Comparison of the DNA damage response in BEAS-2B and A549 cells exposed to titanium dioxide nanoparticles.

For some decades production of titanium dioxide nanoparticle (TiO2-NP) has been increasing at a considerable rate; concerns as to the toxicity of these particles upon inhalation have been raised. Indeed, TiO2-NPs have been shown to induce significant genotoxicity and to adversely affect both major DNA repair mechanisms: base excision repair (BER) and nucleotide excision repair (NER). The aims of the present study were to (i) compare the genotoxicity of TiO2-NPs and their impact on DNA repair processes on A549 alveolar carcinoma and BEAS-2B normal bronchial lung cell lines and (ii) delve deeper into the mechanisms leading to these effects. To achieve these goals, TiO2-NPs effects on cytotoxicity, genotoxicity, DNA repair activity and DNA repair gene expression were investigated in both cell lines upon exposure to 1-100 µg/mL of anatase/rutile, 21 nm TiO2-NPs. Our results show that TiO2-NPs induce comparable cytotoxic and genotoxic responses in BEAS-2B and A549 cells. Functional response to DNA damage is observed in both cell lines and consists of an overall downregulation in DNA repair processes. When evaluating the relative importance of the two DNA repair pathways, we observed a lower impact on BER compared with NER activities, suggesting that repair of oxidatively generated DNA damage is still triggered in these cells. This response becomes measureable at 4 h of exposure in BEAS-2B but only after 48 h of exposure in A549 cells. The delayed response in A549 cells is due to an initial overall and intense downregulation of the genes encoding DNA repair proteins. This overall downregulation correlates with increased methylation of DNA repair gene promoters and downregulation of NRF2 and BRCA1, which may thus be considered as upstream regulators. These results strengthen the evidence that TiO2-NP induces indirect genotoxicity in lung cells, via modulation of DNA repair processes, and shed some light on the mechanisms behind this effect.

[Implementation of the therapeutic hypothermia recommendation after resuscitated cardiac arrest caused by ventricular fibrillation and tachycardia without pulse: a retrospective study in Saint-Pierre Hospital]. / Etude rétrospective au sein du C.H.U. Saint-Pierre sur l'application de la recommandation d'hypothermie post arrêt cardiaque par fibrillation et tachycardie ventriculaire sans pouls.

INTRODUCTION: Therapeutic hypothermia is an essential step for the neurological protection of comatose individuals after cardiorespiratory arrest (CA) and ventricular fibrillation (VF). The evaluation of the application of the Protocol thereto within the C.H.U. Saint-Pierre (SPH) is the subject of this study. METHOD: Retrospective analyzes of the SPH computerized records from 01/01/2005 to 31/12/2010 whose inclusion criteria are out-of-hospital CA admitted alive to the hospital with VF as initial rythm. Transferred patients or NTBR status are excluded. RESULTS: Of the 72 patients studied, 68% were discharged alive from the hospital, 84% of which has no neurologic sequelae. Hypothermia was used for 44 people, unduly in 5 cases and there were also 5 other cases for which it was needed, but not applied. Hypothermia (32-34 degrees C) was reached in 11 h 23 (+/- 144 min) and lasted an average of 19 h 51 (+/- 249 min). Hypothermic patient survival amounted to 72.4%, including 81% with good neurological outcome. CONCLUSION: The results of the protocol application are superior to those of several other studies. Few errors of inclusion and exclusion are present. The implementing of a common protocol for IC--Emergency Units--EMS to accelerate obtaining the target temperature and improve performance seems beneficial. The creation and implementation of a specific register with patients who had AC and were cooled seem interesting for a better medical follow-up, an assessment of the management and an enhancement of the current knowledge related to this technique.

[Effects of T-type calcium channel blockers on spontaneous meiotic maturation of mouse ovarian oocytes in vitro]. / Vlyv blokatoriv kal'tsievykh kanaliv t-typu na spontanne meiotychne dozrivannia ovarial'nykh ootsytiv myshei in vitro.

We studied the effects of blockers of the T-type Ca2+ channels on resumption of meiosis and spontaneous meiotic maturation of murine ovarial oocytes in vitro. We found that the efficiency of suppression of oocyte maturation by blockers of the Ca2+ channels increases in the following succession: amiloride hydrochloride, mebifradil, NiCl2. It is supposed that there is a possibility to use blockers of the T-type Ca2+ channels for creation of new combined intrauterine contraceptives.

Surgeon predictions on growth of minimal invasive therapy: the difficulty of estimating technologic diffusion.

OBJECTIVE: To compare five-year predictions made in 1992 by academic surgeon leaders in UK, US and Canada, with actual experiences in 1997, of increased rates of minimal invasive therapy (MIT) for surgical operations. METHOD: We compared 1992 predictions of percent of operations done by minimal invasive therapy and length of stay in the US with actual 1997 percents found by literature searches. RESULTS: We found sufficient data on 12 operations done by MIT in 1997 of the original 34 operations predicted in 1992 by surgeon experts to be to be amenable to this technique. These 12 operations were among the top 20 most commonly performed procedures in 1992 and 1997. Of these 12 operations, ten had 40-60% lower 1997 percentages than predicted, one had about 10% lower rate, and two had 18% and 100% higher rates of MIT than predicted. Overall mean length of stay (LOS) for all 34 study operations fell from 6.8 days in 1992 to 5.2 days in 1997. Mean LOS in 1997 was 2.5 days by MIT and 6.7 days by open technique (OT). CONCLUSION: Most of the predictions made in 1992 by surgical leaders in Canada, US and UK were incorrect when examined 5 years later. The rate of MIT diffusion and its effect on length of stay were overestimated for most operations, while for two procedures the predictions underestimated extent of diffusion. Also, much of the declines of LOS for surgical care paralleled declines in length of stay for all care, supplemented by the individual contributions of MIT specifically. Relying on expert opinion alone to predict the acceptability, rapidity, scope and extent of technological change is fraught with uncertainty. Unexpected consequences occur when one or a few parts of complex systems are changed. This is a particular problem when predictions are a main basis for informed decision making in the absence of any supporting data from appropriately designed empirical or controlled study.