Amélioration de la dermatite atopique par l'éducation thérapeutique et par l'utilisation de thérapeutiques alternatives

La dermatite atopique est une maladie cutanée inflammatoire chronique dont la prévalence dans la population est forte, surtout dans les pays industrialisés, et a augmenté régulièrement, ce qui en fait un problème de santé publique. Le but de cette thèse est tout d abord de rappeler la prise en charge de référence de l eczéma atopique en termes de prévention et de traitement. Il s agit ensuite de présenter en quoi les probiotiques et la phytothérapie, en tant que thérapeutiques alternatives, puis l éducation thérapeutique, peuvent apporter une amélioration dans la prise en charge des poussées d eczéma ou dans la qualité de vie des patients atteints de dermatite atopique. Le pharmacien a un rôle primordial à jouer dans le conseil et l information auprès des patients souffrant de cette maladie, notamment en matière de corticophobie.Atopic dermatitis is a chronic inflammatory skin disease, with high prevalence in the population, especially in industrialized countries, becoming regularly higher, which makes from it a public health problem.First of all, this thesis aims to clarify the mainstay of atopic eczema prevention and treatment. Then we will see how alternative medicines, such as probiotics and phytotherapy, or educational interventions, can support an improvement of both exacerbation management and life quality for patients with atopic dermatitis. Pharmacists have a crucial role to play in advicing and giving information to patients suffering from this disease, especially regarding topical steroid phobia.ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Historique du carnet de santé en France

CAEN-BU Médecine pharmacie (141182102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Cytokines de la famille du TGF-bêta et sérines protéases (Contrôle de la survie neuronale)

De nos jours, le seul traitement de l ischémie cérébrale, troisième cause de mortalité dans les pays industrialisés, est la thrombolyse par l activateur tissulaire du plasminogène (tPA). Cependant, bien que bénéfique au niveau vasculaire, le tPA a une composante délétère dans le parenchyme cérébral, notamment en modifiant les propriétés du récepteur glutamatergique NMDA, conduisant, en dépit d un bénéfice global de la thrombolyse, à une potentialisation de la mort neuronale excitotoxique. Dans cette étude, nous nous sommes intéressés à deux inhibiteurs endogènes du tPA : PAI-1 (type 1 Plasminogen Activator Inhibitor) et la Neuroserpine (NS) comme modulateurs potentiels des effets délétères de tPA au sein du parenchyme cérébral. Dans un premier temps, nous avons montré que pendant leur maturation, les neurones perdaient leur capacité de réponse au TGF-bêta (Transforming Growth Factor-bêta) associée à une chute d expression de PAI-1. Nous avons en parallèle mis en évidence que la sérine protéase : HtrA1 exprimée par les neurones et décrite comme étant un inhibiteur des membres de la famille du TGF-bêta, était capable de dégrader le TGF-bêta, et ainsi diminuer la production de PAI-1 et par conséquent, d augmenter l activité protéolytique du tPA endogène. Au contraire, nous avons démontré que le blocage de l activité protéolytique d HtrA1 conduisait à une restauration de l expression de PAI-1, à une diminution de l activité protéolytique du tPA et à la mort neuronale.Dans un deuxième temps, et parce que PAI-1 est une serpine quasi-ubiquiste, nous nous sommes intéressés à la neuroserpine, inhibiteur endogène du tPA spécifiquement exprimé dans le système nerveux central et plus particulièrement à la régulation du promoteur de cette serpine. Nous avons montré que certains membres de la famille du TGF-bêta sont capables d augmenter l expression de la NS dans les neurones. Parmi ces membres, nous avons identifié les Bone Morphogenetic Proteins (BMP-2, BMP-4 et BMP-7) et de manière plus surprenante l hormone anti-Müllerienne (AMH). Nous avons également mis en évidence dans le cerveau de souriceaux et de souris adultes la présence des récepteurs de type II à l AMH. Enfin, en accord avec le fait que l AMH promeut l expression de la NS et que la NS protège les neurones de la mort excitotoxique, nous avons révélé le potentiel neuroprotecteur de l AMH à la fois in vitro et in vivo.The only approved treatment for stroke, today the third cause of mortality in industrialized countries, is thrombolysis induced by tissue-type Plasminogen Activator (tPA). However, although tPA is beneficial in the vascular compartment, tPA is deleterious in the cerebral parenchyma by modifying properties of the NMDA receptors leading to a potentiation of excitotoxic neuronal death. In this study, we focused on two endogenous inhibitors of tPA : PAI-1 (type 1 Plasminogen Activator Inhibitor) and neuroserpine (NS) as potential modulators of the deleterious effects of tPA in brain parenchyma following stroke. We show that during their maturation, neurons lost their capacity to respond to TGF-bêta(Transforming Growth Factor-bêta), concomitant with a decrease of the expression of PAI-1. In parallel we found that the serine protease, HtrA1, which is expressed by neurons and known to inhibit signalling of members of the TGF-bêta family, was capable to promote the degradation of TGF-b, to decrease the production of PAI-1 and consequently, to increase the proteolytic activity of the endogenous tPA. At the opposite, we show that the blockage of the proteolytic activity of HtrA1 led to a restoration of the expression of PAI-1, to a reduction in the proteolytic activity of endogenous tPA and subsequent neuronal death. In contrast to PAI-1, which is a ubiquitous serpine (serine protease inhibitor), neuroserpine (NS), is an endogenous inhibitor of tPA, mainly expressed in the central nervous system. We investigated the regulation of expression of NS and activity of its promoter in neuronal cultures. We show that members of the TGF-bêta family are able to increase the expression of the NS in neurons. Among these members, we identified the Bone Morphogenetic Proteins (BMP-2, BMP-4 and BMP-7) and more surprisingly the Anti-Müllerian Hormone (AMH). Moreover, we showed a neuronal expression of the AMH type II receptors in brains of pups and in adult mice. Finally, in agreement with the fact that AMH promotes the expression of the NS and thus protects neurons from excitotoxic death, we unravelled the neuroprotective potential of AMH both in vitro and in vivo.CAEN-BU Sciences et STAPS (141182103) / SudocSudocFranceF

PrPC signalling in neurons: From basics to clinical challenges

International audienceThe cellular prion protein PrP(C) was identified over twenty-five years ago as the normal counterpart of the scrapie prion protein PrP(Sc), itself the main if not the sole component of the infectious agent at the root of Transmissible Spongiform Encephalopathies (TSEs). PrP(C) is a ubiquitous cell surface protein, abundantly expressed in neurons, which constitute the targets of PrP(Sc)-mediated toxicity. Converging evidence have highlighted that neuronal, GPI-anchored PrP(C) is absolutely required for prion-induced neuropathogenesis, which warrants investigating into the normal function exerted by PrP(C) in a neuronal context. It is now well-established that PrP(C) can serve as a cell signalling molecule, able to mobilize transduction cascades in response to interactions with partners. This function endows PrP(C) with the capacity to participate in multiple neuronal processes, ranging from survival to synaptic plasticity. A diverse array of data have allowed to shed light on how this function is corrupted by PrP(Sc). Recently, amyloid Aβ oligomers, whose accumulation is associated with Alzheimer's disease (AD), were shown to similarly instigate toxic events by deviating PrP(C)-mediated signalling. Here, we provide an overview of the various signal transduction cascades ascribed to PrP(C) in neurons, summarize how their subversion by PrP(Sc) or Aβ oligomers contributes to TSE or AD neuropathogenesis and discuss the ensuing clinical implications

Hijacking PrPc-dependent signal transduction: when prions impair Aβ clearance

The cellular prion protein PrPC is the normal counterpart of the scrapie prion protein PrPSc, the main component of the infectious agent of Transmissible Spongiform Encephalopathies. The recent discovery that PrPC can serve as a receptor for the amyloid Αβ peptide and relay its neurotoxicity is sparking renewed interest on this protein and its involvement in signal transduction processes. Disease-associated PrPSc shares with Αβ the ability to hijack PrPC-dependent signalling cascades, and thereby instigate pathogenic events. Among these is an impairment of Αβ clearance, uncovered in prion-infected neuronal cells. These findings add another facet to the intricate interplay between PrPC and Αβ. Here, we summarize the connection between PrP-mediated signalling and Αβ clearance and discuss its pathological implications

Distribution of oxytocin-like and vasopressin-like immunoreactivities within the central nervous system of the cuttlefish, Sepia officinalis

International audienceWe have investigated the distribution of oxytocin/vasopressin (OT/VP) superfamily peptides in the central nervous system (CNS) of the cuttlefish, Sepia officinalis, by using antibodies raised against mammalian OT and VP. Several populations of OT-like and VP-like immunoreactive cell bodies and fibers were widely distributed in cerebral structures involved in learning processes (vertical lobe complex, optic lobes), behavioral communication (peduncle, lateral basal and chromatophore lobes), feeding behavior (inferior frontal, brachial and buccal lobes), sexual activity (dorsal basal, subpedunculate, olfactory lobes), and metabolism (visceral lobes). The two most remarkable findings of this study were the occurrence of OT-like immunoreactivity in many amacrine cells of the vertical lobe and the dense accumulation of VP-like immunoreactive cell bodies in the subpedunculate 1 lobe. No double-immunolabeled cell bodies or fibers were found in any lobes of the CNS, indicating, for the first time in a decapod cephalopod mollusc, the existence of distinct oxytocinergic-like and vasopressinergic-like systems. The widespread distribution of the immunoreactive neurons suggests that these OT-like and VP-like peptides act as neurotransmitters or neuromodulators

PrPc from stem cells to cancer

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Ageing and amyloid-beta peptide deposition contribute to an impaired brain tissue plasminogen activator activity by different mechanisms

Alzheimer’s disease (AD) is the most common form of neurodegenerative disorder in the ageing population. It is characterized by the cerebral accumulation of toxic amyloid-beta peptide assemblies (Aβ). The serine protease plasmin, which is generated from the inactive zymogen plasminogen through its proteolytic cleavage by tissue- (tPA) or urokinase-type plasminogen activator, has been implicated in the catabolism of Aβ peptides. In this report, we studied the regulation of tPA activity in vivo during ageing in normal mice and in a mouse model of AD characterized by an exacerbated endogenous Aβ accumulation. We observed that cerebral tPA activity was decreased during ageing in normal mice and that this effect was worsened in mice overproducing Aβ peptides. These phenomena result, respectively, from a decrease in tPA expression and from an increase in the production of one of the tPA inhibitors, the plasminogen activator inhibitor type 1 (PAI-1). A similar study in sporadic AD and age-matched control brain tissues revealed that the tPA proteolytic activity was negatively correlated to Aβ peptides levels supporting the data observed in mice. Altogether, our data support a model in which amyloid deposition induces a decrease in tPA activity through the overproduction of PAI-1 by activated glial cells.status: publishe