Étude des poly(2-alkyl-2-oxazoline)s munis d'extrémités hydrophobes en solution aqueuse et à linterface eau/air

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

Régénération de l'épithélium respiratoire de surface humain et mucoviscidose et identification des cellues progénitrices épithéliales

REIMS-BU Santé (514542104) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Réparation et régénération de l’épithélium respiratoire

L’épithélium de surface des voies aériennes proximales assure la protection de la muqueuse respiratoire grâce à différents mécanismes, comme la clairance mucociliaire, la régulation des flux d’ions et d’eau et la sécrétion de molécules de défense. La seconde ligne de protection est assurée par des complexes jonctionnels intercellulaires permettant de préserver la fonction de barrière de l’épithélium. En contact permanent avec l’environnement extérieur, l’épithélium des voies aériennes est cependant fréquemment lésé par les agents toxiques, les bactéries ou les virus inhalés : ces lésions peuvent entraîner la perte de l’intégrité de la barrière épithéliale ou la desquamation partielle ou totale des cellules épithéliales. Afin de restaurer sa fonction, l’épithélium respiratoire doit non seulement réparer les lésions, mais aussi reconstituer et régénérer un épithélium fonctionnel. Ces processus complexes allient des fonctions de migration, prolifération et différenciation cellulaire, régulées par divers facteurs de croissance, cytokines, protéines de la matrice extracellulaire et enzymes protéolytiques. La connaissance des mécanismes cellulaires et moléculaires gouvernant la restauration tissulaire est un prérequis indispensable à l’élaboration de stratégies prorégénératrices de l’épithélium de surface des voies aériennes dans de nombreuses pathologies respiratoires telles que l’asthme, les bronchopneumopathies chroniques obstructives, la mucoviscidose ou les bronchiolites oblitérantes

[Regeneration of injured airway epithelium]

The airway surface epithelium is frequently injured by microorganisms and viruses due to its permanent contact with the external medium. Following injury, the epithelium is able to repair itself and regenerate through several mechanisms including spreading and migration of basal cells, cell proliferation and differentiation. The cellular and molecular factors involved in wound repair and epithelial regeneration interact closely, implying the participation of cytoskeleton proteins and integrins receptors, matrix metalloproteinases and their inhibitors as well as cytokines and growth factors secreted by airway epithelial and mesenchymal cells. The spatio-temporal modulation of the pro-inflammatory cytokines such as IL-8, and MMPs (MMP-9 and -7) during the different steps of regeneration suggests that the matrix and secretory environment are markedly involved in these mechanisms and that their dysregulation may induce remodeling of the airway mucosa. A better knowledge of the mechanisms involved in airway epithelium regeneration may pave the way to regenerative therapeutics allowing the reconstitution of a functional airway mucosa in numerous respiratory diseases such as cystic fibrosis, chronic obstructive pulmonary diseases and bronchiolitis

Silicone-recycled pyrolyzed fillers for enhanced thermal - and flame - resistant silicone elastomers

International audienceTwo types of fillers were prepared by controlled pyrolysis of a commercial silicone elastomer. An aerobic process led to the formation of a silica powder while an anaerobic pyrolysis generated a silicon-carbon-oxide (SiOC) ceramic. Each filler was incorporated into a silicone gum and thus-prepared obtained formulations were further crosslinked with peroxide to prepare new silicone materials. Silica powder allowed controlling the mechanical properties of the materials whereas enhanced thermal stability was brought by the ceramic; mixing both fillers generated materials with joint properties (tensile strength of about 2 MPa, elongation at break of 300%, onset of degradation at 470 °C). The flame resistance behavior of these silicone materials was tested by cone calorimetry. Early formation of an insulating layer on the heat-exposed surface moderated the heat release (total heat release of 16.4 kJ/gPDMS) and increased final residue (above 50%) compared to commercial silica-filled elastomers. This work opens new possibilities to transform silicone waste into useful inorganic fillers and produce new performant thermal-resistant silicone materials

Les traitements pharmacologiques des douleurs neuropathiques

International audienceNeuropathic pain is defined as pain caused by a lesion or a disease affecting the somatosensory nervous system. Development of neuropathic pain is induced by many pathophysiological mechanisms affecting pain pathways. Neuropathic pain has diverse origins, making its management difficult, hence, many patients with neuropathic pain do not receive appropriate treatment. In 2015, a revision of the Neuropathic Pain Special Interest Group's (NeuPSIG) previous recommendations, based on a systematic review and meta-analysis, evaluated the efficacy of systemic and topical treatments of neuropathic pain. Treatments lines were established using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), which allows to rate the quality of evidence and the strength of recommendations. First line treatments are gabapentin and pregabalin, noradrenalin and serotonin reuptake inhibitors and tricyclic antidepressants. Capsaicin and lidocaine patches are second line treatments, tramadol and strong opioids are third line treatments. This work also highlighted molecules with inconclusive recommendations or non-recommended pharmacological treatments based on a low quality of evidence, a lack of efficacy or a bad safety profile. The objective of this paper is to present the different treatments and to detail their mechanisms of action

An overview of ongoing clinical trials assessing pharmacological therapeutic strategies to manage chemotherapy‐induced peripheral neuropathy, based on preclinical studies in rodent models

International audienceChemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect induced by a variety of chemotherapeutic agents. Symptoms are mainly sensory: pain, tingling, numbness, and temperature sensitivity. They may require the tapering of chemotherapy regimens or even their cessation; thus, the prevention/treatment of CIPN is critical to increase effectiveness of cancer treatment. However, CIPN management is mainly based on conventional neuropathic pain treatments, with poor clinical efficacy. Therefore, significant effort is made to identify new pharmacological targets to prevent/treat CIPN. Animal modeling is a key component in predicting human response to drugs and in understanding the pathophysiological mechanisms underlying CIPN. In fact, studies performed in rodents highlighted several pharmacological targets to treat/prevent CIPN. This review provides updated information about ongoing clinical trials testing drugs for the management of CIPN and presents some of their proof-of-concept studies conducted in rodent models. The presented drugs target oxidative stress, renin-angiotensin system, glutamatergic neurotransmission, sphingolipid metabolism, neuronal uptake transporters, nicotinamide adenine dinucleotide metabolism, endocannabinoid system, transient receptor potential channels, and serotoninergic receptors. As some clinical trials focus on the effect of the drugs on pain, others evaluate their efficacy by assessing general neuropathy. Moreover, based on studies conducted in rodent models, it remains unclear if some of the tested drugs act in an antinociceptive fashion or have neuroprotective properties. Thus, further investigations are needed to understand their mechanism of action, as well as a global standardization of the methods used to assess efficacy of new therapeutic strategies in the treatment of CIPN

Human airway surface epithelial regeneration is delayed and abnormal in cystic fibrosis.

Cystic fibrosis (CF) at an advanced stage of the disease is characterized by airway epithelial injury and remodelling. Whether CF remodelling is related to infection and inflammation or due to an abnormal regenerative process is still undecided. We have recently established the expression and secretion profiles of interleukin (IL)-8, matrix metalloproteinase (MMP)-7, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1 during non-CF airway epithelial regeneration in a humanized nude mouse xenograft model. To enhance our understanding of CF remodelling, we compared the regeneration process of non-infected human CF and non-CF nasal epithelia. In both CF and non-CF situations, epithelial regeneration was characterized by successive steps of cell adhesion and migration, proliferation, pseudostratification, and terminal differentiation. However, histological examination of the grafts showed a delay in differentiation of the CF airway epithelium. Cell proliferation was higher in the regenerating CF epithelium, and the differentiated CF epithelium exhibited a pronounced height increase and basal cell hyperplasia in comparison with non-CF epithelium. In addition, while the number of goblet cells expressing MUC5AC was similar in CF and non-CF regenerated epithelia, the number of MUC5B-immunopositive goblet cells was lower in CF grafts. The expression of human IL-8, MMP-7, MMP-9, and TIMP-1 was enhanced in CF epithelium, especially early in the regenerative process. Together, our data strongly suggest that the regeneration of human CF airway surface epithelium is characterized by remodelling, delayed differentiation, and altered pro-inflammatory and MMP responses

Influence of lignocellulosic substrate and phosphorus flame retardant type on grafting yield and flame retardancy

International audienceVarious phosphorus flame retardants (FR) have been grafted on lignin-rich miscanthus fibers and lignin-poor flax fibers according to two methods, phosphonic acids condensation in mild conditions and radiation grafting. Phosphorus content and its location on fibers were evaluated. Even if phosphorus FR diffused into the fibers bulk in all cases, chemical modification based on phosphonic acids condensation with hydroxyls of miscanthus fibers appears more suitable for high lignin content fibers. Phosphorus content in miscanthus fibers reached 1.4 wt% using hexane-1,6-diylbisphosphonic acid whereas it reached a lower content (0.3 wt%) for flax fibers. Radiation grafting is suitable for both fibers with limited effect depending on fiber nature. Flame retardancy at microscale was examined using PCFC and TGA. Thermal properties and flame retardancy have been shown to be correlated to the phosphorus content but also to fibers composition and to the thermal stability of the flame retardant. Vinyl phosphonic acid was found to be more efficient as char promoter for flax compared to miscanthus