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Bougault V.,University of Quebec | Bougault V.,University Du Droit Et Of La Sante Of Lille | Turmel J.,University of Quebec | Boulet L.P.,University of Quebec
Clinical and Experimental Allergy | Year: 2010

Background Rhinitis is commonly reported by swimmers. Seasonal allergic rhinitis may impair athletes' performance and quality of life (QOL). No data are currently available on the changes of nasal symptoms during and after a swimming season. We aimed to determine in competitive swimmers: (1) the prevalence of rhinitis and its impact on their QOL during an intense training programme, (2) the changes in nasal symptoms and QOL after a resting period and (3) the relationship between rhinitis and airway hyperresponsiveness (AHR). Methods Thirty-nine swimmers and 30 healthy controls answered the Rhinitis Quality of Life Questionnaire (RQLQ) and scored nasal symptoms on a seven-point Likert scale during the week preceding their visit. Subjects had allergy skin prick tests and a methacholine challenge. Peak nasal inspiratory flows were also measured. The athletes performed these tests during an intense training period (V1), outside the pollen season and after at least 2 weeks without swimming (V2). Results At V1, rhinitis symptoms were reported by 74% of swimmers and 40% of controls (P<0.01). Eighty-four percent of swimmers and 72% of controls were atopic (NS). RQLQ score was higher in swimmers compared with controls at V1 (27.3 ± 28.5 vs. 9.5 ± 12.7, respectively, P<0.005). The presence of AHR during training did not correlate with the presence of rhinitis symptoms. At V2, the nasal symptoms and RQLQ scores were similar in swimmers and controls. Conclusion Intense swimming training is associated with an increase in nasal symptoms and impairment in QOL in most competitive swimmers. Such an increase is not related to seasonal allergen exposure in atopic athletes and probably results from chlorine derivative exposure. © 2010 Blackwell Publishing Ltd.

Couturier C.,University of Lille Nord de France | Couturier C.,French Institute of Health and Medical Research | Couturier C.,University Du Droit Et Of La Sante Of Lille | Couturier C.,Institute Pasteur Lille | And 4 more authors.
Frontiers in Endocrinology | Year: 2012

Each step of the cell life and its response or adaptation to its environment are mediated by a network of protein/protein interactions termed "interactome." Our knowledge of this network keeps growing due to the development of sensitive techniques devoted to study these interactions. The bioluminescence resonance energy transfer (BRET) technique was primarily developed to allow the dynamic monitoring of protein/protein interactions (PPI) in living cells, and has widely been used to study receptor activation by intra- or extra-molecular conformational changes within receptors and activated complexes in mammal cells. Some interactions are described as crucial in human pathological processes, and a new class of drugs targeting them has recently emerged. The BRET method is well suited to identify inhibitors of PPI and here is described why and how to set up and optimize a high throughput screening assay based on BRET to search for such inhibitory compounds. The different parameters to take into account when developing such BRET assays in mammal cells are reviewed to give general guidelines: considerations on the targeted interaction, choice of BRET version, inducibility of the interaction, kinetic of the monitored interaction, and of the BRET reading, influence of substrate concentration, number of cells and medium composition used on the Z' factor, and expected interferences from colored or fluorescent compounds. © 2012 Couturier and Deprez.

Buttner S.,University of Graz | Delay C.,Catholic University of Leuven | Delay C.,French Institute of Health and Medical Research | Delay C.,University of Lille Nord de France | And 20 more authors.
PLoS ONE | Year: 2010

Background: Parkinson's disease is characterized by the presence of cytoplasmic inclusions, known as Lewy bodies, containing both aggregated a-synuclein and its interaction partner, synphilin-1. While synphilin-1 is known to accelerate inclusion formation by a-synuclein in mammalian cells, its effect on cytotoxicity remains elusive. Methodology/Principal Findings:We expressed wild-type synphilin-1 or its R621C mutant either alone or in combination with a-synuclein in the yeast Saccharomyces cerevisiae and monitored the intracellular localization and inclusion formation of the proteins as well as the repercussions on growth, oxidative stress and cell death. We found that wild-type and mutant synphilin-1 formed inclusions and accelerated inclusion formation by a-synuclein in yeast cells, the latter being correlated to enhanced phosphorylation of serine-129. Synphilin-1 inclusions co-localized with lipid droplets and endomembranes. Consistently, we found that wild-type and mutant synphilin-1 interacts with detergent-resistant membrane domains, known as lipid rafts. The expression of synphilin-1 did not incite a marked growth defect in exponential cultures, which is likely due to the formation of aggresomes and the retrograde transport of inclusions from the daughter cells back to the mother cells. However, when the cultures approached stationary phase and during subsequent ageing of the yeast cells, both wild-type and mutant synphilin-1 reduced survival and triggered apoptotic and necrotic cell death, albeit to a different extent. Most interestingly, synphilin-1 did not trigger cytotoxicity in ageing cells lacking the sirtuin Sir2. This indicates that the expression of synphilin-1 in wild-type cells causes the deregulation of Sir2-dependent processes, such as the maintenance of the autophagic flux in response to nutrient starvation. Conclusions/Significance: Our findings demonstrate that wild-type and mutant synphilin-1 are lipid raft interacting proteins that form inclusions and accelerate inclusion formation of a-synuclein when expressed in yeast. Synphilin-1 thereby induces cytotoxicity, an effect most pronounced for the wild-type protein and mediated via Sir2-dependent processes. © 2010 Bü ttner et al.

Grandgenevre P.,CHRU de Lille | Grandgenevre P.,University Du Droit Et Of La Sante Of Lille | Warembourg F.,CHRU de Lille | Carriere N.,University Du Droit Et Of La Sante Of Lille | And 4 more authors.
Presse Medicale | Year: 2015

Objective: To improve the management of hypersexuality caused by antiparkinsonian treatment and its psychopathological implications in patients with Parkinson's disease (PD). If hypersexuality is a classic form of impulse control disorder (ICD) observed in PD, its rate is certainly underestimated. Methods: We have proposed to meet patients with Parkinson's disease, referred by the neurology department of Lille University Hospital, for detection or suspicion of hypersexuality, in the presence of their spouse. The session consisted of an interview conducted by our psychiatry team. This evaluation was conducted between January 1and August 31, 2011. Nine patients were referred to our service, 7agreed to meet us, 6of them with their spouse. Results: An interview in the presence of the spouse has improved hypersexuality screening and information given to the patient and his close contacts regarding the side effects of treatment, and particularly the occurrence of hypersexuality. It also highlighted the various expressions of these behavioral changes, often minimized by patients, as spouses had great difficulty dealing with this. It helped them to improve verbal communication and, therefore, to be more informative concerning sexual behavior changes in connection with the treatment and its management. Finally, it has enabled improved support for secondary consequences of this impulse control disorder, such as guilt, jealousy or shame. Our interest has also focused on the impact of this hypersexuality on patients' families. Among the six sets partners, four had symptoms requiring specific psychiatric care: depression, suicidal intention or post-traumatic stress disorder. Perspective: Hypersexuality seems underestimated in patients receiving antiparkinsonian treatment. This underestimation is probably linked to some defense mechanisms such as denial or minimization, but also to the feelings generated by these behavioral problems, such as shame or guilt. On the other hand, some patients do not experience stress related behavioral changes (even though the family may complain). Systematic partner interview could be a solution to improving this screening. © 2014 Elsevier Masson SAS.

Woldt E.,Institute Pasteur Of Lille | Woldt E.,Institute National Of La Sante Et Of La Recherche Medicale Unite Mixte Of Recherche 1011 Nuclear Receptors | Woldt E.,University of Lille Nord de France | Woldt E.,University Du Droit Et Of La Sante Of Lille | And 52 more authors.
Nature Medicine | Year: 2013

The nuclear receptor Rev-erb-α modulates hepatic lipid and glucose metabolism, adipogenesis and the inflammatory response in macrophages. We show here that Rev-erb-α is highly expressed in oxidative skeletal muscle and that its deficiency in muscle leads to reduced mitochondrial content and oxidative function, as well as upregulation of autophagy. These cellular effects resulted in both impaired mitochondrial biogenesis and increased clearance of this organelle, leading to compromised exercise capacity. On a molecular level, Rev-erb-α deficiency resulted in deactivation of the Lkb1-Ampk-Sirt1- Ppargc-1α signaling pathway. These effects were recapitulated in isolated fibers and in muscle cells after knockdown of the gene encoding Rev-erb-α, Nr1d1. In complementary experiments, Rev-erb-α overexpression in vitro increased the number of mitochondria and improved respiratory capacity, whereas muscle overexpression or pharmacological activation of Rev-erb-α in vivo increased exercise capacity. This study identifies Rev-erb-α as a pharmacological target that improves muscle oxidative function by modulating gene networks controlling mitochondrial number and function. © 2013 Nature America, Inc. All rights reserved.

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