Synthèse et étude physico-chimique de copolymères amphiphiles à base de poly(2-méthyl-2-oxazoline)

Ce travail de thèse décrit l'élaboration de copolymères amphiphiles obtenus par couplage de deux homopolymères. La synthèse des copolymères s'est effectuée en deux étapes. Dans un premier temps, des homopolymères de type poly(2-méthyl-2-oxazoline) (P(MOx)) et poly(acrylate de tert-butyle) (P(At-Bu)) ont été préparés par polymérisation par ouverture de cycle cationique (CROP) et par polymérisation radicalaire contrôlée de type RAFT ou ATRP, respectivement. Puis les copolymères amphiphiles diblocs ont finalement été obtenus par une réaction de couplage polymère-polymère de type cycloaddition de Huisgen. Une étude physico-chimique de ces copolymères dans l'eau a mis en évidence la présence d'agrégats qui présentent une morphologie sphérique, des tailles inférieures à 100 nm et des concentrations d'agrégation critique de l'ordre de 10-6 mol.L-1.Les connaissances acquises sur la synthèse et l'étude des copolymères à blocs amphiphiles ont également permis le développement de copolymères greffés amphiphiles poly( -caprolactone)-g-poly(2-méthyl-2-oxazoline) (PCL-g-P(MOx)), constitués d'un bloc hydrophobe PCL sur lequel des chaînes hydrophiles P(MOx) ont été greffées. L'étude du comportement de ces copolymères dans l'eau montre la formation d'agrégats avec des caractéristiques proches de celles obtenues pour les copolymères diblocs amphiphiles. Un autre point intéressant est que la P(MOx) permet de solubiliser la PCL dans l'eau.Ces deux études illustrent l'apport de la chimie macromoléculaire pour la préparation de structures amphiphiles parfaitement définies qui s'organisent en phase aqueuse en agrégats. Ces derniers pourraient notamment être utilisés dans le domaine biomédical.This manuscript deals with the synthesis of amphiphilic diblock copolymers obtained by the coupling of both hydrophobic and hydrophilic homopolymers. The copolymers were achieved in two steps. On the one hand, homopolymers poly(2-methyl-2-oxazoline) P(MOx)s and poly(tert-butyl acrylate)s (P(At-Bu) were synthesized by cationic ring opening polymerization (CROP) and by Reversible Addition-Fragmentation Transfer (RAFT) polymerization and atom transfer radical polymerization (ATRP), respectively. Finally, amphiphilic diblock copolymers were achieved by Huisgen's cycloaddition. Physical chemistry studies in water proved the formation of aggregates. The latter had a spherical morphology, sizes below 100 nm and critical aggregation concentration around 10-6 mol.L-1.Knowledge acquired on the synthesis and the study of amphiphilic block copolymers led to the development of poly( -caprolactone)-g-poly(2-methyl-2-oxazoline) (PCL-g-P(MOx)) amphiphilic graft copolymers, made of a hydrophobic PCL grafted with hydrophilic P(MOx) moieties. The study of aqueous solution of such copolymers showed the formation of aggregates with characteristics close from those obtained for the diblock copolymers. Another interesting point is that P(MOx) permitted the solubilization of PCL in water.The reported work illustrated the importance of macromolecular chemistry for the obtaining of amphiphilic copolymers with controlled molecular weight and narrow molar mass distributions which self-assemble in water. Such kind of materials could be used in the biomedical field.MONTPELLIER-BU Sciences (341722106) / SudocSudocFranceF

How to modulate chemical structure of polyoxazolines by appropriate functionalization

International audiencePolyoxazolines (POx) are increasingly studied as polymeric building blocks due to the possibility of affording tunable properties. Additionally, as it was proved that biocompatibility and stealth behavior of POx are similar to that of poly(ethylene glycol) (PEG), it became challenging to develop polyoxazoline-based (co)polymers. Even if POx have a lot of advantages, they also show an important drawback as it is to date impossible to prepare high molecular weight polyoxazolines, with low polydispersity indexes. So, it appears important to judiciously functionalize them. This review covers the multiple ways of functionalization of polyoxazolines. The use of functional initiators, functional terminating agents, and 2-R-2-oxazolines with R functional side group is detailed. In conclusion, some perspectives on POx functionalizations are also reported, with functions permitting selective "click" reactions

Well-defined poly(oxazoline)-b-poly(acrylate) amphiphilic copolymers: from synthesis by polymer-polymer coupling to self-organization in water

Additional Supporting Information may be found in the online version of this article

Novel Investigations on Kinetics and Polymerization Mechanism of Oxazolines Initiated by Iodine

International audienceThe cationic ring-opening polymerization of 2-methyl-2-oxazoline (MOx) using iodine initiating system was reported. Uncolored polyoxazolines were produced in spite of the use of iodine initiator, well-known dye molecule. Low molecular weight asymmetric telechelic polyoxazolines carrying an acetylimine head group and an oxazolinium end group were synthesized, with a good control over the molecular weight. NMR and MALDI-Tof experiments allowed the full determination of the chemical structures of the produced poly(2-methyl-2-oxazoline)s, notably with the acetylimine head group, explained by spontaneous α-HI elimination. Finally, to our knowledge, we reported the first detailed mechanism of cationic ring-opening polymerization of 2-methyl-2-oxazoline in acetonitrile according to UV experiments. An ionic-type mechanism was involved with the dissociation of molecular iodine to active initiating species

Fish oil attenuates adrenergic overactivity without altering glucose metabolism during an oral glucose load in haemodialysis patients

International audienceHaemodialysis patients display an increased cardiac mortality, which may be partly related to increased sympathoadrenal activity and insulin resistance. Fish oil decreases adrenal activation induced by mental stress and has an insulin sensitizing effect in healthy subjects. Whole-body glucose metabolism after oral glucose was studied in eight haemodialysis patients before and after a 3-week oral fish oil supplementation (i.e. EPA + DHA at 1·8 g/d). Plasma glucose fluxes were traced by using [6,6-2H2]glucose infusion. Substrate oxidation was determined by using indirect calorimetry. Each patient was studied in the basal state and over the 6 h following absorption of a 1 g/kg glucose load. Energy expenditure in response to glucose re-increased over the last 2 h of the experiment (P < 0·05), which coincided with an increase in plasma catecholamines, especially epinephrine (P < 0·05), strongly suggesting a sympathoadrenal overactivity. Fish oil supplementation blunted both re-increase in thermogenic response and concomitant increase in plasma epinephrine, but not in plasma norepinephrine, over the last 2 h of the experiment. Fish oil did not alter either whole-body glucose metabolism or substrate oxidation. These data show that in haemodialysis patients, fish oil attenuates adrenal overactivity induced by oral glucose but does not modulate whole-body glucose metabolism and insulin sensitivity

Synthesis and evaluation of triazole-linked poly(e-caprolactone)-graft-poly(2-methyl-2-oxazoline) copolymers as potential drug carriers

International audienceWell-defined graft copolymers were obtained using a coppercatalysed azide-alkyne Huisgen's cycloaddition click reaction from both biocompatible and non-toxic poly(e-caprolactone) and poly(2-methyl-2-oxazoline) homopolymers. Resulting amphiphilic copolymers proved to form micelles that could be used as potential drug carriers

Laparoscopic sleeve gastrectomy versus laparoscopic mini gastric bypass: One year outcomes.

International audienceSleeve gastrectomy (LSG) and mini gastric bypass (LMGB) was considered as emerging procedures but are now considered for many authors as an alternative of the Roux-Y gastric bypass because of similar percentages of weight loss and better postoperative morbidity profiles. However, studies comparing LSG and LMGB are scarce.From January 2010 to July 2014, 262 and 161 patients underwent LSG or LMGB in two centre of bariatric surgery, respectively. At one year, rate of follow-up was 88.4%. Main outcome was % of Total Weight Loss (%TWL) at one year. Propensity score matching and multivariable analyses were used to compensate for differences in some baseline characteristics.After matching LSG (N = 136) and LMGB (N = 136) groups did not differ for initial BMI (kg/m(2)) (43.4 ± 6.5 vs. 42.8 ± 5.0; P = 0.34), % of female patients (91.9% vs. 93.4%; P = 0.64), age (years) (41.2 ± 12.3 vs. 41.2 ± 11.3; P = 0.99) and diabetes (15.4% vs. 19.9%; P = 0.34). At one year, %TWL, change in BMI and rate of stenosis were higher for LMGB group, respectively: 38.2 ± 8.4 vs. 34.3 ± 8.4 (P < 0.0001); -16.5 ± 4.6 vs. -14.9 ± 4.4 (P = 0.005) and 16.9% vs. 0% (P < 0.0001). In multivariate analyses (β coefficient), LMGB was a positive independent factor of %TWL (2.8; P = 0.008).LMGB seems to have better weight loss at one year compared to LSG with higher gastric complications. Further long term studies are needed

Preserved auditory cognitive ERPs in severe akinetic mutism: a case report.

kinetic mustism is a dramatic deficit in spontaneous initiation of voluntary motor and speech acts, usually secondary to bilateral lesions of the anterior cingulate cortices and supplementary motor areas [Principles of Neurology, McGraw-Hill, New York, 1989]. Given the obvious limitations of traditional neuropsychological testing in this clinical context, the use of neurophysiological tools such as bedside auditory cognitive event-related potentials (ERPs), recently proven to be relevant to evaluate comatose and vegetative patients [Clin. Neurophysiol. 110 (9) (1999) 1601; News Physiol. Sci. 17 (2002) 38], may constitute an interesting alternative. Here, we present the ERPs of a 38-year-old right-handed woman with severe akinetic mutism recorded in a passive auditory odd-ball paradigm. In spite of this severe clinical state, we could observe the presence of a "Mismatch Negativity", and of a larger P300 in rare trials than in frequent ones. By revealing a high level of cognitive integration of environmental auditory information, our study emphasizes the potential clinical relevance of MMN and P300 recordings in akinetic mutism to assess patient cognitive functioning

Urinary function and quality of life after radiotherapy for prostate cancer in patients with prior history of surgical treatment for benign prostatic hyperplasia

Abstract Background To evaluate long-term IPSS score and urinary quality of life after radiotherapy for prostate cancer, in patients with prior history of surgical treatment for benign prostatic hyperplasia (BPH). Methods In this retrospective study, we reviewed medical records of patients treated in our department, between 2007 and 2013 with surgery for BPH followed by radiotherapy for localized prostate cancer. Patients were contacted to fill in IPSS questionnaire and they were also asked for urinary quality of life. Predictive factors known to be associated with bad urinary function were also analysed. Results Fifty-nine patients were included in our study. Median age was 70 years. Median follow-up was 4.6 years. Median radiotherapy dose was 78 Gy (5 × 2 Gy/week). Thirty patients (48.5%) received hormone therapy in combination with RT. Main surgery indications were urinary symptoms (65%) and urinary retention (20%). Five-year biochemical-disease free survival was 75% and 5-year clinical relapse free survival was 84%. At the time of the study, the IPSS after radiotherapy was as follows: 0–7: 77.6%; 8–19:20.7%; 20–35: 1.7%. Urinary quality of life was satisfactory for 74.2% of patients. After multivariate analysis, a high dose of RT and a medical history of hypertension were associated with a poorer quality of urinary life (p = 0.04). Conclusion External radiotherapy remains an appropriate treatment option without a major risk for deterioration in urinary function in patient with antecedent surgery for BPH. High dose of RT and a medical history of hypertension were associated with a poorer quality of urinary life

Rhizocarpon geographicum Lichen Discloses a Highly Diversified Microbiota Carrying Antibiotic Resistance and Persistent Organic Pollutant Tolerance

International audienceAs rock inhabitants, lichens are exposed to extreme and fluctuating abiotic conditions associated with poor sources of nutriments. These extreme conditions confer to lichens the unique ability to develop protective mechanisms. Consequently, lichen-associated microbes disclose highly versatile lifestyles and ecological plasticity, enabling them to withstand extreme environments. Because of their ability to grow in poor and extreme habitats, bacteria associated with lichens can tolerate a wide range of pollutants, and they are known to produce antimicrobial compounds. In addition, lichen-associated bacteria have been described to harbor ecological functions crucial for the evolution of the lichen holobiont. Nevertheless, the ecological features of lichen-associated microbes are still underestimated. To explore the untapped ecological diversity of lichen-associated bacteria, we adopted a novel culturomic approach on the crustose lichen Rhizocarpon geographicum. We sampled R. geographicum in French habitats exposed to oil spills, and we combined nine culturing methods with 16S rRNA sequencing to capture the greatest bacterial diversity. A deep functional analysis of the lichen-associated bacterial collection showed the presence of a set of bacterial strains resistant to a wide range of antibiotics and displaying tolerance to Persistent Organic Pollutants (POPs). Our study is a starting point to explore the ecological features of the lichen microbiota