Paul A. Komesaroff

Soy Isoflavones Improve Systemic Arterial Compliance but Not Plasma Lipids in Menopausal and Perimenopausal Women

The possibility that the heightened cardiovascular risk associated with the menopause, which is said to be ameliorated by soybeans, can be reduced with soy isoflavones was tested in 21 women. Although several were perimenopausal, all have been included. A placebo-controlled crossover trial tested the effects of 80-mg daily isoflavones (45 mg genistein) over 5- to 10-week periods. Systemic arterial compliance (arterial elasticity), which declined with age in this group, improved 26% (P < .001) compared with placebo. Arterial pressure and plasma lipids were unaffected. The vasodilatory capacity of the microcirculation was measured in nine women; high acetylcholine-mediated dilation in the forearm vasculature was similar with active and placebo treatments. LDL oxidizability measured in vitro was unchanged. Thus, one important measure of arterial health, systemic arterial compliance, was significantly improved in perimenopausal and menopausal women taking soy isoflavones to about the same extent as is achieved with conventional hormone replacement therapy.

Hormonal Therapy Increases Arterial Compliance in Postmenopausal Women

OBJECTIVESnThis study investigated the effects of hormonal therapy on large arterial properties.nnnBACKGROUNDnArterial stiffness is an emerging risk marker for coronary heart disease and is potentially modifiable. Postmenopausal use of hormonal therapy is associated with a lower risk of coronary heart disease.nnnMETHODSnTotal systemic arterial compliance (SAC) and pulse wave velocity (PWV) were determined in 26 premenopausal and 52 postmenopausal women, 26 of whom were taking hormonal therapy.nnnRESULTSnArterial compliance was greater in the premenopausal group (mean +/- SEM 0.57 +/- 0.04 arbitrary compliance units [ACU]) than in the postmenopausal group not taking hormonal therapy (0.26 +/- 0.02 ACU, p = 0.001). Postmenopausal women taking hormonal therapy had a significantly increased total SAC compared with women not taking hormonal therapy (0.43 +/- 0.02 vs. 0.26 +/- 0.02 ACU, p = 0.001). PWV in the aortofemoral region in the premenopausal women was 6.0 +/- 0.2 vs. 8.9 +/- 0.3 m/s (p < 0.001) in untreated postmenopausal women. However, postmenopausal women taking hormonal therapy had a significantly lower PWV than those not taking hormonal therapy (7.9 +/- 0.2 vs. 8.9 +/- 0.3 m/s, p = 0.01). Eleven postmenopausal women had their hormone replacement therapy withdrawn for 4 weeks, resulting in a significant decrease in SAC and a significant increase in aortofemoral PWV.nnnCONCLUSIONSnThe increased SAC and decreased PWV in women receiving hormonal therapy suggest that such therapy may decrease stiffness of the aorta and large arteries in postmenopausal women, with potential benefit for age-related cardiovascular disorders. The reduction of arterial compliance with age appears to be altered with hormonal therapy.

6 Mineralocorticoid resistance

Summary Mineralocorticoid resistance, or pseudohypoaldosteronism (PHA), is a rare cause of salt wasting in young children. It may be inherited as an autosomal dominant or recessive trait, it may occur sporadically or, rarely, it may develop secondary to other conditions. It is characterized by episodes of dehydration and hyponatraemia in the face of high aldosterone levels. In most cases, after a short period of salt supplementation no further ill effects are experienced. The condition is of great interest because it provides insights into both the mechanisms by which salt and water balance are controlled and the actions of aldosterone. This article reviews the normal physiology of aldosterone, with particular reference to its biosynthesis and its actions in specific target tissues. Current knowledge regarding the molecular mechanisms involved in aldosterone action is discussed in some detail. The clinical features of PHA are reviewed and diagnostic issues and clinical management considered. Finally, current views regarding the pathophysiology of the condition are presented. Here, considerable uncertainty remains. Whilst in many cases of PHA there is greatly reduced binding of aldosterone to its receptor, the underlying abnormality is yet to be identified; in particular, in spite of strong reasons for suspecting a defect or defects in the mineralocorticoid receptor, there is so far no direct evidence to support this hypothesis. The article concludes with a discussion of other possible explanations for the underlying abnormality in PHA.

Differential Effect of Urotensin II on Vascular Tone in Normal Subjects and Patients With Chronic Heart Failure

Background—Urotensin II (U-II) is a novel vasoactive peptide that also has direct hypertrophic and profibrotic effects on the myocardium. Upregulation of U-II and its receptor has been observed within the heart of patients with chronic heart failure (CHF). Furthermore, plasma levels of U-II have been found to be elevated in some but not all studies in such patients. However, the functional consequences of activation of the U-II system in patients with CHF, assessed by direct administration of exogenous U-II, have not been previously determined. Methods and Results—We compared the effect of iontophoresed U-II on skin microvascular tone in normal subjects and patients with CHF, assessed with the use of laser Doppler velocimetry. U-II mediated a dose-dependent vasodilator response in normal subjects (baseline, 137.9±52; U-II, 10−12 mol/L, 145±134; U-II, 10−9 mol/L, 712±179; U-II, 10−7 mol/L, 943±139 arbitrary flux units [AFUs], P <0.0001). In contrast, a dose-dependent vasoconstrictor response was observed in patients with CHF (baseline, 336.1±129; U-II, 10−12 mol/L, 317±131; U-II, 10−9 mol/L, 129±137; U-II, 10−7 mol/L, 22.4±130 AFUs, P <0.05). Differences in flow between normal subjects and patients with CHF were significant overall (P <0.001, 2-way ANOVA) and at the U-II 10−9 mol/L and U-II 10−7 mol/L dose level by Student’s unpaired t test (P <0.05, P <0.0001, respectively). In contrast, there was no significant difference between baseline blood flux and any dose of U-II in either group (or between groups) when the opposite polarity was applied. Conclusions—In addition to direct effects on the myocardium, U-II may contribute to the increased peripheral vascular tone that is characteristic of human CHF. The present observations support the contention that the U-II system may be a potentially important target for pharmacological blockade in the treatment of this condition.

EFFECTS OF A CHINESE HERBAL PREPARATION ON VASCULAR CELLS IN CULTURE: MECHANISMS OF CARDIOVASCULAR PROTECTION

1.u2002The use of traditional Chinese medicinal herbs or their pharmaceutical products for disease prevention and management is becoming increasingly popular in Western countries. Mixtures of various Chinese herbs have been used for the treatment of syndromes clinically overlapping Western cardiovascular syndromes. One modern preparation, known as the ‘Cardiotonic Pill’ (CP), is a pharmaceutical product derived mainly from a medicinal herb, Salvia miltiorrhiza bunge, and recently widely used in Chinese hospitals for the prevention and management of ischaemic cardiovascular diseases. Although the CP is believed to confer an extensive range of benefits, little is known about the physiological actions of this medicine, particularly at the cellular and molecular levels. Therefore, the aim of the present study was to explore possible cellular mechanisms of the CP on the cardiovascular system.

Cellular mechanisms underlying the cardiovascular actions of oestrogens

Although pre-menopausal women enjoy relative cardiovascular protection, hormone (oestrogen+/-progestin)-replacement therapy has not shown cardiovascular benefits in post-menopausal women, suggesting that the effects of oestrogens on the cardiovascular system are much more complex than previously expected. Endothelial cells, smooth muscle cells, cardiac myocytes and fibroblasts, the cellular components of blood vessels and the heart, play important roles in cardiovascular health and disease. During the development and progression of cardiovascular disease, changes occur both in the structure and function of these cells, resulting in a wide range of abnormalities, which affect growth, death and physiological function. These cells contain functional oestrogen receptors and are targets for oestrogen action. This review focuses on recent studies on the effects of oestrogen on cardiovascular cell function. Oestrogens, particularly 17beta-oestradiol, exert multiple effects on cardiovascular cells, and these effects may contribute to the gender-associated protection against cardiovascular diseases.

Attitudes towards and beliefs about genetic testing in the haemophilia community: a qualitative study

Summary.u2002 Widespread genetic testing for haemophilia has recently been introduced in Victoria, Australia. While attitudes towards predictive testing have been studied in other conditions, such as cancer, there is limited knowledge about the attitudes of members of the haemophilia community towards predictive testing. This study aimed at exploring attitudes towards, and beliefs about, genetic testing amongst members of the haemophilia community in Victoria prior to the widespread introduction of testing. The study was qualitative and descriptive. In‐depth face to face interviews were held with a sample of 39 individuals, including men with haemophilia, female carriers and family members. Data were analysed thematically using cross‐case analysis techniques. There was considerable knowledge about the proposed introduction of widespread genetic testing. However, not everyone thought that testing was accessible or user friendly, and there was confusion about who needed to be tested. Most thought that testing was necessary for adolescent girls to determine carrier status to help prepare families for a child with haemophilia, rather than leading them to choose to terminate a pregnancy or not to have children. A minority of women stated that if there was a history of inhibitors in a family then a termination might be considered. The study revealed strong religious beliefs among those studied, which may have influenced attitudes and approaches towards testing. Further investigation is needed into how people with a possible haemophilia genotype negotiate decisions about their further identification, and how this knowledge is placed within cultural, religious and family contexts.

Combating the obesity epidemic: cultural problems demand cultural solutions.

Health problems related to excessive weight or obesity have acquired great importance in modern developed society. Although estimates vary it is apparent that the scope of these problems is vast. Obesity is now a leading cause of preventable deaths, withmore than 400 000 such deaths occurring yearly in the USA alone. In Australia the incidence of obesity is increasing rapidly. Nearly twothirds of people are overweight and nearly one-third obese: this amounts to approximately 9 million people over the age of 18 who are overweight and approximately 3.3 million who are obese. The list of health problems associated with excessive weight is similarly impressive. It includes, among other conditions, diabetes mellitus, ischaemic heart disease, hypertension, renal and gastroenterological disease, sleep apnoea, lung disease, arthritis and depression. The economic cost is also great: it has been estimated that in the USA the total cost is currently approximately

Complementary medicine use among people living with HIV/AIDS in Victoria, Australia: practices, attitudes and perceptions.

117 000 million per year, which includes more than

The isoflavone metabolite cis-tetrahydrodaidzein inhibits ERK-1 activation and proliferation in human vascular smooth muscle cells.

50 000 million in avoidable medical costs. In Australia, the total financial costs of obesity in 2005 were estimated as