Effect of weight loss on neutrophil resolvins in the metabolic syndrome.

BACKGROUND: Non-resolving inflammation associates with obesity and insulin resistance, and may be dependent on the balance of inflammatory substances and specialised pro-resolving mediators of inflammation (SPM) that act to halt the inflammatory response. This controlled trial examined the effect of weight loss on neutrophil synthesis of SPM in volunteers with the metabolic syndrome (MetS). METHODS: Volunteers with MetS (n = 42) were matched for age and gender and randomly assigned to a 12-wk weight loss program followed by 4-wk weight stabilization or a 16-wk weight maintenance program. At baseline and 16 weeks, isolated neutrophils were stimulated with calcium ionophore and the released SPM were measured by LC-MS/MS. RESULTS: At baseline the SPM resolvin (Rv) E1, 18R-RvE3, RvD2 and Maresin-1 (MaR-1) were detected from stimulated neutrophils. The concentration of released RvE1 was at least 6-fold that of other detected SPM. Weight loss of 4.7 ±â€¯0.8 kg, led to a 2-fold increase in RvE1, P = 0.013, relative to the weight maintenance group. The increase in RvE1 after weight loss was related to, but independent of leukotriene B4. CONCLUSION: Following weight loss, human neutrophils from individuals with the metabolic syndrome are capable of releasing larger amounts of RvE1 upon stimulation.

Regular consumption of black tea increases circulating kynurenine concentrations: A randomized controlled trial.

BACKGROUND: Circulating neopterin and the ratio of kynurenine to tryptophan (KYN/TRP) concentrations are biomarkers of immune activation that have been linked to cardiovascular and total mortality. Several in vitro studies indicated that tea flavonoids and other antioxidants can modulate tryptophan breakdown rates and neopterin production in immune cells. We aimed to assess the effects of regular black tea consumption on tryptophan and neopterin metabolisms in vivo. METHODS: Participants were healthy individuals, with no major illnesses and having normal to mildly elevated systolic blood pressure. They were randomly assigned to consume 3 cups/day of either powdered black tea solids (tea; n = 45) or a flavonoid-free caffeine-matched beverage (control; n = 49). Serum concentrations of tryptophan, kynurenine and neopterin were assessed at baseline and again at 3 and 6 months after daily ingestion of the respective beverage. RESULTS: Regular consumption of tea over 6 months, compared to control, did not significantly alter neopterin (p = 0.13) or tryptophan (p = 0.85) concentrations, but did result in significantly higher kynurenine (p = 0.016) and KYN/TRP (p = 0.012). Relative to the control group, in the tea group kynurenine and KYN/TRP increased during the treatment period by 0.28 µmol/L (95% CI: - 0.04, 0.60) and 3.2 µmol/mmol (95% CI: - 1.6, 8.0), respectively at 3 months, and by 0.48 µmol/L (95% CI: 0.16, 0.80) and 7.5 µmol/mmol (95% CI: 2.5, 12.5), respectively at 6 months. CONCLUSIONS: Increased circulation of kynurenine and KYN/TRP following regular black tea consumption may indicate enhanced tryptophan breakdown, possibly due to immune activation-induced tryptophan degrading enzyme indoleamine 2,3-dioxygenase. GENERAL SIGNIFICANCE: The influence of black tea consumption on biomarkers of immune system activation could relate to its general health benefits. Data suggests that the net effect strongly depends on the individual immune state, being stimulatory in healthy individuals, while acting more immune dampening in situations with an inflammatory background.

Relationship of selection criteria to subsequent academic performance in an Australian undergraduate dental school.

In 1998, in addition to previous academic achievement, an aptitude test (UMAT) and a structured interview were introduced into selection for the Bachelor of Dental Science (BDSc), the undergraduate dental course at the University of Western Australia. The aim of this study was to determine the relationship between the combination of school-leaver dental students' entry scores, some demographic characteristics and subsequent student performance in the undergraduate course. Three hundred and ninety-eight school-leavers who enrolled in the BDSc from 1999 through 2011 were studied. Regression models were constructed comprising entry scores, gender and age as predictors in relation to subsequent academic performance. The main outcome measure was the weighted average mark (WAM) for each of five academic year levels as well as results in specific units, defined as either 'knowledge' based or 'clinically' based. Of the variables studied, previous academic performance and female gender had the strongest relationship with yearly WAM for Years 1 through 4 and for both 'knowledge' based and 'clinically' based units. The interview score showed a strong relationship in the major clinical years and in a range of 'clinically' based units. UMAT scores were less consistent in relationship to WAM. These results support assessment through a highly structured interview together with prior academic achievement as an evidence-based approach to selection of students for this undergraduate dental course.

20-Hydroxyeicosatetraenoic acid synthesis is increased in human neutrophils and platelets by angiotensin II and endothelin-1.

The cytochrome P-450 arachidonic acid metabolite 20-HETE is central to the regulation of vascular tone, renal function, and blood pressure and is synthesized in the rat kidney in response to angiotensin II (ANG II) and endothelin-1 (ET-1). There are very few studies examining the cellular synthesis of 20-HETE in humans. We aimed to measure human neutrophil and platelet 20-HETE levels under basal conditions and after ANG II, ET-1, and calcium ionophore (CaI). 20-HETE was measured in human platelets and neutrophils after saline (control), CaI (2.5 µg/ml), and ANG II or ET-1 (10 nmol/l-1 µmol/l) incubations. The effect of cells, which were preincubated with the ω-hydroxylase inhibitor N-hydroxy-N'-(4-butyl-2-methylphenyl) (HET0016, 10 nM), ANG II types 1 or 2 (AT(1) or AT(2)) receptor inhibition with irbesartan (1 µmol/l) or PD-123319 (1 µmol/l), or endothelin receptor subtypes A or B (ET(A) or ET(B)) receptor inhibition with BQ-123 or BQ-778 (100 nmol/l), was studied. Neutrophil and platelet content and release of 20-HETE was significantly increased by CaI and blocked by the ω-hydroxylase inhibitor HET0016. ANG II and ET-1 significantly increased neutrophil and platelet content and release of 20-HETE. ANG II increased 20-HETE via the AT(2) receptor. ET-1 increased 20-HETE through the ET(B) receptor in platelets and both the ET(A) and ET(B) receptors in neutrophils. These studies show that human platelets and neutrophils synthesize 20-HETE in response to ANG II and ET-1. 20-HETE synthesis in both cell types was predominantly mediated via the AT(2) and ET(B) receptors. Stimulation via these receptor pathways has generally been thought to be cardioprotective and requires further studies in clinical situations associated with low-grade inflammation or where ANG II and ET-1 are elevated to clarify the role of 20-HETE.

Effects of lupin-enriched foods on body composition and cardiovascular disease risk factors: a 12-month randomized controlled weight loss trial.

BACKGROUND: Regular consumption of diets with increased protein or fibre intakes may benefit body weight and composition and cardiovascular disease risk factors. Lupin flour is a novel food ingredient high in protein and fibre. OBJECTIVE: To investigate the effects of a lupin-enriched diet, during and following energy restriction, on body weight and composition and cardiovascular disease risk factors in overweight individuals. DESIGN: Participants (n = 131) were recruited to a 12-month parallel-design trial. They were randomly assigned to consume lupin-enriched foods or matching high-carbohydrate control foods. All participants underwent 3 months of weight loss, 1 month of weight stabilization and 8 months of weight maintenance. Body weight and composition and cardiovascular disease risk factors were assessed at baseline, 4 and 12 months. RESULTS: Lupin, relative to control, did not significantly influence (mean difference (95% CI)) weight loss at 4 months (0.1 kg (-1.2, 1.4)) and 12 months (-0.6 kg (-2.0, 0.8)), maintenance of weight loss from 4 to 12 months (-0.7 kg (-1.83, 0.48)) or measures of body fat and fat-free mass. Relative to control, 24-h ambulatory systolic (-1.3 mm Hg (-2.4, -0.3), P = 0.016) and diastolic (-1.0 mm Hg (-1.9, -0.2), P = 0.021) blood pressures were lower at 12 months but not at 4 months; fasting insulin concentrations and homeostasis model assessment (HOMA) scores were significantly lower at 4 months (-1.2 mU l(-1) (-1.3, -1.1), P = 0.004 and -0.6 units (-1.0, -0.19), P = 0.004) and 12 months (-1.3 mU l(-1) (-1.4, -1.1), P < 0.001 and -0.7 units (-1.1, -0.24), P = 0.002). CONCLUSIONS: A diet higher in protein and fibre derived from lupin-enriched foods does not enhance weight loss or improve the maintenance of weight loss. However, such a diet may provide cardiovascular health benefits in terms of insulin sensitivity and blood pressure.

Effects of increasing dietary protein and fibre intake with lupin on body weight and composition and blood lipids in overweight men and women.

BACKGROUND: Lupin kernel flour (LKF) is a novel food ingredient that is high in protein and fibre. We have previously shown that partial substitution of refined wheat-derived carbohydrate in bread with protein and fibre from LKF can reduce appetite and energy intake acutely. In addition, several studies have suggested that lupin may reduce cholesterol concentrations and benefit glucose and insulin metabolism. AIM: The aim of this study was to investigate the effects on body weight and composition and blood lipids, glucose and insulin of an ad libitum LKF-enriched diet higher in dietary protein and fibre. SUBJECTS AND METHODS: A total of 88 overweight and obese men and women were recruited for a 16-week parallel-design randomized controlled trial. Participants replaced 15-20% of their usual daily energy intake with white bread (control) or LKF-enriched bread (lupin) in an ad libitum diet. Measurements of body weight and composition, and fasting blood biochemical measurements were performed at baseline and 16 weeks. The primary analysis included 74 participants (37 per group) who completed the intervention. RESULTS: At baseline, mean (+/-s.d.) body mass index and total cholesterol were 30.6+/-3.5 kg m(-2) and 5.37+/-0.94 mmol l(-1), respectively. Estimated (mean between-group difference (95% confidence interval)) protein (13.7 (2.28, 25.0) g per day) and fibre (12.5 (8.79, 16.2) g per day) intakes were higher during the intervention with lupin than with control. For lupin relative to control, the net effects on body weight (-0.4 (-1.3, 0.6) kg), fat mass (-0.5 (-1.1, 0.2) kg) and percentage (-0.5 (-1.1, 0.1)%), plasma leptin (-1.66 (-4.91, 1.59) ng ml(-1)) and adiponectin (0.20 (-0.73, 1.13) mg l(-1), as well as serum total cholesterol (-0.08 (-0.38, 0.22) mmol l(-1)), triglycerides (0.09 (-0.10, 0.21) mmol l(-1)), glucose (0.10 (-0.11, 0.30) mmol l(-1)) and insulin (0.40 (-1.20, 2.00) mU l(-1)) were not significant. CONCLUSIONS: This study does not support the proposal that an ad libitum diet enriched in LKF resulting in moderate changes in both protein and fibre intakes can benefit body weight and composition or fasting blood lipids, glucose and insulin concentrations in overweight men and women with mildly elevated total cholesterol concentrations.

Sesame supplementation does not improve cardiovascular disease risk markers in overweight men and women.

BACKGROUND AND AIMS: Pre-clinical studies suggest that sesame and its lignans induce beneficial changes in risk factors related to cardiovascular disease and increase the bioavailability of mammalian lignans. However, only very few intervention trials have investigated the potential bioactivities of sesame in humans. We aimed to investigate the effects of sesame supplementation in humans on blood lipids, blood pressure, systemic oxidative stress, inflammatory biomarkers and mammalian lignan metabolism. METHODS AND RESULTS: We conducted a randomized, placebo-controlled cross-over intervention trial at a university research centre. Overweight or obese men and women (n=33) consumed 25g/d of sesame ( approximately 50mg/d of sesame lignan) and an iso-caloric placebo matched for macronutrient composition for 5 wks each. Each intervention period was preceded by a 4-wk washout period. Blood lipid profiles, day time ambulatory blood pressure, oxidative stress and inflammatory biomarkers and urinary mammalian lignans were measured before and after each intervention. Results are presented as the effect of sesame supplementation relative to placebo. Urinary excretion of the mammalian lignans, enterolactone and enterodiol, increased by approximately 8-fold (P<0.001). Blood lipids and blood pressure were not altered. In addition, markers of systemic inflammation (C-reactive protein, interleukin-6, tumor necrosis factor-alpha) and lipid peroxidation (F(2)-isoprostanes) were not affected. CONCLUSION: Supplementation with 25g/d of sesame can significantly increase the exposure to mammalian lignans. However, this did not cause any improvement in markers of cardiovascular disease risk in overweight or obese men and women.

Hospital admissions and length of stay for coronary disease in an Aboriginal cohort.

BACKGROUND AND AIMS: Coronary disease (CHD)-related hospital admission is more common among indigenous than non-indigenous Australians. We aimed to identify predictors of hospital admission potentially useful in planning prevention programs. METHODS AND RESULTS: Length of stay (LOS), interval between, and number of recurrent admissions were modelled with proportional hazards or negative binomial models using lifestyle data recorded in 1988-1989 among Aborigines (256 women, 258 men, aged 15-88years) linked to hospital records to 2002. Among 106 Aborigines with CHD, hypertension (hazard ratio (HR) 1.69, 95% CI 1.05-2.73); smoking (HR 1.90, 95% CI 1.02-3.53); consuming processed meat >4 times/month (HR 1.81, 95% CI 1.01-3.24); >6 eggs/week (HR 1.73, 95% CI 1.03-2.94); and lower intake of alcohol (HR 0.54, 95% CI 0.35-0.83) predicted LOS. Eating eggs (HR 1.05, 95% CI 1.01-1.09) and bush meats > or =7 times/month (HR 0.46, 95% CI 0.23-0.92) predicted interval between recurrent admissions. Hypertension (IRR 4.07; 95% CI 1.32-12.52), being an ex-drinker (IRR 6.60, 95% CI 2.30-19.00), eating red meat >6 times/week (IRR 0.98, 95% CI 0.97-0.99), bush meats >7 times/month (IRR 0.26, 95% CI 0.10-0.67), and adding salt to meals (IRR 3.16, 95% CI 1.12-8.92) predicted number of admissions. CONCLUSION: Hypertension, alcohol drinking, smoking, and diet influence hospital admissions for CHD in Aboriginal Australians.

Impaired ex vivo leukotriene B4 production characterizes the metabolic syndrome and is improved after weight reduction.

CONTEXT: Neutrophil (polymorphonuclear neutrophil) production of leukotriene B4 (LTB4) may be associated with alterations in immune and inflammatory function that characterize the metabolic syndrome (MetS). OBJECTIVE: We investigated whether polymorphonuclear neutrophil production of LTB(4) and its metabolites 20-hydroxy-LTB4 (20-OH-LTB4) and 20-carboxyl-LTB4 were altered in subjects with features of the MetS before and after weight reduction. DESIGN, SETTING, PATIENTS, AND INTERVENTION: In a case-controlled comparison, men and postmenopausal women with features of the MetS were matched with controls. Subjects with MetS were then matched and randomly assigned to either a 12-wk weight reduction study followed by 4-wk weight stabilization or 16-wk weight maintenance. MAIN OUTCOME MEASURES: Measurements were performed at baseline and at the end of the 16-wk period. Stimulated neutrophil LTB4 and its metabolites were measured by HPLC. RESULTS: In the case-controlled study, body mass index, waist circumference, blood pressure, fasting triglycerides, and glucose were all significantly increased in subjects with features of the MetS (P < 0.05). Production of LTB4 and 20-OH-LTB4 was significantly lower compared with controls (P < 0.005). The weight loss intervention resulted in a 4.6-kg reduction in body weight and 6.6-cm decrease in waist circumference relative to controls and a significant increase in LTB4 and 20-OH-LTB4. CONCLUSIONS: Subjects with features of the MetS have lower stimulated LTB4, which is not due to increased metabolism of LTB4. Weight reduction restored the production of neutrophil LTB4, suggesting that in addition to modifying cardiovascular risk, weight loss may also help with the management of perturbed inflammatory responses in overweight subjects.

Health-related behaviours as predictors of mortality and morbidity in Australian Aborigines.

OBJECTIVE: To examine predictors of coronary heart disease (CHD) and all-cause mortality in Aboriginal Australians. METHOD: In 1988-89, a survey of Western Australian Aborigines (256 women, 258 men) aged 15-88 years documented diet, alcohol and smoking habits. Linkage to mortality and hospital admissions to the end of 2002 provided longitudinal data for modelling of coronary heart disease endpoints and all-cause mortality using Cox regression. RESULTS: Coronary heart disease risk increased with smoking (HR 2.62, 95% CI: 1.19, 5.75), consumption of processed meats >once/week (HR 2.21, 95% CI: 1.05, 4.63), eggs >twice/week (HR 2.59, 95% CI: 1.11, 6.04) and using spreads on bread (HR 3.14. 95% CI: 1.03, 9.61). All-cause mortality risk was lower with exercise >once/week (HR 0.51, 95% CI 0.26, 1.05), increased in ex-drinkers (HR 3.66, 95% CI: 1.08, 12.47), heavy drinkers (HR 5.26, 95% CI: 1.46, 7.52) and with consumption of take away foods >nine times/month (HR 1.78, 95% CI 0.96, 3.29). Greater alcohol intake, smoking and adverse dietary choices clustered in 53% of men and 56% of women and increased risk of coronary heart disease (HR 2.1, 95% CI: 1.1, 4.0) and all-cause mortality (HR 2.3, 95% CI: 1.2, 4.2). CONCLUSION: Lifestyle in Aboriginal Australians predicts coronary heart disease and all-cause mortality. Clustering of adverse behaviours is common and increases risk of coronary heart disease and death.

Alcohol intake and incidence of coronary disease in Australian aborigines.

AIMS: To examine risk for coronary heart disease (CHD) and cardiovascular disease (CVD) in relation to alcohol in a cohort of Australian Aborigines. METHODS: In 1988-1989, alcohol intake, drinking pattern, and beverage preference were elicited by interviewer-administered questionnaire in Western Australian Aborigines (258 men and 256 women) and cardiovascular outcomes ascertained through linkage to mortality and hospital admission records to 2002. RESULTS: In proportional hazards models, risk for CHD, relative to lifetime abstainers, was significantly increased in ex-drinkers [Hazard ratio (HR), 2.29; 95% confidence intervals (CI), 1.23-4.27], those drinking 41-60 g/day in men or 21-40 g/day in women (HR 2.80; 95% CI, 1.04-7.53) and those drinking >150 g/day for men or >100 g/day for women (HR, 2.25; 95% CI, 1.03-4.90) with a J-shaped relationship. Low-to-moderate drinkers had lower waist girth, exercised more and had a lower prevalence of overweight and smoking than at-risk drinkers. A preference for wine was associated with lower HR (0.28; 95% CI, 0.10-0.95). With CVD, only ex-drinkers showed significantly increased risk (HR, 1.87; 95% CI, 1.20-2.91). CONCLUSIONS: More favourable health-related behaviours in low-to-moderate drinkers suggest that lower risk could be mediated by lifestyle, as proposed in other populations.

Alcohol intake and incidence of coronary disease in Australian aborigines.

AIMS: To examine risk for coronary heart disease (CHD) and cardiovascular disease (CVD) in relation to alcohol in a cohort of Australian Aborigines. METHODS: In 1988-1989, alcohol intake, drinking pattern, and beverage preference were elicited by interviewer-administered questionnaire in Western Australian Aborigines (258 men, 256 women) and cardiovascular outcomes ascertained through linkage to mortality and hospital admission records to 2002. RESULTS: In proportional hazards models, risk for CHD, relative to lifetime abstainers, was significantly increased in ex-drinkers [Hazard ratio (HR) 2.29, 95% CL 1.23, 4.27], those drinking 41-60 g/day in men or 21-40 g/day in women (HR 2.80, 95% CL 1.04, 7.53), and those drinking >150 g/day for men or >100 g/day for women (HR 2.25, 95% CL 1.03, 4.90) with a J-shaped relationship. Low-to-moderate drinkers had lower waist girth, exercised more, and had a lower prevalence of overweight and smoking than at-risk drinkers. A preference for wine was associated with lower HR (0.28, 95% CL 0.10, 0.95). With CVD, only ex-drinkers showed significantly increased risk (HR 1.87, 95% CL 1.20, 2.91). CONCLUSIONS: More favourable health-related behaviours in low-to-moderate drinkers suggest that lower risk could be mediated by lifestyle, as proposed in other populations.

Exercise behaviour change in 40 to 65-year-old women: The SWEAT Study (Sedentary Women Exercise Adherence Trial).

OBJECTIVE: The purpose of this study was to examine the relation between self-reported psychological processes and changes in exercise behaviour in an 18-month longitudinal stage-based intervention trial in 115 initially sedentary women aged 40-65 years. DESIGN: A two-way factorial design was used. METHODS: Participants were assigned randomly to either moderate or vigorous and either home or centre-based exercise. After six months, all participants exercised at home. Participants completed questionnaires at baseline, six, 12 and 18 months which assessed stage of exercise behaviour, self-efficacy, decisional balance and processes of change. RESULTS: 28 patterns of stage change were identified across the 18 months with 6.1% remaining sedentary and 45% demonstrating linear movement from contemplation to action to maintenance to continued maintenance. Two interpretable clusters were identified within both the contemplation (at baseline) and action (at six months) stages. Cluster membership, however, did not influence behaviour change. For participants demonstrating a linear pattern of change, self-efficacy for overcoming barriers and behavioural processes increased from contemplation to action. Self-efficacy for exercise competence increased from contemplation to action but was more pronounced for the vigorous exercise groups. Decisional balance showed a three-way interaction and there was no change for experimental processes. There was no change in any variable from action to maintenance. CONCLUSIONS: The intervention was seen to be effective regardless of location or intensity of exercise. The relevance of substages is questionable in stage-based interventions as women with a profile suggesting less readiness to change or sustain change were just as likely to adopt or maintain exercise.

Controlled comparison of retention and adherence in home- vs center-initiated exercise interventions in women ages 40-65 years: The S.W.E.A.T. Study (Sedentary Women Exercise Adherence Trial).

BACKGROUND: In an 18-month exercise intervention in previously sedentary older women (40-65 years), we examined whether an initial 6 months of supervised exercise leads to greater long-term retention and adherence to regular physical activity than an unsupervised home-based program and whether these outcomes are influenced by the exercise intensity. METHODS: Women (N = 126) were recruited from the community and randomly assigned to either center-based or home-based exercise three times/week. The center-based group attended supervised sessions for 6 months, while after 10 initial sessions the home-based group exercised at home. After 6 months both groups were home-based for a further 12 months. Within each arm, subjects were further randomized to exercise at either moderate or vigorous intensity. RESULTS: The center-based group had higher retention than the home-based (97, 94, 81 versus 87, 76, and 61%) at 6, 12, and 18 months, respectively (P < 0.05). At 6 months, adherence was higher in the center-based group (84 versus 63%, P < 0.001) and energy expenditure was higher at 6 (P < 0.05) and 12 (P < 0.01) months. At 18 months, retention was higher with moderate exercise (P < 0.05), while adherence was similar with both intensities. CONCLUSION: An initial 6 months of center-based exercise enhanced retention in both the short and the long term and promoted short-term adherence and energy expenditure. Long-term, moderate exercise retained more subjects, but had little influence on adherence.

Persistence of the antihypertensive efficacy of amlodipine and nifedipine GITS after two 'missed doses': a randomised, double-blind comparative trial in Asian patients.

Suboptimal management of hypertension is often a result of poor patient compliance in the form of missed doses of their antihypertensive medication. This multicentre, randomised, double-blind, parallel-group trial was designed to compare the persistence of the antihypertensive efficacy of the amlodipine and nifedipine gastrointestinal therapeutic system (GITS) after two 'missed doses', and also to compare the drugs' overall efficacy and safety in Asian patients with mild-to-moderate essential hypertension. Following a 2-week placebo run-in period, 222 patients were randomised to receive either amlodipine (5 mg daily, increased after 6 weeks if necessary to 10 mg daily, n=109) or nifedipine GITS (30 mg daily, increased after 6 weeks if necessary to 60 mg daily; n=113) for 12 weeks. A placebo was then substituted for further 2 days with continuous ambulatory blood pressure (BP) monitoring. The increases in the last 9 h of mean ambulatory BP on day 2 after treatment withdrawal were significantly less with amlodipine than with nifedipine GITS: 4.4+/-7.0 vs 11.2+/-11.3 mmHg for systolic BP (P

Similarity in the distribution of F(2)-isoprostanes in the lipid subfractions of atherosclerotic plaque and in vitro oxidised low density lipoprotein.

Oxidation of low density lipoprotein (LDL) in vivo is thought to play a critical role in the initiation of atherosclerosis. F(2)-isoprostanes are compounds resulting from non-enzymatic oxidation of arachidonic acid and elevated levels are present in human atherosclerotic plaque. However, little is known about the formation of F(2)-isoprostanes in plaque lesions or their distribution in lipid subclasses. Given that LDL and tissue lipid subfractions (such as phospholipids, cholesterol esters and triglycerides) all contain significant levels of arachidonic acid, the aim of this study was to examine the relative distribution of F(2)-isoprostanes in the different lipid fractions of LDL oxidised in vitro, and compare this to the distribution in atherosclerotic plaque. The results reveal that while the majority of F(2)-isoprostanes are present in the phospholipid or surface lipid fractions, the core lipids (cholesterol esters/triglycerides) contribute at least 10% of the total F(2)-isoprostanes in both LDL oxidised in vitro and human atherosclerotic plaque. The remarkably similar profiles between the oxidised LDL and advanced atherosclerotic plaque suggests oxidation in vivo, is predominantly via non-enzymatic processes directed towards the surface lipids.

Alcohol consumption and the risk of type 2 diabetes mellitus: atherosclerosis risk in communities study.

Evidence regarding the association between alcohol consumption and type 2 diabetes risk remains inconsistent, particularly with regard to male-female differences. The authors conducted a prospective study of type 2 diabetes risk associated with alcohol consumption in a cohort of 12,261 middle-aged participants of the Atherosclerosis Risk in Communities Study (1990-1998), who were followed between 3 and 6 years. Alcohol consumption at baseline was characterized into lifetime abstainers, former drinkers, and current drinkers of various levels. Incident diabetes was determined by blood glucose measurements and self-report. After adjustment for potential confounders, an increased risk of diabetes was found in men who drank >21 drinks/week when compared with men who drank < or =1 drink/week (odds ratio = 1.50, 95% confidence interval: 1.02, 2.20) while no significant association was found in women. This increased diabetes risk among men who drank >21 drinks/week was predominantly related to spirits rather than to beer or wine consumption. The relative odds of incident diabetes in a comparison of men who drank >14 drinks of spirits per week with men who were current drinkers but reported no regular use of spirits, beer, or wine were 1.82 (95% confidence interval: 1.14, 2.92). Results of this study support the hypothesis that high alcohol intake increases diabetes risk among middle-aged men. However, more moderate levels of alcohol consumption do not increase risk of type 2 diabetes in either middle-aged men or women.

Long-term effects of exercise on blood pressure and lipids in healthy women aged 40-65 years: The Sedentary Women Exercise Adherence Trial (SWEAT).

OBJECTIVES: To evaluate the long-term effects of regular moderate or vigorous intensity exercise on blood pressure and blood lipids in previously sedentary older women. DESIGN: Subjects were randomly assigned to either a supervised centre-based (CB) or a minimally supervised home-based (HB) exercise program, initially for 6 months. Within each program, subjects were further randomized to exercise either at moderate (40-55% heart rate reserve, HRres) or vigorous intensity (65-80% HRres). After 6 months, all groups continued a HB moderate or vigorous exercise program for another 12 months. METHODS: Healthy, sedentary women (aged 40-65 years) (n = 126) were recruited from the community. Subjects exercised three times per week for 30 min. They were evaluated at baseline, 6, 12 and 18 months. RESULTS: There was a significant fall of 2.81 mmHg in systolic blood pressure (P = 0.049) and 2.70 mmHg in diastolic blood pressure (P = 0.004) after correction for age and baseline values with moderate exercise, but not with vigorous-intensity exercise. When this analysis was repeated with the change in body mass included, the results were unchanged. After correction for potential confounding factors, there was a significant fall in total cholesterol and low density lipoprotein cholesterol with vigorous but not moderate exercise at 6 months (P < 0.05) but not at 18 months. CONCLUSIONS: In this largely normotensive population of older women, a moderate, but not vigorous exercise program, achieved sustained falls in resting systolic and diastolic blood pressure over 18 months. The study demonstrates that, in older women, moderate intensity exercise is well accepted, sustainable long-term and has the health benefit of reduced blood pressure.

Effects of regular ingestion of black tea on haemostasis and cell adhesion molecules in humans.

OBJECTIVE: To assess the effects in humans of regular ingestion of black tea on haemostasis-related variables and cell adhesion molecules. DESIGN: Twenty-two subjects were recruited from the general population to a randomised-controlled crossover study. Subjects stopped drinking tea, apart from that provided, for the duration of the study. During a 4-week baseline period all subjects drank 5 cups/day (250 ml) of hot water. The effects of 5 cups/day of black tea for 4 weeks were then compared with hot water. Platelet aggregation in response to three doses of collagen and ADP, plasma concentrations of coagulation and fibrinolytic factors (fibrinogen, factor VII, tPA, PAI-1) and plasma concentrations of cell adhesion molecules (soluble P-selectin, E-selectin, ICAM-1, VCAM-1) were assessed twice, one week apart, at the end of each period. Twenty-four hour urinary concentration of 4-O-methylgallic acid (4OMGA), assessed once at the end of each period, was used as a marker of black tea polyphenol intake. RESULTS: The 24 h urinary excretion of 4OMGA was increased during regular ingestion of black tea in comparison to hot water (P<0.0001). Black tea resulted in lower soluble P-selectin (P=0.01) in comparison to hot water, but did not influence other adhesion molecules. Soluble P-selectin was significantly correlated with mean collagen-stimulated platelet aggregation at baseline (r=0.61, P=0.003), and during regular ingestion of hot water (r=0.70, P<0.0001) and black tea (r=0.51, P=0.01). However, platelet aggregation was not different between the black tea and hot water periods for collagen- or ADP-stimulated aggregation at any dose. Coagulation and fibrinolytic factors were also not different between periods. CONCLUSIONS: The effect of black tea on soluble P-selectin provides a potential mechanism for cardiovascular benefits of regular ingestion of tea. SPONSORSHIP: This study was supported by grants from the Tea Trade Health Research Association and the National Heart Foundation of Australia.

Dietary protein and soluble fiber reduce ambulatory blood pressure in treated hypertensives.

In population studies, higher blood pressure has been associated with lower intake of protein and, possibly, lower fiber consumption. In the present randomized controlled trial, we sought to determine whether dietary protein and fiber had additive effects on blood pressure reduction in hypertensives. Treated hypertensive patients changed for 4 weeks (familiarization) to a diet low in protein (12.5% energy) and fiber (15 g/d). Patients (n=41) were then randomized to 1 of 4 groups in an 8-week factorial study of parallel design in which they continued the low-protein, low-fiber diet alone or had supplements of soy protein to increase protein intake to 25% energy, of psyllium to provide an additional 12 g soluble fiber/d, or of both protein and fiber. The 24-hour ambulatory blood pressure was compared from the end of familiarization to the end of intervention. In the 36 subjects who provided complete data, protein and fiber had significant additive effects to lower 24-hour and awake systolic blood pressure. Relative to control subjects, the net reduction in 24-hour systolic blood pressure was 5.9 mm Hg with fiber and with protein. Findings were independent of age, gender, and change in weight, alcohol intake, or urinary sodium and potassium. Relative to reduced fiber and protein intake, dietary protein and soluble fiber supplements lower blood pressure additively in hypertensives. These findings have important implications for the prevention and management of hypertension, particularly in populations in which high blood pressure is prevalent in association with diets low in protein, fiber, or both.