Pigs fed cholesterol neonatally have increased cerebrum cholesterol as young adults

Sixty-eight female neonatal pigs selected for seven (Experiment 1) or eight (Experiment 2) generations for high (HG) or low (LG) plasma cholesterol were used to test the hypothesis that neonatal dietary cholesterol fed during the first 4 or 8 wk of postnatal life increases the cholesterol content of the cerebrum in young adulthood following free access to a high-fat (15%), high-cholesterol (0.5%) diet from 8 to 20 or 24 wk of age. Pigs were removed from their dams at 1 d of age and given free access to a sow-milk replacer diet containing 9.5% coconut fat and 0 or 0.5 % cholesterol. All pigs (except four HG and four LG pigs in Experiment 2, which were deprived of cholesterol throughout the study) were fed the high-fat, high-cholesterol diet from 8 wk to termination at 20 or 24 wk of age. Cerebrum weight and cholesterol concentration were higher in pigs fed cholesterol neonatally than in those deprived of cholesterol neonatally in both experiments, but weight and cholesterol concentration were unaffected by genetic line. Cholesterol concentrations in longissimus and semitendinosus muscles and in subcutaneous fat were unaffected by diet or genetic line. We conclude that dietary cholesterol deprivation during the first 4 to 8 wk of life in piglets is associated with lower cholesterol concentration and total content in the young adult cerebrum than in pigs supplemented with cholesterol in early life. These data support previous observations and suggest the possibility of a metabolic need for neonatal dietary cholesterol in normal brain development.     

Diet, plasma lipoproteins and experimental atherosclerosis in baboons (Papio sp.)

Diet-induced hyperlipidaemia in baboons is similar to that in humans. As in humans, the ratio between low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol is a major determinant of atherosclerosis. Baboons, like humans and other non-human primates, vary in their lipaemic responses to dietary lipids. By selective breeding based on variability in plasma and lipoprotein cholesterol response to diet, lines of baboons with high and low responses of various lipoproteins have been developed. Genetic analyses suggest that lipoprotein patterns in response to dietary cholesterol and fat are heritable. Metabolic and molecular studies of high and low LDL and HDL cholesterol responses to dietary lipids have suggested that different mechanisms regulate plasma LDL cholesterol on the chow and on the high cholesterol-high fat (HCHF) diet. On the chow diet, plasma LDL cholesterol levels are positively associated with cholesterol absorption and negatively associated with hepatic LDL receptor levels and, thus, cholesterol absorption and LDL receptors seem to regulate plasma LDL cholesterol levels. However, when the animals consume a human-like fat- and cholesterol-enriched diet, plasma LDL cholesterol levels are not associated with either cholesterol absorption or hepatic LDL receptor mRNA levels, but are negatively associated with plasma 27-hydroxycholesterol concentrations, hepatic sterol 27-hydroxylase activity, and mRNA levels. Hepatic sterol 27-hydroxylase activity and mRNA levels are induced by dietary cholesterol and fat in low responding baboons more than in high responding baboons. Thus, the ability to induce sterol 27-hydroxylase determines the LDL cholesterol response in baboons. High HDL response baboons often have high levels of HDL1 in their plasma. Our studies suggest that the N-terminal fragment of apo C-I with 38 amino acids and a molecular weight of approximately 4 kDa acts as a cholesteryl ester transfer inhibitor peptide in high HDL1 baboons. The inhibitor peptide associates with apo A-1 in HDL to produce a modified apo A-1 protein with a molecular weight of approximately 31 kDa. The inhibitor peptide is a gene product and the presence of this peptide produces an antiatherogenic high HDL1 phenotype.     

XbaI polymorphism of the apolipoprotein B gene and plasma lipid and lipoprotein response to dietary fat and cholesterol: a clinical trial

A dietary trial was carried out on a group of offspring whose parents were hospitalized for an acute myocardial infarction. The XbaI Restriction Fragment Length Polymorphism (RFLP) was used to examine the genetic contribution of variation at this apo B locus to the response of lipids and lipoproteins to dietary manipulations. Twenty participants were homozygotes for the 8.0 kb fragment (X1X1), two were homozygotes for the 5.0 kb fragment (X2X2), and 15 were heterozygotes (X1X2). Subjects were randomized to a 5-week crossover study. Half began on a low SFA--cholesterol (LSC) diet for 5 weeks and, after a washout period of 4 weeks, they were placed on a high SFA--cholesterol (HSC) diet for a second period of 5 weeks. This order was reversed in the second group of participants. Significant changes in total cholesterol, LDL-C, and apo B were observed when subjects were moved from the LSC to the HSF diet. The corresponding average change induced by the dietary manipulations in X1X1 subjects compared with subjects with X2 allele were: 18.1 +/- 17.6 mg/dl and 9.5 +/- 19.6 mg/dl for total cholesterol and 15.8 +/- 15.3 mg/dl and 4.8 +/- 20.9 mg/dl for LDL-C, respectively. Our observation indicated that variation at the apo B XbaI locus may interact with baseline levels to determine individual dietary response in LDL-C level. However, the differences between the genotypic classes were not statistically significant, suggesting that the apo B XbaI locus is not a major determinant of interindividual differences in lipid and lipoprotein response to diet in this population.     

Liquid chromatographic method for analysis of all-rac-alpha-tocopheryl acetate and retinyl palmitate in milk-based infant formula using matrix solid-phase dispersion

We compared the fasting and postprandial response to a National Cholesterol Education Program (NCEP) II diet with that of a diet high in total (40% of energy) and saturated fat. In free-living conditions, 17 healthy normolipidemic, normoglycemic men and women consumed a high-fat diet, a maintenance diet and the NCEP II diet, for 1 mo each. At the completion of each dietary period, an oral fat load (70 g/m2 body surface area) was administered and plasma triacylglycerol (TAG) determined every 2 h for 8 h. Compared with the high-fat phase, the NCEP II diet was associated with significantly lower energy intake (12.1 +/- 1.1 vs. 7 +/- 0.7 MJ/d) and final body weight (78 +/- 3.8 vs. 76.3 +/- 3.5 kg) (P < 0.01). Plasma high density lipoprotein cholesterol, apolipoprotein (apo) A-I and ApoB concentrations were also significantly lower when subjects consumed the NCEP II diet rather than the high-fat diet (P 相似文献   

An European concerted action investigating the validity of perinatal mortality as an outcome indicator for the quality of antenatal and perinatal care

Genetic variation can influence the effects of hypocholesterolemic dietary interventions on lipoproteins involved in coronary artery disease (CAD). Individuals with the E4 allelic variant of the apo E gene exhibit greater low-density lipoprotein (LDL) cholesterol reductions on low-fat, low-cholesterol diets than subjects with other alleles. Another apolipoprotein structural variant, apo A-IV-2, attenuates the response of LDL cholesterol to dietary cholesterol. Other studies have associated lipoprotein response to dietary modifications with DNA polymorphisms in the genes for apo B and the LDL receptor, and in the promoter region of the apo A-I gene. Studies in our laboratory involving variation in dietary fat and carbohydrate intake have demonstrated that alleles at the apo E gene locus are associated with changes in large, buoyant but not smaller, denser LDL subclasses. On the other hand, a low-fat diet induces a reduction in small, dense LDL in individuals with a genetically influenced metabolic profile characterized by a predominance of these particles. Moreover, reductions in LDL cholesterol and apo B in these subjects are greater than in the majority of subjects with larger LDL. Since in humans a predominance of small LDL signifies a higher risk for coronary artery disease than that associated with larger LDL, metabolic and genetic factors contributing to the small LDL trait may account for a substantial portion of the coronary risk benefit attributed to reduced-fat diets. Studies in large population groups or in suitable animal models will be necessary to determine the impact of genetic influences on dietary response affecting lipoprotein metabolism and their interactions with other environmental and hormonal factors.     

Genetic variation at the apoA-IV gene locus and response to diet in familial hypercholesterolemia

Plasma lipid response to dietary fat and cholesterol is, in part, genetically controlled. The apolipoprotein A-IV (apoA-IV protein; APOA4, gene) has been shown to influence the response to dietary changes in normolipidemic individuals. The response to diet in subjects with familial hypercholesterolemia (FH) is also variable, and no studies are available on the influence of APOA4 mutations on dietary response in these subjects. We studied the effect of 2 common apoA-IV genetic variants (Gln360-->His and Thr347-->Ser) on the lipid response to the National Cholesterol Education Program type I (NCEP-I) diet in 67 FH heterozygotes (43 women and 24 men). Subjects were studied at baseline (after consuming for 1 month a diet with 35% fat [10% saturated] and 300 mg/d cholesterol) and after 3 months of consuming a low-fat diet. No sex-related differences were found, and results were combined for men and women. The APOA4-360 mutation was assessed in 67 subjects, 51 with genotype 1/1 and 16 with genotype 1/2. The APOA4-2 allele was associated with marginally significantly lower (P=0.049) low density lipoprotein (LDL) cholesterol levels and significantly lower (P=0.027) apoB levels independent of diet effects. After consuming an NCEP-I diet, carriers of the APOA4-2 allele showed a significantly lower reduction in apoB concentration (6.2%) than 1/1 subjects (14.1%; P=0.036); however, no significant differences in response were noted for LDL cholesterol. The APOA4-347 mutation was assessed in 63 individuals, 44 with the A/A allele and 19 with the A/T and T/T alleles. No significant differences were observed in baseline or post-NCEP-I diet values for these 2 groups in total, LDL, and high density lipoprotein cholesterol and plasma apoB levels. After dietary intervention, A/A individuals showed significant reductions in plasma triglyceride and very low density lipoprotein cholesterol levels; no changes were found in carriers of the T allele. Haplotype analysis suggested that in these FH subjects, the APOA4-360-2 allele was associated with lower plasma lipid levels during the NCEP-I diet period, whereas no significant effects were observed for the APOA4-347-T allele.     

U-shape relationship between change in dietary cholesterol absorption and plasma lipoprotein responsiveness and evidence for extreme interindividual variation in dietary cholesterol absorption in humans

A possible relationship between change in dietary cholesterol absorption and plasma lipoprotein responsiveness was examined in 18 normal subjects fed low fat low cholesterol, high fat low cholesterol, and high fat high cholesterol diets. For the group, neither dietary cholesterol nor dietary fat affected the percentage dietary cholesterol absorption, whereas dietary cholesterol intake raised total and LDL-C and dietary fat raised total, LDL, and HDL-C. On a fixed diet there was approximately a 2-fold variation among subjects in percentage dietary cholesterol absorption. Subjects also varied in response to dietary cholesterol and fat with regard to dietary cholesterol absorption and plasma lipoprotein responsiveness. There was a U-shaped parabolic relationship between dietary cholesterol-induced percent change in LDL-C and the change in percentage dietary cholesterol absorption (R2 = 0.62, P = 0.005). A similar but weaker relationship characterized the responsiveness of HDL-C (R2 = 0.38, P = 0.05). For the group, increased cholesterol intake raised dietary cholesterol mass absorption from 1.6 to 4.6 mg/kg per day, but the range of increase was from 1 to 4.7 mg/kg per day. Increased fat intake also affected dietary cholesterol mass absorption with most subjects displaying a strong inverse relationship between fat intake and mass absorption (r = -0.77, P < 0.003). In summary: i) the percentage change in dietary cholesterol absorption in response to dietary cholesterol does appear to regulate diet responsiveness of LDL and HDL-C, and ii) the large variability in percent absorption and changes in percentage and mass absorption in response to dietary cholesterol suggest the presence of genetically determined differences among individuals in the regulation of dietary cholesterol absorption.     

Effects of dietary fat and a vegetable-fruit mixture on the development of intestinal neoplasia in the ApcMin mouse

The variation in colorectal cancer (CRC) incidence worldwide strongly suggests a role for dietary influences. Based on epidemiological data, protective effects of vegetables and fruit intake on CRC are widely claimed, while other data indicate a possible increased CRC risk from (higher) dietary fat intake. Therefore, we have investigated single and interactive effects of dietary fat and a vegetable-fruit mixture (VFM) in the ApcMin mouse, a mouse model for multiple intestinal neoplasia. In this study, four different diets (A-D) were compared, which were either low in fat (20% energy diets A/B) or high in fat (40% energy diets C/D). In addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced by a freeze-dried VFM. The diets were balanced so that they only differed among each other in fat/carbohydrate content and the presence of specific plant-constituents. Because the initiation of intestinal tumors in ApcMin mice occurs relatively early in life, exposure to the diets was started in utero. Without the addition of VFM, mice maintained at a high-fat diet did not develop significantly higher numbers of small or large intestinal adenomas than mice maintained at a low-fat diet. VFM added to a low-fat diet significantly lowered multiplicity of small intestinal polyps (from 16.2 to 10.2/mouse, 15 animals/group), but not of colon tumors in male ApcMin mice only. Strikingly, addition of VFM to female mice maintained on a low-fat diet and to both sexes maintained on a high-fat diet significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7 polyps/mouse). In conclusion, our results indicate that neither a lower fat intake nor consumption of VFM included in a high-fat diet decreases the development of polyps in mice genetically predisposed to intestinal tumor development.     

Diet, lipoproteins, and coronary heart disease

Current dietary recommendations to decrease coronary heart disease (CHD) risk in the general population include reduction of total fat intake to less than or equal to 30% of energy, saturated fat to less than 10% of energy, and dietary cholesterol to less than 300 mg/day. Further restrictions in saturated fat to less than 7% of energy and in dietary cholesterol to less than 200 mg/day are indicated for those individuals with elevated low-density lipoprotein (LDL) cholesterol concentrations. Under controlled conditions, such diets reduce LDL cholesterol by 15% to 20%. However, in the out-patient setting, only 5% to 10% reductions in LDL cholesterol have been achieved, and large variability in dietary response is observed due to differences in compliance, as well as to genetic heterogeneity. This article reviews epidemiologic studies and dietary intervention trials that support a direct relationship between diet, lipoproteins, and CHD risk, with the ultimate goal of providing a framework for dietary management of the hyperlipidemic patient.     

Effect of high-fat and low-fat diets on voluntary energy intake and substrate oxidation: studies in identical twins consuming diets matched for energy density, fiber, and palatability

There remains controversy over the effects of dietary fat content on voluntary energy intake. Additionally, the question of whether there is a genetic susceptibility to overeating high-fat diets has not been resolved. To address these issues, we designed two diets: a low-fat diet providing approximately 20% of energy as fat and a high-fat diet with approximately 40% of energy as fat. The diets were matched for energy density, fiber, and palatability. In a two-phase, 18-d intervention study, voluntary energy intakes and macronutrient oxidation rates during the fasting and fed states were determined in seven pairs of identical male twins. In contrast with results of previous intervention studies, in which low-fat and high-fat diets were not matched for energy density and other associated variables, we observed no significant difference in voluntary energy intake between the low-fat and high-fat phases, and mean daily intakes were similar (10.3 and 10.7 MJ/d, respectively). Postprandial rates of fat oxidation tended to reflect fat intakes in the two dietary phases, thus helping to explain the lack of a difference in mean energy intakes. There was also a significant twin-pair similarity in differences in energy intakes between dietary phases (P = 0.013). These results suggest that dietary fat content does not have a major influence on voluntary energy intake when dietary variables usually associated with fat are controlled for and that there may be a familial influence on the effects of dietary fat content on energy intake.     

Effects of added lard fed to broiler chickens during the starter phase. 2. Serum lipids

The effects of lard added to starter diets on various serum lipids were determined in broiler chickens between 14 and 42 d of age. Nonisocaloric starter diets were formulated to contain either 0, 3, or 7% added lard, where the megacaloric percentages of all major nutrients were held constant. Birds received either 0, 3, or 7% added lard in starter diets through 10 d of age (S1), followed by either 3 or 7% added dietary lard through 21 d of age (S2). All possible combinations of the three S1 diets and two S2 diets yielded six total dietary treatments. A common grower diet was provided after 21 d. Concentrations of various serum lipids were determined weekly from 14 to 42 d of age. The effects of both the S1 and S2 diets on total cholesterol, low density lipoprotein cholesterol (LDLC), and high density lipoprotein cholesterol (HDLC) were inconsistent and were influenced by sex between 14 and 42 d of age. However, serum triglycerides and very low density lipoprotein cholesterol concentrations showed progressive increases over the 14 to 42 d period in birds that received dietary lard at either level in the S1 diet. These same serum constituents also increased to the greatest extents over the same period when birds were provided 3% added lard in the S2 diet. It was concluded that the response of broiler chickens between 14 and 42 d to different levels of dietary lard were influenced by age of feeding during the starter period. Furthermore, the specific effects of the diets on serum cholesterol, LDLC, and HDLC concentrations between 14 and 42 d varied with the sex and age of the bird.     

Comparison of the effects of hypercholesterolaemia on relaxation responses in aortas of spontaneously hypertensive rats and Dahl salt-sensitive rats

1. We investigated the effects of hypercholesterolaemia on relaxation responses in thoracic aortas isolated from two different types of hypertensive rats; spontaneously hypertensive rats (SHR) and Dahl salt-sensitive rats (DSR). 2. All rats fed the high cholesterol diet for 8 weeks showed a significant increase in the serum cholesterol level. The high cholesterol diet did not change the blood pressure of SHR, but increased that of hypertensive DSR fed a high-salt diet. 3. In aortas of SHR, the high-cholesterol diet did not change the endothelium-dependent and -independent relaxation induced by acetylcholine (ACh) and sodium nitroprusside (SNP), respectively. 4. In aortas of hypertensive DSR, the high-cholesterol diet notably reduced the ACh-induced relaxations and slightly reduced SNP-induced relaxation. 5. These results suggest that hypercholesterolaemia causes greater impairment of endothelium-dependent relaxation in rat aorta with salt-induced hypertension than genetic hypertension.     

Regression of advanced atherosclerosis in swine: chemical studies

Advanced complicated atherosclerosis was produced in the abdominal aortas of swine by a combination of mechanical injury and of a four-month high-cholesterol, high-fat diet. After discontinuation of the atherogenic diet, the animals were given swine mash for 14 months; subsequent chemical studies showed that regression of lesions had occurred, as delineated by decreased levels of DNA and DNA synthesis, total and esterified cholesterol, and phospholipid but no change in the levels of free cholesterol and triglycerides. The rate of DNA synthesis, but not that of total protein synthesis, had decreased. Collagen content had increased. By all criteria studied, the regressed lesions did not differ greatly from the abdominal aortic tissue of animals that had received only a mash diet for 18 months after mechanical injury. These findings, if extrapolated to man, would make the prognosis for possible regression of atherosclerosis under strictly controlled dietary regimens excellent.     

LDL particle size and LDL and HDL cholesterol changes with dietary fat and cholesterol in healthy subjects

We have conducted a dietary trial in 54 men and 51 women with a wide range of fasting cholesterol values to examine the use of low density lipoprotein (LDL) particle size to predict the lipoprotein response to dietary fat and cholesterol. After a 2-week low fat period, subjects were given two liquid supplements in addition to their low fat diet for 3 weeks each, one containing 31-40 g of fat and 650-845 mg of cholesterol, the other fat free. LDL particle type was determined by 3-15% gradient gel electrophoresis. On multiple regression, LDL type was independently related to plasma triglyceride (P < 0.001), waist circumference (P < 0.01), and high density lipoprotein (HDL) (P < 0.001) accounting for 56% of the variance in LDL type in the whole group. Change in LDL cholesterol with dietary fat and cholesterol was unrelated to LDL particle size in either men or women. However, change in HDL cholesterol in men was strongly related to LDL particle type (r = -0.52, P = 0.001) and change in HDL2 cholesterol in women was related to LDL particle type (r = -0.40, P < 0.01). In conclusion, we are unable to confirm the finding that LDL particle type can predict changes in LDL cholesterol following changes in dietary fat intake. However, LDL particle type can independently predict changes in HDL cholesterol in men and accounts for 27% of the variance.     

The nature of the association between diet and serum lipids in the community: A twin study.

Diet is commonly thought to be an environmental influence on serum lipid concentrations. This study evaluated whether total caloric and fat intake predict total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TRIG) concentrations for environmental, as compared with genetic, reasons among 137 monozygotic and 67 dizygotic young adult twins. When genetic influences were controlled by correlating differences between monozygotic co-twins, a significant association remained between diet and TC, LDL, and HDL, suggesting that these dietary and serum lipid measures correlate for environmental reasons. Twin structural equation modeling confirmed these results. Overall, these results provide additional support for the hypothesis that diet is an environmental influence on TC, LDL, and HDL. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dietary patterns associated with a low-fat diet in the national health examination follow-up study: identification of potential confounders for epidemiologic analyses

To identify systematically the nutrient and food group intakes associated with a low-fat diet, the authors used the detailed dietary information collected from 10,306 individuals aged 32-86 years in the 1982-1984 National Health Epidemiologic Follow-up Study. Intakes of vitamin C and percentages of calories from carbohydrates, dietary fiber, poultry, low-fat dairy products, fruits, vegetables, cereals, and whole grains were markedly higher, while intakes of protein, total fat, saturated fat, oleic and linoleic acids, cholesterol, sodium, all red meats, high-fat dairy products, eggs, nuts, white bread, fried potatoes, desserts, fats, and oils were much lower in the quartile with the lowest percentage of calories from fat. These dietary patterns associated with a low-fat diet were essentially constant across strata of age, sex, race, and socioeconomic status. This study suggests that individuals on a low-fat diet substitute certain carbohydrate-rich foods such as fruits and vegetables for fat. Given these associations between low-fat diets and other dietary factors independently associated with certain cancers, these dietary factors should be considered potential confounders in studies of dietary fat and these cancers.     

Missed opportunities for prevention: smoking cessation counseling and the competing demands of practice

Activating mutations in and expression of the Ha-ras gene were examined in benign and malignant female Sprague-Dawley rat mammary gland tumors induced by the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and promoted by a diet high in polyunsaturated fat. Ha-ras mutations were detected in codons 12 and 13 by selective polymerase chain reaction amplification of mutated sequences and nucleotide sequencing. The percentage of Ha-ras mutations in carcinomas from PhIP-treated rats was significantly higher in rats on a low-fat diet than in rats on a high-fat diet (82% (nine of 11) vs 26% (seven of 27), respectively, P < 0.01). In addition, whereas 56% of the carcinomas with Ha-ras mutations from rats on a low-fat diet carried double Ha-ras mutations, none of the carcinomas from rats on a high-fat diet had double mutations. Ha-ras mutations were also detected in benign tumors (largely adenomas) induced by PhIP in rats on different diets; two of eight and three of four benign tumors examined from rats on low-fat and high-fat diets, respectively, had Ha-ras mutations, suggesting that activating Ha-ras mutations alone are not sufficient for PhIP-induced tumors to become malignant. No differences were observed in the level of Ha-ras mRNA expression in the different groups. In our animal model, a high-fat diet increased the incidence and percentage of malignant PhIP-induced mammary gland tumors yet decreased the percentage of carcinomas showing Ha-ras mutations. Thus, the complement of genetic alterations associated with PhIP-induced mammary gland carcinogenesis is probably altered by the level of dietary fat.     

Applying radiobiological principles to combined modality treatment of head and neck cancer--the time factor

Although gallbladder stasis exists in most patients with cholesterol gallstones, it is unknown whether stasis is a causative factor of gallstone disease or merely a consequence of it. We studied the impact of sustained gallbladder stasis induced by a cholecystokinin (CCK)-A receptor antagonist (MK-329) on gallstone formation in ground squirrels fed either a trace or a high-cholesterol diet. MK-329 markedly inhibited gallbladder contraction in vitro in response to CCK (at EC100, control: 3.6 +/- 0.5 vs. MK-329: 1.1 +/- 0.3 g; P < .05) and increased gallbladder fasting volume in vivo (control: 462 +/- 66 vs. MK-329: 1,004 +/- 121 microL; P < .05). Whereas the high-cholesterol diet alone (1%-cholesterol diet + placebo) increased the cholesterol saturation index (CSI) in control animals (trace-cholesterol diet + placebo), MK-329 significantly (P < .05) decreased the CSI in both hepatic and gallbladder bile in animals on the trace-(trace-cholesterol diet + MK-329) as well as on the high-cholesterol diets (1%-cholesterol diet + MK-329). The mucin content of the mucus layer on the epithelial surface of the gallbladder wall more than doubled (P < .05) with the high-cholesterol diet; adding MK-329 to the latter group produced a further 82% increase (P < .05). The cholesterol diet + MK-329 group had the highest (100%) incidence of cholesterol crystals that were evident in fresh gallbladder bile, coincident with a shortened nucleation time (2.5 +/- 0.6 days; P < .05 vs. the cholesterol diet + placebo group, 5.8 +/- 1.0 days or the other 2 groups, >21 days). Bile from animals on the trace-cholesterol diet, whether or not receiving MK-329, lacked crystals in bile and exhibited a normal nucleation time (>21 days). Thus, stasis per se may lower the CSI, but its detrimental effect on the gallbladder predominates locally, and so accelerates cholesterol crystal formation in this model.     

Nutrient intake and blood pressure in the Dietary Intervention Study in Children

Delineating the role that diet plays in blood pressure levels in children is important for guiding dietary recommendations for the prevention of hypertension. The purpose of this study was to investigate relationships between dietary nutrients and blood pressure in children. Data were analyzed from 662 participants in the Dietary Intervention Study in Children who had elevated low-density lipoprotein cholesterol and were aged 8 to 11 years at baseline. Three 24-hour dietary recalls, systolic pressure, diastolic pressure, height, and weight were obtained at baseline, 1 year, and 3 years. Nutrients analyzed were the micronutrients calcium, magnesium, and potassium; the macronutrients protein, carbohydrates, total fat, saturated fat, polyunsaturated fat, and monounsaturated fat; dietary cholesterol; and total dietary fiber. Baseline and 3-year longitudinal relationships were examined through multivariate models on diastolic and systolic pressures separately, controlling for height, weight, sex, and total caloric intake. The following associations were found in longitudinal analyses: analyzing each nutrient separately, for systolic pressure, inverse associations with calcium (P < .05); magnesium, potassium, and protein (all P < .01); and fiber (P < .05), and direct associations with total fat and monounsaturated fat (both P < .05); for diastolic pressure, inverse associations with calcium (P < .01); magnesium and potassium (both P < .05), protein (P < .01); and carbohydrates and fiber (both P < .05), and direct associations with polyunsaturated fat (P < .01) and monounsaturated fat (P < .05). Analyzing all nutrients simultaneously, for systolic pressure, direct association with total fat (P < .01); for diastolic pressure, inverse associations with calcium (P < .01) and fiber (P < .05), and direct association with total and monounsaturated fats (both P < .05). Results from this sample of children with elevated low-density lipoprotein cholesterol indicate that dietary calcium, fiber, and fat may be important determinants of blood pressure level in children.     

Measurement of blood loss and bleeding pattern from the bleeding time incision

Intervention studies have shown that the adaptation of fat oxidation to fat intake, when changing the dietary fat content, is not abrupt. This study was conducted to measure the time course of adaptation of oxidation rates to increases in the fat content of the diet, when feeding subjects at energy balance. Twelve healthy, non-obese males and females (age: 26 +/- 2, BMI: 21.4 +/- 0.5, habitual fat intake: 29 +/- 1% energy) consumed a low-fat diet for 6 days (days 1-6) followed by a high-fat diet for 7 days (day 7-13). Days 5-9 and day 13 were spent in a respiration chamber. After adjusting energy intake to 24h energy expenditure on day 5, subjects were in energy balance (range -0.15 to +0.23 kJ/day) on days 6-9 and day 13. Fat balance was zero on day 6 but became positive after changing to the high-fat diet (1.06 +/- 0.15, 0.75 +/- 0.15, and 0.55 +/- 0.14 MJ/day for days 7, 8, and 9 respectively, p. < 0.05), reaching a new balance on day 13, 7 days afterwards. Thus, in case of energy balance, lean subjects are capable of adjusting fat oxidation to fat intake within 7 days, when dietary fat content is increased.