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61.
Nicolas Levoin Olivier Labeeuw Stéphane Krief Thierry Calmels Olivia Poupardin-Olivier Isabelle Berrebi-Bertrand Jeanne-Marie Lecomte Jean-Charles Schwartz Marc Capet 《Bioorganic & medicinal chemistry》2013,21(15):4526-4529
Due to its involvement in major CNS functions, the histamine H3 receptor (H3R) is the subject of intensive medicinal chemistry investigation, supported by the range of modern drug discovery tools, such as receptor modeling and ligand docking. Although the receptor models described to date share a majority of common traits, they display discrete alternatives in amino-acid conformation, rendering ligand binding modes quite different. Such variations impede structure-based drug design in the H3R field. In the present study, we used a combination of medicinal chemistry, receptor-guided and ligand-based methods to elucidate the binding mode of antagonists. The approaches converged towards a ligand orientation perpendicular to the membrane plane, bridging Glu206 of the transmembrane helix 5 to acidic amino acids of the extracellular loops. This consensus will help future structure-based drug design for H3R ligands. 相似文献
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Giuseppe Barraco Isabelle Sylvestre Giovanni Iapichino Florent Engelmann 《Plant biotechnology reports》2013,7(2):141-146
In this study, we investigated the possibility of using the droplet-vitrification technique for cryopreserving nodal segments of in vitro plantlets of the endangered plant species Lithodora rosmarinifolia. Among the three vitrification solutions tested, only solutions B1, containing (w/v) 50 % glycerol and 50 % sucrose, and B3, containing 40 % glycerol and 40 % sucrose, were able to induce cryotolerance in nodal explants, resulting in intermediate survival and recovery after cryopreservation. A three-step vitrification protocol, including an additional dehydration treatment with half-strength vitrification solution for 30 min before the treatment with full-strength vitrification solution, did not lead to any improvement in survival and recovery compared with the two-step protocol. The optimal protocol was the following: preculture of nodal segments in liquid medium with 0.3 M sucrose for 16 h and 0.7 M sucrose for 5 h, treatment for 20 min in loading solution containing 1.9 M glycerol + 0.5 M sucrose, dehydration with vitrification solution B1 (glycerol 50.0 %, sucrose 50.0 %, w/v) for 60 min at room temperature, rapid cooling in minute droplets of vitrification solution, and rapid rewarming by immersion of nodal segments for 20 min in unloading solution containing 1.2 M sucrose. Under these conditions, 33 % recovery of cryopreserved nodal explants was achieved. Regrowth of cryopreserved samples was rapid and direct. These results indicate that long-term storage of L. rosmarinifolia by means of cryopreservation of nodal segments is possible, thereby contributing to securing the diversity of this rare and endangered plant species. 相似文献
64.
Fanny Giudicelli Anne-Laure Brabant Isabelle Grit Patricia Parnet Valérie Amarger 《PloS one》2013,8(7)
Methionine, folic acid, betaine and choline interact in the one-carbon metabolism which provides methyl groups for methylation reactions. An optimal intake of these nutrients during pregnancy is required for successful completion of fetal development and evidence is growing that they could be involved in metabolic long-term programming. However, the biological pathways involved in the action of these nutrients are still poorly known. This study investigated the interaction between methyl donors and protein content in maternal diet during the preconceptual, pregnancy and lactation periods and the consequences on the rat offspring in the short and long term. Methyl donor supplementation reduced leptin secretion in offspring, whereas insulin levels were mostly affected by protein restriction. The joint effect of protein restriction and methyl donor excess strongly impaired postnatal growth in both gender and long term weight gain in male offspring only, without affecting food intake. In addition, rats born from protein restricted and methyl donor supplemented dams gained less weight when fed a hypercaloric diet. Methylation of the leptin gene promoter in adipose tissue was increased in methyl donor supplemented groups but not affected by protein restriction only. These results suggest that maternal methyl donor supplementation may influence energy homeostasis in a gender-dependent manner, without affecting food intake. Moreover, we showed that macronutrients and micronutrients in maternal diet interact to influence the programming of the offspring. 相似文献
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Sonia Gaucher Isabelle Boutron Florence Marchand-Maillet Gabriel Baron Richard Douard Jean-Pierre Béthoux AMBUPROG Group Investigators 《PloS one》2016,11(2)
Objectives
To assess the impact of a standardized pre-operative telephone checklist on the rate of late cancellations of ambulatory surgery (AMBUPROG trial).Design
Multicenter, two-arm, parallel-group, open-label randomized controlled trial.Setting
11 university hospital ambulatory surgery units in Paris, France.Participants
Patients scheduled for ambulatory surgery and able to be reached by telephone.Intervention
A 7-item checklist designed to prevent late cancellation, available in five languages and two versions (for children and adults), was administered between 7 and 3 days before the planned date of surgery, by an automated phone system or a research assistant. The control group received standard management alone.Main Outcome Measures
Rate of cancellation on the day of surgery or the day before.Results
The study population comprised 3900 patients enrolled between November 2012 and September 2013: 1950 patients were randomized to the checklist arm and 1950 patients to the control arm. The checklist was administered to 68.8% of patients in the intervention arm, 1002 by the automated phone system and 340 by a research assistant. The rate of late cancellation did not differ significantly between the checklist and control arms (109 (5.6%) vs. 113 (5.8%), adjusted odds ratio [95% confidence interval] = 0.91 [0.65–1.29], (p = 0.57)). Checklist administration revealed that 355 patients (28.0%) had not undergone tests ordered by the surgeon or anesthetist, and that 254 patients (20.0%) still had questions concerning the fasting state.Conclusions
A standardized pre-operative telephone checklist did not avoid late cancellations of ambulatory surgery but enabled us to identify several frequent causes.Trial Registration
ClinicalTrials.gov NCT01732159相似文献67.
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Enantiomerization of Allylic Trifluoromethyl Sulfoxides Studied by HPLC Analysis and DFT Calculations 下载免费PDF全文
Laetitia Bailly Emilie Petit Mayaka Maeno Norio Shibata Oliver Trapp Pascal Cardinael Isabelle Chataigner Dominique Cahard 《Chirality》2016,28(2):136-142
Enantiomerization of allylic trifluoromethyl sulfoxides occurs spontaneously at room temperature through the corresponding allylic trifluoromethanesulfenates via a [2,3]‐sigmatropic rearrangement. Dynamic enantioselective high‐performance liquid chromatography (HPLC) analysis revealed the stereodynamics of these sulfoxides ranging from chromatographic resolution to peak coalescence at temperatures between 5 and 53 °C. The rate constant of enantiomerization and activation parameters were determined and compared with Density Functional Theory (DFT) calculations. Chirality 28:136–142, 2016. © 2015 Wiley Periodicals, Inc. 相似文献