Food allergy enhances allergic asthma in mice

BackgroundAtopic march refers to the typical transition from a food allergy in early childhood to allergic asthma in older children and adults. However the precise interplay of events involving gut, skin and pulmonary inflammation in this process is not completely understood.ObjectivesTo develop a mouse model of mixed food and respiratory allergy mimicking the atopic march and better understand the impact of food allergies on asthma.MethodsFood allergy to ovalbumin (OVA) was induced through intra-peritoneal sensitization and intra-gastric challenge, and/or a respiratory allergy to house dust mite (HDM) was obtained through percutaneous sensitization and intra-nasal challenges with dermatophagoides farinae (Der f) extract. Digestive, respiratory and systemic parameters were analyzed.ResultsOVA-mediated gut allergy was associated with an increase in jejunum permeability, and a worsening of Der f-induced asthma with stronger airway hyperresponsiveness and pulmonary cell infiltration, notably eosinophils. There was overproduction of the pro-eosinophil chemokine RANTES in broncho-alveolar lavages associated with an enhanced Th2 cytokine secretion and increased total and Der f-specific IgE when the two allergies were present. Both AHR and lung inflammation increased after a second pulmonary challenge.ConclusionGut sensitization to OVA amplifies Der f-induced asthma in mice

Il meticciato nell'Italia contemporanea. Storia, memorie e cultura di massa.

L'idea diffusa degli "italiani brava gente" e della diversit\ue0 della nostra storia rispetto alla storia USA, segnata da razzismo istituzionale, si fonda sul silenziamento del passato coloniale e razzista italiano. Il ripudio della categoria di razza da parte dell'Italia repubblicana e la smentita scientifica dell'esistenza biologica della categoria non hanno cancellato la presenza della razza, formazione storico-culturale che paradossalmente esiste e non esiste. Priva di referenti oggettivi nella realt\ue0, la razza produce in essa effetti significativi, opera sia come categoria sociale e strumento di esclusione, sia come costruzione simbolica e istanza identitaria. A fronte del silenziamento del meticciato storico nell'uso pubblico della storia e nella memoria nazionali del secondo dopoguerra, il saggio sottolinea la presenza diffusa del meticciato nei prodotti della cultura di massa italiani contemporanei e ne indaga i significati con gli strumenti degli studi critici sulla razza e in prospettiva comparata tra Italia e Stati Uniti

Dissection de la réponse biologique à la dyspnée expérimentale aigue

Understanding the pathophysiological mechanisms of dyspnea improve its management. Theobjective of this thesis is to describe the biological responses to the induction of experimentaldyspnea in healthy subjects. Two types of dyspnea (sensation of excessive inspiratory effortin response to a threshold inspiratory load - "respiratory effort" -, sensation of "air hunger" inresponse to CO2 stimulation with mechanical restriction of the reflex response - "air hunger")were induced in 34 healthy volunteers (17 men, 17 women). During "air hunger", substance Pmight be synthesized centrally and have a role in response to the psychological stress. Theincrease in blood pressure and galvanic skin response in this dyspnea might suggest aconcomitant activation of the sympathetic nervous system which could occur via substance Prelated to increased anxiety. The increase in substance P in "excessive effort" dyspnea couldbe the result of stimulation of the peripheral C fibers. The secretion of endorphins might notdepend on the peripheral mechanisms and arises probably from a central action. The earlydecrease in the level of BDNF could be related to a direct activation of the hippocampus. Theincrease in IDO without an increase in oxidative stress, cortisol or cytokines could beexplained by the short duration of the experimental dyspnea which does not allow thebiological response to take place at the systemic level. This work thus provides new insightson neurobiological mechanisms of dyspnea. It is now necessary to better understand theinteractions between the identified biological markers, to better dissect the signaling pathwayswith the final objective of targeted therapies.La compréhension des mécanismes de la dyspnée permet d’améliorer sa prise en charge.L'objectif de cette thèse est de décrire les réponses biologiques à l'induction de dyspnéeexpérimentale chez des sujets sains. Deux types de dyspnée (sensation « d’effort respiratoire »en réponse à une charge inspiratoire à seuil, sensation de « soif d'air » en réponse à unehypercapnie associée à une ventilation restreinte) ont été induites chez 34 volontaires sains (17hommes, 17 femmes). L'augmentation de la substance P pourrait résulter de la stimulation desfibres C périphériques dans la dyspnée de type « effort respiratoire », alors qu'elle serait laconséquence d'une sécrétion centrale liée en partie à l'anxiété dans la dyspnée de type « soifd'air ». L'augmentation de la pression artérielle et de l’impédance-métrie cutanée dans cettedyspnée suggérait une activation du système nerveux sympathique. La sécrétion d’endorphinesne semblait pas dépendre de mécanismes périphériques et correspondre à une action centrale.La diminution précoce du taux de Brain-Derived Neurotrophic Factor pourrait être en lien avecune activation de l'hippocampe directement au niveau central. L'augmentation de l'indoleamine2,3 dioxygenase sans augmentation du stress oxydant, du cortisol ou des cytokines pourraits'expliquer par la durée insuffisante de la dyspnée qui ne permettrait pas à la réponse biologiquede se mettre en place au niveau systémique. Ce travail donne des premières pistes de réflexionconcernant les mécanismes biologiques de la dyspnée. Il faut à présent mieux appréhender lesinteractions entre les marqueurs identifiés avec l'objectif final d'aboutir à une ou plusieursthérapeutiques ciblées

Dissection of the biological response to acute experimental dyspnea

La compréhension des mécanismes de la dyspnée permet d’améliorer sa prise en charge. L'objectif de cette thèse est de décrire les réponses biologiques à l'induction de dyspnée expérimentale chez des sujets sains. Deux types de dyspnée (sensation «d’effort respiratoire» en réponse à une charge inspiratoire à seuil, sensation de «soif d'air» en réponse à une hypercapnie associée à une ventilation restreinte) ont été induites chez 34 volontaires sains (17 hommes, 17 femmes).L'augmentation de la substance P pourrait résulter de la stimulation des fibres C périphériques dans la dyspnée de type «effort respiratoire», alors qu'elle serait la conséquence d'une sécrétion centrale liée en partie à l'anxiété dans la dyspnée de type «soif d'air». L'augmentation de la pression artérielle et de l’impédance-métrie cutanée dans cette dyspnée suggérait une activation du système nerveux sympathique. La sécrétion d’endorphines ne semblait pas dépendre de mécanismes périphériques et correspondre à une action centrale. La diminution précoce du taux de Brain-Derived Neurotrophic Factor pourrait être en lien avec une activation de l'hippocampe directement au niveau central. L'augmentation de l'indoleamine 2,3 dioxygenase sans augmentation du stress oxydant, du cortisol ou des cytokines pourrait s'expliquer par la durée insuffisante de la dyspnée qui ne permettrait pas à la réponse biologique de se mettre en place au niveau systémique. Ce travail donne des premières pistes de réflexion concernant les mécanismes biologiques de la dyspnée. Il faut à présent mieux appréhender les interactions entre les marqueurs identifiés avec l'objectif final d'aboutir à un ou plusieurs traitements ciblés.Understanding the pathophysiological mechanisms of dyspnea improve its management. The objective of this thesis is to describe the biological responses to the induction of experimental dyspnea in healthy subjects. Two types of dyspnea (sensation of excessive inspiratory effort in response to a threshold inspiratory load - "respiratory effort", sensation of "air hunger" in response to CO2 stimulation with mechanical restriction of the reflex response-"air hunger") were induced in 34 healthy volunteers (17 men, 17 women). During "air hunger", substance P might be synthesized centrally and have a role in response to the psychological stress. The increase in blood pressure and galvanic skin response in this dyspnea might suggest a concomitant activation of the sympathetic nervous system which could occur via substance P related to increased anxiety. The increase in substance P in "excessive effort" dyspnea could be the result of stimulation of the peripheral C fibers.The secretion of endorphins might not depend on the peripheral mechanisms and arises probably from a central action.The early decrease in the level of BDNF could be related to a direct activation of the hippocampus. The increase in IDO without an increase in oxidative stress, cortisol or cytokines could be explained by the short duration of the experimental dyspnea which does not allow the biological response to take place at the systemic level. This work thus provides new insights on neurobiological mechanisms of dyspnea. It is now necessary to better understand the interactions between the identified biological markers, to better dissect the signaling pathways with the final objective of targeted therapies

Etude du rôle potentiel du micro-ARN-150 dans la leucémie myelomonocytaire chronique

PARIS-BIUP (751062107) / SudocSudocFranceF

Déterminants de la limitation à l'effort chez des patients atteints d'histiocytose langerhansienne

LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

Effects of non-fatiguing respiratory muscle loading induced by expiratory flow limitation during strenuous incremental cycle exercise on metabolic stress and circulating natural killer cells

International audienceExercise induces release of cytokines and increase of circulating natural killers (NK) lymphocyte during strong activation of respiratory muscles. We hypothesised that non-fatiguing respiratory muscle loading during exercise causes an increase in NK cells and in metabolic stress indices. Heart rate (HR), ventilation (VE), oesophageal pressure (Pes), oxygen consumption (VO2), dyspnoea and leg effort were measured in eight healthy humans (five men and three women, average age of 31 ± 4 years and body weight of 68 ± 10 kg), performing an incremental exercise testing on a cycle ergometer under control condition and expiratory flow limitation (FL) achieved by putting a Starling resistor. Blood samples were obtained at baseline, at peak of exercise and at iso-workload corresponding to that reached at the peak of FL exercise during control exercise. Diaphragmatic fatigue was evaluated by measuring the tension time index of the diaphragm. Respiratory muscle overloading caused an earlier interruption of exercise. Diaphragmatic fatigue did not occur in the two conditions. At peak of flow-limited exercise compared to iso-workload, HR, peak inspiratory and expiratory Pes, NK cells and norepinephrine were significantly higher. The number of NK cells was significantly related to ΔPes (i.e. difference between the most and the less negative Pes) and plasmatic catecholamines. Loading of respiratory muscles is able to cause an increase of NK cells provided that activation of respiratory muscles is intense enough to induce a significant metabolic stress

Decreased breathing variability is associated with poorer outcome in mechanically ventilated patients

Rationale Breathing is a cyclic activity that is variable by nature. Breathing variability is modified in mechanically ventilated patients. We aimed to evaluate whether decreased variability on the day of transition from assist-control ventilation to a partial mode of assistance was associated with a poorer outcome. Methods This was an ancillary study of a multicentre, randomised, controlled trial comparing neurally adjusted ventilatory assist to pressure support ventilation. Flow and the electrical activity of the diaphragm (EAdi) were recorded within 48 h of switching from controlled ventilation to a partial mode of ventilatory assistance. Variability of flow and EAdi-related variables were quantified by the coefficient of variation, the amplitude ratio of the spectrum's first harmonic to its zero-frequency component (H1/DC) and two surrogates of complexity. Main results 98 patients ventilated for a median duration of 5 days were included. H1/DC of inspiratory flow and EAdi were lower in survivors than in nonsurvivors, suggesting a higher breathing variability in this population (for flow, 37% versus 45%, p=0.041; for EAdi, 42% versus 52%, p=0.002). By multivariate analysis, H1/DC of inspiratory EAdi was independently associated with day-28 mortality (OR 1.10, p=0.002). H1/DC of inspiratory EAdi was lower in patients with a duration of mechanical ventilation <8 days (41% versus 45%, p=0.022). Noise limit and the largest Lyapunov exponent suggested a lower complexity in patients with a duration of mechanical ventilation <8 days. Conclusion Higher breathing variability and lower complexity are associated with higher survival and lower duration of mechanical ventilation