Paraben esters: review of recent studies of endocrine toxicity, absorption, esterase and human exposure, and discussion of potential human health risks

This toxicology update reviews research over the past four years since publication in 2004 of the first measurement of intact esters of p-hydroxybenzoic acid (parabens) in human breast cancer tissues, and the suggestion that their presence in the human body might originate from topical application of bodycare cosmetics. The presence of intact paraben esters in human body tissues has now been confirmed by independent measurements in human urine, and the ability of parabens to penetrate human skin intact without breakdown by esterases and to be absorbed systemically has been demonstrated through studies not only in vitro but also in vivo using healthy human subjects. Using a wide variety of assay systems in vitro and in vivo, the oestrogen agonist properties of parabens together with their common metabolite (p-hydroxybenzoic acid) have been extensively documented, and, in addition, the parabens have now also been shown to possess androgen antagonist activity, to act as inhibitors of sulfotransferase enzymes and to possess genotoxic activity. With the continued use of parabens in the majority of bodycare cosmetics, there is a need to carry out detailed evaluation of the potential for parabens, together with other oestrogenic and genotoxic co-formulants of bodycare cosmetics, to increase female breast cancer incidence, to interfere with male reproductive functions and to influence development of malignant melanoma which has also recently been shown to be influenced by oestrogenic stimulation. Copyright (C) 2008 John Wiley & Sons, Ltd.

The significance of "nonsignificance" in randomized controlled studies: a discussion inspired by a double-blinded study on St. John's Wort (Hypericum perforatum L.) for premenstrual symptoms

Objectives: This study aimed to investigate the efficacy of St. John's wort extract (SJW) as a treatment for premenstrual symptoms. Design: The study was a randomized, double-blinded, placebo-controlled trial, with two parallel treatment groups. After a no-treatment baseline cycle, volunteers were randomized to either SJW or placebo for a further two menstrual cycles. Settings/location: A postal trial conducted from The University of Reading, Berkshire, England. Subjects: One hundred and sixty-nine (169) normally menstruating women who experienced recurrent premenstrual symptoms were recruited onto the study. One hundred and twenty-five (125) completed the protocol and were included in the analysis. Interventions: Six hundred milligrams (600) mg of SJW (standardized to contain 1800 mug of hypericin) or placebo (containing lactose and cellulose). Outcome measure: A menstrual diary was used to assess changes in premenstrual symptoms. The anxiety-related subgroup of symptoms of this instrument was used as the primary outcome measure. Results: After averaging the effects of treatment over both treatment cycles it was found that there was a trend for SJW to be superior to placebo. However, this finding was not statistically significant. Conclusion: The possibility that this nonsignificant finding resulted from insufficient statistical power in the study, rather than a lack of efficacy of SJW, is discussed. Following this discussion the recommendation is made that, in future, similar studies should be powered to detect a minimum clinically relevant difference between treatments.

Metal complexes of cyclen and cyclam derivatives useful for medical applications: a discussion based on thermodynamic stability constants and structural data

A series of the most common chelators used in magnetic resonance imaging ( MRI) and in radiopharmaceuticals for medical diagnosis and tumour therapy, H(4)dota, H(4)teta, H(8)dotp and H(8)tetp, is examined from a chemical point of view. Differences between 12- and 14-membered tetraazamacrocyclic derivatives with methylcarboxylate and methylphosphonate pendant arms and their chelates with divalent first-series transition metal and trivalent lanthanide ions are discussed on the basis of their thermodynamic stability constants, X- ray structures and theoretical studies.

Mononuclear and binuclear ruthenium(II) complexes with 4-(phenyl) thiosemicarbazone of benzaldehyde: a discussion on the relative stabilities of the four-membered and five-membered chelate rings formed by the ligand

Three new ruthenium complexes of the formulae cis-[Ru(PPh3)(2)(BzTscbz)(2)] (1a), [Ru-2(PPh3)(2)(BzTscbz)(4)] (1b) and [Ru(PPh3)(2)(BzTscHbz)(2)](ClO4)(2) (2) [BzTscHbz = 4-(phenyl) thiosemicarbazone of benzaldehyde] have been synthesized and characterized by various physicochemical methods including X-ray structure determinations for 1a and 1b. The relative stabilities of the four-membered versus five-membered chelate rings formed by the deprotonated ligand BzTscbz are discussed on the basis of the experimental results and some semi-empirical as well as DFT calculations. (c) 2005 Elsevier Ltd. All rights reserved.

The significance of "nonsignificance" in randomized controlled studies: a discussion inspired by a double-blinded study on St. John's Wort (Hypericum perforatum L.) for premenstrual symptoms

Objectives: This study aimed to investigate the efficacy of St. John's wort extract (SJW) as a treatment for premenstrual symptoms. Design: The study was a randomized, double-blinded, placebo-controlled trial, with two parallel treatment groups. After a no-treatment baseline cycle, volunteers were randomized to either SJW or placebo for a further two menstrual cycles. Settings/location: A postal trial conducted from The University of Reading, Berkshire, England. Subjects: One hundred and sixty-nine (169) normally menstruating women who experienced recurrent premenstrual symptoms were recruited onto the study. One hundred and twenty-five (125) completed the protocol and were included in the analysis. Interventions: Six hundred milligrams (600) mg of SJW (standardized to contain 1800 mug of hypericin) or placebo (containing lactose and cellulose). Outcome measure: A menstrual diary was used to assess changes in premenstrual symptoms. The anxiety-related subgroup of symptoms of this instrument was used as the primary outcome measure. Results: After averaging the effects of treatment over both treatment cycles it was found that there was a trend for SJW to be superior to placebo. However, this finding was not statistically significant. Conclusion: The possibility that this nonsignificant finding resulted from insufficient statistical power in the study, rather than a lack of efficacy of SJW, is discussed. Following this discussion the recommendation is made that, in future, similar studies should be powered to detect a minimum clinically relevant difference between treatments.

Childhood obesity: should primary school children be routinely screened? A systematic review and discussion of the evidence

Background: Population monitoring has been introduced in UK primary schools in an effort to track the growing obesity epidemic. It has been argued that parents should be informed of their child's results, but is there evidence that moving from monitoring to screening would be effective? We describe what is known about the effectiveness of monitoring and screening for overweight and obesity in primary school children and highlight areas where evidence is lacking and research should be prioritised. Design: Systematic review with discussion of evidence gaps and future research. Data sources: Published and unpublished studies ( any language) from electronic databases ( inception to July 2005), clinical experts, Primary Care Trusts and Strategic Health Authorities, and reference lists of retrieved studies. Review methods: We included any study that evaluated measures of overweight and obesity as part of a population-level assessment and excluded studies whose primary outcome measure was prevalence. Results: There were no trials assessing the effectiveness of monitoring or screening for overweight and obesity. Studies focussed on the diagnostic accuracy of measurements. Information on the attitudes of children, parents and health professionals to monitoring was extremely sparse. Conclusions: Our review found a lack of data on the potential impact of population monitoring or screening for obesity and more research is indicated. Identification of effective weight reduction strategies for children and clarification of the role of preventative measures are priorities. It is difficult to see how screening to identify individual children can be justified without effective interventions.

Performance of asynchronous channel assignment scheme in non-uniform and dynamic topology WLANs

Dense deployments of wireless local area networks (WLANs) are fast becoming a permanent feature of all developed cities around the world. While this increases capacity and coverage, the problem of increased interference, which is exacerbated by the limited number of channels available, can severely degrade the performance of WLANs if an effective channel assignment scheme is not employed. In an earlier work, an asynchronous, distributed and dynamic channel assignment scheme has been proposed that (1) is simple to implement, (2) does not require any knowledge of the throughput function, and (3) allows asynchronous channel switching by each access point (AP). In this paper, we present extensive performance evaluation of this scheme when it is deployed in the more practical non-uniform and dynamic topology scenarios. Specifically, we investigate its effectiveness (1) when APs are deployed in a nonuniform fashion resulting in some APs suffering from higher levels of interference than others and (2) when APs are effectively switched `on/off' due to the availability/lack of traffic at different times, which creates a dynamically changing network topology. Simulation results based on actual WLAN topologies show that robust performance gains over other channel assignment schemes can still be achieved even in these realistic scenarios.