Re-evaluation of the first synthetic estrogen, 1-keto-1,2,3,4-tetrahydrophenanthrene, and bisphenol A, using both the ovariectomised rat model used in 1933 and additional assays

1-Keto-1,2,3,4-tetrahydrophenanthrene (THP-1) was reported by Cook et al in 1933 as the first synthetic estrogen. Estrogenic activity was assessed by the induction of vaginal cornification in ovariectomised rats. The corresponding 4-isomer (THP-4) was shown to be inactive. Both chemicals have been re-synthesised and assessed for hormonal activity. Each chemical bound weakly and to the same extent to isolated estrogen receptors, but only at high concentrations. However, they each lacked estrogenic or anti-estrogenic activity when evaluated in vitro using a yeast hER assay, and both failed to induce vaginal cornification or uterotrophic effects in ovariectomised rats. THP-1, and to a lesser extent THP-4, were shown to possess weak androgenic and anti-androgenic activity in vitro when evaluated using an hAR yeast assay. Estrogenic activity for bisphenol A (BPA) was subsequently demonstrated by Dodds and Lawson (1936) using the same ovariectomised rat protocol, and this activity has been confirmed and supplemented by positive uterotrophic effects for BPA in the same bioassays. The present results illustrate the complexity of deriving conclusions regarding the hormonal activities of chemicals. First, some activities observed in isolated hormonal receptor binding assays may not be expressed in functional hormonal assays. This indicates the need for functional hormonal assays in any screening programme. Second, that activities observed for a chemical in one hormonal assay may not be reflected in related hormonal assays. This indicates the need to define assay protocols with some precision when incorporating them into screening batteries. Finally, that some literature reports of hormonal activity for chemicals may not be capable of independent confirmation under apparently identical conditions of test. This illustrates the need to use lists of hormonally active chemicals with car

The case for the multi-species ecological system, with special reference to succession and stability

Multi-species life support system based on ecological theor

The rodent uterotrophic assay: Critical protocol features, studies with nonyl phenols, and comparison with a yeast estrogenicity assay

The major protocol features of the immature rat uterotrophic assay have been evaluated using a range of reference chemicals. The protocol variables considered include the selection of the test species and route of chemical administration, the age of the test animals, the maintenance diet used, and the specificity of the assay for estrogens. It is concluded that three daily oral administrations of test chemicals to 21- to 22-day-old rats, followed by determination of absolute uterus weights on the fourth day, provide a sensitive and toxicologically relevant in vivo estrogenicity assay. Rats are favored over mice for reasons of toxicological practice, but the choice of test species is probably not a critical protocol variable, as evidenced by the similar sensitivity of rats and mice to the uterotrophic activity of methoxychlor. Vaginal opening is shown to be a useful, but nondefinitive, adjunct to the uterotrophic assay. The ability of test chemicals to reduce or abolish the uterotrophic response of estradiol is suggested to provide a useful extension of the uterotrophic assay for the purpose of detecting antiestrogens. The results of a series of studies on the environmental estrogen nonyl phenol (NP), and its linear isomer n -nonyl phenol, confirm that branching of the aliphatic side chain is important for activity. 17beta-Desoxyestradiol is shown to be of similar activity to estradiol in the uterotrophic assay and is suggested to represent the "parent" estrogen of NP. Benzoylation of NP and 17-desoxyestradiol did not affect their uterotrophic activity, in contrast to the enhancing effect of benzoylation on estradiol. Selected chemicals shown to be active in the immature rat uterotrophic assay were also evaluated in an in vitro yeast human estrogen receptor transactivation assay. Most of the chemicals gave similar qualitative responses to those seen in the uterotrophic assay, and the detection of the estrogen methoxychlor by the yeast assay evidenced a degree of intrinsic metabolic competence. However, the assay had a reduced ability (compared to rodents) to hydrolyze the benzoate ester of estradiol, and the estrogenic benzoate derivative of NP was not active in the yeast assay. These last results indicate that current metabolic deficiencies of in vitro estrogenicity assays will limit the value of negative data for the immediate future. The results described illustrate the intrinsic complexity of evaluating chemicals for estrogenic activities and confirm the need for rigorous attention to experimental design and criteria for assessing estrogenic activity

Consequences of small storage capacity in nannoplankton pertinent to measurement of primary production in tropical waters

A theory based on the performance of an electrical analogue circuit for balanced ecosystems relates respiration to the storage of labile organic matter during daytime photosynthesis. A very small storage capacitance and time constant may be introduced into the circuit to simulate a nannoplanktonic sygtem. It is found that respiration approaches photosynthesis during the day and almost ceases at night. Consequently, the usual carbon14 measurements of net production, and the conventional light-and-dark-bottle oxygen measurements of net production and nighttime respiration greatly underestimate gross photosy~thesis of tropical seas. An example of this phenomenon is shown in a planktonic brine microcosm

History and philosophy of science in Biology teaching

Neste trabalho, buscamos evidenciar a concepção de História da Biologia que é veiculada nos livros didáticos. Para tanto, analisamos três coleções de livros de Biologia destinados ao Ensino Médio, e alguns livros universitários usados em cursos de formação de professores. Ao analisar este material curricular foi possível observar que a história apresentada é desvinculada do contexto cultural de cada período histórico, o que pode levar o aluno a construir uma falsa representação da ciência e do fazer científico.In this work, we search forto evidences the conception of the History of Biology being is propagated in textbooks. We analyze three Biology book collections designed estined forto middle schooledium education, and some university books used in teacher education courses. When analyzing this curricular material it was possible to observe that the history of biology presented is disengaged from entailedofthe cultural context of each historical period, and this what can lead the student to construct a false representation of science and of scientific meaning making

Continuous Nicotine Exposure Does Not Affect Resurgence of Alcohol Seeking in Rats

Alcohol is the most commonly used drug in the United States and alcohol abuse can lead to alcohol use disorder. Alcohol use disorder is a persistent condition and relapse rates following successful remission are high. Many factors have been associated with relapse for alcohol use disorder, but identification of these factors has not been well translated into preventative utility. One potentially important factor, concurrent nicotine use, has not been well investigated as a causal factor in relapse for alcohol use disorder. Nicotine increases the value of other stimuli in the environment and may increase the value of alcohol. If nicotine increases the value of alcohol, then nicotine use during and after treatment may make relapse more probable. In the current study, we investigated the effect of continuous nicotine exposure (using osmotic minipumps to deliver nicotine or saline, depending on group, at a constant rate for 28 days) on resurgence of alcohol seeking in rats. Resurgence is a type of relapse preparation that consists of three phases: Baseline, Alternative Reinforcement, and Resurgence Testing. During Baseline, target responses produced a dipper of alcohol. During Alternative Reinforcement, target responses were extinguished and responses on a chain produced a chocolate pellet. During Resurgence Testing, responses on the chain were also extinguished and a return to responding on the target lever was indicative of resurgence. Multilevel modeling was used to analyze the effect of nicotine on resurgence. Both the nicotine and saline group showed resurgence of alcohol seeking, but there was no difference in the degree of resurgence across groups. Future directions could involve testing alternative drug delivery techniques

Evolution of avalanche conducting states in electrorheological liquids

Charge transport in electrorheological fluids is studied experimentally under strongly nonequlibrium conditions. By injecting an electrical current into a suspension of conducting nanoparticles we are able to initiate a process of self-organization which leads, in certain cases, to formation of a stable pattern which consists of continuous conducting chains of particles. The evolution of the dissipative state in such system is a complex process. It starts as an avalanche process characterized by nucleation, growth, and thermal destruction of such dissipative elements as continuous conducting chains of particles as well as electroconvective vortices. A power-law distribution of avalanche sizes and durations, observed at this stage of the evolution, indicates that the system is in a self-organized critical state. A sharp transition into an avalanche-free state with a stable pattern of conducting chains is observed when the power dissipated in the fluid reaches its maximum. We propose a simple evolution model which obeys the maximum power condition and also shows a power-law distribution of the avalanche sizes.Comment: 15 pages, 6 figure