Theoretical insights on electron donor-acceptor interactions involving carbon dioxide

Electron donor-acceptor (EDA) interactions are widely involved in chemistry and their understanding is essential to design new technological applications in a variety of fields ranging from material sciences and chemical engineering to medicine. In this work, we study EDA complexes of carbon dioxide with ketones using several ab initio and Density Functional Theory methods. Energy contributions to the interaction energy have been analyzed in detail using both variational and perturbational treatments. Dispersion energy has been shown to play a key role in explaining the high stability of a non-conventional structure, which can roughly be described by a cooperative EDA interaction

What is the effective dielectric constant in a β-cyclodextrin cavity? Insights from Molecular Dynamics simulations and QM/MM calculations

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Ketamine for refractory chronic pain: a 1-year follow-up study

International audienceAbstract Ketamine is often used in pain clinics for refractory chronic pain, but its long-term efficacy is poorly reported. The main objective was to assess the long-term effect of ketamine on pain and health variables in patients with refractory chronic pain. A prospective, multicenter, 1-year follow-up observational study (NCT03319238) was conducted in 30 French pain clinics where ketamine is commonly prescribed. This study focused on patients with 1 ketamine delivery procedure (n = 256). The primary endpoint was pain intensity (0-10 numerical pain rating scale) before and after ketamine every month for 1 year. Secondary outcomes aimed to identify pain trajectories by semiparametric mixture models and to collect adverse events. The following data were obtained for 256 patients: Pain intensity decreased significantly (6.8 ± 1.8, n = 240 at baseline vs 5.7 ± 1.8, n = 93 at 12 months; P < 0.001). The effect size of the main endpoint was 0.61 (95% confidence interval: [0.40-0.80]; P < 0.001). Three pain trajectories were identified: 16.0% of patients in “mild pain” (mostly neuropathic pain), 35.3% in “moderate pain,” and 45.7% in “severe pain” (mostly fibromyalgia) trajectory. Neuropathic pain and fibromyalgia presented opposite outcomes, pain severity being associated with anxiety, depression, and a poorer quality of life. Adverse events occurred at 1 week in 108/218 [50%] patients, and this rate gradually decreased throughout the follow-up. This real-life study in chronic pain identified distinct pain trajectories and predictive variables of ketamine efficacy. It is now pivotal to further study and optimize the subtyping of patients to provide the most effective and safe ketamine treatment in this vulnerable population

Capped guanidino-α-cyclodextrin first synthesis based on intramolecular Staudinger-Aza-Wittig (SAW) reaction

International audienceAn intramolecularly promoted SAW reaction between a phosphinimide and an isocyanate intermediate led to an original bridged trisubstituted ((A,C),E)-α-cyclodextrin. The latter was in a second step converted into a new capped (ACE)-(guanidino)-α-cyclodextrin

Expériences d'animation rurale

Martin M., Crozet M.-A., Gillet J., Lambert Y., Lebot M. Expériences d'animation rurale. In: Études rurales, n°65, 1977. Pouvoir et patrimoine au village - 2. pp. 139-155

Expériences d'animation rurale

Martin M., Crozet M.-A., Gillet J., Lambert Y., Lebot M. Expériences d'animation rurale. In: Études rurales, n°65, 1977. Pouvoir et patrimoine au village - 2. pp. 139-155

Computer simulation of reactions in ß-cyclodextrin molecular reactors: Transition state recognition

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Hormonal status and cognitivo‐emotional profile in real‐life neuropathic pain patients: a case control study

Epub ahead of printOral Presentation: World Institute of Pain (WIP) congress, Dublin, 2018BACKGROUND:The specific impact of neuropathic pain and recommended neuropathic pain treatments on the hormonal and immune status of patients has been so far poorly explored. This study aimed at studying, in real life, the hypothalamic-pituitary-adrenal axis and the cytokine profile of patients with neuropathic pain. It also explored their links with cognition, emotion, quality of life, and drug treatment.METHODS:This prospective study (clinicaltrials.gov NCT01543425) included 60 patients with neuropathic pain and 60 age- and gender-matched healthy volunteers after obtaining signatures of informed consent. A number of parameters were measured: adrenocorticotropic hormone, cortisol, cortisol awakening response, dehydroepiandrosterone sulphate, sex hormone binding globulin, testosterone, 17-β-estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, cytokines, brain-derived neurotrophic factor, and vitamin D. Psychological parameters were assessed by questionnaires.RESULTS:Patients with neuropathic pain had lower levels of adrenocorticotropic hormone (P = 0.009) and dehydroepiandrosterone sulphate (P < 0.001) than controls, and the cortisol awakening response was impaired. Patients were more depressed and anxious (P < 0.001) and had a diminished quality of life (P < 0.001), which was influenced by cytokines (P = 0.0067) and testosterone (P = 0.028). Antidepressants and antiepileptics appeared to interfere with testosterone and cognitivo-emotional domains.CONCLUSION:An impairment of the hormonal status and of the immune system was observed in patients. It identified testosterone as a potential pivotal mediator between antidepressants/antiepileptics and quality of life. Further studies must address the exact impact of different types of drugs on central effects, of gender differences, and of the immune system of neuropathic pain

C-glyco“RGD” as αIIbβ3 and αvβ integrin ligands for imaging applications: synthesis, in vitro evaluation and molecular modeling

International audienceThe design of conjugates displaying simultaneously high selectivity and high affinity for different subtypes of integrins is a current challenge. The arginine-glycine-aspartic acid amino acid sequence (RGD) is one of the most efficient short peptides targeting these receptors. We report herein the development of linear and cyclic fluoro-C-glycoside"RGD" conjugates, taking advantage of the robustness and hydrophilicity of C-glycosides. As attested by in vitro evaluation, the design of these C-glyco"RGD" with a flexible three-carbon triazolyl linker allows distinct profiles towards αIIbβ3 and αvβ3 integrins. Molecular-dynamics simulations confirm the suitability of cyclic C-glyco-c(RGDfC) to target αvβ3 integrin. These C-glyco"RGD" could become promising biological tools in particular for Positron Emission Tomography imaging