| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Effects of the calcium channel blocker amlodipine on serum and aortic cholesterol, lipid peroxidation, antioxidant status and aortic histology in cholesterol-fed rabbits Turgan, N., S. Habif, et al. (2003), J Biomed Sci 10(1): 65-72. Abstract: Reactive oxygen metabolites and oxidized fatty acids are proinflammatory and are involved in the pathophysiology of atherosclerosis. Amlodipine, a unique third-generation dihydropyridine-type calcium channel blocker, seems to exert atheroprotective effects through its antioxidant properties related to its chemical structure and independent of its calcium channel-blocking effect. In this study, the interactions of amlodipine with major cellular antioxidants were investigated in order to elucidate the mechanisms underlying its atheroprotective effects. New Zealand white male rabbits were fed regular chow (group 1), chow with 1% cholesterol (group 2), regular chow plus 5 mg/kg/day amlodipine per os (group 3) and 1% cholesterol plus amlodipine (group 4) for 8 weeks. Total cholesterol, malondialdehyde (MDA) and vitamin E concentrations and catalase and superoxide dismutase (SOD) activities were determined in blood drawn before and after the experimental period. Aortic tissue was examined for atherosclerotic changes and aortic total cholesterol, MDA, catalase and SOD were determined. At the end of the 8-week treatment period, serum total cholesterol and plasma MDA were elevated in groups 2 and 4. In group 2, serum vitamin E and plasma SOD diminished (p < 0.05) and catalase increased (p < 0.05). In group 4, SOD activity increased at the end of treatment. MDA levels were lower and plasma SOD activities were higher in group 4 than in group 2. Aortic tissue investigations revealed higher total cholesterol and MDA concentrations and catalase activities in group 2 than in group 4, and the highest tissue SOD activity was recorded in group 4 (p < 0.05 for all comparisons). Morphological examination of aortic tissues exhibited endothelial disarrangement and lipid deposition in group 2. Histopathological alterations related to atherogenesis were less in group 4 than in group 2. Amlodipine seems to exert atheroprotective effects by reducing aortic cholesterol accumulation and blood and aortic lipid peroxidation, enhancing SOD activity both in blood and aortic tissue and suppressing the consumption of vitamin E. On the other hand, the suppression of catalase activity in blood and the aorta interferes with the drug's well-known antioxidant effects. |
| Effects of the callipyge phenotype on serum creatinine, total cholesterol, low-density lipoproteins, very-low-density lipoproteins, high-density lipoproteins, and triacylglycerol in growing lambs Meyer, H. H., A. Abdulkhaliq, et al. (1996), J Anim Sci 74(7): 1548-52. Abstract: The goals of this study were to investigate the effects of the callipyge (CLPG) phenotype on serum creatinine and lipid profiles of growing lambs. Preliminary studies in our laboratories indicated that creatinine may have utility in distinguishing the CLPG phenotype and that expression of the CLPG gene altered concentrations of serum total cholesterol (TC). As a result, in this study, we examined the influence of the CLPG gene on concentrations of creatinine, TC, very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), high-density lipoproteins (HDL), and triacylglycerol (TG) at varying stages of maturity in lambs. Ten homozygous (c/c) Polypay ewes were crossed with Dorset rams heterozygous for the CLPG gene (C/c). From this cross, 20 lambs (13 females and 7 males) were born, of which 11 were homozygotic (c/c) and 9 were heterozygotic (C/c; CLPG) based on muscle weights and longissimus dorsi (LD) area at slaughter. Blood samples were taken at monthly intervals and serum lipid constituents were assayed. At 1 mo of age, no differences (P >.05) in plasma lipids were detectable between phenotypes. However, at 2 mo age, CLPG lambs had higher (P <.01) concentration of TG, TC, HDL, and VLDL compared to homozygotic (c/c) lambs. Triglycerides and VLDL were elevated (P <.05) in CLPG lambs at 3 mo of age. By slaughter, no differences (P >.05) in serum lipid constituents were detectable between genotypes. Hence, the increase in serum TC is due to elevated levels of HDL and VLDL. These observations indicate that creatinine may be used to distinguish CLPG lambs and that the CLPG gene alters serum lipid profiles during the postnatal period. |
| Effects of the cell wall of Kluyveromyces marxianus YIT 8292 on the plasma cholesterol and fecal sterol excretion in rats fed on a high-cholesterol diet Yoshida, Y., W. Yokoi, et al. (2005), Biosci Biotechnol Biochem 69(4): 714-23. Abstract: The cellular components involved in the hypocholesterolemic activity of Kluyveromyces marxianus YIT 8292 were examined in rats fed on a high-cholesterol diet. Whole cells (KM) were heated at 115 degrees C for 10 minutes and fractionated into water-soluble extract 1 and the insoluble residue (KM-CW). After mechanical disruption by glass beads, KM-CW was separated into the cell wall (KM-W) and water-soluble extract 2. Plasma total cholesterol was decreased by feeding KM-CW or KM-W, but was not changed by feeding extract 1 or extract 2. Feeding KM-CW and KM-W increased the fecal sterol excretion and concentration of short-chain fatty acids (SCFA) in the cecum. The hypocholesterolemic activity of KM-CW was completely abolished by the enzymatic degradation of alpha-mannan and beta-glucan. These results suggest that alpha-mannan and beta-glucan were the major active components of KM, and that its hypocholesterolemic activity may be attributable to the increasing fecal sterol excretion and/or production of SCFA. |
| Effects of the glycemic index of foods on serum concentrations of high-density lipoprotein cholesterol and triglycerides Pelkman, C. L. (2001), Curr Atheroscler Rep 3(6): 456-61. Abstract: The role of carbohydrates in cardiovascular disease prevention has garnered increasing attention due to accumulating evidence showing deleterious effects of low-fat, high-carbohydrate diets on serum triglycerides and high-density lipoprotein (HDL) cholesterol. Researchers argue that classifying carbohydrates based on their capacity for increasing blood glucose (termed the glycemic index) is a useful tool for elucidating the effects of carbohydrate-rich foods on glucose and lipid metabolism. Several epidemiologic reports show that lower dietary GI is associated with lower serum triglycerides and higher HDL cholesterol. Results from intervention studies show that substituting low-GI for high-GI foods in a low-fat, high- carbohydrate diet lowers serum triglycerides by 15% to 25%. The available evidence to date suggests that the glycemic index of foods will be an important factor in future dietary prevention research. |
| Effects of the marine unicellular alga Nannochloropsis sp. to reduce the plasma and liver cholesterol levels in male rats fed on diets with cholesterol Werman, M. J., A. Sukenik, et al. (2003), Biosci Biotechnol Biochem 67(10): 2266-8. Abstract: The effects of Nannochloropsis were studied on rats consuming hypercholesterolemic diets. The whole biomass and the hexane/ethanol extract increased the plasma and hepatic eicosapentaenoic and docosahexaenoic acids levels, and reduced the cholesterol levels. We also observed a higher level of propionate, and a lower ratio between acetate and propionate. These data suggest the efficacy of Nannochloropsis in reducing cholesterol levels. |
| Effects of the National Cholesterol Education Program's Step I and Step II dietary intervention programs on cardiovascular disease risk factors: a meta-analysis Yu-Poth, S., G. Zhao, et al. (1999), Am J Clin Nutr 69(4): 632-46. Abstract: BACKGROUND: Plasma lipid and lipoprotein responses have been variable in dietary intervention studies. OBJECTIVE: The objective of this study was to evaluate the effects of the National Cholesterol Education Program's Step I and Step II dietary interventions on major cardiovascular disease risk factors using meta-analysis. DESIGN: MEDLINE was used to select 37 dietary intervention studies in free-living subjects published from 1981 to 1997. RESULTS: Step I and Step II dietary interventions significantly decreased plasma lipids and lipoproteins. Plasma total cholesterol (TC), LDL cholesterol, triacylglycerol, and TC:HDL cholesterol decreased by 0.63 mmol/L (10%), 0.49 mmol/L (12%), 0.17 mmol/L (8%), and 0.50 (10%), respectively, in Step I intervention studies, and by 0.81 mmol/L (13%), 0.65 mmol/L (16%), 0.19 mmol/L (8%), and 0.34 (7%), respectively, in Step II intervention studies (P < 0.01 for all). HDL cholesterol decreased by 7% (P = 0.05) in response to Step II but not to Step I dietary interventions. Positive correlations between changes in dietary total and saturated fatty acids and changes in TC and LDL and HDL cholesterol were observed (r = 0.59, 0.61, and 0.46, respectively; P < 0.001). Multiple regression analyses showed that for every 1% decrease in energy consumed as dietary saturated fatty acid, TC decreased by 0.056 mmol/L and LDL cholesterol by 0.05 mmol/L. Moreover, for every 1-kg decrease in body weight, triacylglycerol decreased by 0.011 mmol/L and HDL cholesterol increased by 0.011 mmol/L. Exercise resulted in greater decreases in TC, LDL cholesterol, and triacylglycerol and prevented the decrease in HDL cholesterol associated with low-fat diets. CONCLUSION: Step I and Step II dietary interventions have multiple beneficial effects on important cardiovascular disease risk factors. |
| Effects of the thyroid hormone receptor agonist GC-1 on metabolic rate and cholesterol in rats and primates: selective actions relative to 3,5,3'-triiodo-L-thyronine Grover, G. J., D. M. Egan, et al. (2004), Endocrinology 145(4): 1656-61. Abstract: Current drug therapies for obesity are ineffective, and existing treatments for lipid disorders can be further improved. Thyroid hormones affect both conditions, although currently available nonselective thyromimetics are not clinically useful for such treatment due to cardiac side effects. Recent studies suggest that thyroid hormone receptor subtype beta (TRbeta) selective agonists have a profile in which cholesterol can be reduced with minimal tachycardia. The purpose of this study was to determine whether modest (5-10%) increases in metabolic rate could also be observed with minimal tachycardia after TRbeta stimulation. For these studies, the TRbeta selective agonist, GC-1, was used to assess selectivity for lipid-lowering and metabolic rate changes relative to tachycardia. Studies in cholesterol-fed rats (7 d treatment) showed that GC-1 reduced cholesterol (ED(50) = 190 nmol/kg x d) approximately 30 times more potently than it induced tachycardia (ED(15) = 5451 nmol/kg x d). T(3) showed no potency difference between cholesterol lowering and tachycardia. GC-1 showed approximately 10-fold selectivity for increasing metabolic rate (ED(5) = 477 nmol/kg x d) relative to tachycardia compared with T(3), which showed no selectivity. In cynomolgus monkeys treated for 7 d, significant cholesterol-lowering and lipoprotein (a) reduction was noted for both T(3) and GC-1, whereas no tachycardia was observed for GC-1, unlike T(3). T(3) and GC-1 caused a significant (approximately 4%) reduction in body weight in these animals. Therefore, selective TRbeta activation may be a potentially usefully treatment for obesity and reduction of low density lipoprotein cholesterol and reduction of the atherogenic risk factor lipoprotein (a). |
| Effects of the whole seed and a protein isolate of faba bean (Vicia faba) on the cholesterol metabolism of hypercholesterolaemic rats Macarulla, M. T., C. Medina, et al. (2001), Br J Nutr 85(5): 607-14. Abstract: The aim of the present work was to analyse the hypocholesterolaemic efficiency of a Vicia faba-protein isolate in relation to the intact legume. In addition, the mechanisms underlying the effects of this isolate were investigated. Hypercholesterolaemic rats were divided into three groups and fed high-fat diets rich in cholesterol-containing casein, whole seeds of Vicia faba or the protein isolate of faba beans as protein source, for 2 weeks ad libitum. The protein isolate was prepared by isoelectric precipitation and spray dried. Analyses of serum, liver and faeces, as well as of the activity of hepatic 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase, were assessed by enzymatic methods. The rats fed on Vicia faba diets showed significantly lower body weights and energy intakes than rats fed on casein diets. The whole-seed diet induced a significant reduction in plasma triacylglycerol. Feeding rats on diets containing faba bean seeds, or the protein isolate, induced a significant decrease in plasma (LDL+VLDL)-cholesterol but not in HDL-cholesterol. Hepatic cholesterol and triacylglycerol were also reduced. The hypocholesterolaemic effects of Vicia faba were not the result of a reduction in cholesterol synthesis as assessed from HMG-CoA reductase activity, but the result of an increase in steroid faecal excretion. The faba bean-protein isolate obtained under our experimental conditions was useful in improving the metabolic alterations induced by feeding with a hypercholesterolaemic diet compared with casein. The effectiveness of the whole seeds was higher than that of the protein isolate. |
| Effects of three strains of bifidobacteria on cholesterol Tahri, K., J. Crociani, et al. (1995), Lett Appl Microbiol 21(3): 149-51. Abstract: To determine the validity of the hypothesis of assimilation or precipitation of cholesterol by Bifidobacterium species, resting cell assays and cultures were undertaken in TPY medium containing oxgall. With resting cell assays (pH 5), cholesterol was precipitated and redissolved in phosphate buffer (pH 7). At the end of the cultures, only part of the removed cholesterol from the culture medium was found in the phosphate buffer, while the missing cholesterol was in cell extracts. It appeared that removal of cholesterol during culturing was not solely due to its precipitation. It is concluded that growing bifidobacteria cells are able to remove cholesterol both by precipitation and assimilation. |
| Effects of TNF, IL-1, and the combination of both cytokines on cholesterol metabolism in Syrian hamsters Hardardottir, I., A. H. Moser, et al. (1994), Lymphokine Cytokine Res 13(3): 161-6. Abstract: Infection and inflammation are associated with alterations in lipid metabolism that may be mediated by cytokines such as TNF and IL-1. This study determined the effects of TNF and IL-1 on certain aspects of cholesterol metabolism. TNF or IL-1 administration to Syrian hamsters increased serum cholesterol levels by 17 and 21%, respectively, and decreased HDL cholesterol levels by 20 and 15%, respectively. TNF + IL-1 increased serum cholesterol levels by 58% and decreased HDL cholesterol levels by 58%. TNF or IL-1 increased hepatic HMG CoA reductase mRNA levels by 3.5- and 3-fold, respectively. TNF + IL-1 increased HMG CoA reductase mRNA levels by 7-fold. IL-1 increased hepatic LDL receptor mRNA levels by 2-fold while TNF and a combination of TNF + IL-1 had minimal effects. TNF or IL-1 did not affect hepatic apo E or apo A-I mRNA levels while a combination of TNF + IL-1 decreased both mRNA levels by 50%. Our results demonstrate that TNF and IL-1 similarly affect the parameters of cholesterol metabolism studied. Furthermore, the combination of TNF + IL-1 was, in most cases, more effective than either cytokine alone, and reproduced many of the effects of LPS. |
| Effects of trace components of dietary fat on cholesterol metabolism: phytosterols, oxysterols, and squalene Madani, K. A. (2003), Nutr Rev 61(4): 152-3. |
| Effects of trace components of dietary fat on cholesterol metabolism: phytosterols, oxysterols, and squalene Ostlund, R. E., Jr., S. B. Racette, et al. (2002), Nutr Rev 60(11): 349-59. Abstract: The effect of dietary fats on serum cholesterol is widely assumed to be due solely to the fatty acids and cholesterol they contain. Phytosterols, sterol oxidation products, and sterol precursors such as squalene, however, are often present in dietary fats. Little is known of the physiology of these substances in natural foods and most published diet studies do not consider them at all. Supplementation of the diet with high-dose phytosterols is now recommended for prevention of heart disease, but both recent and old data strongly suggest that the lower levels of phytosterols naturally present in vegetable fats may also reduce cholesterol absorption and serum cholesterol substantially. Moreover, unmeasured phytosterols may confound otherwise well-controlled diet studies because there is an inverse correlation between phytosterol and saturated fatty acid content of vegetable fats. Sterol oxidation products, many of which are found in foods, are potent regulators of lipoprotein and cholesterol transport pathways in vitro. Squalene is a phytosterol precursor abundant in olive oil that is at least partly absorbed and then quantitatively converted to cholesterol. The effects of dietary triglyceride-derived fatty acids have not been experimentally separated from the effects of trace fat components in most clinical studies. A better understanding of the activity of sterol-related dietary components is needed to reduce variability in diet studies, accurately assess the effects of dietary fatty acids and to maximize the effectiveness of dietary treatment for hypercholesterolemia. |
| Effects of transection and extrinsic denervation and a model of autotransplantation of the porcine jejunoileum on cholesterol biodynamics Pakarinen, M. P., P. Pirinen, et al. (2003), J Pediatr Surg 38(11): 1585-90. Abstract: BACKGROUND/PURPOSE: Small bowel transplantation impairs enteric function, necessitating transection, extrinsic denervation, and ischemia-reperfusion of the small intestine. The authors investigated how each of these nonimmunologic insides of the transplantation procedure modulates biodynamics of cholesterol and absorption of lipids. METHODS: Twenty-three pigs with similar food, cholesterol, and fat intake underwent sham laparotomy (group 1), transection (group 2), extrinsic jejunoileal denervation (group 3), or a model of autotransplantation, including extrinsic jejunoileal denervation with in situ ischemia-reperfusion (group 4). Serum lipids, absorption, and excretion of cholesterol, bile acids, and fat were determined after 8 weeks. Plasma cholesterol precursors and plant sterols, respective markers of cholesterol synthesis, and absorption, were measured after 2 and 8 weeks. RESULTS: When compared with sham laparotomy and transection groups, denervation and autotransplantation significantly decreased weight gain and increased plasma cholesterol precursors and fecal excretion of bile acids. In relation to sham operated animals, transection alone modestly increased plasma plant sterols at 2 weeks and biliary secretion and mass absorption of cholesterol. The latter changes were not observed after denervation or autotransplantation, ie, fractional and total absorption of cholesterol were significantly decreased in autotransplanted pigs when compared with transected controls. As compared with all the other groups, autotransplantation significantly increased bacterial metabolites of neutral sterols in feces and net fecal elimination of cholesterol, mainly as bile acids. CONCLUSIONS: Extrinsic autonomic denervation of the jejunoileum, with or without synchronous ischemia-reperfusion, results in increased cholesterol synthesis, bile acid malabsorption, and decreased weight gain. Cholesterol malabsorption may develop gradually after intestinal autotransplantation, and even a short period of ischemia further impairs absorptive function of the denervated jejunoileum, resulting in increased fecal elimination of cholesterol mainly as bile acids. |
| Effects of treatment with deoxycholic acid and chenodeoxycholic acid on the hepatic synthesis of cholesterol and bile acids in healthy subjects Einarsson, C., C. G. Hillebrant, et al. (2001), Hepatology 33(5): 1189-93. Abstract: The degradation of cholesterol to bile acids is regulated by a negative-feedback mechanism by the bile acids, especially the hydrophobic bile acids, returning to the liver via the portal vein. Chenodeoxycholic acid (CDCA) is a potent suppressor of the cholesterol 7alpha-hydroxylase, the rate-determining enzyme in bile acid formation. CDCA may also suppress hepatic 3-hydroxy-3-methyl glutaryl coenzyme A (HMG CoA) reductase, the rate-limiting enzyme in cholesterol synthesis. Conflicting reports have appeared regarding the suppression on bile acid synthesis by the most hydrophobic bile acid of human bile, deoxycholic acid (DCA). To study the suppressive effects of CDCA and DCA on hepatic cholesterol and bile acid synthesis in humans, 10 healthy subjects were treated with CDCA or DCA for 3 weeks in a randomized cross-over study with a washout period of 4 weeks in between. Serum levels of 7alpha-hydroxy-4-cholesten-3-one, reflecting cholesterol 7alpha-hydroxylase activity, and 7-dehydrocholesterol, reflecting HMG CoA reductase activity, and bile acids were repeatedly measured during the study periods. After 3 weeks of treatment with CDCA or DCA, CDCA constituted 70% and DCA 74% of the total serum bile acids, respectively. CDCA and DCA decreased the serum levels of 7alpha-hydroxy-4-cholesten-3-one by 80% and 75%, respectively. Negative correlations between the percentages of CDCA and DCA and the serum concentration of 7alpha-hydroxy-4-cholesten-3-one were obtained. CDCA reduced the serum level of 7-dehydrocholesterol by 29%, whereas treatment with DCA tended to increase the level of 7-dehydrocholesterol. Treatment of healthy subjects with CDCA and DCA reduces bile acid synthesis. CDCA also inhibits cholesterol synthesis, whereas DCA does not. |
| Effects of troglitazone on intracellular cholesterol distribution and cholesterol-dependent cell functions in MA-10 Leydig tumor cells Freeman, D. A. and A. Romero (2003), Biochem Pharmacol 66(2): 307-13. Abstract: Troglitazone treatment of MA-10 Leydig tumor cells resulted in cellular cholesteryl esters decreasing and cell free cholesterol increasing. This was not an effect unique to this chemical entity; rosiglitazone and pioglitazone caused these changes also. The excess free cholesterol was recovered largely in the cholesterol oxidase susceptible, plasma membrane cholesterol pool. This effect of troglitazone probably is not mediated by activation of peroxisome proliferator activated receptors since it immediately reversed with washing and did not occur at all in cells treated with the peroxisome proliferator activated receptor agonist, 15-deoxy Delta 12,14 prostaglandin J-2. Plasma membrane cholesterol esterification was inhibited by troglitazone in a dose-dependent manner. Plasma membrane cholesterol esterification was inhibited half-maximally by 14 microM troglitazone and by more than 90% by 40 microM troglitazone. This effect was not unique for MA-10 cells. Similar results were found using fibroblasts. Troglitazone was not simply inhibiting internalization of plasma membrane cholesterol. Dibutyryl-cAMP stimulation of troglitazone-treated cells resulted in more progesterone synthesis than in stimulated control cells; moreover, radioactive plasma membrane cholesterol was readily converted into progesterone in troglitazone-treated cells. Studies of LDL uptake in troglitazone-treated cells indicated that intracellular membranes were cholesterol replete. Troglitazone inhibited plasma membrane cholesterol esterification with kinetics similar to 58-035, a known inhibitor of the acyl coenzyme A: cholesterol acyltranserase (ACAT) enzyme. It is not likely an ACAT inhibitor since troglitazone did not block incorporation of exogenous free fatty acids into cholesteryl esters. Thus, it appears that troglitazone prevented presentation of free fatty acid to the ACAT enzyme. |
| Effects of ursodeoxycholic acid on synthesis of cholesterol and bile acids in healthy subjects Sauter, G. H., K. Thiessen, et al. (2004), Digestion 70(2): 79-83. Abstract: BACKGROUND/AIMS: Ursodeoxycholic acid (UDCA) decreases biliary secretion of cholesterol and is therefore used for the dissolution of cholesterol gallstones. It remains unclear whether these changes in biliary cholesterol excretion are associated with changes in cholesterol synthesis and bile acid synthesis. We therefore studied the activities of rate-limiting enzymes of cholesterol synthesis and bile acid synthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase and cholesterol 7alpha-hydroxylase, respectively, in normal subjects during UDCA feeding. METHODS: UDCA was given to 8 healthy volunteers (5 men, 3 women; age 24-44 years) in a single dose of 10-15 mg/kg body weight for 40 days. Before and during (days 3, 5, 10, 20, 30 and 40) UDCA treatment, urinary excretion of mevalonic acid and serum concentrations of 7alpha-hydroxy-4-cholesten-3-one (7alpha-HCO) were determined as markers of cholesterol and bile acid synthesis, respectively. The Wilcoxon signed rank test and Spearman's rank correlation coefficient were used for statistical analysis. RESULTS: Cholesterol synthesis and serum lipid concentrations remained unchanged during UDCA treatment for 40 days. However, synthesis of bile acids increased during long-term treatment with UDCA as reflected by an increase in 7alpha-HCO serum concentrations from 39.7 +/- 21.3 ng/ml (median 32.8 ng/ml) before treatment to 64.0 +/- 30.4 ng/ml (median 77.5 ng/ml) at days 30-40 of UDCA treatment (p < 0.05). CONCLUSIONS: UDCA treatment does not affect cholesterol synthesis in the liver, but does increase bile acid synthesis after prolonged treatment. This may represent a compensatory change following decreased absorption of endogenous bile acids as observed with UDCA therapy. |
| Effects of ursodeoxycholic acid therapy on in vitro gallbladder contractility in patients with cholesterol gallstones van de Heijning, B. J., P. C. van de Meeberg, et al. (1999), Dig Dis Sci 44(1): 190-6. Abstract: During treatment with ursodeoxycholic acid (UDCA), the fasting gallbladder volume increases by a yet unknown mechanism. The present study tests whether in vitro human gallbladder contractility in response to acetylcholine and cholecystokinin is affected by UDCA therapy. Gallbladder tissue was obtained from 15 patients treated with UDCA (10 mg/kg/day) during three weeks prior to surgery, and from 15 comparable patients not treated. Data were correlated with in vivo contractility, bile composition, and gallbladder wall inflammation. The inflammation score was lower in the treated patient group. UDCA treatment enhanced gallbladder contractility in vitro: Dose-response curves for acetylcholine and cholecystokinin were both shifted to the left, and the maximal contractile stress generated in response to cholecystokinin was higher in the treated group, whereas the maximal acetylcholine-induced stress was not increased. Maximal cholecystokinin-induced stress correlated positively with fasting gallbladder volume and negatively with the biliary cholesterol saturation index, but not with bile salt hydrophobicity or gallbladder wall inflammation score. In conclusion, UDCA treatment improves in vitro gallbladder contractility, possibly related to a reduced biliary cholesterol saturation. Increased fasting gallbladder volumes during UDCA treatment thus do not appear to result from decreased gallbladder muscle contractile strength. |
| Effects of variable doses and formulations of cholestyramine on elevated serum low-density lipoprotein cholesterol Fletcher, G. F., B. J. Fletcher, et al. (1995), Am J Cardiol 75(10): 738-9. |
| Effects of various amounts of dietary plant sterol esters on plasma and hepatic sterol concentration and aortic foam cell formation of cholesterol-fed hamsters Ntanios, F. Y., A. J. van de Kooij, et al. (2003), Atherosclerosis 169(1): 41-50. Abstract: Dietary intake of plant sterol esters (PSE) lowers plasma LDL-cholesterol (LDL-C), but can modestly increase plasma plant sterol concentrations. The objective of the present study was to investigate the impact of increasing doses of dietary PSE on plasma and liver sterol concentrations as well as on aortic foam cell development as a marker of atherogenesis. One-hundred and twenty F(1)B hybrid Syrian golden hamsters (20 per group) were fed a basal atherogenic diet containing 30% of energy as fat and 0.12% (w/w) cholesterol and supplemented with 0, 0.24, 0.48, 0.96, 1.92 and 2.84% (w/w) PSE. After 12 weeks, plasma total cholesterol (TC) and LDL-C were significantly lower in the groups fed PSE compared with control. Plasma plant sterol concentrations increased with increasing dietary PSE intake up to the dietary level of 1.92% and then reached a plateau. On the other hand, hepatic campesterol and sitosterol concentrations plateaued at 0.24% PSE. Foam cell presence in the aortic arch showed an inverse relationship with dietary PSE intake (P<0.0001). Lipid-filled foam cell areas of hamsters receiving 0.24, 0.48 or 2.84% PSE were approximately 70, 90 and 100% smaller than in control hamsters fed no PSE. In summary, dietary PSE lowered plasma TC and LDL-C. Despite an increase in plasma plant sterol concentrations they did not contribute to aortic foam cell development. In fact dietary PSE significantly inhibited aortic foam cell formation. This study supports the concept that PSE through their cholesterol-lowering action prevent development of atherogenesis in this animal model. |
| Effects of various doses of growth hormone on serum total cholesterol, phospholipid, and bile acid in a patient with cholestasis Noda, H., H. Sato, et al. (1990), Endocrinol Jpn 37(6): 851-5. Abstract: To determine whether growth hormone (GH) has any impact on the hyperlipidemia seen in cholestatic patients, graded doses of GH in the sequence of 0.1, 0.2, 0.4, and 0.6 u/kg every other day were administered sc to a patient with Alagille syndrome. Serum total cholesterol, phospholipid, and bile acid were measured. The serum levels of all three decreased markedly after GH administration and the lowest levels were observed on the second day after the GH dose of 0.4 u/kg. However, they increased thereafter despite the administration of an increased dose of GH; especially the serum bile acid level returned to the initial value by day 8. Serum levels of SM-C and fT3 were not correlated with the changes in total cholesterol, phospholipid, and bile acid after GH administration. We suggest that the administration of GH may affect the state of hyperlipidemia seen in cholestatic patients. |