Light-absorption spectroscopy of mutagen-DNA complex in presence of competing biologically active compounds

Abstract Mathematical analysis of absorption spectra of biologically active substances is presented. Two models of interactions of mutagen and caffeine with DNA analyzed and obtained binding parameters show good coincidence. Using different models, which take into account formation of various complexes, it is possible to calculate different binding parameters of such triple systems and choose the model describing corresponding system in the best way

Hetero-association of aromatic molecules in aqueous solution

Knowledge of the physical chemistry of small molecules complexation (the hetero-association) in aqueous solution is increasingly important in view of the rapidly emerging branch of supramolecular chemistry dealing with the formation of heterogeneous polymeric structures having specific functional roles. In this paper, the 50-year history of scientific studies of hetero-association of heterocyclic aromatic molecules in aqueous solution has been reviewed. Some important correlations of structural and thermodynamic parameters of complexation have been reported based on large data-set of hetero-association parameters accumulated to date. The fundamental problem of ‘energetic composition’ of π-stacking is extensively discussed. The review has shown that there are some gaps in our understanding of heteroassociation, which provides a challenge for further studies in this are

Evidence for bystander signalling between human trophoblast cells and human embryonic stem cells

Maternal exposure during pregnancy to toxins can occasionally lead to miscarriage and malformation. It is currently thought that toxins pass through the placental barrier, albeit bilayered in the first trimester, and damage the fetus directly, albeit at low concentration. Here we examined the responses of human embryonic stem (hES) cells in tissue culture to two metals at low concentration. We compared direct exposures with indirect exposures across a bi-layered model of the placenta cell barrier. Direct exposure caused increased DNA damage without apoptosis or a loss of cell number but with some evidence of altered differentiation. Indirect exposure caused increased DNA damage and apoptosis but without loss of pluripotency. This was not caused by metal ions passing through the barrier. Instead the hES cells responded to signalling molecules (including TNF-α) secreted by the barrier cells. This mechanism was dependent on connexin 43 mediated intercellular ‘bystander signalling’ both within and between the trophoblast barrier and the hES colonies. These results highlight key differences between direct and indirect exposure of hES cells across a trophoblast barrier to metal toxins. It offers a theoretical possibility that an indirectly mediated toxicity of hES cells might have biological relevance to fetal development

Effects of maternal thyroid status on thyroid hormones and growth in congenitally hypothyroid goat fetuses during the second half of gestation

Congenital hypothyroidism in Dutch goats is due to a thyroglobulin (TG) synthesis defect that is inherited in an autosomal recessive manner. Minute amounts of mutated TG messenger RNA are translated into glycosylated TG fragments that contain the N-terminal hormonogenic site and are able to form T4, albeit less efficiently. We analyzed the effects of maternal thyroid status on fetal plasma thyroid hormones and growth during the second half of gestation (E90-E150). Maternal hypothyroidism, present from midgestation, resulted in decreased brain and cerebellum weights of affected goitrous fetuses, most evident at term gestation (E150). Brain and cerebellum weights of affected fetuses from unaffected mothers were not decreased. T4 and FT4 levels in affected fetuses were dependent on the maternal phenotype, as was the degree of enlargement of the goiter at E150. Newborn unaffected lambs from affected mothers had plasma T4 levels within the normal range. The present data show that in late gestation, fetal goats have to rely on their own thyroidal T4 production. The results suggest that affected fetuses are able to maintain sufficiently high T4 and T3 levels to prevent severe adverse effects of thyroid hormone deficiency on the brain if maternal iodide supply is adequate, although a possible increased transfer of maternal T4 to affected fetuses cannot be excluded. Under normal conditions, sufficient amounts of iodine are provided by the efficient iodine metabolism in euthyroid mothers. In affected mothers, much iodine is wasted because the thyroid also iodinates proteins other than the aberrant TG, resulting in insufficient iodine provision of the fetus and, consequently, in severe hypothyroidis

RC3/neurogranin structure and expression in the caprine brain in relation to congenital hypothyroidism

In view of the profound effects of thyroid hormone deficiency on the central nervous system (CNS), neuronal genes regulated by thyroid hormone could potentially be involved in the development of the CNS. Expression of the neuronal gene RC3/neurogranin was shown to be induced by thyroid hormone in the rat. No data are available on RC3 expression in mammals with prenatal brain development, like humans. To study RC3 mRNA expression in a genetic in vivo model of congenital hypothyroidism, which also resembles the human situation in the timing of brain development relative to birth, we used an inbred strain of congenitally hypothyroid goats. We isolated a cDNA for the caprine RC3 homolog. The deduced amino acid sequence had 99% similarity with the rat and bovine protein sequence. An analysis of the developmental expression of RC3 mRNA levels showed a 3-fold increase between E90 and P0. In situ hybridization analysis showed that in euthyroid goats, the RC3 expression pattern was region-specific and resembled that in rats. However, in contrast to rats, hypothyroid goats showed only a reduced RC3 mRNA expression in the striatum. Hypothyroidism had no effect on RC3 mRNA expression in all other brain regions. T4-treatment of the hypothyroid fetus increased RC3 mRNA expression in the striatum to euthyroid control levels. These data suggest that thyroid hormone is a regulator of RC3 gene expression in the caprine brain, and that the striatum is highly sensitive to thyroid hormone deficienc

Reconstruction fémorale par allogreffes spongieuses impactées et protégées par un treillis métallique au cours des révisions de prothèses totales de hanche (à propos de 23 cas au recul moyen de 12,5 ans (8-20 ans))

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF