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Biomedical subjects

D J Jenkins

Publications and source records attributed to D J Jenkins.

At least 55 records · Page 3Linked to original sources
PubMed1999

Combined effect of vegetable protein (soy) and soluble fiber added to a standard cholesterol-lowering diet.

Dietary treatment of hyperlipidemia focuses on reducing saturated fat and dietary cholesterol. Other aspects of diet are not emphasized at present, despite growing evidence that a number of plant components decrease serum cholesterol. We therefore determined whether a combination of two plant components, vegetable protein and soluble fiber, further reduce serum lipids when incorporated into the currently advocated low-saturated-fat diet. Thirty-one hyperlipidemic men and women ate two 1-month low-fat (<7% of total energy from saturated fat), low-cholesterol (<80 mg cholesterol/d) metabolic diets in a randomized crossover study. The major differences between test and control diets were an increased amount of vegetable protein (93% v 23% of total protein), of which 33 g/d was soy, and a doubling of soluble fiber. Fasting blood samples were obtained at the start and end of each phase. On the last 3 days of each phase, fecal collections were obtained. Compared with the low-fat control diet, the test diet decreased total cholesterol (6.2% +/- 1.2%, P < .001), low-density lipoprotein (LDL) cholesterol (6.7% +/- 1.7%, P < .001), apolipoprotein B (8.2% +/- 1.2%, P < .001), and the ratios of LDL to high-density lipoprotein (HDL) cholesterol (6.3% +/- 2.0%, P = .004) and apolipoprotein B to A-I (5.4% +/- 1.5%, P = .001). A combination of vegetable protein and soluble fiber significantly improved the lipid-lowering effect of a low-saturated-fat diet. The results support expanding the current dietary advice to include increased vegetable protein and soluble fiber intake so that the gap in effectiveness between a good diet and drug therapy is reduced.

Aged↗
PubMed1999

Effect of wheat bran on serum lipids: influence of particle size and wheat protein.

OBJECTIVE: Wheat fiber appears to protect from cardiovascular disease despite its lack of consistent effect on serum lipids. We therefore wished to determine whether reported inconsistencies in the effect of wheat bran resulted from differences in particle size or its high gluten content. METHODS: Two studies were conducted. In one-month metabolic diets, 24 hyperlipidemic subjects consumed breads providing an additional 19 g/d dietary fiber as medium or ultra-fine wheat bran and extra protein (10% of energy as wheat gluten). In two-week ad libitum diets, 24 predominantly normolipidemic subjects consumed breakfast cereals providing an additional 19 g/d of dietary fiber as coarse or a mixture of ultra-fine and coarse wheat bran with no change in gluten intake. Both studies followed a randomized crossover design with control periods when subjects ate low-fiber breads and cereals respectively with no added gluten. Fasting blood lipids were measured on day zero and at the end of each phase. RESULTS: Wheat bran had no effect on total, LDL or HDL cholesterol irrespective of particle size or level of gluten in the diet. However, consumption of increased gluten in the metabolic study was associated with a 13+/-4% reduction in serum triglycerides (p = 0.005) which was not seen in the normal-gluten ad libitum study. CONCLUSIONS: The protective effect of wheat fiber in cardiovascular disease cannot be explained by an effect of wheat bran in reducing serum cholesterol although in hyperlipidemic subjects displacement of carbohydrate by gluten on the high-fiber phases was associated with lower serum triglycerides.

Adult↗
PubMed1999

The effect of wheat bran particle size on laxation and colonic fermentation.

OBJECTIVE: Due to perceived inferior fecal bulking ability, finely ground wheat bran is not recommended for treatment of colonic disorders, despite possible short chain fatty acid generation with potential benefits for colonic mucosal health. We therefore tested the effects of very fine particle size wheat bran on colonic function. METHODS: Two studies, each with three phases, were undertaken in healthy subjects in a randomized crossover design. In one study (metabolic, n=23) subjects took three diets containing either an additional 19 g/d dietary fiber with mean particle size (MPS) 50 microm or 758 microm in bread or a control low fiber bread. In the other study where the supplement was provided as a breakfast cereal (ad libitum, n=24) the respective wheat bran MPS were 692 microm and 1158 microm and the control was low fiber. Fecal collections were obtained during the last week of each diet. In the metabolic study, fecal short chain fatty acids were measured and 12-hour breath gas collections obtained. RESULTS: In both studies, wheat bran supplements significantly increased fecal bulk compared to the control (p<0.004), with no significant differences between brans of different particle size and no differences in fecal water content. However, higher fecal butyrate concentrations (p<0.007), butyrate output and breath CH4 levels (p=0.025) were seen on the low MPS wheat bran compared to the other two treatments, suggesting increased bacterial fermentation. CONCLUSIONS: Fine MPS wheat bran is an effective fecal bulking agent and may have added advantages if increased butyrate concentrations promote colonic mucosal integrity.

Adult↗
PubMed1999

A novel source of wheat fiber and protein: effects on fecal bulk and serum lipids.

BACKGROUND: Wheat fiber is a laxative and wheat protein may affect blood lipids. OBJECTIVE: We therefore tested the effects on laxation and serum lipid metabolism of a novel source of wheat fiber and protein produced by the amylolytic digestion of starch from wheat. DESIGN: Twenty-four healthy men and women consumed 3 different test cereals in random order, each for 2 wk. The test supplement and the positive control, American Association of Cereal Chemists wheat bran supplement, both provided the same amount of fiber (21 g/d) and the negative control supplement provided 1.7 g fiber/d. RESULTS: The test supplement and the positive control supplement increased fecal bulk similarly (239.5+/-19 and 216.7+/-19 g/d, respectively) and significantly more than did the negative control supplement (165.6+/-16 g/d, P < 0.010). Compared with the negative and positive control supplements, the week 2 value of the test supplement for the ratio of total to HDL cholesterol was significantly reduced (P = 0.046). CONCLUSION: We conclude that the product of amylolytic digestion of starch from wheat flakes, which is high in wheat fiber and protein, has a fecal bulking effect similar to that of wheat bran and may have a beneficial effect on serum lipids.

Adult↗
PubMed1999

Health aspects of partially defatted flaxseed, including effects on serum lipids, oxidative measures, and ex vivo androgen and progestin activity: a controlled crossover trial.

BACKGROUND: Currently there is considerable interest in the potential health benefits of oil seeds, such as soy and flaxseed, especially in relation to cardiovascular disease and cancer. OBJECTIVE: We therefore evaluated health aspects of partially defatted flaxseed in relation to serum lipids, indicators of oxidative stress, and ex vivo sex hormone activities. DESIGN: Twenty-nine hyperlipidemic subjects (22 men and 7 postmenopausal women) completed two 3-wk treatment periods in a randomized, crossover trial. Subjects were given muffins that contributed approximately 20 g fiber/d from either flaxseed (approximately 50 g partially defatted flaxseed/d) or wheat bran (control) while they consumed self-selected National Cholesterol Education Program Step II diets. Both muffins had similar macronutrient profiles. Treatment phases were separated by > or = 2 wk. RESULTS: Partially defatted flaxseed reduced total cholesterol (4.6+/-1.2%; P = 0.001), LDL cholesterol (7.6+/-1.8%; P < 0.001), apolipoprotein B (5.4+/-1.4%; P = 0.001), and apolipoprotein A-I (5.8+/-1.9%; P = 0.005), but had no effect on serum lipoprotein ratios at week 3 compared with the control. There were no significant effects on serum HDL cholesterol, serum protein carbonyl content, or ex vivo androgen or progestin activity after either treatment. Unexpectedly, serum protein thiol groups were significantly lower (10.8+/-3.6%; P = 0.007) at week 3 after the flaxseed treatment than after the control, suggesting increased oxidation. CONCLUSIONS: These data indicate that partially defatted flaxseed is effective in lowering LDL cholesterol. No effects on lipoprotein ratios, ex vivo serum androgen or progestin activity, or protein carbonyl content were observed. The significance of increased oxidation of protein thiol groups with flaxseed consumption requires further investigation.

Adult↗
PubMed1999

Inulin, oligofructose and intestinal function.

Inulin and oligofructose have attracted much attention recently as nonabsorbable carbohydrates with prebiotic properties. When inulin and oligofructose were added to a controlled diet, significant increases were noted in colonic bifidobacterial populations, and it has been proposed that these changes promote both colonic and systemic health through modification of the intestinal microflora. Inulin and oligofructose are rapidly and completely fermented by the colonic microflora with the production of acetate and other short-chain fatty acids. As with lactulose, they may also result in the growth of the fecal biomass, and in doing so, entrap ammonia for bacterial protein synthesis or conversion to the ammonium ion. As with dietary fiber and other nonabsorbable carbohydrates, there is also interest in inulin and oligofructose from the standpoint of inhibition of colonic carcinogenesis, blood cholesterol reduction, immune stimulation and enhanced vitamin synthesis. In these areas, the influence of their molecular weight is also an issue, with the longer chain length providing a more sustained fermentation pattern. More human studies are now required, including studies on the long-term effects of inulin and oligofructose consumption on colonic health, in particular on markers of cancer risk such as reduction in colonic polyp recurrence.

Animals↗
PubMed1999

Konjac-mannan (glucomannan) improves glycemia and other associated risk factors for coronary heart disease in type 2 diabetes. A randomized controlled metabolic trial.

OBJECTIVE: To examine whether Konjac-mannan (KJM) fiber improves metabolic control as measured by glycemia, lipidemia, and blood pressure in high-risk type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 11 hyperlipidemic and hypertensive type 2 diabetic patients treated conventionally by a low-fat diet and drug therapy participated. After an 8-week baseline, all were randomly assigned to take either KJM fiber-enriched test biscuits (0.7 g/412 kJ [100 kcal] of glucomannan) or matched placebo wheat bran fiber biscuits during two 3-week treatment phases separated by a 2-week washout period. The diet in either case was metabolically controlled and conformed to National Cholesterol Education Program Step 2 guidelines, while medications were maintained constant. Efficacy measures included serum fructosamine, lipid profiles, apolipoproteins, blood pressure, body weight, and nutritional analysis. RESULTS: Compared with placebo, KJM significantly reduced the metabolic control primary end points: serum fructosamine (5.7%, P = 0.007, adjusted alpha = 0.0167), total:HDL cholesterol ratio (10%, P = 0.03, adjusted alpha = 0.05), and systolic blood pressure (sBP) (6.9%, P = 0.02, adjusted alpha = 0.025). Secondary end points, including body weight, total, LDL, and HDL cholesterol, triglycerides, apolipoproteins A-1, B, and their ratio, glucose, insulin, and diastolic blood pressure, were not significant after adjustment by the Bonferroni-Hochberg procedure. CONCLUSIONS: KJM fiber added to conventional treatment may ameliorate glycemic control, blood lipid profile, and sBP in high-risk diabetic individuals, possibly improving the effectiveness of conventional treatment in type 2 diabetes.

Apolipoproteins↗
PubMed1998

Modulation of androgen and progesterone receptors by phytochemicals in breast cancer cell lines.

We have used a tissue culture system based on breast carcinoma cell lines to investigate a large number of naturally occurring compounds and beverages for steroid hormone agonist and antagonist activity. The cell lines used, T-47D and BT-474, produce prostate specific antigen (PSA) upon stimulation with androgens, progestins, glucocorticoids and mineralocorticoids. This biomarker is secreted and can be measured in the tissue culture supernatant with very high sensitivity by an immunofluorometric procedure. Steroid hormone antagonist activity can be assessed with the same system by adding the candidate antagonist first and then stimulating the cells with a known agonist. By using this system we have identified three natural compounds, apigenin, naringenin and syringic acid which exhibited weak progestational activity and eleven other compounds which exhibited weak antiandrogenic/antiprogestational activity. Our study indicates that a significant number of natural compounds have the ability to bind to steroid hormone receptors and act as weak blockers. A fewer number of compounds not only bind to the receptors but they also mediate transcriptional activity, acting as agonists. The agonists and antagonists were active at levels around 10(-5) M, in accordance with previous reports for other phytochemicals. In comparison to synthetic and natural steroid hormones, the biological activity of these compounds is weaker by a factor of approximately 10(4)-fold.

Beverages↗
PubMed1998

New 11 beta-aryl-substituted steroids exhibit both progestational and antiprogestational activity.

The syntheses of three 11 beta-aryl-19-norpregna-4,9-dien-3-one derivatives with 17-spirolactone and 17 beta-hydroxy-17 alpha-cyanoethyl substitutions are described. The progesterone agonist/antagonist activities of the new compounds are investigated using a recently developed tissue culture system that relies on the progesterone agonist up-regulation of the prostate-specific antigen (PSA) gene in female breast tumor cell lines. Two of the newly synthesized compounds exhibit mixed agonistic/antagonistic progestational activity.

Female↗
PubMed1998

Physiological effects of resistant starches on fecal bulk, short chain fatty acids, blood lipids and glycemic index.

OBJECTIVE: To assess the effects on fecal bulking, fecal short chain fatty acid (SCFA) production, blood lipids and glycemic indices of two different forms of resistant starch (RS2 and RS3) from a high-amylose cornstarch. METHODS: Twenty-four healthy subjects (12 men; 12 women) consumed four supplements taken for 2 weeks in random order separated by 2-week washout periods. The supplements were a low-fiber (control) and supplements providing an additional 30 g dietary fiber as wheat bran (high-fiber control) or the equivalent amount of resistant starch analyzed gravimetrically as dietary fiber from RS2 or RS3. Four-day fecal collections and 12-hour breath gas collections were obtained at the end of each period. Fasting blood was taken at the beginning and end of each period. Glycemic indices of supplements were also assessed. RESULTS: The wheat bran supplement increased fecal bulk 96+/-14 g/day compared with the low-fiber control (p<0.001) with the mean for both resistant starches also being greater (22+/-8 g/day) than the low-fiber control (p=0.013). On the resistant starch phases, the mean fecal butyrate:SCFA ratio, which has been suggested to have positive implications for colonic health, was significantly above the low-fiber control by 31+/-14% (p=0.035). Resistant starches did not alter serum lipids, urea or breath H2 or CH4. No significant differences in glycemic index were seen between the RS and control supplements. CONCLUSION: The potential physiological benefits of the resistant starches studied appear to relate to colonic health in terms of effects on fecal bulk and SCFA metabolism.

Adult↗
PubMed1998

Factors influencing the development and carbohydrate metabolism of Echinococcus granulosus in dogs.

Echinococcus granulosus adult worms, 35 days postinfection, were measured for dispersion in the intestines of 10 dogs, a range of morphological characters, and the excreted end products of carbohydrate catabolism following 4 hr incubation in vitro. Most worms were found in the proximal sections of the small intestine, but the pattern of dispersion differed between dogs. Worm development varied both between dogs and between different regions of the small intestine of individual dogs. Overall there was a high level of variability with no simple patterns. Worm metabolism was related to worm development and, also independently, to local population density within the intestine. Larger, more mature worms produced less lactate and, at higher densities, worms tended to produce more acetate and succinate (pathways with a higher energy yield than lactate) and less ethanol. Thus, both more developed worms and high population density are associated with a shift from cytosolic to mitochondrial metabolism. The variation between worm populations along the small intestine along with the observed variation between worm populations from sibling dogs infected with genetically identical parasites suggests that the local host environment has a significant effect on parasite development.

Acetates↗
PubMed1997

Disaccharide polyphosphates based upon adenophostin A activate hepatic D-myo-inositol 1,4,5-trisphosphate receptors.

The glyconucleotides adenophostin A and B are the most potent known agonists at type 1 inositol trisphosphate [Ins(1,4,5)P3] receptors, although their stuctures differ markedly from that of Ins(1,4,5)P3. Equilibrium competition binding with [3H]Ins(1,4,5)P3 and unidirectional 45Ca2+ flux measurements were used to examine the effects of adenophostin A in hepatocytes, which express predominantly type 2 Ins(1,4,5)P3 receptors. Both Ins(1,4,5)P3 (Kd = 8.65 +/- 0.98 nM) and adenophostin A (Kd = 0.87 +/- 0.20 nM) bound to a single class of [3H]Ins(1,4,5)P3-binding site and each fully mobilized the same intracellular Ca2+ pool; although, adenophostin A (EC50 = 10.9 +/- 0.7 nM) was more potent than Ins(1,4,5)P3 (EC50 = 153 +/- 11 nM). Working on the assumption that it is the phosphorylated glucose component of the adenophostins that mimics the critical features of Ins(1,4,5)P3, we synthesized various phosphorylated disaccharide analogs containing this structure. The novel disaccharide-based analogs, sucrose 3,4,3'-trisphosphate [Sucr(3,4,3')P3], alpha,alpha'-trehalose 3,4,3',4'-tetrakisphosphate [Trehal(3,4,3',4')P4], alpha,alpha'-trehalose 2,4,3', 4'-tetrakisphosphate [Trehal(2,4,3',4')P4], and methyl 3-O-(alpha-d-glucopyranosyl)-beta-d-ribofuranoside 2,3', 4'-trisphosphate [Rib(2,3',4')P3], were all able to mobilize the same intracellular Ca2+ pool as Ins(1,4,5)P3 and adenophostin A; although, none was as potent as adenophostin A. The rank order of potency of the analogs, adenophostin A > Ins(1,4,5)P3 approximately Rib(2,3',4')P3 > Trehal(2,4,3',4')P4 > Glc(2',3,4)P3 approximately Trehal(3,4,3',4')P4 > Sucr(3,4,3')P3, was the same in radioligand binding and functional assays of hepatic Ins(1,4,5)P3 receptors. Both Rib(2,3',4')P3, which was as potent as Ins(1,4,5)P3, and Trehal(2,4,3',4')P4 bound with significantly higher affinity ( approximately 27 and approximately 3-fold, respectively) than the only active carbohydrate agonist of Ins(1,4,5)P3 receptors previously examined [Glc(2',3,4)P3]. We conclude that phosphorylated disaccharides provide novel means of developing high-affinity ligands of Ins(1,4,5)P3 receptors.

Adenosine↗
PubMed1997

Adenophostin A can stimulate Ca2+ influx without depleting the inositol 1,4,5-trisphosphate-sensitive Ca2+ stores in the Xenopus oocyte.

Adenophostin A possesses the highest known affinity for the inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) receptor (InsP3R). The compound shares with Ins(1,4,5)P3 those structural elements essential for binding to the InsP3R. However, its adenosine 2'-phosphate moiety has no counterpart in the Ins(1,4,5)P3 molecule. To determine whether its unique structure conferred a distinctive biological activity, we characterized the adenophostin-induced Ca2+ signal in Xenopus oocytes using the Ca2+-gated Cl- current assay. In high concentrations, adenophostin A released Ca2+ from Ins(1,4, 5)P3-sensitive stores and stimulated a Cl- current that depended upon the presence of extracellular Ca2+. We used this Cl- current as a marker of Ca2+ influx. In low concentrations, however, adenophostin A stimulated Ca2+ influx exclusively. In contrast, Ins(1,4,5)P3 and (2-hydroxyethyl)-alpha-D-glucopyranoside 2',3, 4-trisphosphate, an adenophostin A mimic lacking most of the adenosine moiety, always released intracellular Ca2+ before causing Ca2+ influx. Ins(1,4,5)P3 could still release Ca2+ during adenophostin A-induced Ca2+ influx, confirming that the Ins(1,4, 5)P3-sensitive intracellular Ca2+ stores had not been emptied. Adenophostin- and Ins(1,4,5)P3-induced Ca2+ influx were not additive, suggesting that both agonists stimulated a common Ca2+ entry pathway. Heparin, which blocks binding to the InsP3R, prevented adenophostin-induced Ca2+ influx. These data indicate that adenophostin A can stimulate the influx of Ca2+ across the plasma membrane without inevitably emptying the Ins(1,4,5)P3-sensitive intracellular Ca2+ stores.

Adenosine↗