We investigated the ability of 37 flavonoids and flavonoid sulfoconjugates, including some abundant dietary constituents, to act as substrates and/or inhibitors of the sulfotransferase and sulfatase enzymes that interconvert active estrogens and inactive estrogen sulfates in human tissues. The enzymes studied include estrogen sulfotransferase, the thermostable phenolsulfotransferase that acts on a range of substrates including estrogens; steroid sulfatase; and two related enzymes, monoamine phenolsulfotransferase and arylsulfatase A. Several dietary flavonoids, including the soy isoflavones genistein and daidzein, were sulfated by these human sulfotransferases. Many flavonoids were potent inhibitors of thermostable phenolsulfotransferase. Genistein and equol were potent mixed inhibitors of hepatic estrogen sulfotransferase, with inhibitory constant values of 500 nM and 400 nM, respectively. Monoamine phenolsulfotransferase activity was relatively unaffected by flavonoids, but this enzyme was mainly responsible for the sulfation of flavonoids at concentrations greater than 1 micro M. Of the compounds tested, only daidzein 4,7-bisulfate, a trace metabolite in humans, significantly inhibited steroid sulfatase in the micromolar concentration range. Hence, dietary flavonoids may be able to influence the bioavailability of endogenous estrogens, and disrupt endocrine balance, by increasing the ratio of active estrogens to inactive estrogen sulfates in human tissues.

Phytoestrogens are natural constituents of our diets that have been suggested to protect against hormone-dependent breast cancer. Some of the diverse effects of these compounds may be at-

Various aspects of the interaction of oestrogen-receptor complexes with calf uterine chromatin covalently coupled to cellulose were analysed. Partially purified [3Hloestradiol-receptor complexes were bound to intact, or partially deproteinized, chromatin resins. Proteins were removed from the chromatin-cellulose resins by extraction with high molarities of salt, including NaCl/urea, guanidine hydrochloride and guanidine thiocyanate. After extensive washing to remove the salt, [3Hloestradiol-receptor-complex solutions were added to the resins and the degree of binding was determined. The extent of [3H]oestradiol-receptor-complex binding to chromatin was enhanced by extraction of chromosomal proteins. By varying the molarity of the salt, and consequently the extent of protein removal, it was possible to resolve [3Hloestradiol-receptor-complex binding to guanidine thiocyanate-extracted chromatin into two components. Similarly, [3Hloestradiol-receptor-complex binding to guanidine hydrochloride-treated chromatin included three regions of enhanced binding capacity. The [3Hloestradiol-receptor-chromatin interaction was saturable with respect to both intact and salt-extracted resins. Thus uterine chromatin may contain three or more specific classes of acceptors for the oestrogen-receptor complex.For many years the hypothesis that steroidhormone receptors interact specifically with a component of the nucleus has been included in the schematic representation of steroid-hormone action (Liao & Fang, 1969;O'Malley & Means, 1974;Gorski & Gannon, 1976). Early data favoured this general concept; however, the precise nature of the acceptor region has been difficult to determine. More recent efforts probing the nuclear site of action of steroid hormones have suggested the acidic-protein fraction of chromatin as being important in steroidhormone-receptor interactions (Spelsberg et al., 1979).The initial binding by oestrogen to its receptor is characterized by specificity, high affinity and saturability; presumably binding to specific regions in the nucleus is regulated by similar parameters. Thus the nucleus represents a second level of specificity.O'Malley et al. (1972) reported that progesteronereceptor complexes interact specifically with an acidic protein fraction of chick oviduct chromatin, suggesting that non-histone proteins constitute the nuclear site of action of steroid-hormone-receptor complexes. Subsequently, the binding activity of thisAbbreviations used: GuHCl, guanidine hydrochloride; GuSCN, guanidine thiocyanate.Vol. 200 non-histone protein fraction was dissociated from isolated chromatin by 7 M-GuHCI (Thrall et al., 1978). When these chromosomal proteins were separated by isoelectrofocusing and selectively reannealed to DNA, the ability of the progesterone receptor to bind was not limited to a single protein.Rather, three distinct sets of acidic protein-DNA complexes exhibited acceptor activity. These reports from cell-free systems are consistent with other studies which suggest the presence of at least two disti...

Summary Aim To document aspirin usage and the prevalence of large and small vessel complications in patients with diabetes mellitus (DM) attending the outpatient diabetes clinics of a large public hospital. Methods All patients attending diabetes outpatient clinics at The Royal Melbourne Hospital in Melbourne, Australia were surveyed over a 3‐month period. Results Complete data were available on 629 of 632 (296 male) patients surveyed. Of the 29.3% of patients who were suffering from one or more macrovascular complication (ischaemic heart disease, cerebrovascular disease or peripheral vascular disease), 63% were currently on aspirin treatment. Of those not on aspirin, 65% had no contra‐indication to aspirin treatment and a further 19% had only a relative contra‐indication of either aspirin or warfarin treatment recorded. Conclusions The published recommendations for the use of aspirin in patients with macrovascular disease were generally being followed in this clinic‐based population. However, a significant proportion of patients without a contra‐indication to treatment were still not receiving aspirin. The lack of clear evidence‐based guidelines for aspirin use may be a factor in its under‐prescription. This survey suggests clear evidence‐based guidelines should be established and disseminated.

Abstract--Multi-energy radiography is a new direction in nondestructive testing. Its specific feature is separate detection of penetrating radiation in several energy channels. Multi-energy radiography allows quantitative determination of the atomic composition of objects. This is its principal advantage over conventional radiography. In particular, dual-energy radiography allows determination of the effective atomic number of a material with an accuracy of up to 80-90%. Development of three-energy radiography and radiography of higher multiplicity makes it possible to further improve the reconstruction of an object's chemical composition. This presents the possibility, for example, of detection of explosives and other illegal objects in luggage with a reliability approaching 100%. These developments can find application not only in anti-terrorist activities, but also in areas such as industrial testing and nuclear medicine.