Comparison of Short-Term Estrogenicity Tests for Identification of Hormone-Disrupting Chemicals

The aim of this study was to compare results obtained by eight different short-term assays of estrogenlike actions of chemicals conducted in 10 different laboratories in five countries. Twenty chemicals were selected to represent direct-acting estrogens, compounds with estrogenic metabolites, estrogenic antagonists, and a known cytotoxic agent. Also included in the test panel were 17β-estradiol as a positive control and ethanol as solvent control. The test compounds were coded before distribution. Test methods included direct binding to the estrogen receptor (ER), proliferation of MCF-7 cells, transient reporter gene expression in MCF-7 cells, reporter gene expression in yeast strains stably transfected with the human ER and an estrogen-responsive reporter gene, and vitellogenin production in juvenile rainbow trout. 17β-Estradiol, 17α-ethynyl estradiol, and diethylstilbestrol induced a strong estrogenic response in all test systems. Colchicine caused cytotoxicity only. Bisphenol A induced an estrogenic response in all assays. The results obtained for the remaining test compounds—tamoxifen, ICI 182.780, testosterone, bisphenol A dimethacrylate, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol dodecylethoxylate, butylbenzylphthalate, dibutylphthalate, methoxychlor, o,p′-DDT, p,p′-DDE, endosulfan, chlomequat chloride, and ethanol—varied among the assays. The results demonstrate that careful standardization is necessary to obtain a reasonable degree of reproducibility. Also, similar methods vary in their sensitivity to estrogenic compounds. Thus, short-term tests are useful for screening purposes, but the methods must be further validated by additional interlaboratory and interassay comparisons to document the reliability of the methods

Quantitative structure-activity relationship for antimalarial activity of artemisinin

The increase in resistance to older drugs and the emergence of new types of infection have created an urgent need for discovery and development of new compounds with antimalarial activity. Quantitative-Structure Activity Relationship (QSAR) methodology has been performed to develop models that correlate antimalarial activity of artemisinin analogs and their molecular structures. In this study, the data set consisted of 197 compounds with their activities expressed as log RA (relative activity). These compounds were randomly divided into training set (n=157) and test set (n=40). The initial stage of the study was the generation of a series of descriptors from three-dimensional representations of the compounds in the data set. Several types of descriptors which include topological, connectivity indices, geometrical, physical properties and charge descriptors have been generated. The number of descriptors was then reduced to a set of relevant descriptors by performing a systematic variable selection procedure which includes zero test, pairwise correlation analysis and genetic algorithm (GA). Several models were developed using different combinations of modelling techniques such as multiple linear regression (MLR) and partial least square (PLS) regression. Statistical significance of the final model was characterized by correlation coefficient, r2 and root-mean-square error calibration, RMSEC. The results obtained were comparable to those from previous study on the same data set with r2 values greater than 0.8. Both internal and external validations were carried out to verify that the models have good stability, robustness and predictive ability. The cross-validated regression coefficient (r2 cv) and prediction regression coefficient (r2 test) for the external test set were consistently greater than 0.7. The QSAR models developed in this study should facilitate the search for new compounds with antimalarial activity

The potential of Symbiont Ba cteria in Melo melo Gastropod found in Pekalongan Waters as a source of MDR antibacterial active compound

The increasing resistance of many pathogenic microorganisms against antibiotics compounds creates an alarming issue in medical world. This concern has created research opportunities in new antibiotics compounds as alternative options. The gastropod Melo melo is a species whose main diet consists of other smaller gastropods. However, Melo-melo does not have any self-defense mechanism save for its thin shell. To protect itself from various pathogenic bacteria existing in its food, Melo melo produces secondary metabolites, which are suspected to contain bioactive compounds with antibacterial properties. This fact puts Melo melo as a marine biota with potential as a source of new antibacterial compounds. This research aims to discover the potency of symbiont bacteria in the gastropod Melo melo with capabilities in producing Multi-drug resistant (MDR) antibacterial compounds. Samples of Melo melo are collected from the vicinity of Pekalongan waters, Central Java, Indonesia. This research begins with the isolation of symbiont bacteria, screening of symbiont bacteria with potency in MDR antibacterial activities, antibacterial test, and isolation of MDR clinical pathogenic bacteria. These protocols are then followed by antibacterial sensitivity test, and identification of bacterial species active against MDR by biochemical test and molecular analysis. Molecular analyses are carried out sequentially by DNA extraction, DNA amplification by PCR, and DNA sequencing. Results of 16S rDNA are analyzed using Genetix program and then followed by sequence analysis of the 16S rDNA. In this research, 11 bacteria in Melo melo are isolated and there are 4 isolates which show antibacterial activities against MDR bacteria from Pseudomonas sp. and Enterobacter sp species. Molecular analysis of the most active isolates identifies that isolate PM 26 matches in characteristics with Brevibacterium celere strain KMM 3637 with 89% homology match. On the other hand, biochemical test shows that isolate PM 26 is identical with Bacillus sp. This research concludes that symbiont bacteria found in Melo melo possess antibacterial activities against bacteria of MDR strain

The Tagish Lake chondrite and the interstellar parent body hypothesis

Investigation of the solvent extractable organic compounds in Tagish Lake. The results are used to test the interstellar parent body hypthesis for the origin of extraterrestrial organic matter

Flammability study of materials in oxygen environments

Report presents flame-propagation rates and flammability ratings of 780 specimens of commercially available plastics, elastomers, coatings, fabrics, and other sheet materials. Test results are also given for over 1970 samples of most commonly used electrical harnesses, connectors, and potting compounds

Several new catalysts for reduction of oxygen in fuel cells

Test results prove nickel carbide or nitride, nickel-cobalt carbide, titanium carbide or nitride, and intermetallic compounds of the transition or noble metals to be efficient electrocatalysts for oxygen reduction in alkaline electrolytes in low temperature fuel cells

Interrelation of Superconducting and Antiferromagnetic Gaps in High-Tc Compounds: a Test Case for a Microscopic Theory

Recent angle resolved photoemission (ARPES) data, which found evidence for a d-wave-like modulation of the antiferromagnetic gap, suggest an intimate interrelation between the antiferromagnetic insulator and the superconductor with its d-wave gap. This poses a new challenge to microscopic descriptions, which should account for this correlation between, at first sight, very different states of matter. Here, we propose a microscopic mechanism which provides a definite correlation between these two different gap structures: it is shown that a projected SO(5) theory, which aims at unifying antiferromagnetism and d-wave superconductivity via a common symmetry principle while explicitly taking the Mott-Hubbard gap into account, correctly describes the observed gap characteristics. Specifically, it accounts for both the dispersion and the order of magnitude difference between the antiferromagnetic gap modulation and the superconducting gap.Comment: 8 pages, 5 figure

Experimental pharmacological research regarding some new quinazolin-4-ones derivatives

A series of new compounds with quinazolin-4-one structure, synthesized by the Pharmaceutical Chemistry Department of the Faculty of Pharmacy of the University of Medicine and Pharmacy “Carol Davila” Bucharest, was studied. Five of them were selected, conventionally named S1, S2, S3, S4, S5, and investigated in terms of their potential influence on the central nervous system (CNS). For this purpose, the antidepressant effect was determined using the forced swimming test; the anxiolytic/ anxiogenic effect was determined using the suspended plus-shaped maze (Ugo Basile); the effect on the motor activity was determined using the Ugo Basile activity cage; and the potential analgesic effect was investigated using the hot plate test (Ugo Basile). Compounds S3 and S5 lowered the motor activity and showed an anxiolytic effect, while S1 and S2 proved to have antidepressant and analgesic effects. A good correlation between antidepressant and analgesic effects was observed, consistent with the fact that analgesic drugs, by increasing norepinephrine and serotonin levels in the pain inhibiting descendent pathways, can be used as co-analgesics in therapy

Experimental pharmacological research regarding some newly synthesized benzamides on central nervous system functions

Three newly synthesized benzamides by the Department of Pharmaceutical Chemistry of the Faculty of pharmacy from the University of Medicine and Pharmacy „Carol Davila” Bucharest were tested in order to determine whether these new molecules have similar effects on the central nervous system as those already in therapeutic use belonging to the same chemical group, such as tiapride (neuroleptic) or lidocaine (local anaesthetic). Tests were carried out on NMRI mice which were given new compounds, conventionally named I5C, I14C, and II5C in a dose of 1/20 of the lethal dose 50% (LD50), as previously determined. They received this treatment daily for 21 days. The evasive–investigating capacity of mice was determined using the platform test, and the motor activity using an Activity cage device. The results have shown that compounds I5C and II5C decrease the investigation capacity of the mice; and compound I5C inhibits motor activity, while II5C stimulates it. Thus we concluded that only compounds I5C and II5C have a neuroleptic potential that might be investigated further

G\mathcal{G}-SELC: Optimization by sequential elimination of level combinations using genetic algorithms and Gaussian processes

Identifying promising compounds from a vast collection of feasible compounds is an important and yet challenging problem in the pharmaceutical industry. An efficient solution to this problem will help reduce the expenditure at the early stages of drug discovery. In an attempt to solve this problem, Mandal, Wu and Johnson [Technometrics 48 (2006) 273--283] proposed the SELC algorithm. Although powerful, it fails to extract substantial information from the data to guide the search efficiently, as this methodology is not based on any statistical modeling. The proposed approach uses Gaussian Process (GP) modeling to improve upon SELC, and hence named $\mathcal{G}$-SELC. The performance of the proposed methodology is illustrated using four and five dimensional test functions. Finally, we implement the new algorithm on a real pharmaceutical data set for finding a group of chemical compounds with optimal properties.Comment: Published in at http://dx.doi.org/10.1214/08-AOAS199 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org