Review : Auto-oxidation of aliphatic polyamides

The literature on oxidation kinetics of polyamides and model compounds has been reviewed in order to try to extract suitable information for non-empirical kinetic modeling. Polyamide characteristics are systematically compared to polyolefin ones, these latter being more extensively studied. From kinetic analysis point of view, it is shown that oxidation attacks predominantly a amino methylenes of which C eH bond is considerably weaker than the other methylenes. As a result, propagation by H abstraction is considerably faster in polyamides than in polyethylene for instance. Termination by radical combination is also very fast. Another cause of PA oxidizability is the instability of a amino hydroperoxides linked to the inductive effect of nitrogen. This instability is responsible for many key features of oxidation kinetics especially the absence of induction period. The main stable oxidation products are imides resulting from disproportionation processes meanwhile chain scissions resulting from rearrangements of a amino alkyls by b-scission are also significant process although their yield appears lower than in polyolefins

Molecular and macromolecular structure changes in polyamide 11 during thermal oxidation

The present article reports a study of thermal oxidation of unstabilized polyamide 11 films at several temperatures (90–165 °C) under atmospheric pressure and under various oxygen pressures (up to 1.6 MPa) at 110 °C. The chemical structure changes are monitored by IR spectroscopy (carbonyl groups) and UV–visible spectrophotometry (yellowing). Molar mass changes are determined by size exclusion chromatography (SEC). By investigating the influence of oxygen pressure it is clearly shown that reactions involving P° radicals other than O2 addition cannot be neglected under atmospheric pressure. Under the conditions of this study limited to relatively low oxidation levels, IR and UV measurements indicate that carbonyl groups and chromophores responsible for yellowing have the same relative yield whatever the temperature and oxygen pressure. SEC measurements highlight the significant predominance of random chain scissions over crosslinking events. Crosslinking only appears after an induction time, presumably because it involves reactions between primary oxidation products. The ratio of carbonyl groups over chain scissions is about 7.5 at low conversion and about 2.5 at high conversion, showing that α amino alkoxy radicals are mainly transformed into imides without chain scission

Investigation of polyamide 11 embrittlement during oxidative degradation

Embrittlement processes occurring during thermal oxidation are investigated for stabilized and unstabilized polyamide 11 samples differing by their thicknesses and initial molar masses. Tensile tests were carried out in the temperature range between room temperature and 110 °C in order to investigate the influence of mechanical testing temperature on the embrittlement coordinates. In the same time, molar mass and crystalline morphology are monitored by size exclusion chromatography (SEC) and DSC/SAXS measurements respectively. The experimental results point out the existence of a critical molar mass for ductile-brittle transition M′c about 10 kg mol−1, independent of sample initial molar mass or stabilization, but depending on tensile testing temperature. However, even if oxidation chain scissions are shown to be clearly responsible for the loss of mechanical properties at failure, the structure-property relationships governing ductile-brittle transition require a mixed criterion involving molar mass and crystalline morphology, especially the interlamellar distance. For this purpose, specific molar mass – crystalline morphology relationships are investigate

Thermal stabilization of polyamide 11 by phenolic antioxidants

This paper addresses the effect of hindered phenols (mainly Irganox 1098 with a few comparisons with other phenolic antioxidants) on the stabilization of polyamide 11 aged at several temperatures (90–165 °C). The effect of several phenol concentrations (up to about 0.4%) on kinetic curves for imide build-up, yellowing, and molar mass changes (in association with embrittlement) was investigated. Phenols significantly contribute to yellowing, even at low imide concentrations. When they are used at high concentrations, a post-polycondensation reaction becomes predominant at earlier exposure times, thus increasing molar mass and significantly delaying embrittlement

Quantification of hindered phenols in polyamide 11 during thermal aging

Polyamide 11 films stabilized by Irganox® 1098, Irganox® 1010 or Irganox® 245 were subjected to thermal oxidation at 110°C. The residual phenol content was assessed by comparing three analytical methods:high performance liquid chromatography (HPLC), determination of the Oxidation Induction Time (OIT)and Onset Oxidation Temperature (OOT) by thermal analyses. Both OIT and OOT are reliable for virgin PA11 after a relevant calibration by HPLC measurement. In the case of oxidized samples, OOT measurements have the benefits of being more easily interpretable than OIT and less time-consuming than HPLC measurements.CIFR

Analogues expérimentaux de dégénérescence striatonigrique et développement d'un modèle systémique chez la souris

La dégénérescence striatonigrique (DSN) est une maladie neurodégénérative qui associe l'atteinte de la substance noire pars compacta (SNc) et du striatum. Après avoir validé un test de mesure de la longueur du pas chez la souris, nous avons étudié les conséquences de lésions induites par l'acide 3-nitropropionique (3-NP) et avons caractérisé un syndrome moteur spécifique corrélé au degré d'atteinte striatale ainsi qu'une altération des performances motrices et une perte neuronale dans la SNc dose-dépendantes. Nous avons ensuite étudié le rôle de la dopamine sur l'intégrité striatale et avons mis en évidence une augmentation de l'effet du 3-NP chez des souris hyperdopaminergiques ainsi que des troubles moteurs spontanés associés à une atteinte striatale modérée. Nous avons ensuite développé un modèle de DSN par intoxication combinée au 3-NP+MPTP, caractérisé par une absence d'interactions entre les deux neurotoxiques et une augmentation des troubles moteurs et de l'atteinte striatale.Striatonigral degeneration (SND) is a neurodegenerative disease combining loss of substantia nigra pars compacta (SNc) and striatal neurons. We first validated a stride length test in the mouse and studied the consequences of 3-nitropropionic acid (3-NP) induced lesions and demonstrated a characteristic motor syndrome correlated with the extent of striatal neuronal loss while a dose-dependant motor impairment and neuronal loss in the SNc. We then studied the role of dopamine upon striatal functioning and demonstrated a hypersensitivity to 3-NP in hyperdopaminergic mice, together with spontaneous motor deficits and striatal neuronal loss. Finally, we developped a model of SND using combined MPTP+3-NP intoxication and characterized by a lack of interactions between the two neurotoxins, increased behavioural troubles, motor impairments and striatal injury.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Protein aggregation in the aging retina.

International audienceThe age-related altered expression of neuron-related proteins as seen in other regions of the central nervous system is expected in the aging retina. Using immunohistochemical techniques, we characterized the distribution and aggregation of tau, βA4-amyloid, α-synuclein, and ubiquitin in human retina obtained from 19 enucleated eyes of patients aged 49 to 87 years and correlated the findings with the ages. Using a phosphorylation-independent antibody, tau aggregates were observed within the cytoplasm of several photoreceptor cells, and there was a positive correlation between age and the number of tau-positive ganglionic cells. Tau deposits were immunonegative with a phosphorylation-dependent antibody. We did not observe βA4-amyloid in subretinal pigment epithelium deposits or in neuroepithelial layers. α-Synuclein and ubiquitin inclusions were found in the inner nuclear layer, and there was colocalization of these proteins. The proportion of patients displaying such α-synuclein and/or ubiquitin intracytoplasmic inclusions was significantly higher with aging. The presence of ubiquitin deposits within drusen was remarkable, but diffuse ubiquitin aggregates between the retinal pigment epithelium and Bruch membrane were also noticed. These results indicate that protein aggregation in the retina increases with aging and that tau, α-synuclein, and ubiquitin should be the subjects of future investigations

Region-Specific Alterations of Matrix Metalloproteinase Activity in Multiple System Atrophy

International audienceMSA is a sporadic progressive neurodegenerative disorder characterized by a variable combination of parkinsonism, cerebellar ataxia, and autonomic dysfunction. The pathological hallmark of MSA is the accumulation of alpha-synuclein aggregates in the cytoplasm of oligodendrocytes along with neuronal loss and neuroinflammation, as well as blood-brain barrier dysfunction and myelin deterioration. Matrix metalloproteinases are zinc-dependent endopeptidases involved in the remodeling of the extracellular matrix, demyelination, and blood-brain barrier permeability. Several lines of evidence indicate a role for these enzymes in various pathological processes, including stroke, multiple sclerosis, Parkinson's, and Alzheimer's disease

Involvement of the bed nucleus of the stria terminalis in L-Dopa induced dyskinesia.

International audienceA whole brain immediate early gene mapping highlighted the dorsolateral bed nucleus of the stria terminalis (dlBST) as a structure putatively involved in L-3,4-dihydroxyphenylalanine (L-Dopa)-induced dyskinesia (LID), the debilitating side-effects of chronic dopamine replacement therapy in Parkinson's disease (PD). dlBST indeed displayed an overexpression of ∆FosB, ARC, Zif268 and FRA2 only in dyskinetic rats. We thus hypothesized that dlBST could play a role in LID hyperkinetic manifestations. To assess the causal role of the dlBST in LID, we used Daun02 inactivation to selectively inhibit the electrical activity of dlBST ΔFosB-expressing neurons. Daun02 is a prodrug converted into Daunorubicin by ß-galactosidase. Then, the newly synthesized Daunorubicin is an inhibitor of neuronal excitability. Therefore, following induction of abnormal involuntary movements (AIMs), 6-OHDA rats were injected with Daun02 in the dlBST previously expressing ß-galactosidase under control of the FosB/ΔFosB promoter. Three days after Daun02 administration, the rats were tested daily with L-Dopa to assess LID. Pharmacogenetic inactivation of ∆FosB-expressing neuron electrophysiological activity significantly reduced AIM severity. The present study highlights the role of dlBST in the rodent analog of LID, offering a new target to investigate LID pathophysiology

Multiple system atrophy: A prototypical synucleinopathy for disease-modifying therapeutic strategies

International audienceDespite active fundamental, translational and clinical research, no therapeutic intervention has yet shown convincing effects on disease progression in Parkinson's disease (PD) patients. Indeed, several disease-modification trials failed or proved to be inconclusive due to lack of consistency between clinical rating scales and putative surrogate markers of disease progression, or confounding symptomatic effects of the tested compound. Multiple system atrophy (MSA) is a rapidly progressing orphan disorder leading to severe motor disability within a few years. Together with PD and dementia with Lewy bodies (DLB), MSA belongs to the synucleinopathies, a group of neurodegenerative disorders characterized by the abnormal accumulation of alpha-synuclein. Crucial milestones have been reached for successfully conducting clinical intervention trials in a large number of patients with MSA. In this personal view, we will review evidence, and discuss why MSA could prove the most relevant clinical model for assessing treatments that target mechanisms operating in all synucleinopathies