Search PubMed⌕ Search

Biomedical subjects

C M Williams

Publications and source records attributed to C M Williams.

At least 73 records · Page 4Linked to original sources
PubMed1998

Dietary interventions affecting chylomicron and chylomicron remnant clearance.

Interest in effects of diet on postprandial lipoproteins has increased in recent years as a result of accumulating evidence for adverse cardiovascular consequences of elevated concentrations of triglyceride rich lipoproteins. Particular attention has been given to ability of different fatty acids to modulate postprandial lipoprotein responses because of evidence for both harmful and protective cardiovascular properties of the saturated, monounsaturated and omega-6 and omega-3 polyunsaturated fatty acid (PUFA) classes. Evidence for direct atherogenic properties of chylomicron remnants has led to attempts to monitor effects of diet specifically on this lipoprotein class. Limitations in the methods employed to measure chylomicron remnants and the small number of human studies which have evaluated effects of meal, and background diet, fatty acid composition, makes it difficult to draw definitive conclusions at the present time. However consideration of data from both animal and human studies tends to support the conclusion that diets, and meals, rich in PUFA (particularly long chain omega-3 PUFA), result in attenuated postprandial responses of the intestinally-derived lipoproteins. Attenuated responses to high PUFA meals appear to be due to greater rates of clearance and greater activation of lipoprotein lipase (LPL). Attenuated responses to high PUFA background diets may be due to adaptive changes involving both accelerated rates of clearance in peripheral tissues and liver, as well as decreased output of the competitor for chylomicron clearance, very low density lipoprotein (VLDL).

Animals↗
PubMed1998

The effect of test meal monounsaturated fatty acid: saturated fatty acid ratio on postprandial lipid metabolism.

Epidemiological evidence shows that a diet high in monounsaturated fatty acids (MUFA) but low in saturated fatty acids (SFA) is associated with reduced risk of CHD. The hypocholesterolaemic effect of MUFA is known but there has been little research on the effect of test meal MUFA and SFA composition on postprandial lipid metabolism. The present study investigated the effect of meals containing different proportions of MUFA and SFA on postprandial triacylglycerol and non-esterified fatty acid (NEFA) metabolism. Thirty healthy male volunteers consumed three meals containing equal amounts of fat (40 g), but different proportions of MUFA (12, 17 and 24% energy) in random order. Postprandial plasma triacylglycerol, apolipoprotein B-48, cholesterol, HDL-cholesterol, glucose and insulin concentrations and lipoprotein lipase (EC 3.1.1.34) activity were not significantly different following the three meals which varied in their levels of SFA and MUFA. There was a significant difference in the postprandial NEFA response between meals. The incremental area under the curve of postprandial plasma NEFA concentrations was significantly (P = 0.03) lower following the high-MUFA meal. Regression analysis showed that the non-significant difference in fasting NEFA concentrations was the most important factor determining difference between meals, and that the test meal MUFA content had only a minor effect. In conclusion, varying the levels of MUFA and SFA in test meals has little or no effect on postprandial lipid metabolism.

Adult↗
PubMed1998

Effect of olive oil on immune function in middle-aged men.

Consumption of diets rich in monounsaturated fatty acids (MUFAs) has been linked with a low prevalence of atherosclerosis and there has been great interest in the effects of MUFAs on lipoprotein metabolism. Less attention has been paid to the effects of MUFAs on the immune system, yet cells of the immune system are an inherent part of the inflammatory events involved in atherosclerosis and several animal studies showed that olive oil has some potent immunomodulatory actions. We therefore considered it important to investigate the effects of chronic consumption of MUFAs on several immune cell functions in healthy humans. Healthy middle-aged males entered a double-blind, randomized, controlled trial in which they consumed either a MUFA diet or a control diet for 2 mo. There was a significant decrease in the expression of intercellular adhesion molecule 1 by peripheral blood mononuclear cells from subjects consuming the MUFA diet. Consumption of the MUFA diet did not affect natural killer cell activity or proliferation of mitogen-stimulated leukocytes. The effects of a MUFA-rich diet on adhesion molecule expression may have implications for the influence of dietary fat on inflammatory diseases, including atherosclerosis.

Adult↗
PubMed1998

Effect of long-term olive oil dietary intervention on postprandial triacylglycerol and factor VII metabolism.

Although the beneficial effects of Mediterranean-type diets, which are rich in olive oil, a good source of monounsaturated fatty acids (MUFAs), are generally accepted, little is known about the effects of long-term dietary MUFA intake on postprandial lipoprotein metabolism and hemostasis. This study used a single-blind, randomized, crossover design to investigate the relative effects of a long-term dietary olive oil intervention and a control [saturated fatty acid (SFA)-enriched] diet on postprandial triacylglycerol metabolism and factor VII activity. The postprandial response to a standard test meal was investigated in 23 healthy men who adhered to both diets for 8 wk. cis-MUFAs were successfully substituted for SFAs in the MUFA diet without affecting total dietary fat or energy intakes. The long-term dietary MUFA intervention significantly reduced plasma and LDL-cholesterol concentrations (P = 0.01). Postprandial triacylglycerol concentrations were significantly greater in the early postprandial period after the MUFA diet (P = 0.003). Postprandial factor VII activation and the concentration of the factor VII antigen were significantly lower after the MUFA diet (P = 0.04 and P = 0.006, respectively). This study showed that isoenergetic substitution of MUFAs for SFAs reduces plasma cholesterol and reduces the degree of postprandial factor VII activation. The alterations in the postprandial triacylglycerol response suggest a greater rate of dietary fat absorption and postprandial triacylglycerol metabolism after a diet rich in MUFAs. This study presents new insights into the biochemical basis of the beneficial effects associated with long-term dietary MUFA consumption, which may explain the lower rates of coronary mortality in Mediterranean regions.

Adult↗
PubMed1998

Insulin, glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide and insulin-like growth factor I as putative mediators of the hypolipidemic effect of oligofructose in rats.

The addition of oligofructose as a dietary fiber decreases the serum concentration and the hepatic release of VLDL-triglycerides in rats. Because glucose, insulin, insulin-like growth factor I (IGF-I) and gut peptides [i.e., glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1)]) are factors involved in the metabolic response to nutrients, this paper analyzes their putative role in the hypolipidemic effect of oligofructose. Male Wistar rats were fed a nonpurified diet with or without 10% oligofructose for 30 d. Glucose, insulin, IGF-I and GIP concentrations were measured in the serum of rats after eating. GIP and GLP-1 contents were also assayed in small intestine and cecal extracts, respectively. A glucose tolerance test was performed in food-deprived rats. Serum insulin level was significantly lower in oligofructose-fed rats both after eating and in the glucose tolerance test, whereas glycemia was lower only in the postprandial state. IGF-I serum level did not differ between groups. GIP concentration was significantly higher in the serum of oligofructose-fed rats. The GLP-1 cecal pool was also significantly higher. In this study, we have shown that cecal proliferation induced by oligofructose leads to an increase in GLP-1 concentration. This latter incretin could be involved in the maintenance of glycemia despite a lower insulinemia in the glucose tolerance test in oligofructose-fed rats. We discuss also the role of hormonal changes in the antilipogenic effect of oligofructose.

Animals↗
PubMed1998

P- and E-selectins are required for the leukocyte recruitment, but not the tissue swelling, associated with IgE- and mast cell-dependent inflammation in mouse skin.

Many studies, in both experimental animal and human systems, have indicated that P- and/or E-selectins may contribute importantly to the leukocyte recruitment that occurs in association with mast cell-dependent inflammatory responses. We used mice that genetically lack P-selectin (P -/-), E-selectin (E -/-), or both selectins (P/E -/-) to investigate the possible roles of these selectins in the IgE- and mast cell-dependent recruitment of neutrophils to the skin of mice. We found that a lack of either or both selectins had little or no effect on the extent of mast cell degranulation or the tissue swelling associated with these reactions. Moreover, a lack of either P- or E-selectin alone did not reduce the neutrophil infiltration at the reaction sites. However, mice lacking both P- and E-selectins exhibited an almost complete ablation of IgE- and mast cell-dependent neutrophil recruitment. These findings show that P- and E-selectins can express overlapping functions in leukocyte recruitment associated with IgE- and mast cell-dependent cutaneous late-phase reactions in mouse skin, and that a lack of both selectins results in a virtual elimination of IgE-dependent leukocyte recruitment.

Animals↗
PubMed1998

Effects of probiotics and prebiotics on blood lipids.

Since the early work of Mann and Spoerry, probiotics in the form of fermented milk products have been reputed to have cholesterol-lowering properties in humans. However, studies conducted since the early 1970s have produced equivocal findings, with interpretation of the outcomes complicated by use of excessive quantities of product, inadequate sample sizes, failure to control nutrient intake and energy expenditure and variations in baseline blood lipids. More recent studies are of better quality, but fail to provide convincing evidence that 'live' fermented milk products have cholesterol-lowering efficacy in man. Future studies using probiotics should ensure adequate sample sizes sufficient to detect relatively small changes in blood cholesterol and should be conducted over longer periods of time. The recent introduction of the concept of prebiotics has directed attention towards the possibility that alterations in gut microflora induced by the fermentation of non-digestible components of the diet may also have the potential to influence systemic lipid metabolism. This possibility has been strengthened by the observation that in animals, dietary oligofructosaccharides cause suppression of hepatic triglyceride and VLDL synthesis, resulting in marked reductions in triglyceride, and to a lesser extent cholesterol, levels. Evidence for similar effects in humans is sparse and more studies are needed, particularly with respect to effects on postprandial triglyceride concentrations.

Animals↗
PubMed1997

The effects of cyclosporin A, dexamethasone and other immunomodulatory drugs on induced expression of IL-3, IL-4 and IL-8 mRNA in a human mast cell line.

We examined by RT-PCR the effect of a number of immunomodulatory compounds on cytokine gene expression at the level of mRNA in the HMC-1 human leukemic mast cell line. Resting cells expressed relatively low constitutive levels of mRNA for the cytokine genes IL-3, IL-4 and IL-8, and mRNA levels for each of these cytokines were significantly enhanced after 4-h stimulation with the calcium ionophore ionomycin. Treatment of the cells with the immunosuppressant CsA at 10(-5) M produced a significant inhibition of ionomycin-induced expression of IL-3, IL-4 and IL-8 mRNA, and at 10(-6) M produced a significant inhibition of induced expression of IL-3 and IL-8 but not IL-4. At both concentrations of CsA, expression of IL-3 was inhibited to a greater extent than that of the other two cytokines. Treatment of the cells with the corticosteroid DEX at 10(-5) M but not 10(-6) M significantly reduced the ionomycin-induced expression of IL-3 but not IL-4 or IL-8 mRNA. Progesterone and methotrexate were both inactive in modulation of induced cytokine expression in this cell line. In conclusion, this study shows that cytokine expression, particularly of IL-3, is inhibited in a human mast cell line by CsA and DEX. These findings may be relevant to the anti-allergic action of these drugs.

Adjuvants, Immunologic↗
PubMed1997

Tumour necrosis factor-alpha expression and cell recruitment in Sephadex particle-induced lung inflammation: effects of dexamethasone and cyclosporin A.

1. Tumour necrosis factor-alpha (TNF-alpha) is a cytokine with diverse properties consistent with a possible role in inflammatory disease. We investigated whether TNF-alpha is induced during the progression of lung inflammation elicited by a particulate non-antigenic stimulus, and whether pharmacological control of TNF-alpha expression influences recruitment of specific inflammatory cell types. 2. A single intravenous injection of Sephadex particles into rats led to extensive granulomatous inflammation in lung alveolar and bronchial tissue that peaked in intensity after 24-72 h. Mononuclear cells were the principal component of granulomas, but neutrophils and eosinophils were also abundant. Numbers of mononuclear cells, neutrophils and eosinophils recovered by bronchoalveolar lavage (BAL) peaked at 72 h, 48 h and 72 h, respectively. 3. Messenger RNA encoding TNF-alpha was induced in lung epithelial cells, lung granulomas and BAL cells 6 h after Sephadex administration and remained elevated for 72 h before declining to baseline by 7 days. In BAL cell populations TNF-alpha protein was localized to mononuclear cells at all times points pre- and post-Sephadex administration. 4. Treatment of rats with dexamethasone significantly reduced the Sephadex-induced recruitment of mononuclear cells, neutrophils and eosinophils into the bronchoalveolar cavity, and significantly reduced TNF-alpha mRNA expression by BAL cells. 5. Treatment of rats with cyclosporin A was without effect on Sephadex-induced elevations of mononuclear cell numbers and expression of TNF-alpha, but did reduce significantly recruitment of neutrophils and eosinophils to BAL cell populations. 6. These results show that a sequential asthma-like recruitment of neutrophils, eosinophils and mononuclear cells into lung tissue can be induced by single exposure to a non-antigenic stimulus. Pharmacological and histological studies reveal that mononuclear cell mobilization relates closely to induced TNF-alpha expression, whereas mobilization of neutrophils and eosinophils appears secondary to expression of the cytokine.

Animals↗
PubMed1997

Use of manufactured foods enriched with fish oils as a means of increasing long-chain n-3 polyunsaturated fatty acid intake.

The objectives of the present study were to determine the feasibility of using manufactured foods, enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as a means of increasing the intake of these n-3 polyunsaturated fatty acids (PUFA), and to determine the effect of the consumption of these foods on postprandial lipaemia and other metabolic responses to a high-fat mixed test meal. Nine healthy, normotriacylglycerolaemic, free-living male volunteers (aged 35-60 years) completed the randomized, controlled, single-blind, crossover study. The study consisted of two periods (each of 22 d) of dietary intervention, separated by a 5-month washout period. During these two periods the subjects were provided with the manufactured foods enriched with EPA and DHA (n-3 enriched) or identical but unenriched foods (control). A mixed test meal containing 82 g fat was given to the fasted subjects on day 22 of each dietary intervention period. Two fasting, and thereafter hourly, blood samples were collected from the subjects for an 8 h period postprandially. Plasma triacylglycerol, total and HDL-cholesterol, non-esterified fatty acids (NEFA), glucose and immunoreactive insulin levels, post-heparin lipoprotein lipase (EC 3.1.1.34) activity and the plasma free fatty acid and phospholipid fatty acid compositions were measured. A mean daily intake of 1.4 g EPA+DHA (0.9 g EPA, 0.5 g DHA) was ingested during the n-3-enriched dietary period, which was significantly higher than the intake during the habitual and control periods (P < 0.001) assessed by a 3 d weighed food intake. A significantly higher level of EPA+DHA enrichment of the plasma fatty acids and phospholipids (P < 0.001) after the n-3-enriched compared with the control intervention periods was also found. The energy intake on both of the dietary intervention periods was found to be significantly higher than on the habitual diet (P < 0.001), with an increase in body weight of the subjects, which reached significance during the n-3 PUFA-enriched dietary intervention period (P < 0.04). The palatability of the enriched foods was not significantly different from that of the control foods. Significantly higher fasting plasma HDL-cholesterol and glucose concentrations were found after the n-3 PUFA-enriched compared with the control intervention period (P < 0.02 and P < 0.05 respectively). No significant differences were found for the postprandial lipid and hormone measurements, except for significantly lower levels of NEFA at 60 min after the n-3-enriched intervention period (P < 0.04). Enriched manufactured foods were a feasible vehicle for increasing n-3 PUFA intake. However the nature of the foods provided as the n-3 vehicle may have contributed to the increased body weight and higher energy intakes which were adverse consequences of the intervention. These factors, together with the short duration of the study may have been responsible for the failure to observe significant plasma triacylglycerol reductions in response to daily intakes of 1.4 g EPA+DHA.

Adult↗