Is the beta3-adrenoceptor (ADRB3) a potential target for uterorelaxant drugs?

The management of premature birth still remains unsatisfactory. Since the relative lack of efficiency and/or safety of current tocolytic agents have been highlighted, it is necessary to develop new uterorelaxant drugs deprived of important maternal and foetal side effects. Our work reported in this review focuses on a potential new target for tocolytic drugs, the β3-adrenoceptor (ADRB3). This third type of ADRB is shown to be present and functional in human myometrium. We demonstrated that ADRB3 agonists are able to inhibit in-vitro spontaneous contractions of myometrial strips, via a cyclic AMP-mediated pathway. Furthermore, we established that ADRB3 is the predominant subtype over the ADRB2 in human myometrium and that its expression is increased in near-term myometrium, compared to non-pregnant myometrium. Finally, we reported that contrary to ADRB2, the human myometrial ADRB3 is resistant to long-term agonist-induced desensitisation. These compelling data confirm the clinical potential interest of ADRB3 agonists in the pharmacological management of preterm labour

Effet de la somatostatine sur la contraction bronchique chez l homme

Des études animales réalisées chez le furet et le lapin ont montré que la somatostatine modulait la contraction bronchique déclenchée par la stimulation du contingent parasympathique du système nerveux autonome. Nous avons étudié l effet modulateur d un analogue de la somatostatine, l octréotide, sur le versant cholinergique de la contractilité bronchique, dans un modèle de bronche humaine en cuve à organe isolé. Nous avons retrouvé un effet potentialisateur de l octréotide sur la contraction bronchique induite par stimulation électrique de champ. Cet effet n existe que pour une concentration inférieure à 10(-9)M, et est maximal à 10(-10)M, la courbe concentration-effet décrivant une courbe en cloche. Nous n avons pas retrouvé d effet sur le tonus bronchique de base. Nous n avons pas retrouvé d effet lorsque la contraction est induite par l acétylcholine ou le KCl. Nous n avons pas retrouvé d effet de la cortistatine, un autre analogue de la somatostatine. Nos résultats laissent à penser que la modulation de la contraction bronchique par la somatostatine fait appel à des récepteurs spécifiques situés sur le corps cellulaire du neurone postganglionnaire de la voie cholinergique, et que la somatostatine agit sur ce récepteur probablement par voie paracrine.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Assessment of an e-nose performance for the detection of COVID-19 specific biomarkers

International audienceEarly, rapid and non-invasive diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is needed for the prevention and control of coronavirus disease 2019 (COVID-19). COVID-19 mainly affects the respiratory tract and lungs. Therefore, analysis of exhaled breath could be an alternative scalable method for reliable SARS-CoV-2 screening. In the current study, an experimental protocol using an electronic-nose (‘e-nose’) for attempting to identify a specific respiratory imprint in COVID-19 patients was optimized. Thus the analytical performances of the Cyranose ® , a commercial e-nose device, were characterized under various controlled conditions. In addition, the effect of various experimental conditions on its sensor array response was assessed, including relative humidity, sampling time and flow rate, aiming to select the optimal parameters. A statistical data analysis was applied to e-nose sensor response using common statistical analysis algorithms in an attempt to demonstrate the possibility to detect the presence of low concentrations of spiked acetone and nonanal in the breath samples of a healthy volunteer. Cyranose ® reveals a possible detection of low concentrations of these two compounds, in particular of 25 ppm nonanal, a possible marker of SARS-CoV-2 in the breath

Optimization of E-nose technology for detecting nonanal: a COVID-19 biomarker in exhaled breath

International audienceA low-cost, rapid and non-invasive diagnosis of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection is needed for the prevention and control of the pandemic. Coronavirus disease 2019 (COVID-19) mainly affects the respiratory tract and lungs. Therefore, analysis of exhaled breath could be an alternative scalable method for reliable SARS-CoV-2 screening. In this work, an experimental protocol using an electronic nose (“e-nose”) for identifying a specific respiratory imprint in COVID-19 patients was optimized. The analytical performances of the Cyranose ® , a commercial e-nose device, were characterized by using a gas rig. In addition, the effect of various experimental conditions on its sensor array response was assessed, including relative humidity, sampling time and flow rate, aiming to select the optimal parameters. We also evaluated whether the Cyranose ® could distinguish between expired air from five healthy patients spiked or not with nonanal, identified as one putative COVID-19 biomarker. Electrical resistance variation of 32 sensors was recorded in real-time by using the PC-nose software during all tests. A statistical data analysis was applied to e-nose sensor response using a software called “Enair” developed on purpose and using a built-in optimized algorithm.Cyranose® reveals a possible detection of low concentrations of nonanal (5 ppb) in breath and a significant discrimination from others Volatile Organic Compounds (VOCs) of healthy patients

Development and characterization of electronic noses for the rapid detection of COVID-19 in exhaled breath

International audienceNon-invasive and rapid approach is potentially needed for diagnosis of COVID-19. In this work, exhaled breath analysis using e-Nose, is presented as an innovative technique to identify the COVID-19 specific VOCs. The analytical performances of Cyranose®, a commercial e-Nose device, were investigated under controlled conditions. Sensitivity, limit of detection and reproducibility of standardized VOCs existing in the breath was assessed. In addition, the effect of various experimental conditions on sensor response was evaluated, including temperature, relative humidity, flow and sampling time, aiming to select the optimal parameters and to validate it in clinical trials to detect the COVID-19 biomarkers. Cyranose® exhibits high sensitivity and reproducible response towards acetone and nonanal, with a limit of detection of 63 ppb and 20 ppb respectively. Furthermore, results show that the variability of relative humidity, temperature and flow sampling, induced a significant sensors response variation, whereas, varying the sampling time does not affect significantly the sensor response

Optimization of E-nose technology for detecting nonanal: a COVID-19 biomarker in exhaled breath

International audienceA low-cost, rapid and non-invasive diagnosis of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection is needed for the prevention and control of the pandemic. Coronavirus disease 2019 (COVID-19) mainly affects the respiratory tract and lungs. Therefore, analysis of exhaled breath could be an alternative scalable method for reliable SARS-CoV-2 screening. In this work, an experimental protocol using an electronic nose (“e-nose”) for identifying a specific respiratory imprint in COVID-19 patients was optimized. The analytical performances of the Cyranose ® , a commercial e-nose device, were characterized by using a gas rig. In addition, the effect of various experimental conditions on its sensor array response was assessed, including relative humidity, sampling time and flow rate, aiming to select the optimal parameters. We also evaluated whether the Cyranose ® could distinguish between expired air from five healthy patients spiked or not with nonanal, identified as one putative COVID-19 biomarker. Electrical resistance variation of 32 sensors was recorded in real-time by using the PC-nose software during all tests. A statistical data analysis was applied to e-nose sensor response using a software called “Enair” developed on purpose and using a built-in optimized algorithm.Cyranose® reveals a possible detection of low concentrations of nonanal (5 ppb) in breath and a significant discrimination from others Volatile Organic Compounds (VOCs) of healthy patients

Development and characterization of electronic noses for the rapid detection of COVID-19 in exhaled breath

International audienceNon-invasive and rapid approach is potentially needed for diagnosis of COVID-19. In this work, exhaled breath analysis using e-Nose, is presented as an innovative technique to identify the COVID-19 specific VOCs. The analytical performances of Cyranose®, a commercial e-Nose device, were investigated under controlled conditions. Sensitivity, limit of detection and reproducibility of standardized VOCs existing in the breath was assessed. In addition, the effect of various experimental conditions on sensor response was evaluated, including temperature, relative humidity, flow and sampling time, aiming to select the optimal parameters and to validate it in clinical trials to detect the COVID-19 biomarkers. Cyranose® exhibits high sensitivity and reproducible response towards acetone and nonanal, with a limit of detection of 63 ppb and 20 ppb respectively. Furthermore, results show that the variability of relative humidity, temperature and flow sampling, induced a significant sensors response variation, whereas, varying the sampling time does not affect significantly the sensor response

Characterization of ion and fluid transport in human bronchioles.

The regulation of the volume and composition of airway surface liquid is achieved through epithelial ion transport processes. In humans, these processes have been characterized in proximal but not distal airways. Segments of human bronchioles were dissected from surgically removed lung pieces. The transmural potential difference of microperfused bronchioles was inhibited by luminal exposure to amiloride and increased when exposed to the Cl secretagogues forskolin and ATP in the presence of amiloride. Human bronchiolar epithelial cells were cultured on permeable supports and studied in Ussing chambers. They generated a short circuit current (Isc) that decreased in response to amiloride and increased in response to forskolin and to ATP in the presence of amiloride. In low-Cl Kreb's Ringer bicarbonate, the baseline Isc and amiloride-induced decrease in Isc were not different, whereas the forskolin- and ATP-induced increases in Isc were smaller. Fluid transport measurement in excised bronchioles revealed a basal absorptive flow that was reduced by amiloride, whereas forskolin and ATP combined induced a secretory flow in the presence of amiloride. We conclude that human bronchioles actively absorb Na and fluid in unstimulated conditions and are capable of active Cl and fluid secretion when exposed to forskolin and to ATP

The Role of Toll-Like Receptors in the Production of Cytokines by Human Lung Macrophages

International audienceBackground: The Toll-like receptor (TLR) family is involved in the recognition of and response to microbial infections. These receptors are expressed in leukocytes. TLR stimulation induces the production of proinflammatory cytokines and chemokines. Given that human lung macrophages (LMs) constitute the first line of defense against inhaled pathogens, the objective of this study was to investigate the expression and function of TLR subtypes in this cell population. Methods: Human primary LMs were obtained from patients undergoing surgical resection. The RNA and protein expression levels of TLRs, chemokines, and cytokines were assessed after incubation with subtype-selective agonists. Results: In human LMs, the TLR expression level varied from one subtype to another. Stimulation with subtype-selective agonists induced an intense, concentration- and time-dependent increase in the production of chemokines and cytokines. TLR4 stimulation induced the strongest effect, whereas TLR9 stimulation induced a much weaker response. Conclusions: The stimulation of TLRs in human LMs induces intense cytokine and chemokine production, a characteristic of the proinflammatory M1 macrophage phenotype. © 2018 The Author(s). Published by S. Karger AG, Basel

Effectiveness of a load-imposing device for cyclic stretching of isolated human bronchi: a validation study.

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.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.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.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