Cyril McMaster

Lycopene intervention reduces inflammation and improves HDL functionality in moderately overweight middle-aged individuals

The management of overweight subjects by interventions aimed at reducing inflammation is highly desirable. To date, observational studies have identified a link between increased dietary antioxidant intake and reduced cardiovascular morbidity. However, direct trial evidence regarding the ability of antioxidants to influence inflammation is lacking. Therefore, this study examined lycopenes ability to lower systemic and high-density lipoprotein (HDL)-associated inflammation in moderately overweight middle-aged subjects. Serum was collected before and after a 12-week intervention from 54 moderately overweight, middle-aged individuals. Subjects were randomised to one of three groups: control diet (<10 mg lycopene/week), lycopene-rich diet (224-350 mg lycopene/week) and lycopene supplement (70 mg lycopene/week). HDL was subfractionated into HDL(2&3) by rapid ultracentrifugation. Compliance was monitored by assessing lycopene concentration in serum and HDL(2&3). Systemic and HDL-associated inflammation was assessed by measuring serum amyloid A (SAA) levels. HDL functionality was determined by monitoring the activities of paraoxonase-1 (PON-1), cholesteryl ester transfer protein (CETP) and lecithin cholesterol acyltransferase (LCAT). Lycopene increased in serum and HDL(2&3) following both lycopene interventions (P<.001, for all), while SAA decreased in serum following the lycopene supplement and in HDL(3) following both lycopene interventions (P<.05 for all). PON-1 activity increased in serum and HDL(2&3) in both lycopene groups (P<.05, for all). Furthermore, the activity of CETP decreased in serum following the lycopene supplement, while the activity of LCAT increased in serum and HDL(3) following both lycopene interventions (P<.05 for all). These results demonstrate that in moderately overweight, middle-aged subjects, increasing lycopene intake leads to changes to HDL(2&3), which we suggest enhanced their antiatherogenic properties. Overall, these results show the heart-protective properties of increased lycopene intake.

Very low density lipoprotein subfractions in Type II diabetes mellitus: alterations in composition and susceptibility to oxidation

Aims/hypothesis. Type II (non-insulin-dependent) diabetes mellitus is associated with raised triglycerides and increased very low density lipoprotein cholesterol. The aim of this study was to assess if very low density lipoprotein subfraction composition and potential to oxidise were altered in this condition.¶Methods. Very low density lipoprotein was separated into four subfractions (A→D) by a novel, rapid ultracentrifugation procedure. Analysis of each subfraction included lipid and fatty acid composition. Preformed peroxides were measured spectrophotometrically and conjugated dienes were used as an indicator of in vitro lipid oxidation.¶Results. In all results we compared patient and control subfractions. Mean fasting plasma glucose was 8.9 ± 2.0 mmol/l in patients vs 5.1 ± 0.4 mmol/l in control subjects (p < 0.001); patient HbA1 c was 7.6 ± 1.4 %. Patient total lipid standardised for apo B was higher than controls in subfractions A, B and C; A, 201 vs 60; B, 191 vs 40; C, 63 vs 21; D, 29 vs 34 μmol lipid per mg apo B (p < 0.05). Preformed peroxides were higher in all patient subfractions compared with controls: A, 340 vs 48; B, 346 vs 42; C, 262 vs 28; D, 54 vs 16 nmol per mg apo B (p < 0.001). Patient subfractions A and D were more susceptible to in vitro oxidation. Monounsaturated fatty acids were lower in patients subfractions, 35.2 vs 36.7; B, 35.1 vs 38.7; C, 34.4 vs 36.5; D, 33.0 vs 35.5 as per cent total (p < 0.05).¶Conclusions/interpretation. These results indicate abnormalities in very low density lipoprotein subfraction composition and oxidation profile in Type II diabetic subjects, which are characteristic of more atherogenic particles and that may contribute to the development of cardiovascular disease in these patients. [Diabetologia (2000) 43: 485–493]

Erythrocyte membrane fatty acid composition as a marker of dietary compliance in hyperlipidaemic subjects.

Dietary intervention is the first treatment step in management of hyperlipidaemia, but there are few objective criteria of compliance. Whether intensive dietary intervention would produce a detectable change in erythrocyte membrane fatty acid composition which could be used as a marker of compliance was examined in 31 new hyperlipidaemic patients. Over a 6 month period, body mass index fell from 29.0 to 26.9 kg/m2 (P < 0.001) and total cholesterol by 19% from 8.16 to 6.58 mmol/l (P < 0.001). The energy derived from fat was reduced from 38.5% to 29.6% (P < 0.001), and the ratio of dietary polyunsaturated to saturated (P:S) fatty acids in the diet increased from 0.45 to 0.66 (P < 0.01). Small but significant changes were recorded in several red cell membrane fatty acids, and the P:S ratio increased from 0.91 to 1.13 (P < 0.001). It would appear, therefore, that red cell membrane changes parallel dietary changes and hence are a potential marker for compliance with dietary changes.

Plasma Clusterin Levels and the rs11136000 Genotype in Individuals with Mild Cognitive Impairment and Alzheimer's Disease

AIM Substantial evidence links atherosclerosis and Alzheimers disease (AD). Apolipoproteins, such as apolipoprotein E, have a causal relationship with both diseases. The rs11136000 SNP within the CLU gene, which encodes clusterin (apolipoprotein J), is also associated with increased AD risk. The aim of this study was to investigate the relationship between plasma clusterin and the rs11136000 genotype in mild cognitive impairment (MCI) and AD. METHODS Plasma and DNA samples were collected from control, MCI and AD subjects (n=142, 111, 154, respectively). Plasma clusterin was determined by ELISA and DNA samples were genotyped for rs11136000 by TaqMan assay. RESULTS Plasma clusterin levels were higher in MCI and AD subjects vs. controls (222.3 ± 61.3 and 193.6 ± 58.2 vs. 178.6 ± 52.3 μg/ml, respectively; p<0.001 for both comparisons), and in MCI vs. AD (p<0.05). Plasma clusterin was not influenced by genotype in the MCI and AD subjects, although in control subjects plasma clusterin was lower in the TT vs. TC genotypes (157.6 ± 53.4 vs. 188.6 ± 30.5 μg/ml; p<0.05). CONCLUSION This study examined control, MCI and AD subjects, identifying for the first time that plasma clusterin levels were influenced, not only by the presence of AD, but also the transitional stage of MCI, while rs11136000 genotype only influenced plasma clusterin levels in the control group. The increase in plasma clusterin in MCI and AD subjects may occur in response to the disease process and would be predicted to increase binding capacity for amyloid-beta peptides in plasma, enhancing their removal from the brain.

The Role of Smoking in Abdominal Aortic Aneurysm Development

Abdominal aortic aneurysm is common. The aim of this study was to assess the effect of smoking on prevalence and management. Patients attending the vascular unit and appropriate controls were prospectively recruited. A smoking history revealed tobacco exposure in pack years. Serum cotinine was assessed biochemically. Independent risk factors were statistically determined. In all, 202 (186 men) patients were recruited, with 202 (197 men) controls. A total of 69 patients tested positive for cotinine, whereas 39 controls were positive (P = .001). Smoking and ischemic heart disease were significant predictors for aneurysm prevalence. Cardiac disease emerged as a more important predictor than smoking in symptomatic patients. In noncardiac patients, smoking and hypercholesterolemia were significant risk factors. Smoking is a significant predictor for aneurysm development. In high-risk patients, the cardiac disease process is the most important factor, with control of this imperative. However, in noncardiac patients, smoking cessation and lipid-lowering therapy are crucial.

Plasma free fatty acid patterns and their relationship with CVD risk in a male middle-aged population

Background/Objectives:The role of individual fatty acids in the development of cardiovascular disease (CVD) is well established, but the effects of an overall pattern of fatty acids in CVD risk has yet to be elucidated. Circulating fatty acid levels are related to metabolic disturbances associated with the metabolic syndrome and CVD, due to disturbances in the activity of enzymes that catalyse fatty acid desaturation (Δ-desaturases). Therefore, we determined patterns of fatty acids and estimated desaturase activity in plasma and analysed how these patterns were related to a 10-year CVD risk estimates in a middle-aged male population in Northern Ireland.Subjects/Methods:Principal components analysis (PCA) was performed for defining fatty acid patterns in 379 men aged 30–49 years. Logistic regression analyses were then carried out for analysing the relationship between these fatty acid patterns and the 10-year CVD risk estimates.Results:The PCA generated three high fatty acid patterns: high saturated fatty acid (SFA), high omega 3 fatty acid (omega 3) and high monosaturated fatty acid (MNFA). Results from logistic regression analyses show that a 1 s.d. increase in the SFA pattern score was significantly and positively associated with an increase in the 10-year CVD risk category (odds ratio 1.71, 95% confidence interval 1.33–2.21, P<0.0001) even after adjustment for lifestyle factors. There were no significant relationships between the other two pattern scores and the 10-year CVD risk.Conclusions:An unhealthy fatty acid pattern representing both dietary intake and in vivo fatty acid metabolism is related to the 10-year CVD risk estimates and provide evidence that, as with dietary patterns, the synergistic effect of multiple fatty acids may be more important in relation to the development of CVD risk.

Placental protein tyrosine nitration and MAPK in type 1 diabetic pre-eclampsia: Impact of antioxidant vitamin supplementation

AIM To examine the role of placental protein tyrosine nitration and p38-Mitogen-Activated Protein Kinase α (p38-MAPKα), Extra Cellular-Signal Regulated Kinase (ERK) and c-Jun NH2-Terminal Kinase (JNK) activity, in the pathogenesis of type 1 diabetic pre-eclampsia, and the putative modulation of these indices by maternal vitamin C and E supplementation. METHODS Placental samples were obtained from a sub-cohort of the DAPIT trial: a randomised placebo-controlled trial of antioxidant supplementation to reduce pre-eclampsia in type 1 diabetic pregnancy. Placenta from placebo-treated: normotensive (NT) [n=17], gestational hypertension (GH) [n=7] and pre-eclampsia (PE) [n=6] and vitamin-treated: NT (n=20), GH (n=4) and PE (n=3) was analysed. Protein tyrosine nitration was assessed by immunohistochemistry in paraffin-embedded tissue. Catalytic activities of placental p38-MAPKα, ERK and JNK were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS Nitrotyrosine immunostaining was present in placebo-treated NT, GH and PE placentae, with no significant difference observed between the groups. There was a non-significant trend towards decreased p38-MAPKα activity in PE vs NT control placentae. ERK and JNK were similar among the three outcome placebo groups and vitamin supplementation did not significantly alter their activity. CONCLUSION Nitrotyrosine immunopositivity in normotensive diabetic placentae indicates some degree of tyrosine nitration in uncomplicated diabetic pregnancy, possibly due to inherent oxidative stress and peroxynitrite production. Our results suggest that p38-MAPKα, ERK and JNK are not directly involved in the pathogenesis of type 1 diabetic pre-eclampsia and are not modulated by vitamin-supplementation.

Lyso-phosphatidylcholine and outcome of preterm babies with respiratory distress syndrome treated with surfactant

Phosphatidylcholine (PC) is the predominant phospholipid in natural surfactant preparations. A metabolic intermediate, lyso-PC, is potentially injurious to the lungs. In the present study, tracheal aspirates from preterm babies with respiratory distress syndrome treated with surfactant were examined for the presence of lyso-PC to determine if there was any correlation with outcome. Eighteen babies were assigned to receive initially either 100 or 200 mg/kg Curosurf followed by up to three further 100-mg/kg doses if required. Lyso-PC was present in aspirates taken 12-24 h after the last treatment from nine of 11 infants who initially received 200 mg/kg but in only one from seven receiving 100 mg/kg initially, and was dependent on the total dose of phospholipid administered. Three babies in the low-dose group developed bronchopulmonary dysplasia, whereas two in the high-dose group were non-survivors, however we could not correlate the presence of lyso-PC with adverse long-term outcome in this group of preterm infants.

Erythrocyte membrane fatty acid profile in chinese children

Abstract Erythrocyte membrane fatty acid profiles, a good indicator of dietary fatty acid intake were measured in seventy-two Hong Kong Chinese children at the age of five. Results were compared to forty-eight of their mothers and ninety-one Irish children with mean age of 40 months. Chinese children were shown to have significantly higher level of saturated fatty acids and monounsaturated fatty acids but lower level of polyunsaturated fatty acids than the Irish children. Mothers of the Chinese children showed a resemblance of their childrens fatty acid profiles. Findings were compatible with the present dietary practices of Hong Kong people: large quantities of meat and lesser quantities of vegetables consumption.