Régénération de l’épithélium des voies aériennes

RésuméIntroductionLa régénération de l’épithélium respiratoire est un phénomène complexe qui peut, en conditions pathologiques (asthme, BPCO, mucoviscidose), aboutir à un remodelage chronique, altérant la fonctionnalité de l’épithélium.État des connaissancesLe développement de modèles d’étude in vivo et in vitro a permis d’étudier les mécanismes du remodelage bronchique. Les principaux acteurs de ce remodelage ont ainsi été mis en évidence : composants de la matrice extracellulaire, protéases, facteurs de croissance, cytokines. Les cellules progénitrices/souches de l’épithélium des voies aériennes ont également été étudiées dans ces modèles, leur identification restant toutefois difficile.ConclusionL’identification et la caractérisation des cellules souches/progénitrices de l’épithélium des voies aériennes ainsi que la compréhension complète des mécanismes de la régénération devraient permettre l’élaboration de nouvelles stratégies thérapeutiques favorisant la reconstitution épithéliale.SummaryIntroductionEpithelial regeneration is a complex process. It can lead to the remodeling of the airway epithelium as in asthma, COPD or cystic fibrosis.BackgroundThe development of in vivo and in vitro models has allowed the analysis of remodeling mechanisms and showed the role of components of extracellular matrix, proteases, cytokines and growth factors. Airway epithelial progenitors and stems cells have been studied in these models. However, their identification remains difficult.ConclusionIdentification and characterization of airway epithelial progenitor/stem-cells, and a better knowledge of the regeneration process may allow the development of new therapeutic strategies for airway epithelial reconstitution

Toxic epidermal necrolysis and Stevens-Johnson syndrome

Toxic epidermal necrolysis (TEN) and Stevens Johnson Syndrome (SJS) are severe adverse cutaneous drug reactions that predominantly involve the skin and mucous membranes. Both are rare, with TEN and SJS affecting approximately 1or 2/1,000,000 annually, and are considered medical emergencies as they are potentially fatal. They are characterized by mucocutaneous tenderness and typically hemorrhagic erosions, erythema and more or less severe epidermal detachment presenting as blisters and areas of denuded skin. Currently, TEN and SJS are considered to be two ends of a spectrum of severe epidermolytic adverse cutaneous drug reactions, differing only by their extent of skin detachment. Drugs are assumed or identified as the main cause of SJS/TEN in most cases, but Mycoplasma pneumoniae and Herpes simplex virus infections are well documented causes alongside rare cases in which the aetiology remains unknown. Several drugs are at "high" risk of inducing TEN/SJS including: Allopurinol, Trimethoprim-sulfamethoxazole and other sulfonamide-antibiotics, aminopenicillins, cephalosporins, quinolones, carbamazepine, phenytoin, phenobarbital and NSAID's of the oxicam-type. Genetic susceptibility to SJS and TEN is likely as exemplified by the strong association observed in Han Chinese between a genetic marker, the human leukocyte antigen HLA-B*1502, and SJS induced by carbamazepine. Diagnosis relies mainly on clinical signs together with the histological analysis of a skin biopsy showing typical full-thickness epidermal necrolysis due to extensive keratinocyte apoptosis. Differential diagnosis includes linear IgA dermatosis and paraneoplastic pemphigus, pemphigus vulgaris and bullous pemphigoid, acute generalized exanthematous pustulosis (AGEP), disseminated fixed bullous drug eruption and staphyloccocal scalded skin syndrome (SSSS). Due to the high risk of mortality, management of patients with SJS/TEN requires rapid diagnosis, evaluation of the prognosis using SCORTEN, identification and interruption of the culprit drug, specialized supportive care ideally in an intensive care unit, and consideration of immunomodulating agents such as high-dose intravenous immunoglobulin therapy. SJS and TEN are severe and life-threatening. The average reported mortality rate of SJS is 1-5%, and of TEN is 25-35%; it can be even higher in elderly patients and those with a large surface area of epidermal detachment. More than 50% of patients surviving TEN suffer from long-term sequelae of the disease

Host hindrance to HIV-1 replication in monocytes and macrophages

Monocytes and macrophages are targets of HIV-1 infection and play critical roles in multiple aspects of viral pathogenesis. HIV-1 can replicate in blood monocytes, although only a minor proportion of circulating monocytes harbor viral DNA. Resident macrophages in tissues can be infected and function as viral reservoirs. However, their susceptibility to infection, and their capacity to actively replicate the virus, varies greatly depending on the tissue localization and cytokine environment. The susceptibility of monocytes to HIV-1 infection in vitro depends on their differentiation status. Monocytes are refractory to infection and become permissive upon differentiation into macrophages. In addition, the capacity of monocyte-derived macrophages to sustain viral replication varies between individuals. Host determinants regulate HIV-1 replication in monocytes and macrophages, limiting several steps of the viral life-cycle, from viral entry to virus release. Some host factors responsible for HIV-1 restriction are shared with T lymphocytes, but several anti-viral mechanisms are specific to either monocytes or macrophages. Whilst a number of these mechanisms have been identified in monocytes or in monocyte-derived macrophages in vitro, some of them have also been implicated in the regulation of HIV-1 infection in vivo, in particular in the brain and the lung where macrophages are the main cell type infected by HIV-1. This review focuses on cellular factors that have been reported to interfere with HIV-1 infection in monocytes and macrophages, and examines the evidences supporting their role in vivo, highlighting unique aspects of HIV-1 restriction in these two cell types

Expression of Tau protein and Tau mRNA in the cerebellum during axonal outgrowth.

"In situ" hybridization and immunohistochemical analysis of the expression of Tau mRNAs and Tau proteins in the developing cerebellum showed that: 1. At early postnatal stages Tau mRNAs are expressed in the deeper region of the external granular layer (EGL II) i.e. in the cells that begin to migrate from the proliferative zone. Little labeling was seen in the upper layer (EGL I) where the cerebellar interneurons actively proliferate during the first two postnatal weeks. Anti-Tau antibodies failed to detect Tau proteins both in EGL I and II. 2. Tau transcripts were also clearly detected in the migrating cells present in the molecular layer; no Tau immunoreactivity was seen in this layer. This suggests that Tau mRNAs remain very poorly translated in the migrating granule cells and in the other interneurons. 3. Tau proteins begin to be detected at postnatal day 8 in the molecular layer but only at the level of the parallel fibers that are present in the Purkinje cell dendritic field. This suggests that the Tau mRNAs transcribed in the migrating cells are not actively translated for several days and that Tau proteins accumulate only in the more mature sections of their axons, the parallel fibers. In conclusion: Tau mRNAs are transcribed in the migrating cells several days before Tau proteins are actively translated and transported to their axons. Tau proteins accumulation occurs only at the end of granule cell migration i.e. when the parallel fibers interact with their post-synaptic counterparts, the dendrites of the Purkinje cells. Thus, axonal outgrowth and differentiation seem to be a multistep process.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

An unusual cause of calcified pulmonary opacity: A metastasis of a benign giant cell tumour of bone

International audienceNo abstract availabl

Opacités pulmonaires multiples révélant une toxocarose

International audienc

Le syndrome des ongles jaunes : présentation de cinq cas. [The yellow nail syndrome: a series of five cases].

International audienceINTRODUCTION: The yellow nail syndrome is a rare disorder described for the first time in 1964. The pathophysiology remains unclear. Its definition is based on a clinical triad of yellow nails, lymphoedema and chronic respiratory disorders including pleural effusions and bronchiectasis. CASES REPORTS: We describe a retrospective series of five patients diagnosed with the yellow nail syndrome. All the patients were male, aged from 52 to 71 years (median=56). Three patients were diagnosed with the classic triad, whereas the other two had only yellow nails and bronchiectasis. Yellow nails and chronic sinusitis were present in all five patients. We also report atypical manifestations such as a transudative pleural effusion and facial oedema. The yellow nail syndrome was associated with cancer in two cases. CONCLUSION: More common alternative diagnoses must be excluded. The association with cancer should be explored. The treatment is only symptomatic

Managing patients with chronic cough: challenges and solutions

Jeanne-Marie Perotin,1,2 Claire Launois,1 Maxime Dewolf,1 Antoine Dumazet,1 Sandra Dury,1 François Lebargy,1 Valérian Dormoy,2 Gaëtan Deslee1,2 1Department of Respiratory Diseases, University Hospital of Reims, Reims, France; 2INSERM UMRS 1250, University Hospital of Reims, Reims, France Abstract: Chronic cough is a common complaint and a frequent cause of medical consultation. Its management can be difficult. We present here an overview of the current guidelines for the management of chronic cough. Different steps are detailed, including the initial research of an obvious etiology and alert signs that should lead to further investigation of underlying condition. The diagnosis of the most frequent causes: asthma, non-asthmatic eosinophilic bronchitis, gastroesophageal reflux disease and upper airway cough syndrome should be considered, assessed and treated accordingly. Recent advances have been made in the comprehension of refractory chronic cough pathophysiology as well as its pharmacologic and non-pharmacologic treatment, especially speech pathology therapy. Keywords: asthma, gastroesophageal reflux, upper airway cough syndrome, chronic hypersensitivity syndrome, refractory chronic cough, speech pathology therap