Inhibition of cholesterol absorption by plant sterols for mass intervention

Mononuclear precursors of the human osteoclast have been identified in both bone marrow and the circulation in man, but osteoclast membership of the mononuclear phagocyte system (MPS) and its precise cellular ontogeny remain controversial. We isolated human hematopoietic marrow cells, blood monocytes, and peritoneal macrophages and incubated each of these cell populations with UMR106 osteoblast-like cells on glass coverslips and dentine slices in both the presence and absence of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3), macrophage-colony stimulating factor (M-CSF), and dexamethasone. Cells isolated from peripheral blood and peritoneal dialysis fluid were positive only for monocyte/macrophage markers (CD11a, CD11b, CD14, and HLA-DR) and negative for osteoclast markers [tartrate-resistant acid phosphatase (TRAP), vitronectin reception (VNR), and calcitonin (CT) receptors and did not form resorption pits on dentine slices after 24 hours in culture. Similarly marrow cells did not form resorption pits on dentine slices after 24 hours in culture. However, after 14 days in co-culture with UMR106 cells, in the presence of 1,25(OH)2D3 and M-CSF, numerous TRAP, CT receptor, and VNR-positive multinucleated cells capable of extensive lacunar resorption were formed in co-cultures of all these preparations. The presence of 1,25 (OH)2D3, M-CSF, and UMR106 were absolute requirements for osteoclast differentiation. It is concluded that precursor cells capable of osteoclast differentiation are present in the marrow compartment, the monocyte fraction of peripheral blood, and in the macrophage compartment of extraskeletal tissues and that these cells are capable of differentiating into mature functional osteoclasts. These findings argue in favor of osteoclast membership of the human MPS.     

Endogenous and copper-induced lipid peroxidation and antioxidant activity of serum in hypercholesterolemic subjects

In order to observe the transport ability of peritoneum to small molecular substances, peritoneal equilibration test (PET) was performed in 52 CAPD patients. By analysing the relationship between peritoneal transport function and dialysis adequacy, we found the average urea KT/V and Cr were significantly lower in high and low transport groups (n = 6 and n = 2) than in high average and low average groups (n = 35 and n = 9). According to the results of PET, we adjusted the dialysis program of 11 patients and the dialysis adequacy was markedly improved. We concluded that PET was helpful for selecting and adjusting CAPD program, and discussed some questions which should be payed more attention in PET operation.     

Effect of garlic and fish-oil supplementation on serum lipid and lipoprotein concentrations in hypercholesterolemic men

The formation of dehydroluciferin (L) from luciferin (LH2) in the reaction catalyzed by firefly luciferase (EC 1.13.12.7) has been studied. The E.LH2-AMP complex may follow two different pathways: towards production of light and towards the synthesis of the E.L-AMP complex. This last step has an inhibitory effect on light emission as molecules of the enzyme are trapped in a light unproductive complex. The effects of CoA and nucleoside 5'-triphosphates (NTPs) on light emission are quantitatively different. CoA combines with the L moiety of the E.L-AMP complex, yielding L-CoA, promoting liberation of free luciferase, and increasing light yield. NTP reacts with the AMP moiety of the same complex, generating adenosine(5')tetraphospho(5')nucleoside (Ap4N) and, probably, the E. L complex and scarcely increasing light production. The results are discussed in relation to previous reports, by others, on luciferase.     

Absorption, metabolism, and serum concentrations of cholesterol in vegetarians: effects of cholesterol feeding

Serum concentrations and metabolism of cholesterol were studied in vegetarians basally and during a dietary cholesterol load. Cholesterol absorption efficiency was normal and synthesis was slightly enhanced, even though serum cholesterol precursors were not increased. The serum concentrations of total and low-density-lipoprotein cholesterol were decreased proportionally to the reduced intake and absolute absorption of cholesterol. Fecal plant sterols were negatively correlated with the absorption efficiency of cholesterol and positively with fecal sterols and cholesterol synthesis, suggesting interference of high plant sterol intakes with cholesterol absorption. Cholesterol saturation and bile acid composition of the bile were not changed. The increased serum plant sterol-cholesterol ratios were positively related to the intake and negatively to the biliary secretion of plant sterols. Cholesterol feeding increased absolute cholesterol absorption and serum concentrations of total and low-density-lipoprotein cholesterol, did not change absorption efficiency or synthesis of cholesterol, but increased fecal cholestanol excretion.     

Resistant starch decreases serum total cholesterol and triacylglycerol concentrations in rats

Rats were meal-fed semipurified diets containing a low (0.8 g/MJ) and a high (9.6 g/MJ) amount of resistant starch (RS) or various amounts of RS (0.8 to 9.6 g/MJ) and guar gum (0 to 8.8 g/MJ). In one experiment, rats were fed the low and high RS diets in three dietary regimens (ad libitum consuming, 12 h ad libitum/12 h food deprived, and meal fed). Effects of RS and guar gum on serum postprandial and postabsorptive concentrations of total cholesterol (TC) and triacylglycerol (TAG), growth, hydrogen excretion, tissue weights and contents of small intestine and cecum, and pH of cecal contents were investigated. In addition, effects of RS on food intake, de novo hepatic synthesis of fatty acids and neutral sterols, and on lipoprotein lipase activity and weight of epididymal fat pads were investigated. Compared with feeding the low RS diet, the high RS diet reduced the serum TC and TAG concentrations, with these effects observed after 1 and 2 wk of feeding, respectively. The dietary regimen did not influence the effect of RS on the serum TC and TAG concentrations, but it did affect the serum TAG concentration. Resistant starch had no effect on the hepatic synthesis of fatty acids and neutral sterols or on the lipoprotein lipase activity in epididymal fat pads. Guar gum also reduced the serum TC concentration, but it had no effect on serum TAG concentration. The tissue weights and contents of small intestine and cecum as well as hydrogen excretion increased with increasing amounts of dietary RS and guar gum, whereas the pH of cecal contents decreased. No effects of RS on food intake and total body weight gain were found, whereas guar gum decreased weight gain. Feeding the high RS diet also led to a lower weight of the epididymal fat pads. We conclude that dietary RS can reduce serum TC and TAG concentrations and fat accretion.     

Greater dietary intake of simple carbohydrate is associated with lower concentrations of high-density-lipoprotein cholesterol in hypercholesterolemic children

This report details the independent laboratory study of the BAX for Screening/Salmonella assay to complete AOAC Performance Tested Method certification. The performance of the BAX system was compared with those of BAM culture methods on food samples inoculated with Salmonella. This study validated product claims. Performance Tested Method status was granted for the screening assay.     

Clinical characteristics and coronary risk factors of patients with low concentrations of serum low-density lipoprotein cholesterol and total cholesterol

We investigated the clinical characteristics and coronary risk factors of Chinese patients with suspected coronary artery disease (CAD) having low serum concentrations of both low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). Of 1,450 patients with suspected CAD (age range, 30-92 years; 948 men and 502 women), 760 had established CAD. The patients were divided into three groups according to lipid profile patterns. Group 1 patients (n = 138) had low LDL-C concentrations (< 100 mg/dL) and low TC concentrations (< 160 mg/dL). They were characterized by lower triglyceride concentrations, lower frequencies of high TC/high-density lipoprotein cholesterol (HDL-C) ratios (> 5) and LDL-C/HDL-C ratios (> 5), and lower frequencies of a family history of CAD and obesity. Group 3 patients (n = 610) had LDL-C concentrations of 130 mg/dL or above and TC concentrations of 200 mg/dL or above, much higher than in group 1. The prevalence of CAD was 41.3% (57/138) in group 1. 46.7% (328/702) in group 2, and 61.5% (375/610) in group 3. Groups with higher TC and LDL-C concentrations had a higher CAD prevalence. Coronary risk factors of group 1 patients appeared to be low HDL-C concentration, high TC/HDL-C ratio, advanced age, cigarette smoking, hypertension, and diabetes mellitus. Among these risk factors, HDL-C and hypertension were independent predictors of CAD. Unlike in the other two groups, hypertension was the only independent nonlipid risk factor. We conclude that in therapy or prevention of CAD, the goals should be to reduce LDL-C concentration to below 100 mg/dL and the TC concentration to below 160 mg/dL. However, other risk factors should also be considered.     

Is the Finnish "healthy margarine" food or medicine? Addition of plant sterols can lower cholesterol levels

Sine the autumn of 1995, Benecol, a proprietary brand of cholesterol-lowering margarine, has been available in ordinary grocery shops in Finland. The active ingredient is a sitostanol ester. Several studies in humans have shown use of the margarine to result in an approximately 10 per cent reduction in total serum cholesterol, and a 13-15 per cent reduction of LDL-cholesterol. However, further studies are required of its phyto-oestrogenic and endocrine effects, and its effects on growing children, particularly regarding subsequent fertility in boys. Although the margarine is classed as a 'functional food' in Finland, the question arises where the line is to be drawn between medicines and food-stuffs.     

Marked decline in serum concentrations of adrenal C19 sex steroid precursors and conjugated androgen metabolites during aging

The present data show a dramatic decline in the circulating levels of dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEA-S), androst-5-ene-3 beta,17 beta-diol (5-diol), 5-diol-sulfate, 5-diol-fatty acid esters, and androstenedione in both men and women between the ages of 20-80 yr. In the 50- to 60-yr-old group, serum DHEA decreased by 74% and 70% from its peak values in 20- to 30-yr-old men and women, respectively. the serum concentrations of the conjugated metabolites of dihydrotestosterone (DHT), namely androsterone (ADT)-G, androstane-3 alpha,17 beta-diol (3 alpha-diol-G), androstane-3 beta,17 beta-diol (3 beta-diol-G), and ADT-sulfate are the most reliable parameters of the total androgen pool in both men and women, whereas serum testosterone and DHT can be used as markers of testicular secretion in men and interstitial ovarian secretion in women. The serum concentration of these various conjugated androgen metabolites decreased by 40.8% to 72.8% between the 20- to 30-yr-old and 70- to 80-yr-old age groups in men and women, respectively, thus suggesting a parallel decrease in the total androgen pool with age. As estimated by measurement of the circulating levels of these conjugated metabolites of DHT, it is noteworthy that women produce approximately 66% of the total androgens found in men. In women, most of these androgens originate from the transformation of DHEA and DHEA-S into testosterone and DHT in peripheral intracrine tissues, whereas in men the testes and DHEA and DHEA-S provide approximately equal amounts of androgens at the age of 50-60 yr. An additional potentially highly significant observation is that the majority of the marked decline in circulating adrenal C19 steroids and their resulting androgen metabolites takes place between the age groups of 20- to 30-yr olds and 50- to 60-yr-olds, with smaller changes are observed after the age of 60 yr.     

Growth performance, intestinal microbial populations, and serum cholesterol of broilers fed diets containing Lactobacillus cultures

A study was conducted to determine the effects of adherent Lactobacillus culture on growth performance, intestinal microbial population, and serum cholesterol level of broilers. Four dietary treatments, consisting of the basal diet (control), basal diet + 0.05, 0.10, or 0.15% Lactobacillus culture (LC), were fed to 2,000 Arbor Acres broiler chicks from 1 to 42 d of age (DOA). The chicks were randomly assigned to 40 cages (50 chicks per cage, 10 cages per diet). The experimental period was 42 d. Body weights and feed to gain ratio were measured at 21 and 42 DOA. The intestinal microbial populations and serum cholesterol levels were determined at 10, 20, 30, and 40 DOA. The results showed that body weights and feed to gain ratios were improved significantly (P < 0.05) when compared to control broilers for broilers fed diets containing 0.05 or 0.10% LC, but not 0.15% LC, at 21 and 42 DOA. Coliform counts in the cecum of birds receiving 0.05% LC at 10, 20, and 30 DOA, and 0.10% at 10 and 20 DOA were significantly lower (P < 0.05) than those of the control birds. The total aerobes, total anaerobes, lactobacilli, and streptococci in the small intestines and ceca of the control birds were not significantly different from those of the treated groups. Serum cholesterol levels were significantly lower (P < 0.05) in broilers fed the three diets containing LC at 30 DOA, and in the birds fed 0.05 or 0.10% LC at 20 DOA.     

The influence of skin flap ischemia on serum nitric oxide concentrations

Nitric oxide (NO), identified as a mediator of endothelium-dependent relaxation of vascular smooth muscle, is known to cause a number of inflammatory diseases, especially ischemia-reperfusion injury. This experimental study, using a rabbit epigastric island flap, was designed to investigate whether skin flap ischemia followed by reperfusion influences serum NO concentrations. In addition, the author investigated the effects of NO synthase inhibitors and heparin on skin flap ischemia. Serum NO concentrations after 15, 30, 45, and 60 minutes of ischemia followed by reperfusion were significantly increased compared with non-ischemic controls and elevated flaps. On the other hand, serum NO concentrations were suppressed in nitro-amino-methyl-L-arginine- and aminoguanidine-treated animals. Furthermore, administration of heparin increased serum NO concentrations in controls and animals with elevated flaps, but decreased serum NO concentrations in ischemic flaps with subsequent reperfusion. These results suggest that NO is one of the factors responsible for ischemia-reperfusion injury and that NO synthase inhibitors and heparin may protect against such injury.     

Psyllium-enriched cereals lower blood total cholesterol and LDL cholesterol, but not HDL cholesterol, in hypercholesterolemic adults: results of a meta-analysis

We conducted a meta-analysis to determine the effect of consumption of psyllium-enriched cereal products on blood total cholesterol (TC), LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) levels and to estimate the magnitude of the effect among 404 adults with mild to moderate hypercholesterolemia (TC of 5.17-7.8 mmol/L) who consumed a low fat diet. Studies of psyllium cereals were identified by a computerized search of MEDLINE and Current Contents and by contacting United States-based food companies involved in psyllium research. Published and unpublished studies were reviewed by one author and considered eligible for inclusion in the meta-analysis if they were conducted in humans, were randomized, controlled experiments, and included a control group that ate cereal providing /=50 y) on blood lipids. The meta-analysis showed that subjects who consumed a psyllium cereal had lower TC and LDL-C concentrations [differences of 0.31 mmol/L (5%) and 0.35 mmol/L (9%), respectively] than subjects who ate a control cereal; HDL-C concentrations were unaffected in subjects eating psyllium cereal. There was no effect of sex, age or menopausal status on blood lipids. Results indicate that consuming a psyllium-enriched cereal as part of a low fat diet improves the blood lipid profile of hypercholesterolemic adults over that which can be achieved with a low fat diet alone.     

Circadian rhythms of serum renin activity and serum corticosterone, prolactin, and aldosterone concentrations in the male rat on normal and low-sodium diets

To investigate the control of aldosterone secretion, non-stress levels of serum aldosterone, corticosterone, and prolactin, and renin activity were determined at 4-h intervals during 24-h light-dark cycles in adult male rats on regular and low-sodium diets. Circadian rhythms of plasma aldosterone, prolactin, and corticosterone concentrations and of serum renin activity were demonstrated during a regular sodium diet. When the rats were on a low-sodium diet, a circadian rhythm of serum corticosterone and aldosterone concentration was observed, but there was no circadian variation in serum renin activity or in serum prolactin concentration. Serum aldosterone concentration correlated with serum corticosterone concentration (r = 0.48) and serum renin activity (r = 0.36) during a low-sodium diet. Serum prolactin concentration did not correlate with serum aldosterone concentration or serum osmolality. These data are compatible with a role for renin and ACTH, but not for prolactin, in the modulation of aldosterone secretion in the rat.     

The effect of supplemental dietary fat on plasma cholesterol levels in lovastatin-treated hypercholesterolemic patients

STUDY OBJECTIVE: A validation study was conducted first to test assumptions about the effect of saturated and unsaturated dietary fat supplements. The second study was conducted to determine the effect on blood cholesterol levels of saturated and unsaturated fat supplements in patients who followed a low-fat diet and were administered lovastatin. DESIGN: Randomized, crossover design, with three periods in the first study and four in the second study, each lasting 6 weeks. SETTING: Cholesterol Research Center. PATIENTS: The first study evaluated adults with total cholesterol levels between 200 and 280 mg/dl (5.172 and 7.241 mmol/L). The second study included adults with low-density lipoprotein (LDL) cholesterol levels above 160 mg/dl (4.138 mmol/L). INTERVENTIONS: Fat supplements with either coconut or canola oil were delivered to patients in oatmeal-raisin cookies. MEASUREMENTS AND MAIN RESULTS: In the validation study, patients' mean prerandomization total cholesterol level of 222 mg/dl was reduced to 213 mg/dl with canola oil and increased to 233 mg/dl with coconut oil cookies (p = 0.0038). In the second study the mean prerandomization total cholesterol level of 214 mg/dl was decreased to 199 mg/dl with canola oil and to 208 mg/dl with coconut oil cookies (p = 0.2342). The LDL cholesterol levels changed in a similar fashion in both studies. CONCLUSIONS: Changes in total and LDL cholesterol levels in the validation study were expected based on established effects of saturated and unsaturated fatty acids, but changes in these levels in lovastatin-cookie study were not expected. They could have occurred because lovastatin reversed the effect of saturated fats and enhanced the effect of unsaturated fats. Alternatively, they may have been due to enhanced bioavailability of lovastatin when administered with a high-fat diet. These findings must be confirmed.     

Linkage between cholesterol 7alpha-hydroxylase and high plasma low-density lipoprotein cholesterol concentrations

Interindividual differences in plasma low-density lipoprotein cholesterol (LDL-C) levels reflect both environmental variation and genetic polymorphism, but the specific genes involved and their relative contributions to the variance in LDL-C are not known. In this study we investigated the relationship between plasma LDL-C concentrations and three genes with pivotal roles in LDL metabolism: the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and cholesterol 7alpha-hydroxylase (CYP7). Analysis of 150 nuclear families indicated statistically significant linkage between plasma LDL-C concentrations and CYP7, but not LDLR or APOB. Further sibling pair analyses using individuals with high plasma LDL-C concentrations as probands indicated that the CYP7 locus was linked to high plasma LDL-C, but not to low plasma LDL-C concentrations. This finding was replicated in an independent sample. DNA sequencing revealed two linked polymorphisms in the 5' flanking region of CYP7. The allele defined by these polymorphisms was associated with increased plasma LDL-C concentrations, both in sibling pairs and in unrelated individuals. Taken together, these findings indicate that polymorphism in CYP7 contributes to heritable variation in plasma LDL-C concentrations. Common polymorphisms in LDLR and APOB account for little of the heritable variation in plasma LDL-C concentrations in the general population.     

Effects of fluvastatin, a new inhibitor of HMG-CoA reductase, and niceritrol on serum lipids, lipoproteins and cholesterol ester transfer activity in primary hypercholesterolemic patients

Effects of a combination therapy of fluvastatin, a new inhibitor of HMG-CoA reductase, and niceritrol on lipid metabolism were investigated measuring a wide range of parameters in 42 patients with primary hypercholesterolemia. After a wash-out period patients were randomly allocated to 1 of the 2 groups, the fluvastatin-preceding group (G-1) and the niceritrol-preceding group (G-2). In G-1 fluvastatin monotherapy (30 mg/day) significantly decreased total cholesterol (TC) and LDL-cholesterol (LDL-C). There was no significant change in HDL-cholesterol (HDL-C), triglyceride (TG) and lipoprotein (a) (Lp(a)). Further effect in HDL-C and TG was observed after the addition of niceritrol (750 mg/day). On the other hand, in G-2, while niceritrol alone (750 mg/day) produced no significant change in TC, LDL-C, HDL-C, TG and Lp(a), the addition of fluvastatin (30 mg/day) reduced TC and LDL-C levels significantly. Cholesterol ester transfer (CET) activity was significantly reduced by niceritrol monotherapy. After the concomitant use of the 2 drugs CET activity was significantly reduced only in G-2. No significant change in lipoprotein lipase and hepatic triglyceride lipase activities were observed in the 2 groups at either point in time. No serious adverse effect was observed in this study. It is concluded that fluvastatin is an effective drug for lowering LDL-cholesterol and causes no adverse alteration in lipid metabolism. Combination with niceritrol at a dose of 750 mg/day dose not appear to augment or attenuate beneficial effects of fluvastatin.     

Expression of progesterone receptor isoforms in corpora lutea of human subjects: correlation with serum oestrogen and progesterone concentrations

To understand the biological significance of progesterone receptor forms A (PR-A) and B (PR-B) in human corpus luteum, the expression of mRNA and serum steroid hormone concentrations were determined simultaneously in the luteal stages. The expression of PR-A mRNA predominated over PR-B mRNA in all samples analysed. Total PR (PR-AB) and PR-B mRNA concentrations at the late secretory phase were significantly (P < 0.01) lower than those at the early and mid secretory phases of the menstrual cycle. The ratio of PR-B to PR-AB mRNA concentration showed no significant change during the secretory phase. In the early and mid secretory phases, there was a negative correlation between PR-B mRNA concentration and serum progesterone concentration, and between the ratio of PR-B to PR-AB mRNA concentrations and serum progesterone concentration (P < 0.01). These findings suggest that human corpus luteum might intracellularly synthesize PR-A and PR-B, and thus be involved in the steroid functional regulation of the corpus luteum, especially at the early and mid secretory phases, and that progesterone might regulate the synthesis of PR-A and PR-B.     

Fibrinolytic response in subjects with hypertriglyceridemia and low HDL cholesterol

The combination of hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) appears to be an excessively high risk factor for coronary artery disease (CAD). In the Helsinki study, both coronary events and mortality were decreased by gemfibrozil, especially in subjects with low HDL-C and high triglycerides (TG). On the other hand, it is known that high levels of TG can be associated with high levels of circulating plasminogen activator inhibitor (PAI), which is also a possible risk factor for CAD. The aim of the present study was to see: 1) whether the combination of low HDL-C and high TG is associated with a more impaired fibrinolytic response than in either isolated condition, and 2) whether gemfibrozil administration can improve fibrinolysis in patients with both high TG and low HDL-C. Twelve non-obese, non-diabetic subjects (eight men, four women; mean age 55 +/- 13 yrs) with low HDL-C (< 35 mg/dL men; < 45 mg/dL women) and high TG (mean 253.6 +/- 42.6 mg/dL) entered the study (Group A). Additionally fourteen comparable subjects with normal HDL-C were also investigated (Group B), plus 12 comparable subjects with isolated low HDL-C (Group C). Ten healthy people served as the control group. The following plasma fibrinolytic parameters were measured: tissue plasminogen activator antigen, PAI antigen and activity, euglobulin fibrinolytic activity (EFA) on fibrin plates, plasminogen and alpha-2-antiplasmin activities. All except the latter two values were also measured after venous occlusion (vo). In baseline conditions, patients in Groups A and B had higher EFA values before vo and higher PAI-1 antigen and alpha-2-antiplasmin levels after vo than those of controls or the subjects in Group C. The relationship between PAI antigen and PAI activity and TG was not confirmed in our population (n = 48). We also saw no interference due to HDL-C, while there was a significant relationship between EFA before vo and both TG and cholesterol. After gemfibrozil treatment (600 mg bid for 12 weeks), the lipid profiles of subjects with high TG and low HDL-C were significantly improved. There was also a slight reduction of PAI activity after vo, while the PAI-1 antigen had decreased significantly from baseline after vo (56.3 +/- 13 ng/mL before vo; 48.4 +/- 21 ng/mL after vo; P = 0.04). The higher risk of CAD in patients with low HDL-C and high TG might be in part related to impairment of fibrinolysis, which occurs in patients with isolated high TG. The close relationship existing between both TG and cholesterol levels and fibrinolytic activity confirm the key role of this latter process in the development of CAD.