Alpha-lipoic acid does not acutely affect resistance and conduit artery function or oxidative stress in healthy men

Aims Alpha-lipoic acid (ALA) is a thiol compound with antioxidant properties used in the treatment of diabetic polyneuropathy. ALA may also improve arterial function, but there have been scant human trials examining this notion. This project aimed to investigate the effects of oral and intra-arterial ALA on changes in systemic and regional haemodynamics, respectively. Methods In study 1, 16 healthy older men aged 58 +/- 7 years (mean +/- SD) received 600 mg of ALA or placebo, on two occasions 1 week apart, in a randomized cross-over design. Repeated measures of peripheral and central haemodynamics were then obtained for 90 min. Central blood pressure and indices of arterial stiffness [augmentation index (AIx) and estimated aortic pulse wave velocity] were recorded non-invasively using pulse wave analysis. Blood samples obtained pre- and post-treatments were analysed for erythrocyte antioxidant enzyme activity, plasma nitrite and malondialdehyde. In study 2 the effects of incremental cumulative doses (0.5, 1.0, 1.5 and 2.0 mg ml(-1) min(-1)) of intra-arterial ALA on forearm blood flow (FBF) were assessed in eight healthy subjects (aged 31 +/- 5 years) by conventional venous occlusion plethysmography. Results There were no significant changes on any of the central or peripheral haemodynamic measures after either oral or direct arterial administration of ALA. Plasma ALA was detected after oral supplementation (95% confidence intervals 463, 761 ng ml(-1)), but did not alter cellular or plasma measures of oxidative stress. Conclusions Neither oral nor intra-arterial ALA had any effect on regional and systemic haemodynamics or measures of oxidative stress in healthy men.

Insulin resistance is a determinant of myocardial dysfunction in apparently healthy obese subjects

Background. Obese pts have subclinical myocardial dysfunction that may account for their risk of heart failure. We sought the contribution of insulin resistance (IR) to myocardial dysfunction in obesity. Methods. Asymptomatic obese subjects without known cardiac disease underwent clinical evaluation, homeostasis model assessment (HOMA score) as a measure of insulin sensitivity and echocardiographic assessment. After exclusion of DM, overt myocardial dysfunction or ischemia, subclinical myocardial function was assessed by myocardial systolic (Sm) and diastolic velocity (Em) in 79 pts. Association was sought between myocardial function with clinical and biochemical characteristics. Results HOMA score categorized 36 pts as non-IR (HOMA

Effect of periodontal treatment on the C-reactive protein and proinflammatory cytokine levels in Japanese periodontitis patients

Background: Recent epidemiological studies have shown that individuals with periodontitis have a significantly increased risk of developing coronary heart disease. In addition to conventional risk factors, chronic infection and subsequent production of systemic inflammatory markers may be associated with this increased risk. Objectives: The aim of the present study was to determine whether the presence of chronic periodontitis and subsequent periodontal treatment could influence the serum levels of C-reactive protein (CRP), interleukin-6 and tumor necrosis factor-alpha (TNF-alpha) in a Japanese population. Methods: Sera were obtained from 24 patients with moderate to advanced periodontitis at the baseline examination and at reassessment after completion of treatment. As a control, sera were also obtained from 21 subjects without periodontitis. High-sensitivity CRP (hs-CRP) was measured using nephelometry with a latex particle-enhanced immunoassay and interleukin-6 and TNF-alpha were determined by sensitive enzyme-linked immunosorbent assay. Results: The levels of hs-CRP and interleukin-6 in the sera of this Japanese population seemed to be much lower than those reported in other populations. TNF-alpha on the other hand, demonstrated similar levels between this Japanese and other populations. Periodontal status demonstrated a significant improvement in all patients following treatment. There was a trend toward higher hs-CRP levels in patients at baseline compared with control subjects. Hs-CRP level tended to decrease with improvement of the periodontal condition following treatment and approached that of control subjects, although this decline was not statistically significant. interleukin-6 and TNF-alpha levels did not change following periodontal treatment. Furthermore, there was no difference in the serum levels of these inflammatory cytokines between patients either at baseline or at reassessment and control subjects. Conclusions: In this pilot study, we were unable to show that periodontal disease significantly affects the serum levels of systemic inflammatory markers. However, this does not necessarily mean that periodontitis does not contribute to the total burden of inflammation as there was a tendency for hs-CRP to decrease following successful periodontal treatment. Large-scale studies are clearly needed to determine the impact of periodontal disease on systemic inflammation.

Interfaces between cardiovascular and kidney disease among Aboriginal Australians

Rates of kidney disease among several indigenous groups have been shown to be substantially higher than corresponding non-indigenous groups. This excess has been clearly shown among Aboriginal Australians with respect to both end-stage kidney disease and early kidney disease. Rates of cardiovascular disease among Aboriginal Australians are also very high, as are rates of diabetes, smoking, and possibly overweight and obesity. These factors have been traditionally linked with cardiovascular and renal disease as part of a broader metabolic syndrome. However, the links and interfaces between cardiovascular and kidney disease in this environment extend beyond these traditional factors. The factors associated with atherosclerosis have expanded in recent years to include markers of inflammation, some infection, antioxidants, and other non-traditional risk factors. Given the high rates of acute infection and poor living conditions endured by many indigenous people, one might expect these non-traditional risk factors to be highly prevalent. In this review, we explore the relationships between markers of inflammation, some serological markers of infection, and other selected markers and both cardiovascular and renal disease. In doing so, we demonstrate links between kidney and cardiovascular disease at a number of levels, beyond the traditional cardiovascular/renal risk factors. Many of these factors are beyond the control of the individual or even community; addressing these issues a broader focus and biopsychosocial model. (C) 2005 by the National Kidney Foundation, Inc.

The effect of exercise on large artery haemodynamics in healthy young men

Background Brachial blood pressure predicts cardiovascular outcome at rest and during exercise. However, because of pulse pressure amplification, there is a marked difference between brachial pressure and central (aortic) pressure. Although central pressure is likely to have greater clinical importance, very little data exist regarding the central haemodynamic response to exercise. The aim of the present study was to determine the central and peripheral haemodynamic response to incremental aerobic exercise. Materials and methods Twelve healthy men aged 31 +/- 1 years (mean +/- SEM) exercised at 50%, 60%, 70% and 80% of their maximal heart rate (HRmax) on a bicycle ergometer. Central blood pressure and estimated aortic pulse wave velocity, assessed by timing of the reflected wave (T-R), were obtained noninvasively using pulse wave analysis. Pulse pressure amplification was defined as the ratio of peripheral to central pulse pressure and, to assess the influence of wave reflection on amplification, the ratio of peripheral pulse pressure to nonaugmented central pulse pressure (PPP : CDBP-P-1) was also calculated. Results During exercise, there was a significant, intensity-related, increase in mean arterial pressure and heart rate (P < 0.001). There was also a significant increase in pulse pressure amplification and in PPP : CDBP-P-1 (P < 0.001), but both were independent of exercise intensity. Estimated aortic pulse wave velocity increased during exercise (P < 0.001), indicating increased aortic stiffness. There was also a positive association between aortic pulse wave velocity and mean arterial pressure (r = 0.54; P < 0.001). Conclusions Exercise significantly increases pulse pressure amplification and estimated aortic stiffness.

Randomized control trial of a smoking cessation intervention directed at men whose partners are pregnant

Background. Although smoking cessation programs significantly reduce smoking rates in the general population, some sectors are poorly motivated by them, especially healthy men from lower socioeconomic classes. Methods. By using a significant life event (approaching birth of a child) we exploited a time of increased receptiveness to smoking cessation influences. A multicomponent intervention was conducted and evaluated using a stratified, randomised control trial, with an intention to treat analysis. Results. Five hundred and sixty-one men were enrolled and 505 (90%) followed to the end of their partners' pregnancy. At 6-month follow-up 16.5% of 291 smokers of the intervention group and 9.3% of 270 in the control group reported they had stopped smoking (P = 0.011, OR = 0.52, 95% CI 0.31 - 0.86). The strongest predictors of smoking cessation were being in a skilled occupation, having a higher number of quit attempts in the previous year and having the first cigarette of the day relatively later. Conclusions. The number of smoking men who had to be treated to achieve one stopping smoking (NNT) during their partner's pregnancy was 13 to 14. Innovative antismoking population health measures for the partners of antenatal patients are effective and perhaps should be more widely adopted. (C) 2003 American Health Foundation and Elsevier Inc. All rights reserved.

Lifestyle still predicts mortality in older men with established vascular disease

Background. It is uncertain whether accepted associations between health behaviors and mortality are pertinent to elderly people. No previous studies have examined the patterns of lifestyle in elderly men with and without clinically evident vascular disease by using a lifestyle score to predict survival. Methods. We measured prevalence of a healthy lifestyle (four or more healthy behaviors out of eight) and examined survival in 11,745 men aged 65-83 years participating in a randomized population-based trial of screening for abdominal aortic aneurysm in Perth, Western Australia. After stratifying participants into five groups according to history and symptoms of vascular disease, we compared survival of men in each subgroup with that of 'healthy' men with no history or symptoms of vascular disease. Results. Invitations to screening produced a corrected response of 70.5%. After adjusting for age and place of birth, having an unhealthy lifestyle was associated with an increase of 20% in the likelihood of death from any cause within 5 years (95% CI: 10-30%). This pattern was consistently evident across subgroups defined by history of vascular disease, but was less evident for deaths from vascular disease. Conclusions. Our results highlight the importance of maintaining a healthy lifestyle through to old age, regardless of history of vascular disease. (c) 2005 Elsevier Inc. All rights reserved.

Assessment of limb muscle and adipose tissue by dual-energy X-ray absorptiometry using magnetic resonance imaging for comparison

OBJECTIVE: To use magnetic resonance imaging (MRI) to validate estimates of muscle and adipose tissue (AT) in lower limb sections obtained by dual-energy X-ray absorptiometry (DXA) modelling. DESIGN: MRI measurements were used as reference for validating limb muscle and AT estimates obtained by DXA models that assume fat-free soft tissue (FFST) comprised mainly muscle: model A accounted for bone hydration only; model B also applied constants for FFST in bone and skin and fat in muscle and AT; model C was as model B but allowing for variable fat in muscle and AT. SUBJECTS: Healthy men (n = 8) and women (n = 8), ages 41 - 62 y; mean (s.d.) body mass indices (BMIs) of 28.6 (5.4) kg/m(2) and 25.1 (5.4) kg/m2, respectively. MEASUREMENTS: MRI scans of the legs and whole body DXA scans were analysed for muscle and AT content of thigh (20 cm) and lower leg (10 cm) sections; 24 h creatinine excretion was measured. RESULTS: Model A overestimated thigh muscle volume (MRI mean, 2.3 l) substantially (bias 0.36 l), whereas model B underestimated it by only 2% (bias 0.045 l). Lower leg muscle (MRI mean, 0.6 l) was better predicted using model A (bias 0.04 l, 7% overestimate) than model B (bias 0.1 l, 17% underestimate). The 95% limits of agreement were high for these models (thigh,+/- 20%; lower leg,+/- 47%). Model C predictions were more discrepant than those of model B. There was generally less agreement between MRI and all DXA models for AT. Measurement variability was generally less for DXA measurements of FFST (coefficient of variation 0.7 - 1.8%) and fat (0.8 - 3.3%) than model B estimates of muscle (0.5-2.6%) and AT (3.3 - 6.8%), respectively. Despite strong relationships between them, muscle mass was overestimated by creatinine excretion with highly variable predictability. CONCLUSION: This study has shown the value of DXA models for assessment of muscle and AT in leg sections, but suggests the need to re-evaluate some of the assumptions upon which they are based.

Variation in coumarin 7-hydroxylase activity associated with genetic polymorphism of cytochrome P450 2A6 and the body status of iron stores in adult Thai males and females

The relationships between catalytic activity of cytochrome P450 2A6 (CYP2A6), polymorphism of CYP2A6 gene, gender and levels of body iron stores were analysed in a sample group of 202 apparently healthy Thais, aged 1947 years. Eleven individuals were found to have high activity of CYP2A6, judged by the relatively large amounts (11.2-14.6 mg) of 7-hydroyxcoumarin (7-OHC) excreted 3 h following administration of 15 mg of coumarin. Ten individuals, however, did not excrete any 7-OHC. Of these 10, four were found to have no CYP2A6 gene (whole gene deletion; CYP2A6*4 allele). The frequency of the CYP2A6 alleles; *1A, *1B and *4 in the whole sample group was 52, 40 and 8% while the frequency of the CYP2A6 gene types; *1A/* 1A, *1A/* 1B, *1B/* 1B, *1A/* 4, *1BI* 4, *4/* 4 was 29, 41, 16, 7, 5 and 2%. Subjects having CYP2A6* 1A/* 1B gene-type group were found to have higher rates of coumarin 7-hydroxylation compared with those of the CYP2A6* 1B/* 1B and CYP2A6* 1A/* 4 gene types. The inter-individual variability in CYP2A6 catalytic activity was therefore attributed in part to the CYP2A6 genetic polymorphism. Variation in CYP2A6 activity in this sample group was not associated with gender but, interestingly, it did show an inverse association with plasma ferritin; an indicator of body iron stores. Higher rates of coumarin 7-hydroxylation were found in individuals with low body iron stores (plasma ferritin < 20 μg/l) compared with subjects having normal body iron store status. Subjects (n = 16) with iron overload (plasma ferritin > 300 mug/l) also tended to have elevated rates of coumarin 7-hydroxylation. These results suggest an increased CYP2A6 expression in subjects who have excessive body iron stores. Further investigations into the underlying factors that may lead to increased expression of CYP2A6 in association with abnormal body iron stores are currently in progress in our laboratory. Pharmacogenetics 12:241-249 (C) 2002 Lippincott Williams Wilkins.

Quadriceps activation in closed and in open kinetic chain exercise

Purpose: For treatment of various knee disorders, muscles are trained in open or closed kinetic chain tasks. Coordination between the heads of the quadriceps muscle is important for stability and optimal joint loading for both the tibiofemoral and the patellofemoral joint. The aim of this study was to examine whether the quadriceps femoris muscles are activated differently in open versus closed kinetic chain tasks. Methods: Ten healthy men and women (mean age 28.5 +/- 0.7) extended the knees isometrically in open and closed kinetic chain tasks in a reaction time paradigm using moderate force. Surface electromyography (EMG) recordings were made from four different parts of the quadriceps muscle. The onset and amplitude of EMG and force data were measured. Results: In closed chain knee extension, the onset of EMG activity of the four different muscle portions of the quadriceps was more simultaneous than in the open chain. In open chain, rectus femoris (RF) had the earliest EMG onset while vastus medialis obliquus was activated last (7 +/- 13 ms after RF EMG onset) and with smaller amplitude (40 +/- 30% of maximal voluntary contraction (MVC)) than in closed chain (46 +/- 43% MVC). Conclusions: Exercise in closed kinetic chain promotes more balanced initial quadriceps activation than does exercise in open kinetic chain. This may be of importance in designing training programs aimed toward control of the patellofemoral joint.

Endurance exercise, plasma oxidation and cardiovascular risk

Objective-Although physical activity is beneficial to health, people who exercise at high intensities throughout their lifetime may have increased cardiovascular risk. Aerobic exercise increases oxidative stress and may contribute to atherogenesis by augmented oxidation of plasma lipoproteins. The aim of this study was to examine the relationship between aerobic power and markers of oxidative stress, including the susceptibility of plasma to oxidation. Methods and results-Aerobic power was measured in 24 healthy men aged 29 9 years (mean +/- SD). Plasma was analysed from subjects of high aerobic power (HAP; VO(2)max, 64.6 +/- 6.1 ml/kg/min) and lower aerobic power (LAP;VO(2)max, 45.1 +/- 6.3 ml/kg/min) for total antioxidant capacity (TAC), malondialdehyde (MDA) and susceptibility to oxidation. Three measures were used to quantify plasma oxidizability: (1) lag time to conjugated diene formation (lag time); (2) change in absorbance at 234 nm and; (3) slope of the oxidation curve during propagation (slope). The HAP subjects had significantly lowerTAC (1.38 +/- 0.04 versus 1.42 +/- 0.06 TEAC units; P < 0.05), significantly higher change in absorbance (1.55 +/- 0.21 versus 1.36 +/- 0.17 arbitrary units; P < 0.05), but no difference in MDA (P = 0.6), compared to LAP subjects. There was a significant inverse association between TAC and slope (r = -0.49; P < 0.05). Lipoprotein profiles and daily intake of nutrients did not differ between the groups. Conclusions-These findings suggest that people with high aerobic power, due to extreme endurance exercise, have plasma with decreased antioxidant capacity and higher susceptibility to oxidation, which may increase their cardiovascular risk.