Bile acids as constituents for dental composites: in vitro cytotoxicity of (meth)acrylate and other ester derivatives of bile acids.

Methacrylic derivatives of bile acids have been synthesized for use as monomers in dental composites. Polymeric dental materials are known to leach cytotoxic unreacted monomers and degradation products. In this study, the in vitro cytotoxicity of bile acids and their derivatives towards 3T3 fibroblasts has been evaluated by colorimetric MTT assay and compared with that of the common dental monomers BisGMA, UDMA and TEGDMA. In general, the bile acids and their derivatives induced mitochondrial dysfunction at similar or higher concentrations than the commercial dental monomers. Certain monomers did not influence MTT response over their entire range of solubility.     

Analysis of Caching and Replication Strategies for Web Applications

Developers often use replication and caching mechanisms to enhance Web application performance. The authors present a qualitative and quantitative analysis of state-of-the art replication and caching techniques used to host Web applications. Their analysis shows that selecting the best mechanism depends heavily on data workload and requires a careful review of the application's characteristics. They also propose a technique for Web practitioners to compare different mechanisms' performance on their own     

Fluage à long terme du bois fléchi en grandeur structurale

Résumé Cet article présente un modèle permettant de calculer le fluage de poutres fléchies de différentes sections soumises à des environnements variables en ce qui concerne l'humidité relative. Ce modèle est utilisé ici pour interpréter de nouveaux essais à long terme sur des poutres en bois massif et lamellé-collé qui ont été chargées pendant plus de 800 jours en conditions extérieures sous abri à Paris

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Summary Long term bending experiments on full size timber and glulam beams have been carried out under external and sheltered climatic conditions in Paris, and more than two years of test results on the creep behaviour of 75 beams are available. A model for predicting the long term mechanical behaviour of timber under variable humidity and load conditions, previously developed by the author, is described. The model is based on transient moisture transfer analysis linked with deformation analysis using a step-by-step computation scheme, and has been compared previously with experiments carried out under laboratory conditions of controlled variable climates by the author as well as with test results obtained from several other institutions. In general, the model has agreed satisfactorily with the experimental results. In the present paper the model is compared with experiments on full size beams carried out under the changeable conditions of a natural climate. The results show that, for low stress levels and corresponding loads, the model provides a reasonable prediction of the end creep levels after two years of loading.

     

Results of a 90-day toxicity study on 1,2,3- and 1,1,2-trichloropropane administered via the drinking water

Trichloropropanes have been identified as environmental contaminants in sediments of the Great Lakes region of North America. Since these chemicals had the potential to find their way into drinking water, a 90-day feeding study was carried out in order to determine their subchronic toxicity. Groups of 10 male and 10 female weanling Sprague-Dawley rats were supplied drinking water ad libitum, containing 1,2,3- or 1,1,2-trichloropropane at concentrations of 1, 10, 100 or 1000 mg/L for 13 weeks. Emulphor (0.5%) was used to solubilize the chemicals. At the end of the study, the animals were killed and examined for gross and microscopic changes. Heart, liver, brain, kidney and spleen were excised and weighed. Blood was collected and subjected to a comprehensive hematological analysis. Serum was collected and profiled for changes in 12 biochemical parameters and a portion of liver was used to determine mixed function oxidase activity. Although three animals died during the study, their deaths could not be related to treatment. Decreased growth rate was observed in both sexes of the group receiving 1000 mg/L 1,2,3-trichloropropane. There was an increase in liver, kidney and brain weights (relative to body weight) in rats of both sexes fed 1000 mg/L 1,2,3-trichloropropane. Fatty livers were observed in some of the treated animals but a clear dose-relationship was not evident. An elevation in serum cholesterol was observed in female rats fed the highest dose of 1,2,3-trichloropropane. This chemical also induced hepatic aminopyrine demethylase and aniline hydroxylase activities in male rats at the highest dose. Administration of both isomers produced only mild histological changes in the liver, thyroid and kidney of rats at the highest dose. The changes in the liver consisted of an increase in cytoplasmic eosinophilia in the periportal area together with vesiculation of biliary epithelial nuclei. Morphological changes were characterized by increased anisokaryosis in the proximal epithelium and occasional pyknosis associated with the accumulation of large eosinophilic inclusions. Changes in the thyroid consisted of a mild reduction in follicular size associated with an increased epithelial height. In general, these changes were more severe in the males than females, but were still mild overall. It was concluded that the no-effect level for both chemicals was 100 mg/L (15–20 mg/kg bw/day) and based on effects on growth rate and other changes, the 1,2,3- isomer was judged to be slightly more toxic than the 1,1,2- isomer.     

Binding characteristics of novel nonsteroidal antiestrogens to the rat uterine estrogen receptors

Tamoxifen (TAM), the only antiestrogen currently available for the endocrine therapy of breast cancer behaves as a mixed agonist/antagonist of estrogen action, thus limiting its therapeutic potential. We report the binding characteristics of a novel series of nonsteroidal antiestrogens to the rat uterine estrogen receptor. As measured by competition studies, the affinity of EM-652, the active metabolite of the prodrug EM-800, for the estrogen receptor is 7-11 times higher than that of 17beta-estradiol (E2), ICI 182780, and hydroxy-tamoxifen (OH-TAM), the active metabolite of Tamoxifen. EM-652 is 20x more potent than ICI 164384 and Droloxifene while it is 400 times more potent than Toremifene in displacing [3H]E2 from the rat uterine estrogen receptor. On the other hand, the prodrug EM-800 and Tamoxifen have respectively 150-fold and 410-fold less affinity for the estrogen receptor than the pure antiestrogen EM-652. No significant binding of EM-652, EM-800, TAM or OH-TAM was observed to the rat uterine progesterone receptor at concentrations up to 10,000 nM except for TAM that caused a 50% displacement of labeled R5020 at 4000 nM. No significant binding of EM-652 or EM-800 was observed on the rat ventral prostate androgen receptor or the rat uterine progesterone receptor. The present data demonstrate the high affinity and specificity of the new antiestrogen, EM-652, for the rat uterine estrogen receptor. The antiestrogen EM-652 thus becomes the compound having the highest known affinity for the estrogen receptor. Due to its unique potency and its pure antiestrogenic activity already demonstrated in many systems, this antiestrogen could well offer an important advance for the endocrine therapy of breast cancer, uterine cancer, and other estrogen-sensitive diseases in women.