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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present investigation was to study the influence of cholesterol feeding on cholesterol synthesis and fecal excretion of bile acids in germfree rats. Four germfree rats were fed a basal diet containing 0.004% cholesterol and four germfree rats received the same diet supplemented with 0.4% cholesterol for 2 weeks. Cholesterol synthesis was studied by assaying the HMG CoA reductase activity in the liver microsomal fraction. Cholesterol feeding decreased the HMG CoA reductase activity from 28.5 +/- 6.6 (mean +/- SEM) to 9.1 +/- 0.7 pmol/mg protein per min. In another experiment four germfree rats received the basal diet and four germfree rats the cholesterol-enriched diet. After 6 weeks feces were collected in two 4-day pools for analysis of bile acids. The main fecal bile acids were cholic acid and beta-muricholic acid (a metabolite of chenodeoxycholic acid), comprising more than 95% of total bile acids. Cholic acid was increased from 3.9 +/- 0.2 to 9.9 +/- 1.2 mg/kg body weight per day and beta-muricholic acid from 6.6 +/- 0.5 to 21.8 +/- 3.1 mg/kg body weight per day. The percentage of cholic acid decreased from 37.1 +/- 1.1 to 31.2 +/- 1.0%. In conclusion, germfree rats like conventional rats have the ability to compensate for an increased input of dietary cholesterol by inhibition of cholesterol synthesis and stimulation of bile acid synthesis. The synthesis of chenodeoxycholic acid (implied from the fecal excretion of beta-muricholic acid) is stimulated to a greater extent than that of cholic acid.
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PMID:Effects of cholesterol feeding on synthesis and metabolism of cholesterol and bile acids in germfree rats. 92 16

Serum cholesterol levels from birth to adulthood in a population of North American (Pima) Indians are described and compared to those of Caucasian populations. Cholesterol levels at birth (mean +/- SEM, 87 +/- 2.6 mg/100 ml) were similar in Pimas and Caucasians, but levels in Pimas from 5 to 16 years (148 +/- 4.6 mg/100 ml) were 20 to 30 mg/100 ml lower than among most white populations. The levels showed little rise with age from 5 to 16, then rose significantly in both sexes from ages 17 to 25. Cholesterol levels in adult Pimas (190 +/- 1.5 mg/100 ml) were up to 50 to 60 mg/100 ml lower than in American whites, and showed little increase after age 25. Two cohorts of children followed prospectively for six years indicated that the prevalence data reflect sequential changes in the population. Cholesterol levels of those subjects were significantly correlated at the first and last examinations. The Pima, in contrast to Caucasian American populations, have relatively low levels of serum cholesterol and low rates of coronary heart disease, but evidence of a causal relationship with the latter remains to be established.
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PMID:Serum cholesterol levels in American (Pima) Indian children and adolescents. 95 Nov 45

1. Cholesterol intake (about 0-25 mmol/day) and the faecal excretion of cholesterol, coprostanol and coprostanone were determined in normolipidaemic control subjects and hyperlipidaemic patients, whose bile acid kinetics had been previously studied. 2. The combined excretion of the neutral steroids (excluding plant sterol and plant sterol metabolites) averaged 1-07 +/- 0-13 (+/-SEM)mmol/day in the control subjects (n=14). The corresponding values in patients with hyperlipoproteinaemia type IIa (n=19), IIb (n=12) and IV (n=23) were 0-86 +/- 0-10, 0-93 +/- 0-11 and 1-48 +/- 0-17 mmol/day respectively. 3. The mean values for the net steroid "balance", defined as the combined amount of bile acid synthesized (determined by an isotope-dilution technique) and the faecal excretion of neutral steroids minus cholesterol intake, were 1-83 +/- 0-22 mmol/day in the control subjects and 1-60 +/- 0-15, 1-81 +/- 0-19 and 3-53 +/- 0-23 mmol/day in patients with type IIa, IIb and IV lipoprotein patterns respectively. 4. No significant correlations between net steroid "balance" and sex, age, serum lipid concentrations, body weight or body surface area were found in any of the groups of subjects. 5. It is concluded that patients with type II hyperlipoproteinaemia eliminate cholesterol as bile acids and neutral faecal steroids normally. The type IV lipoprotein pattern is associated with increased bile acid synthesis and/or elevated faecal excretion of neutral steroids, so that the net steroid "balance" is usually above the normal limit.
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PMID:Elimination of cholesterol in hyperlipoproteinaemia. 97 79

Lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A inhibitor, was given to 14 patients with unremittent nephrotic syndrome (heavy proteinuria with hyperlipidaemia) for 6 months. Treatment was started at an initial dose of 20 mg/day, increasing to a maximum of 80 mg/day. Treatment was well tolerated except in two patients: one developed rhabdomyolysis and one severe hypertriglyceridaemia requiring an additional antihyperlipidaemic agent. Lovastatin was effective in reducing serum cholesterol, LDL-C and apolipoprotein B in the remaining 12 patients. Cholesterol was reduced by 31% from 8.24 +/- 0.49 mmol/l (mean +/- SEM) to 5.7 +/- 0.18 mmol/l after 6 months (P less than 0.001). LDL-C was normalized to 3.26 +/- 0.21 mmol/l from a pretreatment value of 5.76 +/- 0.48 mmol/l (P less than 0.001), a decrease of 43%. Serum apolipoprotein B was also normalized to 1.11 +/- 0.09 g/l from a basal level of 1.51 +/- 0.10 g/l (P less than 0.05). Triglyceride, HDL-C and apolipoprotein A1 concentrations were unchanged. Proteinuria as well as renal albumin clearance were unchanged. GFR by plasma radioisotope Cr-EDTA clearance for the whole group was unaltered by treatment. However, among those with relatively good pretreatment renal function (GFR greater than 70 ml/min per 1.73 m2), GFR increased at the end of 6 months' treatment (118.2 +/- 15 ml/min per 1.73 m2 versus 77.6 +/- 8.4 ml/min per 1.73 m2 in wash-out phase).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lovastatin in glomerulonephritis patients with hyperlipidaemia and heavy proteinuria. 131 86

An increased lipid peroxidation, due to the altered intracellular ratio between free radicals and antioxidant systems, has been recently related to diabetes. To study the possible relationship between lipid peroxidation and metabolic control, we measured the plasma concentrations of malondialdehyde (MDA), end product of the oxidation of polyunsaturated fatty acids, in poorly and well controlled Type 2 diabetic patients. A significant increase in plasma malondialdehyde concentrations was found in poorly controlled diabetics when compared to well controlled patients (p < 0.001) and to healthy normoglycaemic subjects (p < 0.001), whereas no significant difference was observed between the two latter groups. Plasma MDA/Cholesterol and MDA/triglyceride ratios were both higher in poorly controlled diabetics than in well controlled (p < 0.005) and in normal subjects (p < 0.01 and p < 0.02 for MDA/CHOL and MDA/TG respectively). In diabetic patients a positive correlation was found between plasma MDA levels and mean daily blood glucose (p < 0.01), plasma fructosamines (p < 0.001), HbA1 (p < 0.05) and plasma triglycerides (p < 0.05), while no significant correlation was shown between plasma malondialdehyde and total cholesterol. Malondialdehyde levels were followed-up for 7 days running (T1-T7) in five poorly controlled diabetics, treated with conventional insulin therapy. This group showed normalized plasma lipid peroxide values (0.486 +/- 0.13 mumol/l, T5, M +/- SEM) 72 h after the restoration of glycaemic control (145 +/- 25 mg/dl, T2, M +/- SEM). These results confirm the increase of lipid peroxidation during Type 2 diabetes. The correlation with the degree of metabolic imbalance suggests a possible role for lipid peroxidation in the occurrence of glucose-induced macromolecular changes.
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PMID:Increased lipid peroxidation in type 2 poorly controlled diabetic patients. 145 13

The Cholesterol Lowering Atherosclerosis Study, a randomized angiographic clinical trial, demonstrated the beneficial effect of niacin/colestipol plus diet therapy on coronary atherosclerosis. Outcome was determined by panel-based estimates (viewed in both still and cine modes) of percent stenosis severity and change in native artery and bypass graft lesions. Computer-based quantitative coronary angiography (QCA) was also used to measure lesion and bypass graft stenosis severity and change in individual frames closely matched in orientation, opacification, and cardiac phase. Both methods jointly evaluated 350 nonoccluded lesions. The correlation between QCA and panel estimates of lesion size was 0.70 (p less than 0.0001) and for change in lesion size was 0.28 (p = 0.002). Agreement between the two methods in classifying lesion changes (i.e., regression, unchanged, or progression) occurred for 60% (210 of 350) of the lesions kappa +/- SEM = 0.20 +/- 0.05, p less than 0.001). The panel identified 442 nonoccluded lesions for which QCA stenosis measurements could not be obtained. Lesions not measurable by QCA included those with stenosis greater than 85% that could not be reliably edge tracked, segments with diffuse or ecstatic disease that had no reliable reference diameter, and segments for which matched frames could not be located. Seventy-nine lesions, the majority between 21% and 40% stenosis, were identified and measured by QCA but were not identified by the panel. This comparison study demonstrates the need to consider available angiographic measurement methods in relation to the goals of their use.
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PMID:Comparison of computer- and human-derived coronary angiographic end-point measures for controlled therapy trials. 154 94

The effects of aging on the hepatic metabolism of cholesterol were studied in 1-, 6- and 24-month-old male Sprague-Dawley rats. Microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity, which regulates cholesterol biosynthesis, decreased from 835 +/- 144 (SEM) pmol/min/mg protein in the youngest group to 219 +/- 34 and 205 +/- 53 pmol/min/mg protein (p less than 0.001) in the 6- and 24-month-old groups, respectively. Cholesterol 7 alpha-hydroxylase activity, which governs bile acid synthesis, was gradually reduced from 70 +/- 14 pmol/min/mg protein in the 1-month-old group to 32 +/- 7 and 16 +/- 3 pmol/min/mg protein (p less than 0.05) in the 6- and 24-month-old groups, respectively. Acyl coenzyme A:cholesterol acyltransferase activity, which catalyzes the esterification of cholesterol, averaged 431 +/- 47 and 452 +/- 48 pmol/min/mg protein in the 1- and 6-month-old groups, respectively, and was increased to 585 +/- 55 pmol/min/mg protein (p less than 0.05) in the 24-month-old group. The level of total cholesterol showed an age-related increase from 1.56 +/- 0.16 mg/g liver in the 1-month-old group to 1.70 +/- 0.15 and 2.20 +/- 0.19 mg/g liver (p less than 0.05) in the 6- and 24-month-old groups, respectively. The increase was mainly caused by an accumulation of esterified cholesterol. We conclude that a marked decrease in HMG-CoA reductase occurs between 1 and 6 months of age; thereafter the enzyme activity stays unchanged. The activity of cholesterol 7 alpha-hydroxylase decreases progressively and drastically with age, whereas the capacity for esterifying cholesterol increases slightly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Age-related changes in the metabolism of cholesterol in rat liver microsomes. 189 80

Estrogen-replacement therapy is important for the prevention of postmenopausal osteoporosis. However, oral synthetic and conjugated estrogens increase biliary cholesterol saturation index and risk of gallstone disease. To examine whether transdermal estrogen administration could avoid these adverse effects, 17 postmenopausal women were treated with transdermal estradiol (Estraderm TTS; Ciba-Geigy, Arnhem, The Netherlands), 100 micrograms/day for 4 weeks, and after 1 month without therapy, with oral estradiol (Progynova; Schering, Weesp, The Netherlands), 2 mg/day for 4 weeks. The increase in the serum estradiol level was much higher during transdermal than oral estradiol administration. On the contrary, the increase in the serum estrone level was much more pronounced during oral treatment. Both modes of treatment led to a similar reduction of urinary calcium excretion. A highly significant decrease in serum phosphate levels was found during transdermal therapy. Biliary cholesterol saturation index did not change during transdermal therapy (mean +/- SEM, 1.25 +/- 0.06 before and 1.22 +/- 0.07 at the end of transdermal therapy; P = NS). A slight increase in cholesterol saturation index that did not reach statistical significance was found during oral therapy (1.28 +/- 0.09 before and 1.36 +/- 0.09 during oral treatment). However, the subgroup of women with strong increases in serum estrone levels during oral estradiol therapy (greater than 0.5 pmol/mL; n = 8) generally had increased biliary cholesterol saturation index, a decrease in relative percentage chenodeoxycholic acid in bile, and increased serum sex hormone-binding globulin levels during oral treatment. Cholesterol monohydrate crystals were never found in duodenal biles during either treatment. This study indicates that transdermal estradiol does not induce lithogenic bile. On the contrary, oral estradiol leads to lithogenic bile in a subgroup of women with strong increases in serum estrone levels during oral treatment.
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PMID:Different hepatobiliary effects of oral and transdermal estradiol in postmenopausal women. 189 52

Although reduction in total plasma cholesterol has yet to be shown to have a beneficial effect on overall mortality, the weight of experimental and epidemiologic evidence supports efforts to lower total plasma cholesterol levels to reduce the risk of death from coronary heart disease (CHD). This is especially true in patients with heterozygous, type II-A hyperlipoproteinemia, whose total plasma cholesterol levels above the 90th percentile for age and sex place them at markedly increased risk of death from CHD. The lipid results of partial ileal bypass (PIB) were assessed in 110 patients with heterozygous, type II-A hyperlipoproteinemia in the Program on the Surgical Control of the Hyperlipidemias, a randomized, prospective clinical trial assessing the effects of cholesterol reduction on overall mortality and the course of CHD. Compared with dietary control (n = 52), PIB (n = 58) reduced total plasma cholesterol levels 24% +/- 2% (mean +/- SEM), reduced low-density lipoprotein (LDL) cholesterol levels 34% +/- 3%, and increased high-density lipoprotein (HDL) cholesterol levels 5% +/- 5% 5 years after surgery. Very low-density lipoprotein cholesterol levels were 28% +/- 21% higher and plasma triglyceride levels were 24% +/- 11% higher in the surgical group. The HDL cholesterol/total plasma cholesterol and HDL cholesterol/LDL cholesterol ratios were significantly higher after PIB. Apolipoprotein A-I and HDL subfraction 2 levels were significantly higher and apolipoprotein B-100 levels were significantly lower in the surgical group. PIB successfully lowered mean total plasma cholesterol and LDL cholesterol levels below the limits recommended by the National Cholesterol Education Program to minimize the risk of death from CHD. These results confirm the efficacy and support the role of PIB in the management of patients with marked hypercholesterolemia.
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PMID:Lipid results of partial ileal bypass in patients with heterozygous, type II-A hyperlipoproteinemia. Program on the Surgical Control of the Hyperlipidemias. 212 Jul 85

The effects of in vivo administration of high density lipoprotein-very high density lipoprotein (HDL-VHDL) on the development of aortic fatty streaks were studied in cholesterol-fed rabbits. The rabbits received a 0.5% cholesterol-rich diet for 8 weeks. During this period, the HDL-VHDL group was intravenously administered with 50 mg/week of homologous HDL-VHDL protein; the control group received normal saline (0.9% NaCl). HDL-VHDL fraction was obtained at density range 1.063 to 1.25 gm/ml by ultracentrifugation of normal rabbit plasma. Along the study, plasma lipid levels followed a similar profile in both groups. At the completion of the study, atherosclerotic-like lipid-rich lesions covered 37.9 +/- 6% (X +/- SEM) of the intimal aortic surface in the control group, and 14.9 +/- 2.1% in the treated group (p less than 0.001). The values of total and free cholesterol, esterified cholesterol, and phospholipids deposited within vessel wall were significantly lower in the aortas of the HDL-VHDL treated group than those in the control group. Cholesterol accumulation in the livers was also significantly lower (p less than 0.01) in the treated group than in the control. We concluded that administration of homologous HDL-VHDL lipoprotein fraction to cholesterol-fed rabbits, dramatically inhibited the extent of aortic fatty streaks and lowered lipid deposition in the arterial wall and liver without modification of the plasma lipid levels.
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PMID:High density lipoprotein plasma fractions inhibit aortic fatty streaks in cholesterol-fed rabbits. 292 83


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