Embryotoxicity induced by diethylstilbestrol in vitro1

The embryotoxic potential of diethylstilbestrol (DES) was examined in a whole embryo culture system containing a P-450–dependent bioactivating system. Sprague-Dawley rat embryos were explanted on day 10 and cultured for 24 hours. Concentration-dependent effects of DES on embryonic growth parameters, viability, and embryotoxicity were observed. Concentrations of DES greater than 0.26 mM (final concentration) produced 100% embryolethality, while those below 0.15 mM were without significant effects. At a final concentration of 0.19 mM, DES produced only a slight increase in embryolethality. The same concentration elicited a marked increase in observed embryotoxicity, including prosencephalic hypoplasia, incomplete axial rotation, and open neural tubes. In addition, reductions in embryonic length, somite number, and protein and DNA content were observed. An exogenous P-450–dependent hepatic biotransforming (catechol-generating) system failed to alter either the incidence of observed toxic effects or measured growth parameters. Likewise, exposure of cultured embryos to 20% carbon monoxide (CO) failed to reduce DES-induced embryotoxicity, indicating a lack of participation of an endogenous P-450-dependent embryonic bioactivating system. Arachidonic acid (0.20 mM) and/or indomethacin (0.50 mM) also had no observable effect on DES-induced embryotoxicity, suggesting that prostaglandin synthase was not involved in the embryotoxic activity of DES, as has been proposed to explain its carcinogenic effect. The antioxidants N-acetylcysteine (1.14 mM) and α-tocopherol (0.08 mM) failed to protect against DES-induced embryotoxicity, while the antiestrogen tamoxifen (up to 0.85 mM) actually enhanced this effect of DES in culture. The DES analogs Z,Z-dienestrol (DIES, 0.10 mM) and hexestrol (HES, 0.48 mM) were both embryotoxic in vitro. The presence of an exogenous P-450-dependent hepatic biotransforming system appeared to protect against HES-induced embryolethality but had little effect upon DIES-induced embryotoxicity. The results were consistent with a direct effect of DES independent of either estrogenicity or exogenously generated metabolites.     

DASMiner: discovering and integrating data from DAS sources

Background  

DAS is a widely adopted protocol for providing syntactic interoperability among biological databases. The popularity of DAS is due to a simplified and elegant mechanism for data exchange that consists of sources exposing their RESTful interfaces for data access. As a growing number of DAS services are available for molecular biology resources, there is an incentive to explore this protocol in order to advance data discovery and integration among these resources.     

Stable isotope evidence for the localisation of phenylalanine biosynthesis in the bacterium Paracoccus denitrificans

Paracoccus denitrificans was grown on [6-13C]-glucose as the sole carbon source for growth and the extracts were fractionated and analysed by gas chromatography-mass spectrometry. The 13C-labelling pattern observed in phenylalanine indicated that the biosynthetic sequences of enzymes for phenylalanine production were unequally distributed within the cell and that there are at least 2 separate loci of phenylalanine biosynthesis. The principal locus of phenylalanine production was associated with the Entner-Doudoroff and/or the pentose phosphate pathways and it was responsible for producing 3/4 of the bacterium's phenylalanine. A second locus was associated with the G6 oxidation pathway and was responsible for producing the remaining 1/4 of the cell's phenylalanine.     

A review of feeding and nutrition of herbivorous land crabs: adaptations to low quality plant diets

This paper reviews the nutritional ecology, the digestive physiology, and biochemistry of herbivorous land crabs and the adaptations that they possess towards a diet of plant material. Land crab species that breathe air and forage out of water can be divided into three feeding specialisations: primarily carnivorous, deposit feeders feeding on micro-organisms and organic matter in the sediment, and herbivores consuming mainly plant material and its detritus. The last forms the focus of this review. The diets of the herbivores are low in nitrogen and high in carbon, are difficult to digest since they contain cellulose and hemicellulose, and may disrupt digestion due to the presence of tannins. Herbivorous crustaceans are able to efficiently utilise plant material as their primary nutrient source and are indeed able to meet their nitrogen requirements from it. Herbivorous land crabs display a range of adaptations towards a low nitrogen intake and these are discussed in this review. They also appear to endogenously produce cellulase and hemicellulase enzymes for the digestion of cellulose and hemicellulose. Generalised and specific adaptations allow them to inhibit the potentially negative digestive effects of tannins. To digest plant material, they possess a plastic digestive strategy of high food intake, short retention time, high assimilation of cell contents, and substantial digestion of cellulose and hemicellulose.     

Intracellular purine deposits in the gecarcinid land crab Gecarcoidea natalis

The terrestrial crab Gecarcoidea natalis stores large amounts of purine in the body. The major component of the purine deposits is urate (85% of the total purines). The other 15% is comprised of hypoxanthine, guanine, and xanthine. Microscopy studies reveal that these urate deposits are located intracellularly in spongy connective tissue cells throughout the body. Urate exists as numerous membrane-bound crystals 1 μm in diameter. Vesicles thought to represent urate vesicles at various stages of development are also present in the cytoplasm of the cell. Few organelles are visible in the urate storage cells, and it is unlikely that the urate is synthesized on site. Crabs (N = 2) fed a high-nitrogen diet have greater numbers of urate storage cells at more connective tissue sites, and the cells are larger (36.3 ± 1.8 μm (mean ± SE) and 44.0 ± 1.4 μm (mean ± SE)) and contain more urate than urate storage cells in animals collected from the field (N = 3) or maintained in the laboratory on a low-nitrogen diet (N = 1). The mean diameter of urate storage cells in animals fed a diet low in nitrogen and field-collected animals ranges from (13.5 ± 0.5 μm (SE) - 22.3 ± 1.0 μm (SE)). This histological study supports a strong correlation between purine accumulation and the nitrogen content of the diet. J. Morphol. 231:101-110, 1997. © 1997 Wiley-Liss, Inc.     

Copper(II) complexes of a nonsteroidal anti-inflammatory drug niflumic acid. Synthesis, crystal structure of tetrakis-mu-(2-[3-(trifluoromethyl) phenyl]aminonicotinato)bis(dimethylsulfoxide)-dicopper(II) complex at 190 K. Anti-inflammatory properties.

The synthesis and characterization of three complexes with a potent nonsteroidal anti-inflammatory drug niflumic acid {2-[3-(trifluoromethyl)phenyl]aminonicotinic acid} with formula [Cu(niflumato)2L] (L = H2O, DMSO = dimethylsulfoxide, DMF = N,N-dimethylformamide) were investigated. The crystal and molecular structure of the {Cu(niflumato)2(DMSO)}2 was reported. Crystallographic data are as follows: monoclinic system, space group P2(1)/n, Z = 2, a = 11.1318(8), b = 17.513(2), c = 15.336(1) A, beta = 103.316(8) degrees, V = 2909.4(4) A3. The structure was refined to R = 0.030 and wR = 0.037 for 3702 reflections with I > sigma (I). It consists of centrosymmetric binuclear units with the Cu-Cui (symmetry code i: 1-x, -y, 1-z) distance between two centrosymmetrically related ions of 2.6272(5) A. Each Cu(II) ion in [Cu2(DMSO)2(mu-niflumato)4] is coordinated to an apical dimethylsulfoxide O atom on the one hand and to the equatorial carbonyl and carboxylic O atoms of two crystallographically independent niflumate moieties and their centrosymmetric counterparts on the other hand. In spite of the low-temperature (190 K) crystal measurements, one L-CF3 grouping exhibits some disorder. The biological activities of these complexes were compared to that of niflumic acid. Niflumic acid and its various copper complexes significantly inhibited polymorphonuclear leukocyte (PMNL) oxidative metabolism, as assessed by chemiluminescence and O2- generation measurement. This effect was dose-dependent. All copper complexes exerted a similar inhibiting effect which was always significantly higher than that exerted by the parent drug.