Evaluation of Mucociliary Clearance by Three Dimension Micro-CT-SPECT in Guinea Pig: Role of Bitter Taste Agonists

Different image techniques have been used to analyze mucociliary clearance (MCC) in humans, but current small animal MCC analysis using in vivo imaging has not been well defined. Bitter taste receptor (T2R) agonists increase ciliary beat frequency (CBF) and cause bronchodilation but their effects in vivo are not well understood. This work analyzes in vivo nasal and bronchial MCC in guinea pig animals using three dimension (3D) micro-CT-SPECT images and evaluates the effect of T2R agonists. Intranasal macroaggreggates of albumin-Technetium 99 metastable (MAA-Tc99m) and lung nebulized Tc99m albumin nanocolloids were used to analyze the effect of T2R agonists on nasal and bronchial MCC respectively, using 3D micro-CT-SPECT in guinea pig. MAA-Tc99m showed a nasal mucociliary transport rate of 0.36 mm/min that was increased in presence of T2R agonist to 0.66 mm/min. Tc99m albumin nanocolloids were homogeneously distributed in the lung of guinea pig and cleared with time-dependence through the bronchi and trachea of guinea pig. T2R agonist increased bronchial MCC of Tc99m albumin nanocolloids. T2R agonists increased CBF in human nasal ciliated cells in vitro and induced bronchodilation in human bronchi ex vivo. In summary, T2R agonists increase MCC in vivo as assessed by 3D micro-CT-SPECT analysis

BIM, projecte i obra d'arquitectura: una vivenda unifamiliar amb REVIT

[ES] Se pretende identificar y evaluar el impacto del BIM (Building Information Modelling) en la gestión de un proyecto y el seguimiento de una obra de Arquitectura. Para ello se requiere un caso concreto de estudio que reúna las siguientes condiciones: - UN proyecto de una vivienda unifamiliar sencilla. - Dicho proyecto debe haber sido elaborado con herramientas CAD. - Con la obra recién comenzada, o en condiciones de ser iniciada a principio del cuatrimestre (primeros de febrero). Como primera tarea del TFG el alumno re-elaborará completamente el proyecto: modelará la vivienda en REVIT (Autodesk), contando con la tutela del profesor tutor. Al tratarse, en realidad, de la simulación del proceso de ejecución en un entorno virtual 3D, es posible que en esta primara fase surjan conflictos a la hora de definir detalles del modelo, que podrán ser resueltos con la colaboración del equipo redactor del proyecto. En una segunda fase del TFG, el alumno deberá simular un escenario de seguimiento paralelo de la obra, que aproveche las potencialidades del modelo elaborado con REVIT. En el caso de que este seguimiento paralelo permitiera prevenir con antelación conflictos que no se hubieran detectado en el proceso real, se reseñarán en el documento final del TFG, después de haber informado a la dirección facultativa para su consideración. Para alcanzar el objetivo del TFG y poder valorar el impacto del BIM en ambas fases, el alumno deberá identificar y describir una serie de factores en los que haya resultado relevante la incidencia del modelo BIM en la gestión del proceso proyecto-construcción, en comparación con la metodología tradicional (CAD), evaluando su repercusión. Este ejercicio crítico, basado en la experiencia personal llevada a cabo el trabajo, permitirá extraer las conclusiones fundamentales del TFG[EN] The aim is to identify and evaluate the impact of the BIM (Building Information Modeling) in project management and monitoring of an architectural construction. This requires a concrete case study which fulfills the following conditions: - A project of a simple-family house. - This project must be elaborated with CAD tools. - With the construction works just started, or in conditions to be started at the beginning of the semester (first of February). The first task of the student in this TFG will be the completely re-draft of the Project: will model the house in Revit (Autodesk), with the guidance of the tutor. As a simulation of the execution process in a 3D virtual environment, it is possible that in this first phase, when defining details of the model, conflicts arise, which can be solved with the collaboration of the project team. In a second phase of the TFG, the student must simulate a scenario of parallel monitoring of the construction work, which takes advantage of the potential of the model developed with REVIT. In the event that this parallel monitoring would allow to prevent conflicts that had not been detected in the actual process in advance, they will be reviewed in the final document of the TFG, after having informed to the facultative team for its consideration. To achieve the aim of the TFG and be able to assess the impact of the BIM in both phases, the student must identify and describe a series of factors in which the incidence of the BIM model has been relevant in the management of the project-construction process, compared to the traditional methodology (CAD), evaluating its repercussion. This critical exercise, based on the personal experience carried out in the work, will allow to extract the fundamental conclusions of the TFG.Compañ Quilis, D. (2023). BIM, proyecto y obra de arquitectura: una vivienda unifamiliar con REVIT. Universitat Politècnica de València. http://hdl.handle.net/10251/19336

Adjusting tidal volume to stress index in an open lung condition optimizes ventilation and prevents overdistension in an experimental model of lung injury and reduced chest wall compliance

Introduction: The stress index ( SI), a parameter derived from the shape of the pressure-time curve, can identify injurious mechanical ventilation. We tested the hypothesis that adjusting tidal volume (VT) to a non-injurious SI in an open lung condition avoids hypoventilation while preventing overdistension in an experimental model of combined lung injury and low chest-wall compliance (Ccw). Methods: Lung injury was induced by repeated lung lavages using warm saline solution, and Ccw was reduced by controlled intra-abdominal air-insufflation in 22 anesthetized, paralyzed and mechanically ventilated pigs. After injury animals were recruited and submitted to a positive end-expiratory pressure (PEEP) titration trial to find the PEEP level resulting in maximum compliance. During a subsequent four hours of mechanical ventilation, VT was adjusted to keep a plateau pressure (Pplat) of 30 cmH2O (Pplat-group, n = 11) or to a SI between 0.95 and 1.05 (SI-group, n = 11). Respiratory rate was adjusted to maintain a 'normal' PaCO2 (35 to 65 mmHg). SI, lung mechanics, arterial-blood gases haemodynamics pro-inflammatory cytokines and histopathology were analyzed. In addition Computed Tomography (CT) data were acquired at end expiration and end inspiration in six animals. Results: PaCO2 was significantly higher in the Pplat-group (82 versus 53 mmHg, P = 0.01), with a resulting lower pH (7.19 versus 7.34, P = 0.01). We observed significant differences in VT (7.3 versus 5.4 mlKg-1, P = 0.002) and Pplat values (30 versus 35 cmH2O, P = 0.001) between the Pplat-group and SI-group respectively. SI (1.03 versus 0.99, P = 0.42) and end-inspiratory transpulmonary pressure (PTP) (17 versus 18 cmH2O, P = 0.42) were similar in the Pplat-and SI-groups respectively, without differences in overinflated lung areas at end-inspiration in both groups. Cytokines and histopathology showed no differences. Conclusions: Setting tidal volume to a non-injurious stress index in an open lung condition improves alveolar ventilation and prevents overdistension without increasing lung injury. This is in comparison with limited Pplat protective ventilation in a model of lung injury with low chest-wall compliance

Maximum relaxation (Emax) and potency (log EC50)observed with non-selective T2R agonists on human bronchi.

<p>Maximum relaxation (Emax) and potency (log EC50)observed with non-selective T2R agonists on human bronchi.</p

Diethylene-triamine-pentaacetate (DTPA)-Tc99^m evaluation as a radiotracer to monitor mucociliary clearance.

<p>A) micro-computer tomography (CT) representative image to locate SPECT images. B) SPECT representative image of nebulized DTPA-Tc99^m at time 0. C) SPECT representative image of nebulized DTPA-Tc99^m at time 360 min. D) Effects of bitter taste agonists chloroquine, denatonium and saccharin on % DTPA-Tc99^m radiation intensity. E) Representative image of extra-pulmonary location of DTPA-Tc99^m at time 360 min. Representative images of n = 12 guinea pig per experimental condition are showed. Colorimetric intensity scale adjusted for all images is shown. 100% DTPA-Tc99^m intensity corresponds to the start of experiments (t = 0min) for all experimental conditions). Results are expressed as mean ± SD. One-way repeated measures analysis of variance (ANOVA): P>0.05. Post hoc Bonferroni test: P>0.05 compared with controls.</p

Concentration-response curves for bitter taste receptor agonists (chloroquine, denatonium and saccharin) on human bronchi.

<p>The results are expressed as a percentage of the relaxation observed with 0.1 mM papaverine (mean ± SD) of n = 4 human bronchi per condition.</p

Nasal mucociliary transport rate (NMTR) measurement with combined micro-CT-SPECT macroaggregated albumin (MAA)-Technetium 99 metaestable (Tc99^m) in guinea pig.

<p>A) MAA-Tc99^m traveled distance at time 0. B) MAA-Tc99^m traveled distance after 60 min of nasal administration. C) Bitter taste receptor agonists chloroquine, denatonium and saccharin were aerosolized during 10 min before nasal MAA-Tc99^m administration and the distance traveled during 60 min was monitored. Nasal mucociliary transport rate was calculated as mm/min. Representative images of n = 9 guinea pig per condition are showed. Colorimetric intensity scale adjusted for all images is shown. Results are expressed as mean ± SD. One-way repeated measures analysis of variance (ANOVA): P<0.001. Post hoc Bonferroni test: *P<0.001 compared with controls.</p

Tc99^m albumin nanocolloids evaluation as a radiotracer to monitor mucociliary clearance.

<p>A) Representative micro-CT-coupled SPECT two dimension sections at time 0, 2h and 4h after aerosolized Tc99m albumin nanocolloids. B) Representative micro-CT-coupled SPECT three dimension images at time 0, 2h and 4h after aerosolized Tc99m albumin nanocolloids. C) Representative SPECT three dimension images at time 0, 2h and 4h after aerosolized Tc99m albumin nanocolloids. Colorimetric Colorimetric intensity scale adjusted for all images is shown. Representative images of n = 12 guinea pig are showed.</p

Macroaggreggate albumin (MAA)-Tc99^m evaluation as a radiotracer to monitor mucociliary clearance.

<p>A) Micro-CT coupled to SPECT representative image of intratracheal instillated MAA-Tc99m at time 0. B) Micro-CT coupled to SPECT representative image of intratracheal instillated MAA-Tc99^m at time 360 min. C) Effects of bitter taste agonists chloroquine, denatonium and saccharin on % MAA-Tc99^m radiation intensity. Representative images of n = 12 guinea pig per condition are showed. Colorimetric intensity scale adjusted for all images is shown. 100% MAA-Tc99m intensity corresponds to the start of experiments (t = 0min) for all experimental conditions). Results are expressed as mean ± SD. One-way repeated measures analysis of variance (ANOVA): P>0.05. Post hoc Bonferroni test: P>0.05 compared with controls.</p

Concentration-response curves for bitter taste receptor (T2R) agonists on human nasal ciliary beat frequency CBF (Hz).

<p>CBF₀ correspond to basal values of CBF when only vehicle was added to the culture medium. Non-selective agonists (chloroquine, denatonium, quinine, saccharin and diphenidol) induced increases in CBF at the concentrations represented, with the exception of phenanthroline. The results are expressed as a mean ± SD. Two-way repeated measures analysis of variance (ANOVA): P<0.001. Post hoc Bonferroni test: *P<0.05; **P<0.01; ***P<0.001 <i>vs</i> CBF₀.</p