The estrogenic activity of phthalate esters in vitro

A large number of phthalate esters were screened for estrogenic activity using a recombinant yeast screen. a selection of these was also tested for mitogenic effect on estrogen-responsive human breast cancer cells. A small number of the commercially available phthalates tested showed extremely weak estrogenic activity. The relative potencies of these descended in the order butyl benzyl phthalate (BBP) > dibutyl phthalate (DBP) > diisobutyl phthalate (DIBP) > diethyl phthalate (DEP) > diisiononyl phthalate (DINP). Potencies ranged from approximately 1 x 10(6) to 5 x 10(7) times less than 17beta-estradiol. The phthalates that were estrogenic in the yeast screen were also mitogenic on the human breast cancer cells. Di(2-ethylhexyl) phthalate (DEHP) showed no estrogenic activity in these in vitro assays. A number of metabolites were tested, including mono-butyl phthalate, mono-benzyl phthalate, mono-ethylhexyl phthalate, mon-n-octyl phthalate; all were wound to be inactive. One of the phthalates, ditridecyl phthalate (DTDP), produced inconsistent results; one sample was weakly estrogenic, whereas another, obtained from a different source, was inactive. analysis by gel chromatography-mass spectometry showed that the preparation exhibiting estrogenic activity contained 0.5% of the ortho-isomer of bisphenol A. It is likely that the presence of this antioxidant in the phthalate standard was responsible for the generation of a dose-response curve--which was not observed with an alternative sample that had not been supplemented with o,p'-bisphenol A--in the yeast screen; hence, DTDP is probably not weakly estrogenic. The activities of simple mixtures of BBP, DBP, and 17beta-estradiol were assessed in the yeast screen. No synergism was observed, although the activities of the mixtures were approximately additive. In summary, a small number of phthalates are weakly estrogenic in vitro. No data has yet been published on whether these are also estrogenic in vitro. No data has yet been published on whether these are also estrogenic in vivo; this will require tests using different classes of vertebrates and different routes of exposure

Anonymous shell companies: A global audit study and field experiment in 176 countries

To test whether firms behave consistently with international law prohibiting anonymous incorporation, we conducted a global audit study and field experiment, using data from 1639 incorporation firms in 176 countries. We requested anonymous incorporation and randomly assigned references to international law, threat of penalties, norms of appropriate behavior, or a placebo. We find a substantial number of firms willing to flout international standards and show that those in OECD countries proved significantly less compliant with rules than in developing countries or tax havens. Firms in tax havens displayed significantly greater compliance and were sensitive to experimental interventions invoking international law

Generalized information entropies depending only on the probability distribution

Systems with a long-term stationary state that possess as a spatio-temporally fluctuation quantity $\beta$ can be described by a superposition of several statistics, a "super statistics". We consider first, the Gamma, log-normal and $F$-distributions of $\beta$. It is assumed that they depend only on $p_l$, the probability associated with the microscopic configuration of the system. For each of the three $\beta-$distributions we calculate the Boltzmann factors and show that they coincide for small variance of the fluctuations. For the Gamma distribution it is possible to calculate the entropy in a closed form, depending on $p_l$, and to obtain then an equation relating $p_l$ with $\beta E_l$. We also propose, as other examples, new entropies close related with the Kaniadakis and two possible Sharma-Mittal entropies. The entropies presented in this work do not depend on a constant parameter $q$ but on $p_l$. For the $p_l$-Gamma distribution and its corresponding $B_{p_l}(E)$ Boltzmann factor and the associated entropy, we show the validity of the saddle-point approximation. We also briefly discuss the generalization of one of the four Khinchin axioms to get this proposed entropy.Comment: 13 pages, 3 figure

Blood pressure, aortic stiffness, hemodynamics and cognition in twin pairs discordant for type 2 diabetes

Background: Type 2 diabetes (T2D) is associated with an increased risk of cognitive impairment and dementia with poorly understood underlying mechanisms. Objective: We examined the role of blood pressure (BP), aortic stiffness, and hemodynamics in this association. Methods: Cross-sectional sample of late middle-aged twins discordant for T2D from the Australian Twin Registry. Measurements included neuropsychological battery and brain MRI including arterial spin labelling (ASL) to measure cerebral perfusion. Mobil-o-Graph devices were used to non-invasively obtain 24-hour BP, aortic stiffness, and hemodynamic measures. Using mixed modelling, we studied associations of T2D with cognition, MRI measures, BP, aortic stiffness, and hemodynamics. Results: There were 23 twin pairs with mean age 63.7 (SD = 6.1) years. T2D (β=-0.45, p < 0.001) and age (β=-0.05, p = 0.022) were independently associated with poorer attention but not with memory or perceptual speed. T2D was associated with reduced nocturnal central systolic BP dipping (β=-3.79, p = 0.027), but not with BP, aortic stiffness, cerebral perfusion, or other hemodynamic measures. There was a statistically significant interaction between T2D and central systolic BP dipping in predicting attention scores (both p < 0.05 for the interaction term) whereby there was a positive association between BP dipping and attention scores in those with T2D, but not in those without T2D. Conclusion: We found an association between T2D and reduced nocturnal central systolic dipping, but not with any other measures of BP, stiffness or hemodynamic measures. Further study of the role of nocturnal central BP dipping in the association between T2D and cognitive impairment may help identify potential mechanisms

Quantitative trait loci for bone traits segregating independently of those for growth in an F-2 broiler X layer cross

An F broiler-layer cross was phenotyped for 18 skeletal traits at 6, 7 and 9 weeks of age and genotyped with 120 microsatellite markers. Interval mapping identified 61 suggestive and significant QTL on 16 of the 25 linkage groups for 16 traits. Thirty-six additional QTL were identified when the assumption that QTL were fixed in the grandparent lines was relaxed. QTL with large effects on the lengths of the tarsometatarsus, tibia and femur, and the weights of the tibia and femur were identified on GGA4 between 217 and 249 cM. Six QTL for skeletal traits were identified that did not co-locate with genome wide significant QTL for body weight and two body weight QTL did not coincide with skeletal trait QTL. Significant evidence of imprinting was found in ten of the QTL and QTL x sex interactions were identified for 22 traits. Six alleles from the broiler line for weight- and size-related skeletal QTL were positive. Negative alleles for bone quality traits such as tibial dyschondroplasia, leg bowing and tibia twisting generally originated from the layer line suggesting that the allele inherited from the broiler is more protective than the allele originating from the layer

IUPHAR-DB: An Open-Access, Expert-Curated Resource for Receptor and Ion Channel Research

[Image: see text] This contribution highlights efforts by the International Union of Basic and Clinical Pharmacology (IUPHAR) Nomenclature Committee (NC-IUPHAR) to classify human receptors and ion channels, to document their properties, and to recommend ligands that are useful for characterization. This effort has inspired the creation of an online database (IUPHAR-DB), which is intended to provide free information to all scientists, summarized from primary literature by experts

Oocyst wall formation and composition in coccidian parasites

The oocyst wall of coccidian parasites is a robust structure that is resistant to a variety of environmental and chemical insults. This resilience allows oocysts to survive for long periods, facilitating transmission from host to host. The wall is bilayered and is formed by the sequential release of the contents of two specialized organelles - wall forming body 1 and wall forming body 2 - found in the macrogametocyte stage of Coccidia. The oocyst wall is over 90% protein but few of these proteins have been studied. One group is cysteine-rich and may be presumed to crosslink via disulphide bridges, though this is yet to be investigated. Another group of wall proteins is rich in tyrosine. These proteins, which range in size from 8-31 kDa, are derived from larger precursors of 56 and 82 kDa found in the wall forming bodies. Proteases may catalyze processing of the precursors into tyrosine-rich peptides, which are then oxidatively crosslinked in a reaction catalyzed by peroxidases. In support of this hypothesis, the oocyst wall has high levels of dityrosine bonds. These dityrosine crosslinked proteins may provide a structural matrix for assembly of the oocyst wall and contribute to its resilience

Exploring access to end of life care for ethnic minorities with end stage kidney disease through recruitment in action research

BACKGROUND: Variation in provision of palliative care in kidney services and practitioner concerns to provide equitable access led to the development of this study which focussed on the perspectives of South Asian patients and their care providers. As people with a South Asian background experience a higher risk of Type 2 Diabetes (T2DM) and end stage kidney failure (ESKF) compared to the majority population but wait longer for a transplant, there is a need for end of life care to be accessible for this group of patients. Furthermore because non English speakers and people at end of life are often excluded from research there is a dearth of research evidence with which to inform service improvement. This paper aims to explore issues relating to the process of recruitment of patients for a research project which contribute to our understanding of access to end of life care for ethnic minority patients in the kidney setting. METHODS: The study employed an action research methodology with interviews and focus groups to capture and reflect on the process of engaging with South Asian patients about end of life care. Researchers and kidney care clinicians on four NHS sites in the UK recruited South Asian patients with ESKF who were requiring end of life care to take part in individual interviews; and other clinicians who provided care to South Asian kidney patients at end of life to take part in focus groups exploring end of life care issues. In action research planning, action and evaluation are interlinked and data were analysed with emergent themes fed back to care providers through the research cycle. Reflections on the process of patient recruitment generated focus group discussions about access which were analysed thematically and reported here. RESULTS: Sixteen patients were recruited to interview and 45 different care providers took part in 14 focus groups across the sites. The process of recruiting patients to interview and subsequent focus group data highlighted some of the key issues concerning access to end of life care. These were: the identification of patients approaching end of life; and their awareness of end of life care; language barriers and informal carers' roles in mediating communication; and contrasting cultures in end of life kidney care. CONCLUSIONS: Reflection on the process of recruitment in this action research study provided insight into the complex scenario of end of life in kidney care. Some of the emerging issues such as the difficulty identifying patients are likely to be common across all patient groups, whilst others concerning language barriers and third party communication are more specific to ethnic minorities. A focus on South Asian ethnicity contributes to better understanding of patient perspectives and generic concepts as well as access to end of life kidney care for this group of patients in the UK. Action research was a useful methodology for achieving this and for informing future research to include informal carers and other ethnic groups.Peer reviewedFinal Published versio