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Biomedical subjects

J A Story

Publications and source records attributed to J A Story.

At least 19 recordsLinked to original sources
PubMed1992

Lymph chylomicron composition and size are modified by level of intestinally infused cholesterol and triglyceride source in rats.

Mesenteric lymph chylomicrons were characterized following acute continuous intestinal infusion of triglyceride emulsions in rats. Emulsions were prepared using corn, olive or butter oils with graded doses of cholesterol (0, 3, 10, 20, 30, 60, 100 mg/g triglyceride) added to each. Chylomicron cholesterol content varied directly with dose of cholesterol infused, ranging from approximately 1.5% (by weight) with no added cholesterol to 5-10% at 100 mg cholesterol/g triglyceride. Minimum effective dose for increasing chylomicron cholesterol content (about twofold) was 20 mg/g triglyceride regardless of the triglyceride source. Esterified cholesterol accounted for most of the increase in chylomicron total cholesterol with corn oil infusion, whereas increases in the unesterified fraction accounted for 10-30% of the increase in total cholesterol during infusion of olive or butter oils. The effect of infused cholesterol on chylomicron lipid composition was dependent on triglyceride source: no effect on phospholipid:triglyceride ratio with corn and butter oils, but increased phospholipid:triglyceride ratio with olive oil at cholesterol doses greater than 20 mg/g triglyceride. Infusion of butter emulsions produced smaller chylomicrons than those produced during infusion of corn or olive oil emulsions.

Animals↗
PubMed1992

Lymph chylomicron size is modified by fat saturation in rats.

Mesenteric lymph chylomicrons were characterized during and after the establishment of steady-state triglyceride transport. Chylomicrons were isolated from lymph at 0, 2, 4, 6, 8 and 12 h after the start of an 8-h infusion of triglyceride emulsion (prepared using either corn or butter oil) at 160 mumol/(kg.h). Lymph flow was not influenced by triglyceride source. Output of triglyceride, measured both in whole lymph and in the chylomicron fraction, was not significantly affected by triglyceride source. Butter oil infusion produced a higher output of chylomicron phospholipid and unesterified cholesterol than was observed in response to corn oil emulsion. Ratios of transported phospholipid to triglyceride for butter oil chylomicrons were higher (1.3- to 1.7-fold) than those for corn oil chylomicrons at every time point examined after the start of lipid infusion. No other compositional differences in chylomicrons due to triglyceride source were observed. These results support the hypothesis that differences in efficiency of absorption and transport between saturated and unsaturated fat are sufficient to explain size differences in secreted chylomicrons in response to corn and butter oil infusions, and suggest that chylomicron number may be influenced by dietary fat saturation.

Animals↗
PubMed1992

Effects of psyllium hydrophilic mucilloid on LDL-cholesterol and bile acid synthesis in hypercholesterolemic men.

The goal of the current study was to determine the mechanism of the hypocholesterolemic effect of psyllium using a randomized, double-blind, crossover design. Twenty males (age 44 +/- 4 yr, weight 79 +/- 10 kg) with moderate hypercholesterolemia (total 265 +/- 17 mg/dl, low density lipoprotein (LDL) 184 +/- 15 mg/dl) were studied at baseline (B) and after randomization to receive a 40-day course of 15 g/day of either psyllium (Ps) or placebo (Pl) (cellulose). After a washout period (11 +/- 2 days), subjects were crossed over to the other fiber treatment for an additional 40 days and restudied. Intestinal cholesterol absorption, cholesterol synthesis in isolated peripheral blood mononuclear cells, bile acid kinetics, gallbladder motility, and intestinal transit were measured at each study period. Psyllium lowered LDL cholesterol (x:184 (B), 169 (Ps), and 179 (Pl) mg/dl; Ps vs. B,Pl: P less than 0.004, P less than 0.02), decreased relative cholesterol absorption (x:51 (B), 45 (Ps), and 49 (Pl) %; Ps vs. B,Pl: P less than 0.03, P less than 0.03), did not alter absolute cholesterol absorption, and increased the fractional turnover of both chenodeoxycholic acid (x:0.176 (B), 0.203 (Ps), and 0.170 (Pl) day-1; Ps vs. B,Pl: P less than 0.0001, P less than 0.01) and cholic acid (x:0.303 (B), 0.411 (Ps), and 0.301 (Pl) d-1; Ps vs. B, Pl: P less than 0.006, P less than 0.002). Bile acid synthesis increased in subjects whose LDL cholesterol was lowered by more than 10% (Ps vs. B: 1304 +/- 489 vs 992 +/- 307 mumol/day, P less than 0.006; Ps vs. PI: 1304 +/- 489 vs. 914 +/- 321 mumol/day, P less than 0.0002). We conclude that psyllium lowers LDL cholesterol primarily via stimulation of bile acid synthesis.

Adult↗
PubMed1991

Studies of women eating diets with different fatty acid composition. I. Plasma lipoproteins and steroid excretion.

Moderate changes in dietary fat composition have been recommended to improve plasma cholesterol status. Such changes have not been studied extensively in women. This research evaluates plasma lipoprotein and steroid excretion changes in young women who consumed a diet similar to US average consumption in 1974 [40 en% fat, polyunsaturated (P) to saturated fatty acid (S) ratio, P/S = 0.3, US74] or a diet modified to contain 30 en% fat, P/S = 1.0 (MOD). Following a preexperimental period of self-selected diets, young women were fed the diets for 28-day periods in a crossover design with 10 women at the University of Nebraska, Lincoln, and 10 at Iowa State University, Ames. Plasma lipoproteins and steroid excretion were quantitated and the compositions determined. Data were analyzed for race (five Chinese, 14 Caucasians) and for diet carryover effects, as well as for primary diet effects. In the Chinese women, the US74 diet raised total and very-low-density lipoprotein (VLDL) cholesterol compared to prior self-selected or modified diets; in the Caucasian women the MOD diet lowered total, low-density lipoprotein (LDL), and VLDL cholesterol. The diet carryover was evident in total high-density lipoprotein (HDL) and HDL3 cholesterol. Total HDL and HDL3 cholesterol in response to the US74 diet were unchanged from the MOD diet when the US74 diet followed the MOD diet, but were lower than modified when the US74 diet followed self-selected diets. The US74 diet resulted in greater neutral sterol excretion than the MOD diet; this response was more marked in the self-selected, US74, MOD sequence than in the self-selected, MOD, US74 sequence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Bile acid analysis: methods and problems.

What is the ideal method for analysis of faecal bile acids? Selection of an ideal system for a specific situation requires consideration of several factors, eg the information sought, availability of equipment and time constraints. Each laboratory will select procedures based on these constraints. A situation in which a large number of subjects are to be screened for total bile acid concentration might suggest use of single-day collections, lyophilization prior to homogenization, extraction using the Evrard and Janssen method and quantification by 3 alpha-hydroxysteroid dehydrogenase. However if the ratio of glycine to taurine conjugates and the daily excretion were of interest, separation of subclasses with Lipidex 1000 followed by both gas chromatography (of free bile acids) and HPLC (of conjugated bile acids) would be selected. There is not a best method for all situations. What does the future hold for improving this methodology in order to improve our ability to use faecal bile acid analysis clinically? The biggest problem facing the application of faecal bile acid analysis to clinical situations in the lack of ability to devise a rapid method (24-48 h) which retains the accuracy of current methods. One promising development is the potential application of immunological methods to faecal bile acids. These detection methods have been applied primarily to serum to date but if extraction and/or purification methods could be coupled with this method of quantification, a clinically acceptable method may result.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile Acids and Salts↗
PubMed1988

Stress- and morphine-induced elevations of plasma and tissue cholesterol in mice: reversal by naltrexone.

Our earlier studies indicated that stress-induced facilitation of gallstone formation could be prevented by the opiate antagonist naltrexone. In view of the possible link between gallstone formation and atherosclerosis, the present study examined the possibility that endogenous opioids might also mediate stress-induced hypercholesterolemia. A 28-day immobilization stress schedule was used to induce increases in plasma, aortic and liver cholesterol of mice maintained on a high cholesterol diet. These stress-induced increases in plasma, hepatic and aortic cholesterol were reversed by pretreatment with the opiate antagonist, naltrexone (1 mg/kg). Exposure of mice to morphine (0.1% in the drinking water for 28 days) resulted in elevations of plasma, liver, and aortic cholesterol levels, similar to those observed following immobilization. In contrast, chronic exposure to the peripherally restricted opiate agonist, loperamide (0.1% in the drinking water for 28 days), was ineffective. The antagonism by naltrexone and duplication by morphine but not loperamide suggest that stress-induced hypercholesterolemia may require the activation of central endogenous opioid systems.

Animals↗
PubMed1987

Morphine-induced alterations in plasma and tissue cholesterol levels.

In rats fed a cholesterol-cholic acid supplemented diet, implantation of a 75 mg morphine pellet elevated total plasma cholesterol, raised low density lipoprotein (LDL) plus very low density lipoprotein (VLDL) cholesterol, and lowered high density lipoprotein (HDL) cholesterol levels. The resultant increase of the atherogenic index was accompanied by enhanced aortic cholesterol deposition. These alterations were prevented by daily administration of naltrexone (1.0 mg/kg, sc), and were not associated with hyperphagic or hepatotoxic actions of morphine. An increase in total plasma cholesterol and in LDL plus VLDL cholesterol was also observed in morphine pelleted rats maintained on a normal diet. The possible implications of opiate-induced hypercholesterolemia are discussed.

Animals↗
PubMed1987

Short-term changes in hepatic HMG-CoA reductase in rats fed diets containing cholesterol or oat bran.

In vivo regulation of hepatic HMG-CoA reductase (HMGR) (mevalonate:NADP+ oxidoreductase [acylating CoA]; EC 1.1.1.34] by phosphorylation/dephosphorylation has not been demonstrated. Rats were meal-fed semipurified diets; effects of inclusion of cholesterol (2%) or oat bran (15%) in a single meal on expressed (phosphorylated) and total (dephosphorylated) activities of HMGR were measured from 15 min to 4 hr after presentation of the meal. Expressed activity was not significantly altered in response to the control diet during the time periods examined, while total HMGR activity declined by 15 min and increased through 4 hr to an activity about 1.5 times control levels. Addition of cholesterol resulted in little change in expressed activity but a greater and more sustained reduction in total activity. Oat bran caused reductions in both total and expressed activities, which were maintained through 4 hr. Total HMGR activity was best correlated with apparent demand for cholesterol synthesis.

Animals↗
PubMed1987

Dietary fiber supplementation and fecal bile acids, neutral steroids and divalent cations in rats.

Young adult rats were fed ad libitum for 4 wk on defined diets containing either no fiber, 10% levels of insoluble fiber sources [cellulose, wheat bran, alfalfa, mixed fibers (Fibyrax)], 5% levels of soluble fiber sources [pectin, guar gum, psyllium (Metamucil)] or 2% cholestyramine (Questran), a bile acid sequestrant. Fecal samples were obtained from paired rats over a 3-d period, were analyzed for neutral and acidic steroid levels and compositions and, together with the food, were assayed for divalent cations (Ca2+, Mg2+, Fe2+ and Zn2+). Animals in all groups were in balance for divalent cations, and there appeared to be no relationship between the extent of cation balance and the type of fiber fed. All insoluble fiber diets and the guar gum and psyllium diets resulted in significantly higher daily fecal mass and, in general, resulted in significant dilution of total fecal steroids. With the insoluble fibers, there was a general dilution of fecal neutral steroids, which was not apparent with the soluble fibers or cholestyramine. In addition, except for the pectin- and mixed fiber-containing diets, there was reduced bacterial conversion of the primary bile acids to secondary bile acids or metabolites.

Animals↗
PubMed1986

Fatty acid composition of mature human milk of Egyptian and American women.

Fatty acid composition of mature human milk of rural Egyptian and American women was determined by gas-liquid chromatography. Milk of Egyptian women contained significantly higher percentages of capric, lauric, myristic, linoleic and arachidonic acids, saturated fatty acids (SFA), and polyunsaturated fatty acids (PUFA). Conversely, milk of American women contained higher percentages of stearic and oleic acids, total unsaturated fatty acids, and monounsaturated fatty acids. The PUFA:SFA ratio in Egyptian samples was 0.54 +/- 0.18 compared to 0.47 +/- 0.22 in American samples. Increased percentages of medium-chain SFA in Egyptian milk suggested increased mammary gland lipid synthesis. Analysis of Egyptian diets indicated high-carbohydrate and low-fat intakes may have resulted in limited availability and incorporation of dietary fatty acids into milk triglycerides. Thus, increased percentages of medium-chain SFA observed in Egyptian milk may reflect mammary gland synthesis in an attempt to maintain lipid concentrations in milk.

Adult↗
PubMed1986

Effect of increasing levels of hard wheat fiber on fecal weight, minerals and steroids and gastrointestinal transit time in healthy young women.

Hard red wheat bran (HRWB) baked in a yeast-leavened bread was fed to 36 healthy young college women consuming a basal diet of traditional foods, which contained 15 +/- 3 g/d dietary fiber (DF). Three levels of HRWB were added supplying, respectively, 5.7, 17.1 and 28.5 g/d DF; an additional treatment group did not receive any HRWB. Fecal collections were carried out in the last 5 d of treatment. Fecal wet weight, fecal dry weight and fecal ash increased significantly for each increase in HRWB (P less than 0.05). Fecal dry matter percent changed significantly only at the highest level of HRWB (P less than 0.05). After accounting for the minerals in the HRWB, there was an increased fecal loss of Ca, but not of Zn, Cu, Fe or Mg compared to the women fed no HRWB. HRWB at a level of 17.2 g/d induced faster transit times (TT) than no HRWB and 66 g/d HRWB induced faster TT than either 17.2 or 39.6 g/d HRWB (P less than 0.05). Total daily fecal steroids were not altered by changes in HRWB. Daily total bile acid excretion increased significantly (P less than 0.05) at the two higher levels of HRWB due primarily to higher excretion of chenodeoxycholic acid.

Adolescent↗
PubMed1985

Effect of type of diet and feeding status on modulation of hepatic HMG-CoA reductase in rats.

The effect of diet type and feeding status on hepatic HMG-CoA reductase (HMGR) [mevalonate: NADP+ oxidoreductase (acylating CoA); EC 1.1.1.34] was studied in rats. Animals fed a ground, commercial, stock diet exhibited higher expressed and total activities of HMGR in the fed state than animals fed a semi-purified diet. The differences did not appear in meal-trained animals when measured before the onset of the meal after a 22-hr fast. When expressed activity was taken as a per cent of total activity, fed animals from both diet groups used about 10% of their available activity. When animals on commercial diets were fasted, 20% of the activity was expressed. Fasted animals on the semi-purified diet also increased the per cent of expressed reductase activity, but this increase was not as great (13.3%). These data suggest that, in the rat, regulation of cholesterol synthesis in response to decreased total HMGR during fasting and increased levels after a meal results from alterations in the percentage of enzyme which is expressed. The semi-purified diet used here resulted in consistently lower levels of HMG-CoA reductase activity than the commercial diet regardless of feeding pattern.

Animals↗
PubMed1985

An improved assay for cholesterol 7 alpha-hydroxylase activity using phospholipid liposome solubilized substrate.

A persistent problem in measurement of cholesterol 7 alpha-hydroxylase (7 alpha-OHase) activity by isotope incorporation has been solubilization of cholesterol substrate. Solubilization with Tween 20, for example, resulted in a 75% reduction in 7 alpha-OHase activity after a 60 min incubation of substrate with microsomes. Incorporation of cholesterol substrate into small, unilamellar phospholipid vesicles (liposomes) prevented this effect, resulting in a 50% increase in activity over the same 60 min incubation at optimal concentrations. Using cholesterol in liposomes as substrate, standard assay conditions were determined to be: preparation of liposomes with 180 microM cholesterol substrate and 0.5 mg phospholipid/assay; incubation of these liposomes with 0.5 mg microsomal protein at 37 C for 60 min; addition of a NADPH generating system to start the reaction, and incubation at 37 C for 30 min before stopping the reaction and determining the amount of 7 alpha-hydroxycholesterol formed. In addition to preventing the detergent-related inhibition of the enzyme, liposome-solubilized substrate also reduced the variation among replicates from a coefficient of 45% with Tween 20 to 4.2% with phospholipid. This method provides a sensitive and reliable alternative to methods which require more sophisticated equipment and allows total control of substrate concentration in a form readily accessible to the enzyme.

Animals↗
PubMed1984

Alteration of regression of cholesterol accumulation in rats by dietary pectin.

Male, Wistar rats (50-74 g) were given a semi-purified diet containing cholesterol (10 g/kg diet) for 4 weeks, groups of control and experimental animals killed, and the remainder of the cholesterol-fed animals given either a semi-purified cholesterol-free diet without a fibre source or a similar diet with pectin (50 g/kg diet) for 8 weeks. Animals were killed at 2-week intervals and serum and liver cholesterol and triglycerides, faecal neutral steroids and acidic steroids measured. Animals given pectin had significantly lower serum cholesterol levels than animals given the basal diet after 4 and 6 weeks. Both experimental groups efficiently decreased their liver cholesterol levels during regression. Bile acid excretion was elevated in both groups, especially in rats receiving pectin, but neutral steroid excretion was unchanged. The increase in bile acid excretion was primarily in the form of chenodeoxycholic acid and its metabolites. This increased bile acid excretion is postulated to result from stimulation of the normal mechanism for increased steroid excretion in the rat, i.e. a change in the value of cholic: chenodeoxycholic acid or from a mechanism not yet elucidated.

Animals↗
PubMed1984

Interactions of alfalfa plant and sprout saponins with cholesterol in vitro and in cholesterol-fed rats.

The in vitro interactions of saponins from alfalfa plant and alfalfa sprouts with cholesterol and the effects of alfalfa plant and sprout and saponin-free alfalfa plant on diet-induced liver cholesterol accumulation, bile acid excretion, and jejunal and colonic morphology were examined. Cholesterol-saponin interactions have been suggested as mechanisms for the observed hypocholesterolemic effects of alfalfa as well as the changes in intestinal morphology. Alfalfa plant saponins bound significant quantities of cholesterol both from ethanol solution and from micellar suspension. Alfalfa sprout saponins interacted with cholesterol to a lesser but significant extent. Sprout saponins also inhibited growth of Trichoderma viride significantly, another measure of saponin-cholesterol interaction. Bile acid adsorption was greatest for alfalfa plant and was not reduced by removal of saponins from the plant material. The ability of alfalfa to reduce liver cholesterol accumulation in cholesterol-fed rats was enhanced by removal of saponins and alfalfa sprouts did not prevent accumulation. Removal of saponins from alfalfa reduced the changes in intestinal morphology previously reported, but interaction with membrane cholesterol did not appear to be the cause of this effect of saponins. Saponin-cholesterol interaction is an important part of the hypocholesterolemic action of alfalfa but interaction of bile acids with other components of alfalfa may be of equal importance.

Animals↗