The Experts below are selected from a list of 258 Experts worldwide ranked by ideXlab platform
Eric Rousseau - One of the best experts on this subject based on the ideXlab platform.
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pro resolving effects of resolvin d2 in ltd4 and tnf α pre treated human Bronchi
PLOS ONE, 2016Co-Authors: Rayan Khaddajmallat, Chantal Sirois, Marco Sirois, Edmond Rizcallah, Sofia Marouan, Caroline Morin, Eric RousseauAbstract:Inflammation is a major burden in respiratory diseases, resulting in airway hyperresponsiveness. Our hypothesis is that resolution of inflammation may represent a long-term solution in preventing human Bronchial dysfunctions. The aim of the present study was to assess the anti-inflammatory effects of RvD2, a member of the D-series resolving family, with concomitant effects on ASM mechanical reactivity. The role and mode of action of RvD2 were assessed in an in vitro model of human Bronchi under pro-inflammatory conditions, induced either by 1 μM LTD4 or 10 ng/ml TNF-α pre-treatment for 48h. TNF-α and LTD4 both induced hyperreactivity in response to pharmacological stimuli. Enhanced 5-Lipoxygenase (5-LOX) and cysteinyl leukotriene receptor 1 (CysLTR1) detection was documented in LTD4 or TNF-α pre-treated human Bronchi when compared to control (untreated) human Bronchi. In contrast, RvD2 treatments reversed 5-LOX/β-actin and CysLTR1/β-actin ratios and decreased the phosphorylation levels of AP-1 subunits (c-Fos, c-Jun) and p38-MAP kinase, while increasing the detection of the ALX/FPR2 receptor. Moreover, various pharmacological agents revealed the blunting effects of RvD2 on LTD4 or TNF-α induced hyper-responsiveness. Combined treatment with 300 nM RvD2 and 1 μM WRW4 (an ALX/FPR2 receptor inhibitor) blunted the pro-resolving and broncho-modulatory effects of RvD2. The present data provide new evidence regarding the role of RvD2 in a human model of airway inflammation and hyperrresponsiveness.
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eet displays anti inflammatory effects in tnf alpha stimulated human Bronchi putative role of cpi 17
American Journal of Respiratory Cell and Molecular Biology, 2008Co-Authors: Caroline Morin, Marco Sirois, Vincent Echave, Marcio M Gomes, Eric RousseauAbstract:The aim of the present study was to investigate the anti-inflammatory effects of 14,15-epoxyeicosatrienoic acid (EET) on reactivity and Ca(2+) sensitivity in TNF-alpha-stimulated human Bronchi. Tension measurements performed on either control, TNF-alpha-, or TNF-alpha + EET-pretreated Bronchi revealed that 100 nM 14,15-EET pretreatments significantly reduced the reactivity of TNF-alpha-pretreated tissues to contractile agonists. EET also normalized the relaxing response to isoproterenol in TNF-alpha-treated Bronchi. Pretreatment with 100 nM 14,15-EET prevented TNF-alpha-induced IkappaBalpha degradation, as demonstrated by an increase in IkappaBalpha protein levels on Western blot analysis. The anti-inflammatory properties of EET were mediated by the inhibition of IkappaBalpha degradation, suggesting a lower activation of NF-kappaB. The Ca(2+) sensitivity of TNF-alpha-stimulated Bronchi was also evaluated on beta-escin-permeabilized preparations. Observed mean responses demonstrated that EET pretreatments abolished Ca(2+) hypersensitivity developed by TNF-alpha-stimulated Bronchial explants. Moreover, 14,15-EET significantly reduced PDBu-induced Ca(2+) sensitivity in TNF-alpha-stimulated Bronchi. Western blot and RT-PCR analyses revealed that CPI-17 protein and transcript levels were increased in TNF-alpha-treated Bronchi, as opposed to being decreased in the presence of 14,15-EET. This eicosanoid also reduced U-46619-induced Ca(2+) sensitivity, which is related to the activation of Rho-kinase pathway. These results were also correlated with an increase in protein staining and transcription level of p116(Rip), a RhoA inhibitory-binding protein. Altogether, these data demonstrate that 14,15-EET is a potent modulator of the hyperreactivity triggered by TNF-alpha in human airway smooth muscle cells.
Christophe Faisy - One of the best experts on this subject based on the ideXlab platform.
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effectiveness of a load imposing device for cyclic stretching of isolated human Bronchi a validation study
PLOS ONE, 2015Co-Authors: Morgan Le Guen, Emmanuel Naline, Stanislas Grassindelyle, Philippe Devillier, Christophe FaisyAbstract:Background Mechanical ventilation may induce harmful effects in the airways of critically ill patients. Nevertheless, the effects of cyclic stretching caused by repetitive inflation-deflation of the Bronchial compartment have not been well characterized in humans. The objective of the present study was to assess the effectiveness of a load-imposing device for the cyclic stretching of human Bronchi. Methods Intact Bronchial segments were removed from 128 thoracic surgery patients. After preparation and equilibration in an organ bath, Bronchi were stretched repetitively and cyclically with a motorized transducer. The peak force imposed on the Bronchi was set to 80% of each individual maximum contraction in response to acetylcholine and the minimal force corresponded to the initial basal tone before stretching. A 1-min cycle (stretching for 15 sec, relaxing for 15 sec and resting for 30 sec) was applied over a time period ranging from 5 to 60 min. The device's performance level was assessed and the properties of the stretched Bronchi were compared with those of paired, non-stretched Bronchi. Results Despite the intrinsic capacities of the device, the targets of the tension adjustments remained variable for minimal tension (156–178%) while the peak force set point was unchanged (87–115%). In the stretched Bronchi, a time-dependent rise in basal tone (P <.05 vs. non-stretched) was apparent after as little as 5 min of cyclic stretching. The stretch-induced rise in basal tone continued to increase (P <.01) after the stretching had ended. Only 60 min of cyclic stretching was associated with a significant (P <.05) increase in responsiveness to acetylcholine, relative to non-stretched Bronchi. Conclusions Low-frequency, low-force, cyclic loading of human Bronchi is associated with elevated basal tone and acetylcholine responsiveness. The present experimental model is likely to be a useful tool for future investigations of the Bronchial response to repetitive stress during mechanical ventilation.
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Nociceptin inhibits vanilloid TRPV-1-mediated neurosensitization induced by fenoterol in human isolated Bronchi
Naunyn-Schmiedeberg's Archives of Pharmacology, 2004Co-Authors: Christophe Faisy, Emmanuel Naline, Céline Rouget, Paul-andré Risse, Emmanuel Guerot, Jean-yves Fagon, Thierry Chinet, Nicolas Roche, Charles AdvenierAbstract:Chronic exposure to β_2-adrenoceptor agonists, especially fenoterol, has been shown to increase smooth muscle contraction to endothelin-1 in human Bronchi partly through tachykinin-mediated pathways. The purpose of this work was to further investigate the role of sensory nerves in fenoterol-induced sensitization of human airways and the effect of nociceptin, a nociceptin/orphanin FQ (NOP) receptor agonist, on the increase in contraction after fenoterol exposure. Human Bronchi from 62 patients were sensitized to endothelin-1 by prolonged incubation with fenoterol (0.1 μM, 15 h). The sensitizing effect of fenoterol was inhibited by high concentration of capsaicin (10 μM, 30 min before fenoterol sensitization), which induces depletion of mediators from sensory nerves, or co-incubation of fenoterol and capsazepine (1 μM), a vanilloid TRPV-1 receptor antagonist. Moreover, short pretreatment of Bronchi with capsaicin (10 μM) or capsazepine (1 μM) after sensitization by fenoterol decreased the rise in smooth muscle contraction to endothelin-1. Nociceptin (1 μM) also inhibited the increased contraction in fenoterol-sensitized Bronchi. Tertiapin (10 μM), an inhibitor of the inward-rectifier K^+ channels, but not naloxone (0.1 μM), a DOP/KOP/MOP receptor antagonist, prevented the inhibitory effect of nociceptin. In conclusion, fenoterol induces sensitization of human isolated Bronchi to endothelin-1 in part through the stimulation of the vanilloid TRPV-1 receptor on tachykininergic sensory nerves. Nociceptin inhibits airway hyperresponsiveness via NOP receptor activation. This effect involves inward-rectifier K^+ channels.
Annemarie Lauzon - One of the best experts on this subject based on the ideXlab platform.
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human trachealis and main Bronchi smooth muscle are normoresponsive in asthma
American Journal of Respiratory and Critical Care Medicine, 2015Co-Authors: Gijs Ijpma, Linda Kachmar, Oleg S Matusovsky, Jason H T Bates, Andrea Benedetti, James G Martin, Annemarie LauzonAbstract:Rationale: Airway smooth muscle (ASM) plays a key role in airway hyperresponsiveness (AHR) but it is unclear whether its contractility is intrinsically changed in asthma.Objectives: To investigate whether key parameters of ASM contractility are altered in subjects with asthma.Methods: Human trachea and main Bronchi were dissected free of epithelium and connective tissues and suspended in a force–length measurement set-up. After equilibration each tissue underwent a series of protocols to assess its methacholine dose–response relationship, shortening velocity, and response to length oscillations equivalent to tidal breathing and deep inspirations.Measurements and Main Results: Main Bronchi and tracheal ASM were significantly hyposensitive in subjects with asthma compared with control subjects. Trachea and main Bronchi did not show significant differences in reactivity to methacholine and unloaded tissue shortening velocity (Vmax) compared with control subjects. There were no significant differences in resp...
Joost J Nuyttens - One of the best experts on this subject based on the ideXlab platform.
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dose and volume of the irradiated main Bronchi and related side effects in the treatment of central lung tumors with stereotactic radiotherapy
Seminars in Radiation Oncology, 2016Co-Authors: M Duijm, W Schillemans, Joachim G J V Aerts, Ben J M Heijmen, Joost J NuyttensAbstract:High radiation dose to the main Bronchi can result in stenosis, occlusion or fistula formation, and death. Only 8 articles have reported side effects to the main Bronchi from stereotactic body radiation therapy (SBRT), mostly with only one symptomatic complication per article. Therefore, we calculated the dose to the Bronchial structures, such as trachea; mainstem Bronchi; intermediate bronchus; upper-, middle-, and lower-lobe bronchus; and the segmental Bronchi in 134 patients with central tumors and calculated the normal tissue complication probability (NTCP) for each of these structures, with toxicity determination based upon computed tomography imaging. No side effects were found in the trachea, and only stenosis occurred in the main bronchus and bronchus intermedius. Higher grades of side effects, such as occlusion and atelectasis, were only seen in the upper-, middle-, and lower Bronchi and the segmental Bronchi. When 0.5cc of a segmental Bronchi was irradiated to 50Gy in 5 fractions, it was about 50% likely to be occluded radiographically. For grade 1 radiographically evident side effects, the 50% risk level for a 5-fraction Dmax was 55Gy for mid-Bronchi and 65Gy for mainstem Bronchi. To assure the relationship between clinical toxicity and side effects to the Bronchi, further investigation is needed.
Caroline Morin - One of the best experts on this subject based on the ideXlab platform.
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pro resolving effects of resolvin d2 in ltd4 and tnf α pre treated human Bronchi
PLOS ONE, 2016Co-Authors: Rayan Khaddajmallat, Chantal Sirois, Marco Sirois, Edmond Rizcallah, Sofia Marouan, Caroline Morin, Eric RousseauAbstract:Inflammation is a major burden in respiratory diseases, resulting in airway hyperresponsiveness. Our hypothesis is that resolution of inflammation may represent a long-term solution in preventing human Bronchial dysfunctions. The aim of the present study was to assess the anti-inflammatory effects of RvD2, a member of the D-series resolving family, with concomitant effects on ASM mechanical reactivity. The role and mode of action of RvD2 were assessed in an in vitro model of human Bronchi under pro-inflammatory conditions, induced either by 1 μM LTD4 or 10 ng/ml TNF-α pre-treatment for 48h. TNF-α and LTD4 both induced hyperreactivity in response to pharmacological stimuli. Enhanced 5-Lipoxygenase (5-LOX) and cysteinyl leukotriene receptor 1 (CysLTR1) detection was documented in LTD4 or TNF-α pre-treated human Bronchi when compared to control (untreated) human Bronchi. In contrast, RvD2 treatments reversed 5-LOX/β-actin and CysLTR1/β-actin ratios and decreased the phosphorylation levels of AP-1 subunits (c-Fos, c-Jun) and p38-MAP kinase, while increasing the detection of the ALX/FPR2 receptor. Moreover, various pharmacological agents revealed the blunting effects of RvD2 on LTD4 or TNF-α induced hyper-responsiveness. Combined treatment with 300 nM RvD2 and 1 μM WRW4 (an ALX/FPR2 receptor inhibitor) blunted the pro-resolving and broncho-modulatory effects of RvD2. The present data provide new evidence regarding the role of RvD2 in a human model of airway inflammation and hyperrresponsiveness.
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eet displays anti inflammatory effects in tnf alpha stimulated human Bronchi putative role of cpi 17
American Journal of Respiratory Cell and Molecular Biology, 2008Co-Authors: Caroline Morin, Marco Sirois, Vincent Echave, Marcio M Gomes, Eric RousseauAbstract:The aim of the present study was to investigate the anti-inflammatory effects of 14,15-epoxyeicosatrienoic acid (EET) on reactivity and Ca(2+) sensitivity in TNF-alpha-stimulated human Bronchi. Tension measurements performed on either control, TNF-alpha-, or TNF-alpha + EET-pretreated Bronchi revealed that 100 nM 14,15-EET pretreatments significantly reduced the reactivity of TNF-alpha-pretreated tissues to contractile agonists. EET also normalized the relaxing response to isoproterenol in TNF-alpha-treated Bronchi. Pretreatment with 100 nM 14,15-EET prevented TNF-alpha-induced IkappaBalpha degradation, as demonstrated by an increase in IkappaBalpha protein levels on Western blot analysis. The anti-inflammatory properties of EET were mediated by the inhibition of IkappaBalpha degradation, suggesting a lower activation of NF-kappaB. The Ca(2+) sensitivity of TNF-alpha-stimulated Bronchi was also evaluated on beta-escin-permeabilized preparations. Observed mean responses demonstrated that EET pretreatments abolished Ca(2+) hypersensitivity developed by TNF-alpha-stimulated Bronchial explants. Moreover, 14,15-EET significantly reduced PDBu-induced Ca(2+) sensitivity in TNF-alpha-stimulated Bronchi. Western blot and RT-PCR analyses revealed that CPI-17 protein and transcript levels were increased in TNF-alpha-treated Bronchi, as opposed to being decreased in the presence of 14,15-EET. This eicosanoid also reduced U-46619-induced Ca(2+) sensitivity, which is related to the activation of Rho-kinase pathway. These results were also correlated with an increase in protein staining and transcription level of p116(Rip), a RhoA inhibitory-binding protein. Altogether, these data demonstrate that 14,15-EET is a potent modulator of the hyperreactivity triggered by TNF-alpha in human airway smooth muscle cells.
