References of "Lefebvre, Philippe"
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See detailPotential use of estetrol in sensorineural hearing loss protection
DELHEZ, Amandine ULg; Manfroid, Isabelle ULg; LEFEBVRE, Philippe ULg et al

in B-ENT (2017)

Introduction and Aims: Estrogens have a positive impact on the auditory function. Indeed, estradiol (E2) treatment in animals protects against acoustic trauma and aminoglycoside toxicity and its depletion ... [more ▼]

Introduction and Aims: Estrogens have a positive impact on the auditory function. Indeed, estradiol (E2) treatment in animals protects against acoustic trauma and aminoglycoside toxicity and its depletion can contribute to age-related hearing loss. However, estradiol is not suitable in clinical practice, given the increased risk of cancer and thromboembolic events. There is a need to find new treatments that present a higher benefit/risk ratio. In this work, we studied a new natural estrogen derivative, estetrol (E4), that was shown to act as a Selective Estrogen Receptor Modulator (SERM). Estetrol is thus able to display estrogen-like as well as antiestrogen activity depending on the target tissue. Interestingly, E4 allows the prevention of menopause symptoms such as osteoporosis or hot flushes through an agonistic action, whereas it exerts anti-estrogenic effects on the mammary gland. These preclinical data suggest that E4 presents a safer profile than E2. Material and Methods: To investigate whether this molecule presents otoprotective actions, we exposed P2 cultured organs of Corti to gentamicin, with or without estetrol (E4). After 48 hours of culture, hair cell survival was evaluated following anti-myosin VII Immunohistochemistry. We next moved on to in vivo studies using young zebrafish larvae (5dpf), since they constitute a highly effective model to determine the potential ototoxicity of drugs and to screen for candidates of hair cell protective agents. We monitored the survival of hair cells within neuromasts following chronic or acute exposure to gentamicin. Results: In cochlear culture, gentamicin-induced hair cell loss was significantly reduced by E4. Interestingly, the toxicity of aminoglycoside was also reduced in vivo upon treatment of zebrafish larvae with E4. Conclusion: The survival rate of hair cells was increased in the presence of estetrol both in vitro and in vivo indicating that estetrol constitutes an interesting protective drug against hearing loss. [less ▲]

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See detailDerivation of cochlear cells from pathological or isogenic human iPSCs for modeling hereditary hearing loss
Czajkowski, Amandine ULg; Grobarczyk, Benjamin; Hanon, Kevin ULg et al

Poster (2016, May)

Alström Syndrome (AS) is a human autosomal recessive genetic disorder characterized by numerous clinical symptoms including deafness. AS is caused by mutations in the ALMS1 gene encoding for ALMS1 protein ... [more ▼]

Alström Syndrome (AS) is a human autosomal recessive genetic disorder characterized by numerous clinical symptoms including deafness. AS is caused by mutations in the ALMS1 gene encoding for ALMS1 protein expressed at the basal body and implicated in ciliogenesis, cell cycle and proliferation (Jagger et al., 2011; Zulato et al., 2011 & Shenje et al., 2014). We are interesting in understanding the unknown mechanisms involving this protein in the genetic deafness of AS patients. To develop a model as closer as possible to the human pathology, we are using human induced pluripotent stem cells (hiPSCs) generated from fibroblasts of healthy and AS patients. Using a stepwise protocol, we demonstrated that healthy hiPSCs (waiting for isogenic hiPSCs) can generate a population of cells with gene and protein expression patterns consistent with the ones of otic progenitor cells (OSCs). At this differentiation stage, we observed some proliferation and apoptotic defects between healthy and AS cells. When human OSCs are co-cultured with mouse feeder cells, they are able to differentiate into hair cells (HCs). We successfully differentiated AS hiPSCs generated from AS patients into HCs. We are currently confirming gene expression pattern and testing HCs functionality.  To exclude patient linked epigenetics and differentiation defects, we are correcting the genomic mutation in the AS hiPSCs to generate isogenic hiPSCs using the CRIPSR/Cas9 system. Thanks to the isogenic hiPSCs we will be able to confirm that these defects are well due to the ALMS1 mutation. [less ▲]

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See detailFunctional respiratory imagning-aided virtual preoperative planning in nasal surgery: towards a personalized approach.
Ansari, Edward; Vos, Wim; Van Holsbeke, Cedric et al

in B-ENT (2016)

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See detailFunctional respiratory imagning-aided virtual preoperative planning in nasal surgery: towards a personalized approach
Ansari, Edward; Vos, Wim; Van Holsbeke, Cedric et al

Conference (2016)

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See detailDopaminergic neurons differentiating from LRRK2 G2019S induced pluripotent stem cells show early neuritic branching defects.
Borgs, Laurence; Peyre, Elise ULg; Alix, Philippe et al

in Scientific Reports (2016), 6

Some mutations of the LRRK2 gene underlie autosomal dominant form of Parkinson's disease (PD). The G2019S is a common mutation that accounts for about 2% of PD cases. To understand the pathophysiology of ... [more ▼]

Some mutations of the LRRK2 gene underlie autosomal dominant form of Parkinson's disease (PD). The G2019S is a common mutation that accounts for about 2% of PD cases. To understand the pathophysiology of this mutation and its possible developmental implications, we developed an in vitro assay to model PD with human induced pluripotent stem cells (hiPSCs) reprogrammed from skin fibroblasts of PD patients suffering from the LRKK2 G2019S mutation. We differentiated the hiPSCs into neural stem cells (NSCs) and further into dopaminergic neurons. Here we show that NSCs bearing the mutation tend to differentiate less efficiently into dopaminergic neurons and that the latter exhibit significant branching defects as compared to their controls. [less ▲]

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See detailAudiometric results after stapedotomy operations in patients with otosclerosis and preoperative small air-bone gaps
SALMON, Caroline ULg; BARRIAT, Sébastien ULg; DEMANEZ, Laurent CH P ULg et al

in Audiology & Neuro-otology (2015), 20

Objectives: The efficacy of stapedotomies performed on patients with small air-bone gaps (<25 dB, sABG) was compared to the efficacy of the operation in patients who had otosclerosis with high air-bone ... [more ▼]

Objectives: The efficacy of stapedotomies performed on patients with small air-bone gaps (<25 dB, sABG) was compared to the efficacy of the operation in patients who had otosclerosis with high air-bone gaps (≥25 dB, hABG). Methods: This retrospective study evaluates the short-term postoperative air and bone conduction thresholds and air-bone gaps after 181 CO2 laser stapedotomies. Results: A significantly smaller air-bone gap (ABG) and lower air conduction thresholds after surgery were observed in the group of patients who underwent surgery with preoperative ABGs of less than 25 dB. Bone conduction thresholds improve in sABG group after surgery. Conclusions: The results after stapedotomies are good even if the preoperative air-bone gap is small and that the overall risk of hearing deterioration due to stapes surgery remains low. [less ▲]

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See detailSwallowing in disorders of consciousness
Bicego, Aminata; Lejoly, Kelly ULg; Maudoux, Audrey et al

in Revue Neurologique (2014), 170(10),

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See detailFrench adaptation and validation of the SinoNasal Outcome Test (SNOT)-22: a prospective cohort study on quality of life among 422 subjects.
de Dorlodot, Clotilde; Horoi, Mihaela; Lefèbvre, Philippe ULg et al

in Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery (2014)

OBJECTIVES: ENT surgeons are facing an ever-increasing demand to demonstrate their efficacy. The 22-item Sino-Nasal Outcome Test (SNOT-22) is a fully validated and easy-to-use outcome measure in rhinology ... [more ▼]

OBJECTIVES: ENT surgeons are facing an ever-increasing demand to demonstrate their efficacy. The 22-item Sino-Nasal Outcome Test (SNOT-22) is a fully validated and easy-to-use outcome measure in rhinology. Our goal was to translate and validate the SNOT-22 in a cohort of 422 French-speaking subjects. DESIGN, SETTING AND PARTICIPANTS: The French version of the SNOT-22 was obtained by forward and backward translations by 6 independent interpreters. Five experienced rhinologists compared the translations to each other and a group of 12 naive patients selected the most appropriate translation of each item. To evaluate this questionnaire, we conducted a prospective cohort study on 376 rhinological patients and 46 healthy volunteers in 3 University-affiliated teaching Hospitals. MAIN OUTCOME MEASURES: reproducibility (test-retest reliability), internal consistency, known group differences, responsiveness to treatment, validity and correlation to other clinical instruments (visual analogue scale, Nasal Obstruction Symptoms Evaluation score and Lund-Mackay score). RESULTS: The test-retest reliability coefficient was 0.78, indicating a good reliability when administering the instrument on two different occasions. The internal consistency was high with a Cronbach's alpha value of 0.93. Our questionnaire was able to detect differences between rhinological patients and control subjects (p<0.0001) and improved significantly after nose and sinus surgery (p<0.0001), indicating a good responsiveness. There was a relative correlation with visual analogue scale and NOSE score, but no correlation with Lund-Mackay score. CONCLUSION: The SNOT-22 is a reliable and valid tool to assess quality of life in French-speaking patients and correlates well with known indices of disease severity. This article is protected by copyright. All rights reserved. [less ▲]

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See detailIn vivo protection of spiral ganglion neurons by bryostatin 1: preliminary results
POIRRIER, Anne-Lise ULg; Van Den Ackerveken, Priscilla ULg; Defourny, Jean et al

in Advances in Cellular and Molecular Otolaryngology (2013), 1

Background: We aim to demonstrate the effect of bryostatin 1, a macrocyclic lactone that activates protein kinase C, on spiral ganglion neurons (SGNs) of adult guinea pigs deafened by aminoglycoside ... [more ▼]

Background: We aim to demonstrate the effect of bryostatin 1, a macrocyclic lactone that activates protein kinase C, on spiral ganglion neurons (SGNs) of adult guinea pigs deafened by aminoglycoside. Methodology: Twenty-one guinea pigs were deafened by the aminoglycoside gentamicin and then treated by continuous infusion of experimental molecule for 1 month. The experimental molecule was bryostatin 1, artificial perilymph (negative control), or neurotrophins and an apoptosis inhibitor (positive control). Neuronal density in the spiral ganglia was quantified. Results: Bryostatin 1 protected SGNs after a gentamicin challenge. Conclusions: Bryostatin 1 has a neuroprotective effect when administered continuously at low doses in adult guinea pigs. [less ▲]

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See detailcomment j'explore une otite séromuqueuse chez l'enfant
Dachy, Angélique ULg; LEFEBVRE, Philippe ULg; Battisti, Oreste ULg

in Revue Médicale de Liège (2013), 68

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See detailNovel association between vasoactive intestinal peptide and CRTH2 receptor in recruiting eosinophils: a possible biochemical mechanism for allergic eosinophilic inflammation of the airways.
EL SHAZLY, Amr ULg; Begon, Dominique ULg; KUSTERMANS, Gaëlle ULg et al

in Journal of Biological Chemistry (2013), 288(2), 1374-84

We explored the relation between vasoactive intestinal peptide (VIP), CRTH2, and eosinophil recruitment. It is shown that CRTH2 expression by eosinophils from allergic rhinitis (AR) patients and ... [more ▼]

We explored the relation between vasoactive intestinal peptide (VIP), CRTH2, and eosinophil recruitment. It is shown that CRTH2 expression by eosinophils from allergic rhinitis (AR) patients and eosinophils cell line (Eol-1 cells) was up-regulated by VIP treatment. This was functional and resulted into exaggerated migratory response of cells against PGD2. Nasal challenge of AR patients resulted into significant increase of VIP contents in nasal secretion (ELISA), and the immunohistochemical studies of allergic nasal tissues, showed significant expression of VIP in association with intense eosinophil recruitment. Biochemical assays showed that VIP-induced eosinophils chemotaxis from AR patients and Eol-1 cells, was mediated through CRTH2 receptor. Cells migration against VIP was sensitive to protein kinase C (PKC) and protein kinase A (PKA) inhibition, but not to tyrosine kinase or P38 MAP-kinase inhibition, or calcium chelation. Western blot demonstrated a novel CRTH2 mediated cytosol to membrane translocation of PKC-epsilon, PKC-delta and PKA-alpha, gamma and IIalpha reg in Eol-1 cells upon stimulation with VIP. Confocal images and FACS demonstrated a strong association and co-localization between VIP peptide and CRTH2 molecules. Further, VIP induced PGD2 secretion from eosinophils. Our results demonstrate the first evidence of association between VIP and CRTH2 in recruiting eosinophils. [less ▲]

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See detailNovel cooperation between CX3CL1 and CCL26 inducing NK cell chemotaxis via CX3CR1: a possible mechanism for NK cell infiltration of the allergic nasal tissue
EL SHAZLY, Amr ULg; Castillo-Doloriert, Hugo; Bisig, Bettina et al

Poster (2013)

Background: Recent data indicated that natural killer (NK) cells and chemokines could play a pivotal role in nasal inflammation. CX3CR1, the only receptor for fractalkine/ CX3CL1, is abundantly expressed ... [more ▼]

Background: Recent data indicated that natural killer (NK) cells and chemokines could play a pivotal role in nasal inflammation. CX3CR1, the only receptor for fractalkine/ CX3CL1, is abundantly expressed by NK cells, and was recently shown to also be a receptor for eotaxin-3/CCL26. However, no reports explored the NK cells-CX3CL1-CCL26 axis via CX3CR1 in allergy.
Objective: Our goals were first to determine specifically NK cell recruitment pattern in nasal tissue of allergic chronic rhinosinusitis (ACRS) and non-allergic chronic rhinosinusitis (NACRS) patients in comparison with healthy controls, and secondly, to investigate the function of CX3CR1 in NK cell migration. Methods: Immunohistochemistry, microchemotaxis chambers, flow cytometry and confocal microscopy were used in this study. Results: Herein, we showed that NK cells infiltrated the epithelial layers of nasal tissue only in ACRS patients and not in NACRS patients or controls. NK cells were also more numerous in the stroma of the nasal tissue from ACRS patients compared with NACRS patients or controls. This migration could be mediated by both CX3CL1 and CCL26, as these two chemokines induced NK cell migration. Moreover, both molecules also stimulated cytoskeleton changes and F-actin reorganisation in NK cells. Chemotaxis and cytoskeleton changes were sensitive to genistein, a tyrosine kinase inhibitor. By flow cytometry, we demonstrated that a single antigen nasal provocation challenge increased the expression of CX3CR1 on NK cells in allergic rhinitis (AR) patients. The function of this receptor was associated with a significant augmentation of NK cell chemotaxis against the optimal doses of CX3CL1 and CCL26. Conclusions and Clinical Relevance: Our results highlight a novel role for CX3CR1 in NK cell migration that may contribute to the NK cell trafficking to the allergic upper airway. This could be mediated largely by CX3CL1 and CCL26 stimulation of the tyrosine kinase pathway. [less ▲]

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See detailNovel cooperation between CX3CL1 and CCL26 inducing NK cell chemotaxis via CX3CR1: a possible mechanism for NK cell infiltration of the allergic nasal tissue.
EL SHAZLY, Amr ULg; Castillo- Doloriert, Hugo; Bisig, Bettina et al

in Clinical & Experimental Allergy : Journal of the British Society for Allergy & Clinical Immunology (2013), 43(3), 322-31

BACKGROUND: Recent data indicated that natural killer (NK) cells and chemokines could play a pivotal role in nasal inflammation. CX3CR1, the only receptor for fractalkine/CX3CL1, is abundantly expressed ... [more ▼]

BACKGROUND: Recent data indicated that natural killer (NK) cells and chemokines could play a pivotal role in nasal inflammation. CX3CR1, the only receptor for fractalkine/CX3CL1, is abundantly expressed by NK cells, and was recently shown to also be a receptor for eotaxin-3/CCL26. However, no reports explored the NK cells-CX3CL1-CCL26 axis via CX3CR1 in allergy. OBJECTIVE: Our goals were first to determine specifically NK cell recruitment pattern in nasal tissue of allergic chronic rhinosinusitis (ACRS) and non-allergic chronic rhinosinusitis (NACRS) patients in comparison with healthy controls, and secondly, to investigate the function of CX3CR1 in NK cell migration. METHODS: Immunohistochemistry, microchemotaxis chambers, flow cytometry and confocal microscopy were used in this study. RESULTS: Herein, we showed that NK cells infiltrated the epithelial layers of nasal tissue only in ACRS patients and not in NACRS patients or controls. NK cells were also more numerous in the stroma of the nasal tissue from ACRS patients compared with NACRS patients or controls. This migration could be mediated by both CX3CL1 and CCL26, as these two chemokines induced NK cell migration. Moreover, both molecules also stimulated cytoskeleton changes and F-actin reorganisation in NK cells. Chemotaxis and cytoskeleton changes were sensitive to genistein, a tyrosine kinase inhibitor. By flow cytometry, we demonstrated that a single antigen nasal provocation challenge increased the expression of CX3CR1 on NK cells in allergic rhinitis (AR) patients. The function of this receptor was associated with a significant augmentation of NK cell chemotaxis against the optimal doses of CX3CL1 and CCL26. CONCLUSIONS AND CLINICAL RELEVANCE: Our results highlight a novel role for CX3CR1 in NK cell migration that may contribute to the NK cell trafficking to the allergic upper airway. This could be mediated largely by CX3CL1 and CCL26 stimulation of the tyrosine kinase pathway. [less ▲]

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See detailThe neuroscience of tinnitus: Perspectives from human neuroimaging studies
Maudoux, Audrey ULg; Vanneste, Sven; De Ridder, Dirk et al

Conference (2012, November)

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