| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Effects of isoenergetic high-carbohydrate compared with high-fat diets on human cholesterol synthesis and expression of key regulatory genes of cholesterol metabolism Vidon, C., P. Boucher, et al. (2001), Am J Clin Nutr 73(5): 878-84. Abstract: BACKGROUND: High-carbohydrate diets improve plasma cholesterol concentrations but increase triacylglycerol concentrations; the latter effect increases the risk of cardiovascular disease (CVD). Triacylglycerol concentrations increase only during very-high-carbohydrate diets consisting mainly of simple sugars. OBJECTIVE: We compared the CVD risk profile, cholesterol metabolism, and glucose tolerance of 7 healthy subjects during 2 isoenergetic diets: a high-fat, low-carbohydrate diet (HF diet) and a moderately high-carbohydrate, low-fat diet (HC diet). DESIGN: In a randomized crossover study, we measured the effects of the HF diet 40% carbohydrate and 45% fat (15% saturated, 15% monounsaturated, and 15% polyunsaturated) and HC diet 55% carbohydrate (mainly complex) and 30% fat (10% saturated, 10% monounsaturated, and 10% polyunsaturated) (3 wk each) on plasma lipid concentrations, oral glucose tolerance, cholesterol synthesis rate, and the messenger RNA (mRNA) concentrations of beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase, the LDL receptor, and the LDL-receptor-related protein (LRP). RESULTS: Compared with the HF diet, the HC diet lowered total, LDL, and HDL cholesterol (P < 0.05 for all) without modifying the ratio of LDL to HDL cholesterol; triacylglycerol concentrations were unchanged. Lower cholesterol concentrations occurred despite a higher cholesterol synthesis rate (P < 0.05) and higher HMG-CoA reductase mRNA concentrations (P < 0.05). LDL receptor mRNA concentrations were unchanged, LRP mRNA concentrations were lower (P < 0.01), and oral glucose tolerance was better (P < 0.05) with the HC diet. CONCLUSION: The beneficial effects of the HC diet on glucose tolerance and plasma cholesterol concentrations without increases in triacylglycerol show that this diet had favorable effects on both insulin sensitivity and the plasma lipid profile. |
| Effects of isorhamnetin, rhamnetin, and quercetin on the concentrations of cholesterol and lipoperoxide in the serum and liver and on the blood and liver antioxidative enzyme activities of rats Igarashi, K. and M. Ohmuma (1995), Biosci Biotechnol Biochem 59(4): 595-601. Abstract: The effects of isorhamnetin, rhamnetin and quercetin on the serum and liver cholesterol concentrations, liver lipoperoxide (thiobarbituric acid-reactive substances: TBARS) content, and antioxidative enzyme activities were examined with rats fed on cholesterol-enriched and cholesterol-free diets. The total serum cholesterol of those rats fed with the cholesterol-enriched diet was decreased by feeding each all these flavonoids. The total liver cholesterol concentration and TBARS content in the rats fed with the cholesterol-free diet were decreased by feeding isorhamnetin, rhamnetin and quercetin. The activities of liver superoxide dismutase and catalase were almost unaffected by feeding these flavonoids. These results, the in vitro antioxidative activities of isorhamnetin, rhamnetin and quercetin, and the activities of these flavonoids in suppressing the generation of the superoxide anion in vitro suggest the possibility that the lower liver TBARS content in those rats fed on the cholesterol-free diet with added flavonoids is ascribable in part to the direct antioxidative and superoxide anion generation-suppressing activities of flavonoids and/or their metabolites absorbed from the gastrointestinal tract. |
| Effects of ketoconazole on cholesterol precursors and low density lipoprotein kinetics in hypercholesterolemia Gylling, H., H. Vanhanen, et al. (1993), J Lipid Res 34(1): 59-67. Abstract: Ketoconazole, an inhibitor of cholesterol synthesis at 14 alpha-demethylation of lanosterol, effectively reduces serum total and low density lipoprotein (LDL) cholesterol levels. We studied the effects of ketoconazole (400 mg/day for 5 weeks) on serum lipids, free and esterified noncholesterol sterols, and kinetics of LDL apolipoprotein B (apoB) in seven patients with heterozygous familial hypercholesterolemia (FH) and in three patients with primary hypercholesterolemia (nonFH). The total, intermediate density, and LDL cholesterol levels were significantly reduced by 24, 27, and 29%, respectively, and LDL apoB by 23%. Serum total and lipoprotein triglycerides were unchanged. The LDL cholesterol/apoB ratio decreased significantly. Serum ratios of lanosterols to cholesterol were increased over 50 times, almost the same in all lipoproteins and mainly as the unesterified form; free delta 8-precursor sterols, 2-5 times; cholestanol, slightly; while ratios of lanosterol of desmosterol, lathosterol, and plant sterols were virtually unchanged. Inconsistent esterification of methyl sterols might indicate unaltered acyl CoA:cholesterol acyltransferase activity. LDL apoB transport was decreased in all nonFH subjects but inconsistently in FH. The fractional catabolism rate (FCR) for LDL apoB was increased significantly in FH by 13% and inconsistently by 4% in nonFH. In a subgroup of three FH patients, more dense LDL (d 1.037-1.055 g/ml) was transported and catabolized faster on than off ketoconazole so that the serum level of this more dense LDL subfraction was unchanged, the decrease of LDL being due to a reduction of the less dense LDL subfraction.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Effects of Lactobacillus amylovorus and Bifidobacterium breve on cholesterol Grill, J. P., C. Cayuela, et al. (2000), Lett Appl Microbiol 31(2): 154-6. Abstract: To determine the validity of the hypothesis of assimilation and/or precipitation of cholesterol by Lactobacillus and Bifidobacterium species, culture were undertaken in TPY medium containing oxgall or taurocholic acid. In the case of growing cells, both strains were able to remove cholesterol in the presence of bile salts. Nevertheless, the behaviour was different according to the kind of bile salt. In the presence of taurocholic acid, the removal of cholesterol was due to both bacterial uptake and precipitation. In the presence of Oxgall, bacterial uptake and precipitation were observed for Lactobacillus but only precipitation occurred for Bifidobacterium. |
| Effects of LDL cholesterol on vascular function Rosendorff, C. (2002), J Hum Hypertens 16 Suppl 1: S26-8. Abstract: Oxidised low-density lipoprotein (LDL) cholesterol is vasoconstrictor, mitogenic, pro-inflammatory and thrombogenic. This review summarises the evidence for its vasoconstrictor properties. LDL cholesterol potentiates noradrenaline vasoconstriction in the peripheral vasculature, and in the coronary, cerebral and renal vascular beds. There is also blunting of endothelium-dependent vasodilator responses to acetylcholine. These effects are reversed, or at least reduced, by lipid-lowering agents and (because LDL cholesterol down-regulates endothelial nitric oxide synthase) by the administration of L-arginine, the substrate for nitric oxide (NO) formation. Anti-oxidants also improve endothelial function in hypercholesterolaemic animals and human patients. More research is needed to assess the possible beneficial effects of lipid lowering on vascular structure and function, and on cardiovascular morbidity and mortality, in normocholesterolaemic individuals. |
| Effects of LDL, cholesterol, and their oxidized forms on the precipitation kinetics of calcium phosphates Wang, H. P., X. J. Feng, et al. (2003), Clin Chem 49(12): 2027-36. Abstract: BACKGROUND: LDL, cholesterol, and their oxidized forms are known cardiovascular risk factors and are often found in atherosclerotic lesions of various stages. Little is known, however, about whether they are directly involved in the formation of calcium phosphate compounds. METHODS: We used the pH-stat technique to follow the kinetics of calcium phosphate precipitation at pH 7.4, 37 degrees C, and ionic strength 0.150 mol/L, in the presence or absence of LDL, oxidized LDL, cholesterol, cholestane-3beta,5alpha,6beta-triol, and cholesteryl linoleate. The precipitates were characterized by x-ray diffraction, scanning and transmission electronic microscopy coupled with energy-dispersion x-ray analysis, and inductively coupled plasma atomic emission spectroscopy. RESULTS: Under the experimental conditions, LDL (14.8 and 43.1 mg/L protein) had no significant effect on the precipitation kinetics. Oxidized LDL (14.8 and 43.1 mg/L protein) prolonged the nucleation phase and diminished the amount of total precipitate, and both the extent of oxidation and the concentration of the protein affected the kinetics. Cholesterol microcrystals (71.4 and 143 mg/L) made the nucleation phase shorter (300 min vs 390 min for the control), and the precipitated particles had an organic core and a shell composed of calcium phosphates. L-alpha-Phosphatidylcholine vesicles (143 mg/L), cholesterol (71.4 mg/L)/phospholipid (143 mg/L) mixed vesicles, cholesteryl linoleate (143 mg/L), and cholestane-3beta,5alpha,6beta-triol (71.4 mg/L) prolonged the nucleation phase. CONCLUSIONS: LDL is not involved directly in the precipitation of calcium phosphates. Oxidized LDL inhibits both nucleation and crystal growth, possibly by attracting calcium ions in the solution and thus reducing supersaturation. Cholesterol microcrystals serve as seeds for the precipitation of hydroxyapatite, whereas L-alpha-phosphatidylcholine, cholesteryl linoleate, and cholestane-3beta,5alpha,6beta-triol exhibit inhibitive effects on the nucleation of calcium phosphates. |
| Effects of lectins on calcification by vesicles isolated from aortas of cholesterol-fed rabbits Hsu, H. H., O. Tawfik, et al. (2000), Biochim Biophys Acta 1464(2): 262-72. Abstract: Advanced vascular calcification in atherosclerosis weakens arterial walls, thereby imposing a serious rupturing effect. However, the mechanism of dystrophic calcification remains unknown. Although accumulating morphological and biochemical evidence reveals a role for calcifiable vesicles in plaque calcification, the mechanism of vesicle-mediated calcification has not been fully explored. To study whether vesicles' membrane components, such as carbohydrates, may have a role in vesicle-mediated calcification, the effect of sugar-binding lectins on calcification was investigated. Atherosclerosis was developed by feeding rabbits with a diet supplemented with 0.5% cholesterol and 2% peanut oil for 4 months. Calcifiable vesicles were then isolated from thoracic aortas by collagenase digestion. The histological examination of aortas with hematoxylin counter-staining indicated abnormal formation of large plaques enriched with macrophage-derived foam cells. Fourier transform spectroscopy revealed mild calcification in aortas indicating that advanced stages of heavy calcification have yet to be reached. However, vesicles isolated from the aortas were capable of calcification in the presence of physiological levels of Ca(2+), Pi, and ATP. Thus, at this stage of atherosclerosis, aortas may start to produce calcifiable vesicles, but at a level insufficient for substantial formation of mineral in aortas. The assessments by FT-IR analysis and Alizarin red staining indicated that concanavalin A (Con A) substantially increased mineral formation by isolated vesicles. Con A also exerted a marked stimulatory effect on (45)Ca and (32)Pi deposition in a dose-dependent fashion with a half-maximal effect at 6-10 microg/ml. Either alpha-methylmannoside or alpha-methylglucoside, but not mannitol, at 10 mM abolished the stimulation. Con A stimulation was abolished after Con A was removed from calcifying media, suggesting that covalent binding may not be involved in the effect. Galactosides appear to also be implicated in (45)Ca and (32)Pi deposition since Abrus precartorius agglutinin, which specifically binds galactosides, enhanced the deposition. Neither wheat-germ agglutinin that binds N-acetylglucoside nor N-acetylgalactoside-specific Helix pomatia agglutinin was effective, suggesting that the acetylated forms of carbohydrate moieties are either absent in vesicles or may not be involved in calcification. None of these lectins exerted an effect on ATPase. Thus, the effects of lectins appeared to be mediated through interactions with carbohydrate moieties of calcifiable vesicles. Whether stimulation of vesicle-calcification by lectins is of pathological significance in atherosclerotic calcification requires further investigation. |
| Effects of legume consumption on serum cholesterol, biliary lipids, and sterol metabolism in humans Duane, W. C. (1997), J Lipid Res 38(6): 1120-8. Abstract: Legume consumption appears to lower serum cholesterol and to increase cholesterol saturation of bile, but the mechanisms of these effects have not been established. We studied nine human subjects on a metabolic ward during two randomly ordered 6-7 week periods: one during consumption of a control diet and the other during consumption of the same diet with 120 gm mixed legumes substituted for foods having equivalent calories, fat, protein, and carbohydrate. Mean serum LDL cholesterol was significantly lower during legume consumption (126 vs. 138 mg/dl, P = 0.039). Legume consumption significantly increased mean cholesterol saturation index of gallbladder bile from 1.07 to 1.26 (P = 0.016), largely because of an increase in hepatic secretion of cholesterol from a mean of 90.2 mumol/h to 100.8 mumol/h (P = 0.042). Fecal neutral sterol output was unaffected by legumes, but fecal acidic sterols increased from a mean of 861 to 1202 mumol/day (P = 0.002) during legume consumption. Mean sterol balance became significantly more negative during legume consumption (-2140 vs. -2700 mumol/day, P = 0.037) indicating an increase in cholesterol synthesis. Mean fractional absorption of bile acid was lower during legume consumption than (0.947 vs. 0.960, P = 0.003). These data suggest that legume consumption lower LDL cholesterol by partially interrupting the enterohepatic circulation of bile acids and increases cholesterol saturation of bile by increasing hepatic secretion of cholesterol. |
| Effects of life style on serum cholesterol levels and atherogenic index Takasaki, Y. (1994), Nippon Koshu Eisei Zasshi 41(1): 46-55. Abstract: Life style as related to levels of serum total, HDL and LDL cholesterol, and atherogenic index (AI) were studied in the context of prevention of atherosclerosis and cardiovascular diseases, and maintenance of an active long life. Mean values of serum cholesterol, AI and elements of life style were compared on the basis of responses to a questionnaire and results of a medical examination for 369 men and women aged over 30 years in a district of Akita prefecture. Life style appeared to have a tendency of influence in men and AI appeared to be elevated with a life style of limited physical activity that was comparatively light and with no drinking. Many men reporting a life style of light activity were unemployed and tended to attempt to make up for the activity by an exercise program. As for women, there appeared to be no influence of life style on the aging phenomena. Many of the women who were unemployed tended to be single, to have limited and light daily activity, a regular exercise program, and reported getting adequate sleep. Personal awareness of body fat and health conditions seemed to be reflected in levels of cholesterol and AI, and therefore raising a person's awareness level is important for adopting personal health management habits. |
| Effects of lipid lowering by pravastatin on progression and regression of coronary artery disease in symptomatic men with normal to moderately elevated serum cholesterol levels. The Regression Growth Evaluation Statin Study (REGRESS) Jukema, J. W., A. V. Bruschke, et al. (1995), Circulation 91(10): 2528-40. Abstract: BACKGROUND: Intensive lowering of serum cholesterol may retard progression of coronary atherosclerosis in selected groups of patients. However, few data are available on the potential benefit of serum cholesterol reduction in the broad range of patients with coronary atherosclerosis and normal to moderately elevated serum cholesterol levels who undergo various forms of treatment. The Regression Growth Evaluation Statin Study (REGRESS) addresses this group of patients. METHODS AND RESULTS: REGRESS is a double-blind, placebo-controlled multicenter study to assess the effects of 2 years of treatment with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor pravastatin on progression and regression of coronary atherosclerosis in 885 male patients with a serum cholesterol level between 4 and 8 mmol/L (155 and 310 mg/dL) by quantitative coronary arteriography. Primary end points were (1) change in average mean segment diameter per patient and (2) change in average minimum obstruction diameter per patient. Clinical events were also analyzed. Of the 885 patients, 778 (88%) had an evaluable final angiogram. Mean segment diameter decreased 0.10 mm in the placebo group versus 0.06 mm in the pravastatin group (P =.019): The mean difference between treatment groups was 0.04 mm, with a 95% CI of 0.01 to 0.07 mm. The median minimum obstruction diameter decreased 0.09 mm in the placebo group versus 0.03 mm in the pravastatin group (P =.001): The difference of the medians between the treatment groups was 0.06 mm, with a CI of 0.02 to 0.08 mm. At the end of the follow-up period, 89% (CI, 86% to 92%) of the pravastatin patients and 81% (CI, 77% to 85%) of the placebo patients were without new cardiovascular events (P =.002). CONCLUSIONS: In symptomatic men with significant coronary atherosclerosis and normal to moderately elevated serum cholesterol, less progression of coronary atherosclerosis and fewer new cardiovascular events were observed in the group of patients treated with pravastatin than in the placebo group. |
| Effects of long term 2% fish oil supplements on tissue fatty acids, phospholipids, cholesterol, and arterial histology in Japanese quail (Coturnix coturnix japonica) Chamberlain, J. G., L. E. Dittmann, et al. (1991), Artery 18(6): 291-314. Abstract: The effects of 2% olive oil (OO) or fish oil (FO) (Super epa500) dietary supplementation (9 months) on Japanese "SEA" quail was investigated. The animals were examined for tissue biochemical changes and possible blood vessel fatty deposition. The fatty acids of blood and tissue extracts from heart, liver and fat were analyzed by gas-chromatography/mass spectrometry. The ratio of arachidonic acid to eicosapentaenoic or docosahexaenoic acid was markedly decreased in FO treated animals compared to OO or control diet treated animals. Tissue cholesterol and total phospholipids were present in elevated amounts in the heart and liver of FO treated animals. After the 9-month regimen many animals had residual atherosclerotic lesions but the FO treated birds had considerably more fatty streaks and fatty deposition in their large vessels compared to control or OO treated animals. Although the lipid composition of tissues of FO treated animals would indicate that the purported cardioprotective omega-3 fatty acids are enriched in the various tissues examined compared to olive oil and control diet treated animals, the possible detrimental effect of saturated fat, cholesterol, or some other component of the fish oil preparations is suggested from the histological appearance of fatty deposition in the blood vessels (aortae) of these inbred animals. These results in quail are strikingly similar to that seen in the omega-3 FA treated WHHL rabbit (15). |
| Effects of long term cholesterol lowering on coronary atherosclerosis in patient risk factor subgroups: the Simvastatin/enalapril Coronary Atherosclerosis Trial (SCAT) Burton, J. R., K. K. Teo, et al. (2003), Can J Cardiol 19(5): 487-91. Abstract: This study examined the effects of long term cholesterol lowering therapy with simvastatin on progression and regression of coronary atherosclerosis, as determined by quantitative angiographic end points, in subgroups of patients with known coronary risk factors. In this randomized, placebo controlled clinical trial, the effect of simvastatin on coronary atherosclerosis was compared with that of placebo in 394 patients who had paired coronary angiograms taken an average of four years apart. The effects of treatment on the following prespecified subgroups were examined: sex, age (less than 65 years versus at least 65 years), smoking status (current or previous/never), history of diabetes mellitus or hypertension, and severity of coronary artery lesions (diameter at least 50% versus less than 50%). There were significantly smaller decreases in the average minimum diameters, between closeout and baseline angiograms, in all simvastatin-treated subgroups, compared with placebo. Trends toward or significantly smaller decreases in the average of the mean diameters, and similar smaller increases in percentage diameter stenosis were also seen in all subgroups. The slowing of angiographically demonstrable coronary atherosclerotic narrowing supports the contention that this treatment effect is causally related to the reduction of coronary events repeatedly seen in large outcome clinical trials of lipid lowering therapy. Also, this treatment effect occurs in the presence or absence of the traditional coronary risk factors. |
| Effects of long term feeding of Quillaja saponins on sex ratio, muscle and serum cholesterol and LH levels in Nile tilapia (Oreochromis niloticus (L)) Francis, G., B. Levavi-Sivan, et al. (2002), Comp Biochem Physiol C Toxicol Pharmacol 133(4): 593-603. Abstract: Seventeen-day-old Nile tilapia fry were fed a standard diet (C) or diets containing 50-700 mg kg(-1) Quillaja saponin (QS) extract (groups S50, S150, S300, S500 and S700). After the first 8 weeks, 30 randomly selected tilapia from each of the treatments were placed in separate aquaria and fed the standard diet without saponins from then on (these were designated S50/C, S150/C, S300/C, S500/C and S700/C). The fish grew from an initial average weight of approximately 30 mg to a final average weight of 79 g during the 6-month feeding period. The difference between the average weight of C-fed tilapia and the treatment with the highest average weight after 6 months was 53.5%. The sex ratio of tilapia in the saponin-fed groups deviated from the normal 50:50 male:female ratio, with the S700 group showing a significantly higher number of males. Quillaja saponin stimulated LH release from dispersed tilapia pituitary cells in vitro. This effect was abolished in the presence of dilute calf serum. Serum LH values did not show any diet-dependent trend in either male or female tilapia in vivo. In both continuously saponin-fed and only-initially saponin-fed groups, the average serum (but not muscle) cholesterol levels in males showed an increasing trend (R(2) values of 0.62 and 0.69) with increasing dietary saponin level. It was concluded that dietary QS has the potential to change the sex-ratio in favour of males. More investigations are required to determine the mechanism of action and the optimum dietary level of QS for maximum effects. |
| Effects of long-term administration of HMG-CoA reductase inhibitors on cholesterol synthesis in lens Kalinowski, S. S., R. D. Tanaka, et al. (1991), Exp Eye Res 53(2): 179-86. Abstract: The effects of long-term dosing with inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase on the rate of cholesterol biosynthesis were examined in the lens and liver of rats and hamsters. While both pravastatin and lovastatin inhibited incorporation of 14Cacetate into cholesterol in liver slices 2-4 hr after an oral dose, lovastatin, but not pravastatin, inhibited sterol synthesis in lens as well. At 24 hr after a single oral dose, cholesterol synthesis in livers from drug-treated animals was increased compared to controls. This induction of the cholesterol synthetic pathway was observed for both drugs in the liver but only for lovastatin in the lens. After 4 days of once-daily oral doses, synthesis in the lens was induced two to threefold by lovastatin but not by pravastatin. When the drug was included in the continuous diet for 4-5 days, lovastatin caused increases in cholesterol synthesis in the lens whereas lenses from pravastatin-treated animals were identical to controls. This was not a species-specific effect since a similar tissue selectivity was observed in the hamster. The increase in cholesterol synthesis in lenses observed in lovastatin-treated rats was accompanied by an increase in the activity of HMG-CoA reductase enzyme. These studies demonstrate that non-selective HMG-CoA reductase enzyme inhibitors can inhibit cholesterol synthesis in the lens, and following this inhibition a marked induction in the cholesterol biosynthetic pathway develops in the lens and this induction is associated with an increase in HMG-CoA reductase enzyme activity. |
| Effects of long-term treatment with taurine in mice fed a high-fat diet: improvement in cholesterol metabolism and vascular lipid accumulation by taurine Murakami, S., Y. Kondo, et al. (2000), Adv Exp Med Biol 483: 177-86. Abstract: Hypocholesterolemic effects of taurine in rats fed a high-fat and high-cholesterol diet are well established. However, there are few studies on long-term effects of taurine on cholesterol metabolism. In the present study, taurine was dissolved in drinking water and given to C57BL/6J mice during 6 months-feeding of a high fat diet. Taurine treatment significantly decreased serum LDL and VLDL cholesterol, while it significantly increased serum HDL cholesterol. In the liver, taurine decreased cholesteryl ester contents, accompanied by decrease in acyl CoA:cholesterol acyltransferase (ACAT) activity. Hepatic activity of cholesterol 7alpha-hydroxylase, a rate-limiting enzyme for bile acid synthesis, was doubled with taurine. Taurine reduced by 20% the high-fat diet-induced arterial lipid accumulation. Thus, taurine prevented elevation of serum and liver cholesterol levels, as possibly related to accelerated cholesterol elimination from the body through the stimulation of bile acid synthesis. Long-term treatment with taurine is beneficial for prevention of hypercholesterolemia and atherosclerosis. |
| Effects of long-term ursodeoxycholate administration on expression levels of secretory low-molecular-weight phospholipases A2 and mucin genes in gallbladders and biliary composition in patients with multiple cholesterol stones Kano, M., J. Shoda, et al. (1998), Hepatology 28(2): 302-13. Abstract: Group IIA phospholipase A2 (PLA2), a secretory low-molecular-weight PLA2, may play a critical role in the process of gallbladder mucosal inflammation in multiple cholesterol stones, which in turn may produce biliary pronucleating proteins as well as mucin. On the other hand, ursodeoxycholate (UDC) decreases biliary levels of various pronucleating proteins, possibly because of its membrane-protective effects on the inflamed gallbladder mucosa. To elucidate that beneficial effect of UDC, the expression levels of low-molecular-weight PLA2s, group IIA PLA2 (PLA2-IIA), and group V PLA2 (PLA2-V), and mucin core polypeptide genes in the gallbladders were studied for UDC-treated patients and untreated patients with multiple cholesterol stones. Furthermore, the results were correlated with alterations in biliary composition. With long-term administration of UDC, the PLA2-IIA protein mass (2.7 +/- 0.5 vs. 5.0 +/- 0.4 ng/mg x protein mean +/- SEM; P <.01) and steady-state mRNA level, as well as the PLA2-V mRNA level, were significantly decreased in the gallbladders, where the prostaglandin E2 (PGE2) level was concomitantly decreased (190.7 +/- 27.9 vs. 393.6 +/- 55.3 pg/mg x protein; P <.01). In the gallbladder bile, the immunoradiometrically determined PLA2-IIA levels were significantly decreased in the UDC-treated patients (43 +/- 4 ng/dL; P <.01) in comparison with untreated patients (78 +/- 6 ng/dL). Significant decreases were similarly found for total protein, mucin, and free arachidonate concentrations, as well as nucleation activity in the bile. The degree of the changes was found to be rather small in solitary stones. In contrast to the decreased mucin concentration, however, there were no significant changes in the expression levels of mucin core polypeptide genes (MUC1-MUC6) between the UDC-treated and untreated patients. Long-term UDC administration was observed to lower the increased PLA2-IIA protein mass and mRNA level, as well as the PLA2-V mRNA level, in the gallbladders of patients with multiple cholesterol stones, which in turn may be of therapeutic importance in improving the gallbladder mucosal inflammation. Effects of UDC on secretory low-molecular-weight PLA2s as inflammatory mediators may relate to the reported efficacy of UDC treatment in cholesterol gallstone disease. |
| Effects of long-term use of testosterone enanthate. II. Effects on lipids, high and low density lipoprotein cholesterol and liver function parameters Tyagi, A., M. Rajalakshmi, et al. (1999), Int J Androl 22(6): 347-55. Abstract: The present study was designed to evaluate the effects of long-term administration of testosterone enanthate (TE) on lipid and liver function parameters in rhesus monkeys (n = 9) maintained under controlled dietary conditions. Bimonthly administration of 50 mg of TE increased serum testosterone into the supraphysiological range one day after injection and peak levels were seen on day 3, followed by a decrease to above baseline values by day 14. High density lipoprotein cholesterol (HDL-C) levels decreased gradually; compared to baseline values, the decline was significant from the 19th month of injection until the first month of recovery. The increase in low density lipoprotein cholesterol (LDL-C) levels and the LDL-C/HDL-C ratio during the treatment period was not significant compared to baseline values; however, when compared to control animals, HDL-C and LDL-C levels and the LDL-C/HDL-C ratio were significantly elevated from the 12th month until the end of the treatment period. All lipid parameters recovered by the end of the treatment period. Control animals (n = 9) did not show significant changes in HDL-C and LDL-C levels and the LDL-C/HDL-C ratio during the study period. Total cholesterol levels decreased in control (n = 9) and treated animals from 6 to 15th months of the treatment period, coinciding with the feeding of sprouted grams to animals. TE injections did not change the levels of triglycerides, alkaline phosphatase or bilirubin in control and treated animals. However, transaminase (SGOT and SGPT) levels increased following TE injections and remained elevated until the end of injections followed by a return to baseline values or below during the recovery period. These effects could be due to the pharmacokinetic profile of TE in which testosterone levels were elevated to supraphysiological values after injections. The recovery of the TE-induced changes in lipid parameters and liver transminases is reassuring but the changes in these parameters during TE injections indicate the need for long-acting androgens with better pharmacokinetic properties. |
| Effects of lovastatin and dietary cholesterol on bile acid kinetics and bile lipid composition in healthy male subjects Duane, W. C. (1994), J Lipid Res 35(3): 501-9. Abstract: We measured bile acid kinetics and bile lipids in 12 human subjects on a metabolic ward in four randomly allocated, 6-7 week periods: 1) lovastatin (40 mg b.i.d) + low cholesterol diet (mean 246 mg/day); 2) lovastatin+high cholesterol diet (mean 1071 mg/day); 3) low cholesterol diet alone; and 4) high cholesterol diet alone. Lovastatin did not significantly alter fractional turnover, synthesis, absorption, enterohepatic cycling, or pool sizes of bile acid measured by the Lindstedt method. The high cholesterol diet increased fractional turnover and synthesis rate of cholic acid, but not chenodeoxycholic acid, without altering pool size of either bile acid. The high cholesterol diet decreased bile acid absorption, but only during lovastatin treatment, suggesting the possibility of a "cholestyramine-like" effect of dietary cholesterol, appreciable at least when biliary cholesterol secretion is reduced by lovastatin. As in previous studies, lovastatin markedly lowered saturation index of gallbladder bile. Increased cholesterol consumption did not significantly alter cholesterol saturation index, suggesting that dietary cholesterol may not be a major factor in cholesterol gallstone pathogenesis. |
| Effects of lovastatin and dietary cholesterol on sterol homeostasis in healthy human subjects Duane, W. C. (1993), J Clin Invest 92(2): 911-8. Abstract: We measured biliary and fecal sterol outputs in 12 human subjects on a metabolic ward in four randomly allocated, 6-7 wk periods: (a) lovastatin (40 mg b.i.d.) + low cholesterol diet (mean 246 mg/d), (b) lovastatin + high cholesterol diet (mean 1,071 mg/d), (c) low cholesterol diet alone, (d) high cholesterol diet alone. In addition to lowering serum LDL cholesterol, lovastatin significantly lowered biliary secretion of cholesterol, fecal output of endogenous neutral sterols, cholesterol balance, and systemic cholesterol input (the sum of cholesterol synthesis and absorbed dietary cholesterol). The high cholesterol diet significantly lowered cholesterol balance, but significantly increased systemic cholesterol input and fecal output of acidic sterols. There was no significant interaction between lovastatin and dietary cholesterol for any parameter measured. Judging from these data, the primary action of lovastatin is to lower cholesterol synthesis and systemic cholesterol input, the main compensatory response being reduced biliary cholesterol secretion. Conversely, increased dietary cholesterol appears to increase systemic cholesterol input, the major compensatory response being increased bile acid synthesis. There appears to be no interaction between these two perturbations of systemic cholesterol input. |
| Effects of lovastatin and gemfibrozil in subjects with high ratios of total cholesterol to high-density lipoprotein cholesterol Hung, Y. J., D. Pei, et al. (1999), J Formos Med Assoc 98(2): 104-10. Abstract: Insulin resistance is associated with hypertriglyceridemia, low serum high-density lipoprotein cholesterol (HDL-C) concentrations and high serum total cholesterol (TC) to HDL-C ratios. Several reports have demonstrated that either lovastatin or gemfibrozil may favorably lower serum lipid concentrations. However, their effects on insulin sensitivity are unknown. The primary aim of this study was to compare the effects of lovastatin and gemfibrozil on insulin sensitivity and serum leptin concentrations in subjects with high TC/HDL-C ratios. We enrolled 25 nondiabetic patients, similar in terms of age and weight with TC/HDL-C ratios greater than 5. Thirteen subjects were treated with lovastatin 20 mg per day, and 12 received gemfibrozil 300 mg twice per day. Plasma lipids, glucose, and leptin were measured, and a 75-g oral glucose tolerance test (OGTT) and a modified insulin suppression test were performed before and after 3 months of treatment. The study showed the mean plasma TC, low-density lipoprotein cholesterol (LDL-C) concentrations, and TC/HDL-C ratio were significantly reduced in the lovastatin-treated group, but no obvious effects on plasma triglyceride (TG) and HDL-C were noted. In the gemfibrozil group, plasma TG and HDL-C were markedly lowered, but no significantly different effects in other plasma lipids were found. Gemfibrozil did not affect steady-state plasma glucose (SSPG) concentrations, whereas lovastatin significantly increased SSPG concentrations. Neither drug affected the serum leptin concentration during the OGTT. We conclude that lovastatin significantly lowers plasma TC and LDL-C ratio, and TC/HDL-C concentrations and adversely affects insulin sensitivity, while gemfibrozil markedly reduces plasma TG concentrations without altering insulin sensitivity in subjects with high TC/HDL-C ratios. |