Metalloestrogens: an emerging class of inorganic xenoestrogens with potential to add to the oestrogenic burden of the human breast

Many compounds in the environment have been shown capable of binding to cellular oestrogen receptors and then mimicking the actions of physiological oestrogens. The widespread origin and diversity in chemical structure of these environmental oestrogens is extensive but to date such compounds have been organic and in particular phenolic or carbon ring structures of varying structural complexity. Recent reports of the ability of certain metal ions to also bind to oestrogen receptors and to give rise to oestrogen agonist responses in vitro and in vivo has resulted in the realisation that environmental oestrogens can also be inorganic and such xenoestrogens have been termed metalloestrogens. This report highlights studies which show metalloestrogens to include aluminium, antimony, arsenite, barium, cadmium, chromium (Cr(II)), cobalt, copper, lead, mercury, nickel, selenite, tin and vanadate. The potential for these metal ions to add to the burden of aberrant oestrogen signalling within the human breast is discussed. Copyright (c) 2006 John Wiley & Sons, Ltd.

Excess burden of constipation in Parkinson's disease: A pilot study

An analysis was undertaken of clinic-based questionnaires that asked people with Parkinson's disease and a control group of older people without a known neurological condition about their experiences of constipation. People with Parkinson's disease report higher constipation on a validated objective measure, the Rome criterion (59% vs. 20.9%); a behavioral indicator, laxative-taking (38.4% vs. 14.2%); and subjective self-report of being always or often concerned by it (33.4% vs. 6.1%). Many people with Parkinson's disease experience constipation problems but they may not bring these to the attention of their healthcare providers. More research is required to understand the causes and management options. (C) 2006 Movement Disorder Society.

Rapid-onset opioids and the management of episodic pain

This is the fourth in a short series of articles that focus on what GPs should consider when monitoring and prescribing specialist-initiated palliative-care medicines. Here, the authors summarise the key issues around the use of apid onset opioids in palliative care.

HDAC inhibitors attenuate the development of hypersensitivity in models of neuropathic pain

Histone deacetylase inhibitors (HDACIs) interfere with the epigenetic process of histone acetylation and are known to have analgesic properties in models of chronic inflammatory pain. The aim of this study was to determine whether these compounds could also affect neuropathic pain. Different class I HDACIs were delivered intrathecally into rat spinal cord in models of traumatic nerve injury and antiretroviral drug-induced peripheral neuropathy (stavudine, d4T). Mechanical and thermal hypersensitivity was attenuated by 40% to 50% as a result of HDACI treatment, but only if started before any insult. The drugs globally increased histone acetylation in the spinal cord, but appeared to have no measurable effects in relevant dorsal root ganglia in this treatment paradigm, suggesting that any potential mechanism should be sought in the central nervous system. Microarray analysis of dorsal cord RNA revealed the signature of the specific compound used (MS-275) and suggested that its main effect was mediated through HDAC1. Taken together, these data support a role for histone acetylation in the emergence of neuropathic pain.

The representation of bodily pain in late nineteenth-century English culture

This book deals with bodily pain in the late Victorian period, considering the ways in which its understanding is shaped by medicine and theology.

Individual differences in the effects of perceived controllability on pain perception: critical role of the prefrontal cortex

The degree to which perceived controllability alters the way a stressor is experienced varies greatly among individuals. We used functional magnetic resonance imaging to examine the neural activation associated with individual differences in the impact of perceived controllability on self-reported pain perception. Subjects with greater activation in response to uncontrollable (UC) rather than controllable (C) pain in the pregenual anterior cingulate cortex (pACC), periaqueductal gray (PAG), and posterior insula/SII reported higher levels of pain during the UC versus C conditions. Conversely, subjects with greater activation in the ventral lateral prefrontal cortex (VLPFC) in anticipation of pain in the UC versus C conditions reported less pain in response to UC versus C pain. Activation in the VLPFC was significantly correlated with the acceptance and denial subscales of the COPE inventory [Carver, C. S., Scheier, M. F., & Weintraub, J. K. Assessing coping strategies: A theoretically based approach. Journal of Personality and Social Psychology, 56, 267–283, 1989], supporting the interpretation that this anticipatory activation was associated with an attempt to cope with the emotional impact of uncontrollable pain. A regression model containing the two prefrontal clusters (VLPFC and pACC) predicted 64% of the variance in pain rating difference, with activation in the two additional regions (PAG and insula/SII) predicting almost no additional variance. In addition to supporting the conclusion that the impact of perceived controllability on pain perception varies highly between individuals, these findings suggest that these effects are primarily top-down, driven by processes in regions of the prefrontal cortex previously associated with cognitive modulation of pain and emotion regulation.

Preserved emotional awareness of pain in a patient with extensive bilateral damage to the insula, anterior cingulate, and amygdala

Functional neuroimaging investigations of pain have discovered a reliable pattern of activation within limbic regions of a putative "pain matrix" that has been theorized to reflect the affective dimension of pain. To test this theory, we evaluated the experience of pain in a rare neurological patient with extensive bilateral lesions encompassing core limbic structures of the pain matrix, including the insula, anterior cingulate, and amygdala. Despite widespread damage to these regions, the patient's expression and experience of pain was intact, and at times excessive in nature. This finding was consistent across multiple pain measures including self-report, facial expression, vocalization, withdrawal reaction, and autonomic response. These results challenge the notion of a "pain matrix" and provide direct evidence that the insula, anterior cingulate, and amygdala are not necessary for feeling the suffering inherent to pain. The patient's heightened degree of pain affect further suggests that these regions may be more important for the regulation of pain rather than providing the decisive substrate for pain's conscious experience.

World Health Organization dietary norms: a quantitative evaluation of potential consumption impacts in the United States, United Kingdom, and France

The member countries of the World Health Organization have endorsed its Global Strategy on Diet, Physical Activity, and Health. We assess the potential consumption impacts of these norms in the United States, France, and the United Kingdom using a mathematical programming approach. We find that adherence would involve large reductions in the consumption of fats and oils accompanying large rises in the consumption of fruits, vegetables, and cereal. Further, in the United Kingdom and the United States, but not France, sugar intakes would have to shrink considerably. Focusing on sub-populations within each country, we find that the least educated, not necessarily the poorest, would have to bear the highest burden of adjustment.

Food consumption impacts of adherence to dietary norms in the United States: a quantitative assessment

Promotion of adherence to healthy-eating norms has become an important element of nutrition policy in the United States and other developed countries. We assess the potential consumption impacts of adherence to a set of recommended dietary norms in the United States using a mathematical programming approach. We find that adherence to recommended dietary norms would involve significant changes in diets, with large reductions in the consumption of fats and oils along with large increases in the consumption of fruits, vegetables, and cereals. Compliance with norms recommended by the World Health Organization for energy derived from sugar would involve sharp reductions in sugar intakes. We also analyze how dietary adjustments required vary across demographic groups. Most socio-demographic characteristics appear to have relatively little influence on the pattern of adjustment required to comply with norms, Income levels have little effect on required dietary adjustments. Education is the only characteristic to have a significant influence on the magnitude of adjustments required. The least educated rather than the poorest have to bear the highest burden of adjustment. Out- analysis suggests that fiscal measures like nutrient-based taxes may not be as regressive as commonly believed. Dissemination of healthy-eating norms to the less educated will be a key challenge for nutrition policy.

Food consumption impacts of adherence to dietary norms in the United States: a quantitative assessment

Promotion of adherence to healthy-eating norms has become an important element of nutrition policy in the United States and other developed countries. We assess the potential consumption impacts of adherence to a set of recommended dietary norms in the United States using a mathematical programming approach. We find that adherence to recommended dietary norms would involve significant changes in diets, with large reductions in the consumption of fats and oils along with large increases in the consumption of fruits, vegetables, and cereals. Compliance with norms recommended by the World Health Organization for energy derived from sugar would involve sharp reductions in sugar intakes. We also analyze how dietary adjustments required vary across demographic groups. Most socio-demographic characteristics appear to have relatively little influence on the pattern of adjustment required to comply with norms, Income levels have little effect on required dietary adjustments. Education is the only characteristic to have a significant influence on the magnitude of adjustments required. The least educated rather than the poorest have to bear the highest burden of adjustment. Out- analysis suggests that fiscal measures like nutrient-based taxes may not be as regressive as commonly believed. Dissemination of healthy-eating norms to the less educated will be a key challenge for nutrition policy.

An assessment of the potential consumption impacts of WHO dietary norms in OECD countries

The member countries of the World Health Organization (WHO) have recently endorsed its global strategy on diet, physical activity and health. The strategy emphasises the need to limit the consumption of saturated fats and trans-fatty acids, salt and sugars, and to increase consumption of fruits and vegetables in order to combat the growing burden of non-communicable diseases. This paper attempts a broad quantitative assessment of the consumption impacts of these norms in OECD countries using a mathematical programming approach. We find that adherence to the WHO norms would involve a significant decrease in the consumption of vegetable oils (30%), dairy products (28%), sugar (24%), animal fats (30%) and meat (pig meat, 13.5%, mutton and goat 14.5%) and a significant increase in the human consumption of cereals (31%), fruits (25%) and vegetables (21%). (c) 2005 Elsevier Ltd. All rights reserved.

Comparison of the global gene expression profiles produced by methylparaben, n-butylparaben and 17 beta-oestradiol in MCF7 human breast cancer cells

Since the alkyl esters of p-hydroxybenzoic acid (parabens) can be measured intact in the human breast and possess oestrogenic properties, it has been suggested that they could contribute to an aberrant burden of oestrogen signalling in the human breast and so play a role in the rising incidence of breast cancer. However, although parabens have been shown to regulate a few single genes (reporter genes, pS2, progesterone receptor) in a manner similar to that of 17 beta-oestradiol, the question remains as to the full extent of the similarity in the overall gene profile induced in response to parabens compared with 17 beta-oestradiol. The GE-Amersham CodeLink 20 K human expression microarray system was used to profile the expression of 19881 genes in MCF7 human breast cancer cells following a 7-day exposure to 5 x 10(-4) m methylparaben, 10(-5) m n-butylparaben and 10(-8) m 17 beta-oestradiol. At these concentrations, the parabens gave growth responses in MCF7 cells of similar magnitude to 17 beta-oestradiol. The study identified genes which are upregulated or downregulated to a similar extent by methylparaben, n-butylparaben and 17 beta-oestradiol. However, the majority of genes were not regulated in the same way by all three treatments. Some genes responded differently to parabens from 17 beta-oestradiol, and furthermore, differences in expression of some genes could be detected even between the two individual parabens. Therefore, although parabens possess oestrogenic properties, their mimicry in terms of global gene expression patterns is not perfect and differences in gene expression profiles could result in consequences to the cells that are not identical to those following exposure to 17 beta-oestradiol. Copyright (c) 2006 John Wiley & Sons, Ltd.

Effect of viral load on the outcome of herpes zoster

Varicella-zoster virus (VZV) is a member of the Herpesviridae family, primary infection with which causes varicella, more commonly known as chicken pox. Characteristic of members of the alphaherpesvirus subfamily, VZV is neurotropic and establishes latency in sensory neurons. Reactivation of VZV causes herpes zoster, also known as shingles. The most frequent complication following zoster is chronic and often debilitating pain called postherpetic neuralgia (PHN), which can last for months after the disappearance of a rash. During episodes of acute zoster, VZV viremia occurs in some, but not all, patients; however, the effect of the viral load on the disease outcome is not known. Here we describe the development of a highly specific, sensitive, and reproducible real-time PCR assay to investigate the factors that may contribute to the presence and levels of baseline viremia in patients with zoster and to determine the relationship between viremia and the development and persistence of PHN. VZV DNA was detected in the peripheral blood mononuclear cells (PBMCs) of 78% of patients with acute zoster and in 9% of healthy asymptomatic blood donors. The presence of VZV in the PBMCs of patients with acute zoster was independently associated with age and being on antivirals but not with gender, immune status, extent of rash, the age of the rash at the time of blood sampling, having a history of prodromal pain, or the extent of acute pain. Prodromal pain was significantly associated with higher baseline viral loads. Viral load levels were not associated with the development or persistence of PHN at 6, 12, or 26 weeks.

The gas-phase ozonolysis of unsaturated volatile organic compounds in the troposphere

The gas-phase reactions of ozone with unsaturated hydrocarbons are significant sources of free radical species (including (OH)-O-center dot) and particulate material in the Earth's atmosphere. In this tutorial review, the kinetics, products and mechanisms of these reactions are examined, starting with a discussion of the original mechanism proposed by Criegee and following with a summary presentation of the complex, free radical-mediated reactions of carbonyl oxide (Criegee) intermediates. The contribution of ozone-terpene reactions to the atmospheric burden of secondary organic aerosol material is also discussed from the viewpoint of the formation of non-volatile organic acid products from the complex chemistry of ozone with alpha-pinene. Throughout the article, currently accepted understanding is supported through the presentation of key experimental results, and areas of persistent or new uncertainty are highlighted.

Commentary on 'Prebiotics, immune function, infection and inflammation: a review of the evidence'

There is a growing awareness that the gut microbiota and an appropriately functioning immune system play an important role in maintaining human health. Recent population statistics have highlighted some worrying trends, specifically that there is a growing burden of immunological disease in Western populations, that Western populations are ageing, and that obesity, with its strong inflammatory component, is reaching epidemic proportions.