Impact of acoustic airflow on intrasinus drug deposition: New insights into the vibrating mode and the optimal acoustic frequency to enhance the delivery of nebulized antibiotic

International audienceAim: We investigated the impact of vibrating acoustic airflow, the high frequency (f ≥ 100 Hz) and the low frequency (f ≤ 45 Hz) sound waves, on the enhancement of intrasinus drug deposition.Methods: 81mKr-gas ventilation study was performed in a plastinated human cast with and without the addition of vibrating acoustic airflow. Similarly, intrasinus drug deposition in a nasal replica using gentamicin as a marker was studied with and without the superposition of different modes of acoustic airflow.Results: Ventilation experiments demonstrate that no sinus ventilation was observed without acoustic airflow although sinus ventilation occurred whatever the modes of acoustic airflow applied. Intrasinus drug deposition experiments showed that the high frequency acoustic airflow led to 4-fold increase in gentamicin deposition into the left maxillary sinus and to 2-fold deposition increase into the right maxillary sinus. Besides, the low frequency acoustic airflow demonstrated a significant increase of 4-fold and 2-fold in the right and left maxillary sinuses respectively.Conclusion: We demonstrated the benefit of different modes of vibrating acoustic airflow for maxillary sinus ventilation and intrasinus drug deposition. The degree of gentamicin deposition varies as a function of frequency of the vibrating acoustic airflow and the geometry of the ostia

EROS 2 intensive observation of the caustic crossing of microlensing event MACHO SMC-98-1

We report on intensive photometric monitoring on 18 June 1998 of MACHO SMC-98-1, a binary-lens microlensing event seen toward the Small Magellanic Cloud (SMC). The observations cover 5.3 hours (UT 5:17 -- 10:37), and show a sharp drop of 1.8 mag during the first 1.8 hours, followed by an abrupt flattening at UT 7:08 +- 0:02. We interpret the kink at 7:08 as the end of the second caustic crossing (when the source first moved completely outside the caustic). These results indicate that mu sin(phi) <~ 1.5 km/s/kpc at the 2 sigma level, where mu is the proper motion of the lens (relative to the line of sight to the source), and phi is the unknown (and so random) angle of the caustic crossing. Hence, the source probably does not lie in either the Galactic halo or disk and so is most likely in the SMC itself. Our data can be combined with those of other groups to give more precise constraints on the proper motion (and hence the nature) of the lens

Les effets biologiques des rayonnements ionisants

L’étude de l’impact des rayonnements ionisants sur l’ADN, les organes et l’organisme est un sujet de recherche vivant et très actif. La compréhension des mécanismes biologiques et des effets-seuil est au coeur des stratégies de radioprotection

ILA, Bordeaux, 1, (16/1/9/1) Dédicace à Auguste et au Génie de la cité des Bituriges Vivisques

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Acoustic Aerosol Delivery: Assessing of Various Nasal Delivery Techniques and Medical Devices on Intrasinus Drug Deposition

This study aims to evaluate the impact of the nasal delivery technique and nebulizing technologies (using different frequencies of oscillating airflow) for acoustic aerosol targeting of maxillary sinuses. Sodium fluoride (chemical used as a marker), tobramycin (drug used as a marker) and 99mTc-DTPA (radiolabel aerosol) were used to assess the intrasinus aerosol deposition on a nasal cast. Two commercial medical devices (PARI SINUS nebulizer and NL11SN ATOMISOR nebulizer) and various nasal delivery techniques (one or two nostrils connected to the aerosol inlet, the patient with the soft palate closed or open during the acoustic administration of the drug, the presence or not of flow resistance in the nostril opposite to the one allowing the aerosol to be administered) were evaluated. The closed soft palate condition showed a significant increase in drug deposition even though no significant difference in the rest of the nasal fossae was noticed. Our results clearly demonstrated a higher intrasinus aerosol deposition (by a factor 2&ndash;3; respectively 0.03 &plusmn; 0.007% vs. 0.003 &plusmn; 0.0002% in the right maxillary sinus and 0.027 &plusmn; 0.006% vs. 0.013 &plusmn; 0.004% in the left maxillary sinus) using the acoustic airflow generated by the PARI SINUS compared to the NL11SN ATOMISOR. The results clearly demonstrated that the optimal conditions for aerosol deposition in the maxillary sinuses were obtained with a closed soft palate. Thus, the choice of the nebulizing technology (and mainly the frequency of the pulsating aerosol generated) and also the recommendation of the best nasal delivery technique are key factors to improve intrasinus aerosol deposition

Impact of gas humidification and nebulizer position under invasive ventilation: preclinical comparative study of regional aerosol deposition

Abstract Successful aerosol therapy in mechanically ventilated patients depends on multiple factors. Among these, position of nebulizer in ventilator circuit and humidification of inhaled gases can strongly influence the amount of drug deposited in airways. Indeed, the main objective was to preclinically evaluate impact of gas humidification and nebulizer position during invasive mechanical ventilation on whole lung and regional aerosol deposition and losses. Ex vivo porcine respiratory tracts were ventilated in controlled volumetric mode. Two conditions of relative humidity and temperature of inhaled gases were investigated. For each condition, four different positions of vibrating mesh nebulizer were studied: (i) next to the ventilator, (ii) right before humidifier, (iii) 15 cm to the Y-piece adapter and (iv) right after the Y-piece. Aerosol size distribution were calculated using cascade impactor. Nebulized dose, lung regional deposition and losses were assessed by scintigraphy using 99mtechnetium-labeled diethylene-triamine-penta-acetic acid. Mean nebulized dose was 95% ± 6%. For dry conditions, the mean respiratory tract deposited fractions reached 18% (± 4%) next to ventilator and 53% (± 4%) for proximal position. For humidified conditions, it reached 25% (± 3%) prior humidifier, 57% (± 8%) before Y-piece and 43% (± 11%) after this latter. Optimal nebulizer position is proximal before the Y-piece adapter showing a more than two-fold higher lung dose than positions next to the ventilator. Dry conditions are more likely to cause peripheral deposition of aerosols in the lungs. But gas humidification appears hard to interrupt efficiently and safely in clinical use. Considering the impact of optimized positioning, this study argues to maintain humidification

Development of an ex vivo respiratory pediatric model of bronchopulmonary dysplasia for aerosol deposition studies

Abstract Ethical restrictions are limitations of in vivo inhalation studies, on humans and animal models. Thus, in vitro or ex vivo anatomical models offer an interesting alternative if limitations are clearly identified and if extrapolation to human is made with caution. This work aimed to develop an ex vivo infant-like respiratory model of bronchopulmonary dysplasia easy to use, reliable and relevant compared to in vivo infant data. This model is composed of a 3D-printed head connected to a sealed enclosure containing a leporine thorax. Physiological data and pleural-mimicking depressions were measured for chosen respiratory rates. Homogeneity of ventilation was assessed by 81mkrypton scintigraphies. Regional radioaerosol deposition was quantified with 99mtechnetium-diethylene triamine pentaacetic acid after jet nebulization. Tidal volumes values are ranged from 33.16 ± 7.37 to 37.44 ± 7.43 mL and compliance values from 1.78 ± 0.65 to 1.85 ± 0.99 mL/cmH2O. Ventilation scintigraphies showed a homogenous ventilation with asymmetric repartition: 56.94% ± 9.4% in right lung and 42.83% ± 9.36 in left lung. Regional aerosol deposition in lungs exerted 2.60% ± 2.24% of initial load of radioactivity. To conclude the anatomical model satisfactorily mimic a 3-months old BPD-suffering bronchopulmonary dysplasia and can be an interesting tool for aerosol regional deposition studies

Oxidative stress-induced inflammation in susceptible airways by anthropogenic aerosol

Ambient air pollution is one of the leading five health risks worldwide. One of the most harmful air pollutants is particulate matter (PM), which has different physical characteristics (particle size and number, surface area and morphology) and a highly complex and variable chemical composition. Our goal was first to comparatively assess the effects of exposure to PM regarding cytotoxicity, release of pro-inflammatory mediators and gene expression in human bronchial epithelia (HBE) reflecting normal and compromised health status. Second, we aimed at evaluating the impact of various PM components from anthropogenic and biogenic sources on the cellular responses. Air-liquid interface (ALI) cultures of fully differentiated HBE derived from normal and cystic fibrosis (CF) donor lungs were exposed at the apical cell surface to water-soluble PM filter extracts for 4 h. The particle dose deposited on cells was 0.9–2.5 and 8.8–25.4 μg per cm2 of cell culture area for low and high PM doses, respectively. Both normal and CF HBE show a clear dose-response relationship with increasing cytotoxicity at higher PM concentrations. The concurrently enhanced release of pro-inflammatory mediators at higher PM exposure levels links cytotoxicity to inflammatory processes. Further, the PM exposure deregulates genes involved in oxidative stress and inflammatory pathways leading to an imbalance of the antioxidant system. Moreover, we identify compromised defense against PM in CF epithelia promoting exacerbation and aggravation of disease. We also demonstrate that the adverse health outcome induced by PM exposure in normal and particularly in susceptible bronchial epithelia is magnified by anthropogenic PM components. Thus, including health-relevant PM components in regulatory guidelines will result in substantial human health benefits and improve protection of the vulnerable population