| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| The effect of verapamil and nifedipine on cholesterol esterification and accumulation in macrophages Dushkin, M. I. and M. V. Ivanova (1992), Eksp Klin Farmakol 55(3): 37-9. Abstract: Administration of verapamil and nifedipine in doses of 10-75 microM into the culture of mouse peritoneal macrophages incubated in a non-lipid medium with acetylated low density lipoproteins (50 g protein/ml) decreased the incorporation of 14C oleate into cholesterol esters by 50-90%, increased the content of intracellular free cholesterol by 19-79% and did not influence the content of total cholesterol in macrophages. Administration of verapamil and nifedipine in doses of 25 and 50 microM in the culture of macrophages previously enriched with cholesterol reduced the rate of cholesterol esterification by 22-62%. After combined administration of verapamil and nifedipine in doses of 25 microM into the medium the rate of cholesterol esterification in macrophages fell by 72.4%. |
| The effect of vitamin C in high doses on plasma and biliary lipid composition in patients with cholesterol gallstones: prolongation of the nucleation time Gustafsson, U., F. H. Wang, et al. (1997), Eur J Clin Invest 27(5): 387-91. Abstract: Vitamin C deficiency in guinea pigs leads to cholesterol supersaturation of bile and formation of cholesterol gallstones. It has been suggested that there may also exist an association between vitamin C and cholesterol gallstones in man, but such a relationship has not been studied in gallstone patients. In order to study the possible effects of vitamin C on gallstone disease in humans, plasma lipid levels, hepatic cholesterol metabolism, biliary lipid composition, cholesterol saturation and nucleation time of gallbladder bile were analysed in 16 consecutive gallstone patients, who were planned for laparoscopic cholecystectomy and were treated with vitamin C (500 mg, four times a day) for 2 weeks before surgery. The plasma concentration of vitamin C increased by 42% in the treatment group. The concentrations of plasma lipids did not differ before and after vitamin C treatment; nor did the plasma levels of lathosterol and 7 alpha-hydroxy-4-cholesten-3-one, reflecting cholesterol and bile acid synthesis respectively. The relative concentrations of cholesterol, bile acids and cholesterol concentration of bile did not differ significantly between the two groups, but the relative concentration of phospholipids was slightly higher in the treated group. The bile acid composition was changed; the percentage of cholic acid being lower and those of deoxycholic acid, ursodeoxycholic acid and lithocholic acid higher in the vitamin C-treated patients compared with the untreated group. The nucleation time was significantly longer in the treatment group (7 days) compared with the untreated group (2 days). Our findings indicate that vitamin C supplementation may also influence the conditions for cholesterol gallstone formation in humans. |
| The effect of VLDL particles on the accuracy of a direct LDL-cholesterol method in type 2 diabetic patients Wagner, A. M., E. Zapico, et al. (2003), Clin Biochem 36(3): 177-83. Abstract: OBJECTIVE: To assess the accuracy of the direct method LDL-c Plus, in type 2 diabetic patients.LDL-c Plus was measured in 64 consecutive samples of type 2 diabetic patients and compared with betaquantification (BQ), Friedewald's and an alternative formula. METHODS: LDL-c Plus was also measured in the VLDL (d<1.006 Kg/L) fraction of these samples and in total serum and the VLDL fraction of a phenotype III patient, before and after diluting it with saline or VLDL from normolipidemic subjects. RESULTS: LDL-c Plus showed a significant, constant bias (-8.5 +/- 5.6%) against BQ which correlated with VLDL-cholesterol/total triglyceride ratio (r = 0.760, p < 0.0005); bias decreased to zero when the ratio increased. In the VLDL fraction of the diabetic patients and the phenotype III patient LDL-c Plus measured 20.7 +/- 11.6% and 56.2% of the cholesterol, respectively. Dilution with saline did not alter the latter percentage, whereas dilution with normolipidemic VLDL reduced it showing that LDL-c Plus recognized cholesterol-enriched particles in the d<1.006 Kg/L. Friedewald's formula also showed a significant, constant bias (-3.1 +/- 6.4%) against BQ, whereas the alternative formula did not (0.5 +/- 6.1%). Both calculations classified patients better than LDL-c Plus did at NCEP cut-off points. CONCLUSIONS: In type 2 diabetic patients, LDL-c Plus underestimates LDL-c but measures cholesterol associated to IDL particles in the d<1.006 Kg/L fraction. Although LDLc-Plus might be a better cardiovascular risk estimator when well standardized, at the moment, it does not seem to be superior to calculations. |
| The effect of ximedon on cholesterol metabolism and experimental atherosclerosis in rabbits Dautova, G. S., V. A. Kosykh, et al. (1995), Eksp Klin Farmakol 58(1): 25-9. Abstract: The effects produced by the two pyrimidine derivatives pyridinol carbamate (parmidine) and xymedon on cholesterol metabolism and experimental atherosclerosis were comparatively studied in rabbits. The rabbits were fed either a chow containing cholesterol (200 mg/kg body weight) or the same diet also containing xymedon (30 mg/kg body weight) or pyridinol carbamate (30 mg/kg body weight). Total plasma cholesterol showed 5.5- and 4.7-fold increases in the rabbits receiving only cholesterol or cholesterol + pyridinol carbamate, respectively, as compared with that in the animals on a standard laboratory chow. In the rabbits given cholesterol+xymedon, cholesterol levels were 24% less than that in the animals taking cholesterol alone. In these animals, the aortic atherosclerotic damage index (ADI) was equal to 24.1%, which was 1.8-fold less than that in the cholesterol-fed rabbits. In the rabbits given cholesterol+pyridinol carbamate, ADI was decreased by 1.7 times, but it did not differ from that in the hypocholesterolemic rabbits. At the same time xymidone and pyridinol carbamate reduced the hepatic levels of total and esterified cholesterol. To elucidate the mechanism of action of xymedon, it was studied for effects on cholesterol metabolism in cultured rabbit hepatocytes and murine macrophage J774. Xymedon did not alter the esterification and other parameters of cholesterol metabolism in the cultured hepatocytes. It is suggested that the hypocholesterolemic effect was realized at the level of intestinal rather than hepatic cholesterol metabolic changes. The investigations made on the murine macrophage J744 showed that xymedone reduced cholesterol esterification in macrophages, evidently by inhibiting the activity of the enzyme acyl-CoA: cholesterol acyltransferase. The anti-atherosclerotic effect of xymedon seems to result from reductions in plasma cholesterol levels and cholesterol esterification in blood vascular cells. |
| The effects of a single dose of dilevalol on 3H-noradrenaline plasma kinetics and plasma lipoprotein cholesterol concentrations Howes, L. G., P. R. Rowe, et al. (1990), Br J Clin Pharmacol 29(3): 281-7. Abstract: 1. A single oral dose of dilevalol (200 mg or 400 mg) or placebo was administered to 15 normal male volunteers in a double-blind, random order crossover study. 2. Dilevalol had no significant effect on supine blood pressures or heart rates, but caused a significant fall in systolic blood pressure 1 and 30 min following standing, and attenuated the rise in diastolic blood pressure and heart rate that accompanies standing. 3. Dilevalol caused a dose dependent increase in plasma noradrenaline levels from arterialized blood which was due to an increase in noradrenaline spillover with no change in clearance. 4. Dilevalol increased plasma levels of the noradrenaline metabolite 3,4-dihydroxyphenylethylene glycol (DHPG) (which is formed in sympathetic nerves following neuronal uptake of noradrenaline), indicating that the increase in noradrenaline spillover was not due to the blockade of neuronal uptake. 5. Acute dilevalol administration had no effect on total plasma cholesterol, HDL-cholesterol or LDL-cholesterol levels. |
| The effects of amphotericin B on pure and ergosterol- or cholesterol-containing dipalmitoylphosphatidylcholine bilayers as viewed by 2H NMR Paquet, M. J., I. Fournier, et al. (2002), Chem Phys Lipids 119(1-2): 1-11. Abstract: Amphotericin B (AmB) is a widely used polyene antibiotic to treat systemic fungal infections. This drug is known to be lethal to fungal cells but it has also side effect toxicity on mammalian cells. The mechanism of action of AmB is thought to be related to the difference of the main sterol present in the mammalian and the fungal cells, namely cholesterol and ergosterol, respectively. The effect of AmB has been investigated on pure dipalmitoylphosphatidylcholine (DPPC) and on cholesterol- and ergosterol-containing DPPC bilayers by 2H NMR spectroscopy. The 2H NMR results first confirm that AmB forms a complex with sterol-free DPPC bilayers, the interaction causing the structurization of the lipids and the increase of the gel-to-lamellar fluid DPPC phase transition temperature with increasing concentration of the antibiotic. The results also show that the effects of AmB on cholesterol- and ergosterol-containing DPPC bilayers are remarkably different. On one hand, the drug causes an increase of the orientational order of the lipid acyl chains in cholesterol-containing membranes, mostly in high cholesterol content membranes. On the other hand, the addition of AmB disorders the DPPC acyl chains when ergosterol is present. This is thought to be due to the direct complexation of the ergosterol by AmB, causing the sterol ordering effect to be weaker on the lipids. |
| The effects of Ananas comosus L. leaves on diabetic-dyslipidemic rats induced by alloxan and a high-fat/high-cholesterol diet Xie, W., D. Xing, et al. (2005), Am J Chin Med 33(1): 95-105. Abstract: The aim of this study is to demonstrate the effects of Ananas comosus L. leaves on diabetic-dyslipidemic rats. Hypoglycemic and hypolipidemic activities of the ethanolic extract of Ananas comosus L. leaves (EEACL) were evaluated in normal and alloxan-induced diabetic rats by oral glucose tolerance test and an olive oil load test. Anti-diabetic, anti-hyperlipidemic and anti-oxidative activities of EEACL were also investigated in diabetic-dyslipidemic rats induced by alloxan and a high-fat/high-cholesterol diet. EEACL at the dose of 0.40 g/kg significantly inhibited the increase in blood glucose in diabetic rats in oral glucose tolerance test, but did not cause any hypoglycerimic activity in normal rats. It also significantly inhibited the increase in postprandial triglycerides (TG) levels in both normal and diabetic rats in olive oil load test. After 15 days of treatment of diabetic dyslipidemic rats, EEACL significantly decreased blood glucose (-51.0%, P < 0.01), TG (-50.1%, P < 0.01), TC (-23.3%, P < 0.01), LDL-c (-47.9%, P < 0.01) and glycated albumin (-25.4%, P < 0.01) levels, significantly increased serum high-density lipoprotein cholesterol levels (66.2%, P < 0.01) and prevented lower body weight of diabetes (11.8%, P < 0.05), significantly lowered lipid peroxidation productions of blood (-27.8%, P < 0.01), brain (-31.6%, P < 0.05), liver (-44.5%, P < 0.01) and kidneys (-72.2%, P < 0.05) compared with those in untreated diabetic dyslipidemic rats. These data suggest that EEACL has anti-diabetic, anti-dyslipidemic and anti-oxidative activities, which may be developed into a new plant medicine for treatment of diabetes and its complications. |
| The effects of bitter melon (Momordica charantia) extracts on serum and liver lipid parameters in hamsters fed cholesterol-free and cholesterol-enriched diets Senanayake, G. V., M. Maruyama, et al. (2004), J Nutr Sci Vitaminol (Tokyo) 50(4): 253-7. Abstract: The hypolipidemic effect of dietary methanol fraction (BMMF) extracted from bitter melon (Koimidori variety), at the levels of 0.5% and 1.0%, was examined in male golden Syrian hamsters fed diets supplemented with and without cholesterol. The feeding of BMMF at 0.5% and 1.0% levels in the diets for 4 wk tended to reduce food intake and growth, although there was no difference in food efficiency (weight gain/food intake). An effect of dietary BMMF on serum triglyceride was not seen in hamsters fed diets free of cholesterol, while hypertriglyceridemia induced by dietary cholesterol was significantly lowered in a dose-dependent manner in those fed diets containing the BMMF Serum total cholesterol concentration also tended to decrease in a dose-dependent manner following feeding of increasing amounts of BMMF in the presence and absence of cholesterol in the diet. The effects of dietary BMMF on liver triglyceride and total cholesterol levels were marginal, although dietary cholesterol caused a marked accumulation of these lipid molecules in the liver. These results suggest that the BMMF contains some components that could ameliorate lipid disorders such as hyperlipidemia. |
| The effects of changing statins on cholesterol levels Mann, S. and G. Clare (1999), N Z Med J 112(1091): 260. |
| The effects of cholesterol depletion on the sodium pump in human red cells Lucio, F. J., B. M. Hendry, et al. (1991), Exp Physiol 76(3): 437-43. Abstract: Sodium pump function has been studied in human erythrocytes depleted of membrane cholesterol by incubation with phosphatidylcholine liposomes. The cells were sodium loaded by incubation in alkaline sodium phosphate and sodium pump activity was assessed by measurements of ouabain-sensitive 86Rb uptake at 37 degrees C. Cholesterol depletion had a biphasic effect; depletion by 5-25% increased sodium pump activity by a mean of 16.1% (S.D. 3.2%), whereas depletion by 35-50% decreased sodium pump activity by a mean of 14.8% (S.D. 3.8%). Cholesterol depletion had no reproducible effect on the ouabain-insensitive uptake of Rb. These results support the hypothesis that there may be an optimum membrane cholesterol content for sodium pump function. |
| The effects of cholesterol hemisuccinate and other membrane fluidity perturbing agents on inositol 1,4,5-trisphosphate-induced calcium release from cerebellar microsomes Tovey, S., M. Mezna, et al. (1995), Biochem Soc Trans 23(3): 429S. |
| The effects of cholesterol inclusion on the vesicular membranes of cationic lipids Bhattacharya, S. and S. Haldar (1996), Biochim Biophys Acta 1283(1): 21-30. Abstract: Small unilamellar vesicles formed from four cationic lipids in the absence and the presence of varying amounts of cholesterol were studied using fluorescence polarization and 1H-NMR techniques. The fluorescence polarization data clearly indicate that the packing order in the cationic lipid bilayers are affected by inclusion of cholesterol. Importantly, this effect exists also with a cationic lipid that is devoid of any formal linkage region where the interaction of the lipid with cholesterol through hydrogen bonding is not feasible. The interactions of cholesterol with different types of cationic lipids in excess water have also been examined in multilamellar dispersions using proton magnetic resonance spectroscopy. In all the cases, the methylene proton linewidths in the NMR spectra respond to the addition of cholesterol to vesicles. Hydrophobic association of the lipid and cholesterol imposes restriction on the chain (CH2)n motions, leaving the terminal CH3 groups relatively mobile. On the basis of energy-minimized structural models, a rationale of the cholesterol-cationic lipid assembly has also been presented. |
| The effects of cholesterol levels on hemorheological parameters in diabetic patients Ercan, M., D. Konukoglu, et al. (2002), Clin Hemorheol Microcirc 26(4): 257-63. Abstract: Red blood cell (RBC) deformability is an important hemorheological parameter to determine the passage of RBC through narrow capillaries and the reduction of blood viscosity under high shear rates. Although it has been substantial evidence that diabetes mellitus (DM) and hypercholesterolemia increase the risk of coronary heart disease, the mechanism is unclear. In this study the relationship between hemorheological parameters and plasma cholesterol in type 2 diabetic patients (n=55, mean age 43.4+/-9.2 years) was examined. Type 2 diabetic patients were classified as normocholesterolemic (n=25; cholesterol < or = 200 mg/dl) and hypercholesteroloemic (n=30; cholesterol > 200 mg/dl) subgroups. Hypercholesterolemic type 2 diabetic patients had the highest blood and plasma viscosity and the lowest RBC deformability. The results were significantly different from normocholesterolemic type 2 diabetic patients (p<0.001).Our data suggest that elevated plasma cholesterol may impair RBC deformability and increase in blood and plasma viscosity by an additional effect to hyperglycemia in type 2 diabetic patients. |
| The effects of cholesterol oxidation products in sickle and normal red blood cell membranes Kucuk, O., L. J. Lis, et al. (1992), Biochim Biophys Acta 1103(2): 296-302. Abstract: The oxysterol content in normal and sickle red blood cell (RBC) membranes was assessed using thin-layer chromatography and capillary gas chromatography/mass spectrometry. Several more oxysterols were present in sickle RBCs compared to normal RBCs. Sickle RBC membranes had a higher concentration of 5 alpha,6 alpha-epoxycholesterol, 5 alpha-cholestane-3 beta,5,6 beta-triol, 7-ketocholesterol and 19-hydroxycholesterol than normal RBC membranes. The increased oxysterols in sickle RBC may be an effect of the increased oxidative stress which occurs in sickle RBC membranes. Physical characteristics of normal and sickle RBC membrane ghosts with and without inserted oxysterols were examined by Fourier transform infrared spectroscopy. The data are consistent with a greater sterol content in sickle cells compared to normal RBC membranes, and a possible oxysterol-cholesterol synergism. |
| The effects of cholesterol uptake from high-density lipoprotein subfractions on biliary sterol secretion in rats with essential fatty-acid deficiency Wanon, J., F. Guertin, et al. (1998), Hepatology 27(3): 779-86. Abstract: High-density lipoprotein (HDL) participates in the transfer of cholesterol to the liver, in which it is subsequently excreted into bile as bile acid and cholesterol. In this study, the effect of essential fatty-acid (EFA) deficiency on cholesterol contribution from HDL subfractions to bile was investigated. Rats that were rendered EFA-deficient over 4 weeks displayed changes in their plasma HDL subfractions and liver tissue fatty acids. Plasma linoleic (18:2n6), linolenic (18:3n3) and arachidonic (20:4n6) acids decreased, whereas palmitoleic (16:1n7) and eicosatrienoic (20:3n9) acids increased. EFA deficiency was confirmed by an elevation of the 20:3(n-9)/20:4(n-6) index. To examine the hepatic handling of lipoprotein-derived cholesterol, HDL2 and HDL3 from donor rats were isolated, labeled with 14C-cholesterol, and injected iv into EFA-deficient and normal rats with a bile fistula. In HDL subfractions from control rats, no significant variations were noted in the specific activity of cholesterol output in both groups of EFA recipient rats; however, the output of biliary bile acids was significantly decreased in EFA-deficient rats following the administration of labeled HDL3. In HDL2 and HDL3 originating from EFA-deficient rats, a decrease in the specific activity of both biliary cholesterol and bile acid output was recorded in EFA-deficient rats. Concomitant with the defective HDL2- and HDL3-14C cholesterol translocation into bile of EFA-deficient rats, increased hepatic very-low-density lipoprotein (VLDL)-14C cholesterol secretion was observed in vivo. HDL2 and HDL3 particles, derived from EFA-deficient rats, had an altered composition including a depletion in apo A-I and an enrichment in apo E isoforms, which are the the two major HDL apolipoproteins involved in the delivery of cholesterol to the liver. Taken together, these results show that normal EFA status is necessary for efficient HDL-cholesterol processing by the liver. |
| The effects of cholesterol-3-sulfate (CH-3S) on the phosphorylation of human C3a (hC3a) in vitro and on the ability of hC3a to induce vascular permeability in rats Kawakami, F., M. Ito, et al. (2004), Biol Pharm Bull 27(3): 282-7. Abstract: The phosphorylation of human C3a (hC3a, anaphylatoxin) by two distinct protein kinases (PKA and CK-I) and the effect of cholesterol-3-sulfate (CH-3S) on this phosphorylation were biochemically investigated in vitro. It was found that (i) hC3a functions as a phosphate acceptor for PKA and CK-I, but not for CK-II; (ii) the CK-I-mediated phosphorylation of hC3a requires the presence of 3 microM CH-3S in a manner similar to the phosphorylation of HMG1 (CH-3S-binding protein) by CK-I; and (iii) CH-3S inhibits the PKA-mediated phosphorylation of hC3a in a dose-dependent manner (ID50=approximately 2 microM). As expected, hC3a containing high levels of Arg- and Lys-residues stimulated approx. 3-fold CK-II activity (phosphorylation of alpha-casein) in vitro. However, no significant effect of hC3a on CK-II activity was observed when hC3a was preincubated with CH-3S or fully phosphorylated by PKA in vitro. Furthermore, preincubation of hC3a with CH-3S diminished the ability of hC3a to induce vascular permeability in rats. The results provided here suggest that (i) hC3a is a CH-3S-binding protein; and (ii) CH-3S functions as a potent inhibitor for its physiological activities, including phosphorylation by PKA and CK-I, in vitro. |
| The effects of clofibrate and bezafibrate on cholesterol metabolism in the liver of the male rat Shand, J. H. and D. W. West (1994), Lipids 29(11): 747-52. Abstract: Fibric acid derivatives are used to treat hyperlipidemia and have wide ranging effects on lipid metabolism. The action of these compounds on cholesterol esterification, catalyzed by acyl-coenzyme A:cholesterol acyltransferase (ACAT), has been quite widely studied, but their effect on cholesteryl ester hydrolysis and the enzyme neutral cholesteryl ester hydrolase (nCEH) has been largely ignored. Male rats were therefore fed for 10 d on a standard chow diet supplemented with either clofibrate or bezafibrate, to study their effects on plasma lipid levels and hepatic cholesterol metabolism. Plasma triacylglycerols were not significantly altered by these diets, but bezafibrate significantly lowered plasma cholesterol levels (29.7%, P < 0.01). When expressed per unit weight of DNA, both fibrates reduced the hepatic content of triacylglycerol, cholesterol and cholesteryl esters (40, 18.7, 16.5 and 66.7, 28.6, 34.2% for clofibrate and bezafibrate, respectively). ACAT activity was significantly reduced by both drugs, but clofibrate (65% inhibition) was more effective than bezafibrate (35% inhibition). The most dramatic effect of the diets was a marked increase in the activity of both the microsomal and the cytosolic nCEH. When expressed on a whole liver basis, the effect of bezafibrate on the cytosolic enzyme (13.6-fold increase in activity) was much greater than that of clofibrate (4.8-fold increase). Increases in the activity of a cytosolic protein that inhibits the activity of nCEH were also noted, but these changes were relatively small. The results suggest that the activation of nCEH, in combination with the inhibition in ACAT activity, contributes to a decrease in the cholesteryl ester content of the liver which may influence the secretion of very low density lipoprotein. |
| The effects of clozapine on levels of total cholesterol and related lipids in serum of patients with schizophrenia: a prospective study Dursun, S. M., A. Szemis, et al. (1999), J Psychiatry Neurosci 24(5): 453-5. Abstract: OBJECTIVE: To investigate the effects of 12 weeks of clozapine treatment on levels of cholesterol and related lipids in patients with schizophrenia. DESIGN: Prospective study. SETTING: University department associated with a teaching hospital. PARTICIPANTS: Eight patients (6 women and 2 men) with a clinical diagnosis of schizophrenia consistent with DSM-IV criteria. The patients were classified as treatment-resistant and had not responded to treatment with at least 2 conventional antipsychotics. INTERVENTIONS: Current antipsychotic medications were tapered and treatment with clozapine was initiated. OUTCOME MEASURES: Cholesterol and serum lipid levels, as well as Brief Psychiatric Rating Scale (BPRS) scores were measured before and after 12 weeks of treatment with clozapine. RESULTS: Clozapine treatment significantly improved the BPRS scores but did not significantly alter serum lipid levels, except triglyceride levels, which increased. CONCLUSION: The previously reported lower levels of cholesterol in treatment-resistant patients with schizophrenia cannot be attributed to the effects of clozapine administration. Further research is required to support and clarify the effects of antipsychotic drugs on lipid levels. |
| The effects of coadministration of dietary copper and zinc supplements on atherosclerosis, antioxidant enzymes and indices of lipid peroxidation in the cholesterol-fed rabbit Alissa, E. M., S. M. Bahijri, et al. (2004), Int J Exp Pathol 85(5): 265-75. Abstract: It has previously been shown that dietary copper can modulate the extent of atherosclerosis in the thoracic aorta of cholesterol-fed rabbits. The metabolism of copper and zinc are closely related, and it has been hypothesized that the balance of dietary copper to zinc may be important in determining coronary risk. Hence, we have investigated the interaction between dietary copper and zinc in atherogenesis in the New Zealand White rabbit. Juvenile male rabbits were randomly allocated to eight groups. Four groups were fed a normal chow diet with zinc (0.5%, w/w), copper (0.2%, w/w), copper plus zinc or neither in their drinking water for 12 weeks. Four other groups were fed a diet containing 0.25-1% (w/w) cholesterol plus zinc, copper, both or neither. Serum cholesterol of individual animals was maintained at approximately 20 mmol/l. Integrated plasma cholesterol levels were similar for all groups receiving cholesterol and significantly higher than those in the chow-fed groups (P < 0.001). Aortic copper concentrations were higher in the animals receiving cholesterol diets with copper compared to rabbits receiving normal chow and copper (P < 0.001). Aortic zinc content was significantly higher in cholesterol-fed rabbits supplemented with zinc alone or with copper than in those fed cholesterol alone (P < 0.001). Plasma ceruloplasmin concentrations were significantly higher in groups receiving cholesterol, irrespective of their trace element supplementation (P < 0.001). However, trace element supplementation increased the level significantly (P < 0.05). Trace element supplements did not appear to affect erythrocyte superoxide dismutase in the cholesterol-fed animals; however, zinc supplementation was associated with a significant increase in the enzyme in chow-fed animals (P < 0.05). The activity of the enzyme per mg of protein in aortic tissue was higher in animals receiving copper in the presence of cholesterol (P < 0.05) but not significantly so in its absence. Dietary trace element supplementation in cholesterol-fed animals was associated with a significant reduction in aortic lesion area. Plasma thiobarbituric acid-reactive substances and FOX concentrations were both significantly higher in the cholesterol-fed rabbits compared with the animals that fed on a chow diet (P < 0.001), and these were reduced significantly by dietary copper or zinc supplementation (P < 0.001). Hence, dietary supplements of copper or zinc at the doses used both inhibited aortic atherogenesis in the cholesterol-fed rabbits, although there was no significant additional effect when given in combination. |
| The effects of colestipol tablets compared with colestipol granules on plasma cholesterol and other lipids in moderately hypercholesterolemic patients Insull, W., Jr., M. H. Davidson, et al. (1995), Atherosclerosis 112(2): 223-35. Abstract: The purpose of this study was to investigate and compare the efficacy, safety, and patient acceptability of a new formulation of colestipol, colestipol tablets (T), with those of colestipol granules (G), in a randomized, double-blind, placebo-controlled, multicenter study. Three hundred and seventeen patients with primary hypercholesterolemia who were following a low-fat, low-cholesterol diet (NCEP Step I diet), and had low-density lipoprotein cholesterol (LDL-C) levels > or = 4.14 mmol/l (160 mg/dl) and < or = 6.46 mmol/l (250 mg/dl) were studied. Study medication was taken twice a day, with breakfast and supper, for 8 weeks. The six parallel treatment groups consisted of colestipol tablets 2 g b.i.d. and 8 g b.i.d., matching placebo tablets b.i.d., colestipol granules 2 g b.i.d. and 8 g b.i.d., and matching placebo granules b.i.d. Study endpoints included absolute change and percentage change from baseline in selected lipid, lipoprotein, and apolipoprotein measurements; LDL-C lowering was the primary efficacy endpoint. Treatment with colestipol tablets and colestipol granules resulted in virtually identical, statistically significant (P < or = 0.05) reductions of LDL-C, total cholesterol (TC), TC/HDL-C, and apolipoprotein B (apo B). Compared with placebo, all active treatments (tablets 4 g/day, tablets 16 g/day, granules 4 g/day, granules 16 g/day) significantly reduced LDL-C (12%, 24%, 12%, 25%, respectively), TC (7%, 15%, 8%, 15%, respectively), TC/HDL-C (8%, 14%, 9%, 15%, respectively) and apo B (12%, 20%, 13%, 22%, respectively). All active treatments significantly increased lipoprotein particle AI (LpAI) (5%, 23%, 14%, 18%, respectively). VLDL-C and triglycerides increased significantly in the high-dose groups. The proportions of patients reporting adverse events, largely gastrointestinal-related, were not different among the active treatment groups. The treatments were well-tolerated, and no drug-related serious adverse events were reported. Patients experienced with granule medication prior to this study preferred tablets over granules. This study demonstrates that colestipol tablets are an effective treatment to reduce LDL-C in patients with primary hypercholesterolemia, are equivalent to colestipol granules, are well-tolerated, and are preferred over granules by patients. |