Effects of metopirone on the structure of endocrine glands in the male lizard,Cnemidophorus l. lemniscatus (L.)

Summary Adrenals, pituitary glands, thyroids, testes and kidneys of metopirone-treated and control male lizards were studied by light microscopy. Pituitary-interrenal axis: A great hypertrophy and hyperplasia of the interrenal cells and the pituitary corticotrophs were found in the experimental group. Pituitary-thyroid axis: Metopirone-treated animals showed a moderate hypertrophy and degranulation of pituitary thyrotrophs, and signs of uneven hyperactivity of the thyroid. Pituitary-testicular axis: By effect of metopirone, a marked regression of pituitary interstitiotrophs and a virtual disappearance of the testicular interstitial gland took place. The second portion of the kidney sexual segments appeared degranulated as in castrated animals. The pituitary folliculotrophs and the seminiferous epithelium of the testis did not show alterations.     

The Effects of the Organic Flame‐Retardant 1,2‐Dibromo‐4‐(1,2‐dibromoethyl) Cyclohexane (TBECH) on Androgen Signaling in Human Prostate Cancer Cell Lines

The effects of the organic flame retardant 1,2‐Dibromo‐4‐(1,2‐dibromoethyl) cyclohexane (TBECH) on androgen receptor target gene expression were examined in the human LNCaP prostate cancer cell line. While γ‐/δ‐TBECH alone led to a significant increase in prostate‐specific antigen (PSA) mRNA accumulation, both the α‐/‐TBECH and γ‐/δ‐TBECH mixtures repressed androgen‐inducible PSA mRNA and protein accumulation in human LNCaP cells. Thus, we hypothesize that isomeric mixtures of TBECH may act as partial agonists of the androgen receptor.     

Greenhouse Gas and Energy Life Cycle Assessment of Pine Chemicals Derived from Crude Tall Oil and Their Substitutes

Pine chemicals are co‐products of papermaking that are upgraded into diverse products from inks to adhesives. They can also be utilized for energy purposes. This research investigates the carbon and energy life cycle assessment (LCA) of pine chemicals derived from crude tall oil (CTO). The study goals are to determine the cradle‐to‐gate carbon and energy footprint for CTO‐derived chemicals, compare CTO‐derived chemicals to their likely substitutes, and calculate the carbon and energy effects of shifting CTO resources from current chemical production to biodiesel production. The data collected represent 100% of the U.S. and 90% of the European CTO distillation industry for 2011. This analysis is the first industry‐level LCA of pine chemicals. The carbon footprint for CTO‐derived pine chemical products is 50% lower than the likely mix of alternative products, including hydrocarbon resins for rubber, ink, and adhesive, alkyl succinic anhydride for paper size, and heavy fuel oil for heat. Current and proposed European policies could result in CTO being classified as renewable biomass for energy production, creating incentive to convert CTO into fuel rather than chemicals. The differences in the carbon and energy footprints of utilizing CTO for biodiesel versus chemicals are not meaningful when comparing European CTO biodiesel, which displaces conventional diesel, to European CTO‐derived chemicals, which displace the previously discussed substitutes. Therefore, there is no additional carbon or energy benefit that accrues by diverting CTO from current chemical feedstock applications to use for biodiesel production in Europe.     

Characterizing the effect of endocrine disruptors on human health: The role of epidemiological cohorts

Research on endocrine disruptors (EDs) developed from numerous disciplines. In this concert of disciplines, epidemiology is central to inform on the relevance for humans of mechanisms and dose-response functions identified in animals, to characterize the health impact (number of attributable disease cases), the cost associated with ED exposure, and the efficiency of the measures taken to limit exposure. Here, we present epidemiological tools to draw valid inference regarding effects of potential EDs. Epidemiology is generally observational, requiring care to control confounding bias. Many potential EDs have a short biological half-life; approaches relying on repeated biospecimens sampling allow limiting exposure misclassification and the resulting bias. For non-persistent compounds, couple–child cohorts are a central study design. Cohorts can now rely on molecular biology approaches to characterize exposures and intermediate pathways, which corresponds to the advent of molecular epidemiology and allows stronger interactions between epidemiology, toxicology, and molecular epidemiology to characterize the health effects of EDs.     

Structural and functional evidences for the interactions between nuclear hormone receptors and endocrine disruptors at low doses

Endocrine-disrupting chemicals (EDCs) represent a broad class of exogenous substances that cause adverse effects in the endocrine system mainly by interacting with nuclear hormone receptors (NRs). Humans are generally exposed to low doses of pollutants, and current researches aim at deciphering the mechanisms accounting for the health impact of EDCs at environmental concentrations. Our correlative analysis of structural, interaction and cell-based data has revealed a variety of, sometimes unexpected, binding modes, reflecting a wide range of EDC affinities and specificities. Here, we present a few representative examples to illustrate various means by which EDCs achieve high-affinity binding to NRs. These examples include the binding of the mycoestrogen α-zearalanol to estrogen receptors, the covalent interaction of organotins with the retinoid X- and peroxisome proliferator-activated receptors, and the cooperative binding of two chemicals to the pregnane X receptor. We also discuss some hypotheses that could further explain low-concentration effects of EDCs with weaker affinity towards NRs.     

无功能垂体瘤的术后评估

垂体瘤是常见的颅内良性肿瘤,患病率高,预后较好。在我国,其发病率仅次于胶质瘤和脑膜瘤。无功能垂体瘤约占垂体瘤22.5%,手术是其首选的治疗方式,以解除肿瘤的占位效应,减少对正常垂体组织的压迫。然而手术本身可能引起垂体功能减退,术后应对患者垂体功能的监测并予以处理。同时,由于手术及患者个体身体、心理原因,患者术后的生活质量也越来越受到重视。本文综述了无功能垂体瘤患者术后各内分泌轴功能的临床检测方法,以帮助临床医生对术后患者的垂体功能进行评估并重建;同时对术后患者生活质量的评估加以讨论,帮助指导患者恢复生理及心理健康。     

Comparison of ESR1 Mutations in Tumor Tissue and Matched Plasma Samples from Metastatic Breast Cancer Patients

BACKGROUND: ESR1 mutation in circulating cell-free DNA (cfDNA) is emerging as a noninvasive biomarker of acquired resistance to endocrine therapy, but there is a paucity of data comparing the status of ESR1 gene in cfDNA with that in its corresponding tumor tissue. The objective of this study is to validate the degree of concordance of ESR1 mutations between plasma and tumor tissue. METHODS: ESR1 ligand-binding domain mutations Y537S, Y537N, Y537C, and D538G were analyzed using droplet digital PCR in 35 patients with metastatic breast cancer (MBC) (35 tumor tissue samples and 67 plasma samples). RESULTS: Of the 35 paired samples, 26 (74.3%) were concordant: one patient had detectable ESR1 mutations both plasma (ESR1 Y537S/Y537N) and tumor tissue (ESR1 Y537S/Y537C), and 25 had WT ESR1 alleles in both. Nine (25.7%) had discordance between the plasma and tissue results: five had mutations detected only in their tumor tissue (two Y537S, one Y537C, one D538G, and one Y537S/Y537N/D538G), and four had mutations detected only in their plasma (one Y537S, one Y537N, and two Y537S/Y537N/D538G). Furthermore, longitudinal plasma samples from 19 patients were used to assess changes in the presence of ESR1 mutations during treatment. Eleven patients had cfDNA ESR1 mutations over the course of treatment. A total of eight of 11 patients with MBC with cfDNA ESR1 mutations (72.7%) had the polyclonal mutations. CONCLUSION: We have shown the independent distribution of ESR1 mutations between plasma and tumor tissue in 35 patients with MBC.     

Establishing Life Cycle Inventories of Chemicals Based on Differing Data Availability (9 pp)

Goal, Scope and Background In contrast to inventory data of energy and transport processes, public inventory data of chemicals are rather scarce. Chemicals are important to consider in LCA, because they are used in the production of many, if not all, products. Moreover, they may cause considerable environmental impacts. For these reasons, it was one goal of the new ecoinvent database to provide LCI data on chemicals. In this paper, the methods and procedures used for establishing LCIs of chemicals in ecoinvent are presented.Methods Three different approaches are suggested for situations of differing data availability. First, in the case of good data availability, the general quality guidelines of ecoinvent can be followed. Second, a procedure is proposed for the translation of aggregated inventory data (cumulative LCI results) from industry into the ecoinvent format. This approach was used, if adequate unit process data was not available. Third, a procedure is put forward for estimating inventory data using stoichiometric equations from technical literature as a main information source. This latter method was used if no other information was available. The application of each of the three procedures is illustrated with the help of a case study.Results and Conclusion When sufficient information is available to follow the general guidelines of ecoinvent, the resulting dataset is characterized by a high degree of detail, and it is thus of high quality. For chemicals, however, the application of the standard procedure is possible in only a few cases. When using industrial data, the main drawback is the fact that those data are often available only as aggregated data, thus being out of tune with the quality guidelines of ecoinvent and its main aim, the harmonization of LCI data. As a third approach, the use of the stoichiometric reaction equation is used for the compilation of LCI datasets of chemicals. This approach represents an alternative to neglecting chemicals completely, but it contains a high risk to not consider important aspects of the life cycle of the respective substance.Outlook Further work in the area of chemicals should focus on an improvement of datasets, so far established by either of the two estimation procedures (APME method; estimation based on technical literature) described. Besides the improvement of already established inventories, the compilation of further harmonized inventories of specific types of chemicals (e.g. solvents) or of chemicals for new industrial sectors (e.g. electronics industry) are in discussion.     

Early learning of volatile chemical cues leads to interspecific recognition between two ant species

Nestmate recognition in social insects generally involves matching a label to the template that is acquired through the early learning of non-volatile cuticular hydrocarbon cues. However, a possible role of the volatile chemical cues that exist in the nest, and which may also affect template formation, has not been studied. We investigated this possibility using experimental mixedspecies groups composed of the two ant species Manica rubida and Formica selysi. The experimental set-up either allowed full contact between workers of the two species or interspecific contact was hindered or prohibited by a single or a double mesh. After three months, workers of M. rubida ants were selected as focal ants for aggression tests including the following target ants: F. selysi workers from the same mixed-species group (for each of the three rearing conditions) or from a single-species group (control). Workers of M. rubida were always amicable towards their group-mates, irrespective of the experimental group (contact, single or double mesh). However, M. rubida that were not imprinted on F. selysi, expressed high levels of aggression towards the non-familiar F. selysi workers. The finding that F. selysi workers in the mixed-species groups appeared familiar to their M. rubida group-mates even without physical contact between them, suggests that the volatile cues produced by F. selysi affected nestmate recognition in M. rubida. In an attempt to identify these volatile cues we performed SPME analysis of the head space over groups of F. selysi workers. The findings revealed that F. selysi Dufour’s gland constituents, with undecane as the major product, are released into the head space, rendering them likely candidates to affect template formation in M. rubida. Analysis of Dufour’s gland secretion of F. selysi revealed a series of volatile alkanes, including undecane as a major product. These alkanes were not present in the glandular secretion of M. rubida, whose secretion was mainly composed of isomers of farnesene. We therefore hypothesize that callow M. rubida workers in the mixed-species groups had become imprinted by the above alkanes (in particular undecane, being the major heterospecific volatile in the head space) and incorporated them into their own template. Received 18 October 2007; revised 2 January 2008; accepted 7 January 2008.     

Systemic administration of diarylpropionitrile (DPN) or phytoestrogens does not affect anxiety-related behaviors in gonadally intact male rats

The development of highly selective agonists for the two major subforms of the estrogen receptor (ERα and ERβ) has produced new experimental methodologies for delineating the distinct functional role each plays in neurobehavioral biology. It has also been suggested that these compounds might have the potential to treat estrogen influenced behavioral disorders, such as anxiety and depression. Prior work has established that the ERβ agonist, diarylpropionitrile (DPN) is anxiolytic in gonadectomized animals of both sexes, but whether or not this effect persists in gonadally intact individuals is unknown. Isoflavone phytoestrogens, also potent but less selective ERβ agonists, have also been shown to influence anxiety in multiple species and are becoming more readily available to humans as health supplements. Here we determined the effects of 0.5, 1 or 2 mg/kg DPN, 1 mg/kg of the ERα agonist propyl-pyrazole-triol (PPT), 3 or 20 mg/kg of the isoflavone equol (EQ) and 3 or 20 mg/kg of the isoflavone polyphenol resveratrol (RES) on anxiety behavior in the gonadally intact male rat using the light/dark box and the elevated plus maze. We first determined that DPN can be successfully administered either orally or by subcutaneous injection, although plasma DPN levels are significantly lower if given orally. Once injected, plasma levels peak rapidly and then decline to baseline levels within 3 h of administration. For the behavioral studies, all compounds were injected and the animals were tested within 3 h of treatment. None of the compounds, at any of the doses, significantly altered anxiety-related behavior. Plasma testosterone levels were also not significantly altered suggesting that these compounds do not interfere with endogenous androgen levels. The results suggest that the efficacy of ERβ agonists may depend on gonadal status. Therefore the therapeutic potential of ERβ selective agonists to treat mood disorders may be limited.