+/-16 vs 143+/-21 mmHg, p=0.03, diastolic: 99+/-11 vs 90+/-11, p=0.02 and group II: systolic 155+/-17 vs 142+/-14, p<0.001, diastolic: 99+/-11 vs 91+/-8 mmHg, p<0.001). Likewise, the cholesterol levels improved (group I: 6.6+/-0.5 vs 5.7+/-0.3 mmol/L, p=0.001 and group II: 7.1+/-1.7 vs 6.1+/-1.7 mmol/L, p=0.001). When patients were treated with TAC the ongoing rejections (n=4) resolved and gum hyperplasia disappeared (n=5). Conversion was associated with a two-fold lower TGF-beta 1 type I receptor expression on peripheral lymphocytes and monocytes (p=0.02 and p=0.002, respectively). Conversion from CsA to TAC results in improvement of blood pressure and cholesterol levels and does not induce immune activation. These beneficial effects were accompanied with lower TGF-beta 1 type I receptor expression. |
| Conversion of cholesterol to coprostanol by the intestinal microflora during the first two years of human life Midtvedt, A. C. and T. Midtvedt (1993), J Pediatr Gastroenterol Nutr 17(2): 161-8. Abstract: The establishment of the conversion of cholesterol to coprostanol by the intestinal microflora was followed in 25 healthy Swedish children by gas-chromatographic analysis of fecal samples taken at 0, 1, 3, 6, 9, 12, 15, 18, 21, and 24 months of age. In 15 children, the microbial conversion of cholesterol to coprostanol started during the second half of the first year of life. During the second year of life, a sequestered distribution of the conversion rate could be distinguished. At the end of the study, 13 of the children were stable high converters, 3 were stable low converters, and 6 were unstable converters while the conversion pattern of three children could not be determined. The initiation of the establishment of conversion was delayed by breast-feeding, and only one child had coprostanol in feces while still being breast-fed. Those children exclusively breast-fed for more than 4 months or weaned after 6 months of age had significantly lower conversion rates at 12 months of age than did the other children (p < 0.05). Once conversion started, previous breast-feeding tended to result in a stable, later high rate of conversion of cholesterol. Between 6 and 15 months of age, the conversion rate increased with age, but after standardization for the period of exposure to foods other than breast milk, no age factor could be identified. |
| Conversion of cholesterol to pregnenolone mobilizes cytochrome P-450 in the inner membrane of adrenocortical mitochondria: protein rotation study Ohta, Y., F. Mitani, et al. (1990), J Biochem (Tokyo) 107(1): 97-104. Abstract: Rotation of cytochrome P-450 was examined in bovine adrenocortical mitochondria before and after an enzymatic transformation of cholesterol into pregnenolone by cytochrome P-450scc in the presence of malate. Rotational diffusion was measured by observing the decay of absorption anisotropy, r(t), after photolysis of the heme.CO complex by a vertically polarized laser flash. Analysis of r(t) was based on a "rotation-about-membrane normal" model. The measurements were used to investigate substrate-dependent intermolecular interactions of cytochrome P-450 with other redox components. Rotational mobility of cytochrome P-450 was significantly dependent on the decrease in cholesterol content by side chain cleavage reaction catalyzed by cytochrome P-450scc. In a typical experiment, the observed value for the normalized time-independent anisotropy r(infinity)/r(0) was decreased from 0.78 in control mitochondria to 0.60 after conversion of 21% of cholesterol to pregnenolone, while no significant change was observed for the average rotational relaxation time phi of about 700 microseconds. Significantly high values of r(infinity)/r(0) = 0.78 and 0.60 imply co-existence of mobile and immobile populations of cytochrome P-450. Since we observed that the heme angle tilted 55 degrees from membrane plane, 22% (control mitochondria) and 40% (after conversion of cholesterol to pregnenolone) of cytochrome P-450 in mitochondria are calculated to be mobile in the preparation. The significant mobilization of cytochrome P-450scc molecules caused by the conversion of cholesterol to pregnenolone is likely due to changes in protein-protein interactions with its redox partners, since the lipid fluidity was kept unchanged by the cholesterol depletion.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Conversion of the myometrial oxytocin receptor from low to high affinity state by cholesterol Fahrenholz, F., U. Klein, et al. (1995), Adv Exp Med Biol 395: 311-9. Abstract: Reconstitution experiments with the myometrial oxytocin receptor from guinea pig showed a strong requirement of the oxytocin receptor binding function for the presence of cholesterol in preformed liposomes. To investigate the effect of cholesterol on the oxytocin receptor in the plasma membrane, a new method to modify the membrane cholesterol content was developed. With substituted cyclodextrins we were able to selectively deplete the myometrial plasma membrane of cholesterol. Vice versa, incubation of cholesterol-depleted membranes with a soluble cholesterol cyclodextrin complex restored the cholesterol content of the plasma membrane. Binding experiments showed, that with the removal of cholesterol from the membrane, the oxytocin receptor was converted from high to low affinity state. Increasing the cholesterol content of the membrane again restored the high binding affinity. Substitution of membrane cholesterol with other steroids showed a strong dependence of the oxytocin receptor function on the structure of the cholesterol molecule. Experiments with the detergent solubilized oxytocin receptor and with oxytocin receptors expressed in the Baculovirus/Sf9 cell system provided further evidence for a direct interaction of the oxytocin receptor with cholesterol. |
| Convex-concave curvatures in bilayers of dipalmitoylphosphatidylcholine and cholesterol induced by amphotericin B/deoxycholate after prolonged storage Meyer, H. W., W. Richter, et al. (1994), Biochim Biophys Acta 1190(1): 9-19. Abstract: Freeze-fracture investigations on the influence of amphotericin B/deoxycholate on multilamellar vesicles (MLV) of DPPC containing cholesterol have revealed a new phase structure. Alternating convex and concave curvatures are observed after storage of the vesicles at temperatures below 25 degrees C for at least 4 weeks. Three types of these patterns occur, a small-dimensional (repeat distance approximately 100 nm), an intermediate-dimensional (repeat distance approximately 400 nm) and a large-dimensional (repeat distance approximately 700 nm). The types can be formed on the same bilayer side by side. Additionally, the types differ in the morphology of the tops. In the case of the small-dimensional type the shape of the top can be described as a circular flat plane or opening and in the other cases as a hemispherical cap. The large dimensional type differs from the others by involvement of bilayer stacks. The formation of this new phase after prolonged storage could be confirmed by DSC measurements. The new structure can be explained in the framework of bicontinuous cubic phases and periodically curved bilayer structures. From the electron micrographs a lo (liquid ordered) phase is suggested. |
| Cookies enriched with psyllium or oat bran lower plasma LDL cholesterol in normal and hypercholesterolemic men from Northern Mexico Romero, A. L., J. E. Romero, et al. (1998), J Am Coll Nutr 17(6): 601-8. Abstract: BACKGROUND: Psyllium and oat bran have been shown to lower plasma LDL cholesterol levels in different populations. Hypercholesterolemia is prevalent in the Northern part of Mexico and might be associated to dietary habits and sedentary lifestyle. METHODS: Sedentary normal (cholesterol<200 mg/dL) (n=36) and hypercholesterolemic (cholesterol>220 mg/dL) (n=30) men from the Northern part of Mexico aged 20 to 45 years of age participated in an 8-week study to determine the effects of dietary soluble fiber, either psyllium or oat bran, in lowering plasma LDL cholesterol in this population. Fiber was administered by feeding the subjects an amount of cookies (100 g) equivalent to 1.3 or 2.6 g/day of soluble fiber from psyllium or oat bran, respectively. Subjects were randomly allocated to three groups: a control group consuming cookies with wheat bran, a known source of fiber with no cholesterol lowering effects, psyllium, or oat bran. RESULTS: Food frequency questionnaires indicated that subjects from the three groups had similar intakes of foods classified as hypercholesterolemic (p>0.05). Plasma LDL cholesterol concentrations were reduced by an average of 22.6 and 26% in the psyllium and oat bran groups (p<0.001) while a non-significant reduction of 8.4% was observed in the hypercholesterolemic individuals from the control group. No effects on plasma HDL or triglycerides levels were observed among the three dietary treatments except for hypercholesterolemic individuals supplemented with oat bran where a 28% reduction in plasma triglycerides was observed after 8 weeks (p<0.01). CONCLUSION: These results indicate that psyllium and oat bran are efficacious in lowering plasma LDL cholesterol in both normal and hypercholesterolemic individuals from this population. |
| Cooking oils, cholesterol and CAD: facts and myths Enas, E. A. (1996), Indian Heart J 48(4): 423-7. Abstract: Elevated blood cholesterol is the strongest risk factor for coronary artery disease, and dietary excess of saturated fats is its largest contributor. Contrary to common belief, the contribution of dietary cholesterol to blood cholesterol is small. As a matter of fact, one need not consume cholesterol to have high blood cholesterol. Most vegetable cooking oils are low in saturated fats and are "heart healthy" with the important exception of tropical oils, such as coconut and palm oil, which are very rich in saturated fats. Though these oils contain no cholesterol, their cholesterol-raising potential is similar to or higher than most animal fats. Liberal use of these oils should be discouraged. |
| Cooperative unit and enthalpy studies of cholesterol and cholesteryl esters in dimyristoylphosphatidylcholine liposomes Malcolmson, R. J., P. H. Beswick, et al. (1992), Biochem Soc Trans 20(4): 349S. |
| Coordinate diurnal regulation of hepatic acyl-coenzyme A: cholesterol acyltransferase and cellular levels of esterified cholesterol Szanto, A., J. Ruys, et al. (1994), Biochim Biophys Acta 1214(1): 39-42. Abstract: Hepatic ACAT, HMG-CoA reductase and both cellular free and esterified cholesterol were measured at 3 h intervals over a 24 h period in the rat. ACAT exhibited a characteristic low amplitude diurnal rhythm with maximum activity at the mid-light phase that was significantly higher than the minimum activity observed at the mid-dark phase. The cellular esterified cholesterol concentration showed a diurnal rhythm that closely paralleled the rhythm of ACAT activity. The cellular free cholesterol concentration was not significantly altered during the 24 h cycle. In rats fed cholesterol, the diurnal rhythm of ACAT was still maintained despite the increase in ACAT activity during the entire 24 h cycle suggesting that the ACAT rhythm is the result of changes in the level of ACAT protein expression. The results also indicate that the diurnal rhythms of ACAT and HMG-CoA reductase are generated by a process independent of the LDL receptor rhythm. All three rhythms are also independent of changes in the level of free cholesterol in the cell. |
| Coordinate regulation of cholesterol 7 alpha-hydroxylase and HMG-CoA reductase in the liver Bjorkhem, I., E. Lund, et al. (1997), Subcell Biochem 28: 23-55. |
| Coordinated control of cholesterol catabolism to bile acids and of gluconeogenesis via a novel mechanism of transcription regulation linked to the fasted-to-fed cycle De Fabiani, E., N. Mitro, et al. (2003), J Biol Chem 278(40): 39124-32. Abstract: Bile acid metabolism plays an essential role in cholesterol homeostasis and is critical for the initiation of atherosclerotic disease. However, despite the recent advances, the molecular mechanisms whereby bile acids regulate gene transcription and cholesterol homeostasis in mammals still need further investigations. Here, we show that bile acids suppress transcription of the gene (CYP7A1) encoding cholesterol 7alpha-hydroxylase, the rate-limiting enzyme in bile acid biosynthesis, also through an unusual mechanism not involving the bile acid nuclear receptor, farnesoid X receptor. By performing cell-based reporter assays, protein/protein interaction, and chromatin immunoprecipitation assays, we demonstrate that bile acids impair the recruitment of peroxisome proliferator-activated receptor-gamma coactivator-1alpha and cAMP response element-binding protein-binding protein by hepatocyte nuclear factor-4alpha, a master regulator of CYP7A1. We also show for the first time that bile acids inhibit transcription of the gene (PEPCK) encoding phosphoenolpyruvate carboxykinase, the rate-limiting enzyme in gluconeogenesis, through the same farnesoid X receptor-independent mechanism. Chromatin immunoprecipitation assay revealed that bile acid-induced dissociation of coactivators from hepatocyte nuclear factor-4alpha decreased the recruitment of RNA polymerase II to the core promoter and downstream in the 3'-untranslated regions of these two genes, reflecting the reduction of gene transcription. Finally, we found that Cyp7a1 expression was stimulated in fasted mice in parallel to Pepck, whereas the same genes were repressed by bile acids. Collectively, these results reveal a novel regulatory mechanism that controls gene transcription in response to extracellular stimuli and argue that the transcription regulation by bile acids of genes central to cholesterol and glucose metabolism should be viewed dynamically in the context of the fasted-to-fed cycle. |
| Coping with cholesterol. The waxy buildup in our blood vessels is a leading cause of fatal heart disease. Do dietary supplements add anything to the arsenal against it? Kalb, C. (2000), Newsweek 135(25): 73, 75. |
| Copper oxidation of in vitro dioleolylphosphatidylcholine-enriched high-density lipoproteins: physicochemical features and cholesterol effluxing capacity Therond, P., D. Bonnefont-Rousselot, et al. (1999), Arch Biochem Biophys 362(1): 139-47. Abstract: Susceptibility of lipoproteins to oxidation is partly determined by their content in endogenous antioxidants, but also by the polyunsaturated fatty acids (PUFA)/monounsaturated fatty acids (MUFA) ratio. The aim of our study was to enrich human high-density lipoproteins (HDLs) with dioleoylphosphatidylcholine (DOPC) in order to modify the PUFA/MUFA ratio while maintainig the alpha-tocopherol/PUFA ratio constant and to appreciate the consequences of this enrichment before and after copper-induced oxidation. The enrichment of HDLs with DOPC was obtained by incubation of these lipoproteins with DOPC liposomes and further reisolation of HDLs. The consequent 40% HDL enrichment in MUFA was concomitant with a 35% loss in PUFA (MUFA/PUFA ratio = 1.43). The enrichment of HDLs with DOPC led to a 40% decrease in alpha-tocopherol content, which kept a constant alpha-tocopherol/PUFA ratio. The DOPC-HDLs exhibited a lower oxidizability by copper than the nonenriched HDLs (NE-HDLs), as shown by their twofold longer lag phase and the threefold lower propagation rate. Moreover, DOPC-HDLs led to a six- to sevenfold lower production of hydroperoxide molecular species from phosphatidylcholine and cholesteryl esters than NE-HDLs after 24 h copper oxidation. With regard to the cholesterol effluxing capacity, copper oxidation of HDLs led to a decrease of this property. However, our results clearly showed that DOPC enrichment of HDLs allowed us to keep a better effluxing capacity than in NE-HDLs after 24 h oxidation (22.3% vs 17.4%, respectively). Since apo A-I was degraded as well in DOPC-HDLs as in NE-HDLs, the better effluxing capacity of DOPC-HDLs could not come from a preserved integrity of apo A-I. It could be partly related to the improved fluidity of oxidized DOPC-HDLs compared to oxidized NE-HDLs, as shown by electron spin resonance data (correlation-relaxation time at 24 degreesC = 2.20 ns vs 3.00 ns after 24 h oxidation, in DOPC-HDLs and in NE-HDLs, respectively). Besides, it could also be hypothesized that the sevenfold lower content of phosphatidylcholine hydroperoxides in DOPC-HDLs than in NE-HDLs after 24 h copper oxidation could be involved in the better ability of oxidized DOPC-HDLs to mobilize cellular cholesterol. |
| Copper status, serum cholesterol, and milk fatty acid profile in Holstein cows fed varying concentrations of copper Engle, T. E., V. Fellner, et al. (2001), J Dairy Sci 84(10): 2308-13. Abstract: An experiment was conducted to determine the effects of dietary copper (Cu) on Cu status and lipid metabolism in Holstein cows. Three primiparous and 21 multiparous Holstein cows were utilized in this experiment. Groups of three cows similar in parity, days in milk, and milk yield were assigned randomly to one of the following three treatments: 1) control (no supplemental Cu), 2) 10 mg of Cu/kg of DM from Cu sulfate (CuSO4), and 3) 40 mg of Cu/kg of DM from CuSO4. Liver Cu concentrations were higher in Cu supplemented cows at the end of the 61-d study. Cows receiving 40 mg of Cu/kg of DM had higher liver Cu concentrations than cows receiving 10 mg of Cu. Plasma Cu concentrations were similar across treatments. Total serum cholesterol concentrations were higher in cows receiving supplemental Cu. Cows receiving 40 mg of Cu/kg of DM had higher serum cholesterol concentrations than cows receiving 10 mg of Cu. Dry matter intake, average daily milk production, and milk lipid, protein, and somatic cell numbers were similar across treatments. On d 61, milk fatty acids C18:1 trans and C18-conjugated dienes were lower in cows receiving supplemental Cu relative to the nonsupplemented controls. Cows receiving 40 mg of Cu/kg of DM had higher C12:0 and lower C18:2 and total polyunsaturated fatty acids in milk than cows receiving 10 mg of Cu/kg of DM. These results indicate that Cu supplementation alters lipid metabolism in high producing dairy cows and that Cu supplementation at 40 mg/kg of DM for 61 d can elevate liver Cu concentrations to levels considered to be marginally toxic in dairy cattle. |
| Copper supplementation effects on indicators of copper status and serum cholesterol in adult males Medeiros, D. M., A. Milton, et al. (1991), Biol Trace Elem Res 30(1): 19-35. Abstract: Two 6-wk double-blind studies evaluated the effects of supplements of 2 or 3 mg Cu/d on serum copper, ceruloplasmin, red-blood-cell super oxide dismutase (RBC-SOD), total serum cholesterol, and serum lipoprotein-cholesterol fractions in adult males. Study I had 6 supplemented and 8 placebo subjects, whereas study II had 7 and 6, respectively. Copper supplementation did not appear to affect serum copper levels, RBC-SOD, hematocrit, and ceruloplasmin levels when assayed by radial immunoassay diffusion. Supplementation with 2 mg Cu/d produced an increase in LDL cholesterol and the percentage of cholesterol as LDL at wk 4 compared to the placebo group, and a concomitant decline in VLDL-cholesterol levels and the percentage of cholesterol as VLDL. At wk 6, the percentage of cholesterol as LDL increased and that of cholesterol as VLDL decreased compared to baseline values in the supplemented group. Supplements of 3 mg Cu/d increased hemoglobin levels, ceruloplasmin activity, and serum total-cholesterol levels at wk 6 compared to placebos. Differences in cholesterol may be partly explained by variability in the placebo groups in both studies. Copper supplementation effects on cholesterol deserves further investigation. |
| Copper-induced and photosensitive oxidation of serum low-density lipoprotein. The relation to cholesterol level and inter-species differences Mosinger, B. J. (1995), Biochim Biophys Acta 1270(1): 73-80. Abstract: Hypercholesterolemia is associated with a higher risk for developing atherosclerotic coronary heart disease. During the past few years, evidence has been increasing that modification of lipoproteins, particularly low-density lipoprotein (LDL) oxidation, might be involved in the pathogenesis of atherosclerosis. To compare these factors metal-dependent and -independent photodynamic methods were used for the screening of several indexes of LDL oxidation. Lipid oxidation has been continuously monitored by the increase of conjugated dienes and verified by iodometric and thiobarbituric reaction assay. A close association between LDL cholesterol concentration (and/or serum cholesterol concentration) and LDL maximum diene formation was found using both methods and different sources of sera. With copper-induced oxidation, highly significant correlation coefficient r = 0.86, and with photo-sensitive oxidation r = 0.84 were noted. The data standardized to protein unit showed a reduced but still significant correlation. The extent of LDL oxidation was also closely related to preformed dienes, i.e., to the data obtained before the start of oxidation (r = 0.91). The rate of LDL oxidation was positively linked to LDL cholesterol using both oxidation methods but with photo-sensitive oxidation the rate was much higher. The lag time was inversely related to LDL cholesterol (standardized data) with Cu2+ induced oxidation but it was absent in the photosensitive oxidation. In animals known to be resistant to spontaneous atherosclerosis (rats, guinea pigs) a prolonged lag time, markedly reduced diene formation and lower LDL cholesterol in LDL in parallel was demonstrated. The fact that, using various methods (epidemiology, arteriography, autopsy), the cholesterol level in men was found positively linked to atherosclerosis development on the one hand, and positively associated to oxidation of human LDL on the other, strongly supports the concept on the important role of LDL oxidative modification in this pathological process. |