Development of an in vitro system to study the interactions of aerosolized drugs with pulmonary mucus

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Mucus is the first biological component inhaled drugs encounter on their journey towards their pharmacological target in the upper airways. Yet, how mucus may influence drug disposition and efficacy in the lungs has been essentially overlooked. In this study, a simple in vitro system was developed to investigate the factors promoting drug interactions with airway mucus in physiologically relevant conditions. Thin layers of porcine tracheal mucus were prepared in Transwell® inserts and initially, the diffusion of various fluorescent dyes across those layers was monitored over time. A deposition system featuring a MicroSprayer® aerosolizer was optimized to reproducibly deliver liquid aerosols to multiple air-facing layers and then exploited to compare the impact of airway mucus on the transport of inhaled bronchodilators. Both the dyes and drugs tested were distinctly hindered by mucus with high logP compounds being the most affected. The diffusion rate of the bronchodilators across the layers was in the order: ipratropium ≈ glycopyronnium > formoterol > salbutamol > indacaterol, suggesting hydrophobicity plays an important role in their binding to mucus but is not the unique parameter involved. Testing of larger series of compounds would nevertheless be necessary to better understand the interactions of inhaled drugs with airway mucus

Biomechanical Impact of the Sclera on Corneal Deformation Response to an Air-Puff: A Finite-Element Study

Aim or Purpose: To describe the effect of varying scleral stiffness on the biomechanical deformation response of the cornea under air-puff loading via a finite-element (FE) model.Methods: A two-dimensional axisymmetric stationary FE model of the whole human eye was used to examine the effects varying scleral stiffness and intraocular pressure (IOP) on the maximum apical displacement of the cornea. The model was comprised of the cornea, sclera, vitreous, and surrounding air region. The velocity and pressure profiles of an air-puff from a dynamic Scheimpflug analyzer were replicated in the FE model, and the resultant profile was applied to deform the cornea in a multiphysics study (where the air-puff was first simulated before being applied to the corneal surface). IOP was simulated as a uniform pressure on the globe interior. The simulation results were compared to data from ex vivo scleral stiffening experiments with human donor globes.Results: The FE model predicted decreased maximum apical displacement with increased IOP and increased ratio of scleral-to-corneal Young's moduli. These predictions were in good agreement (within one standard deviation) with findings from ex vivo scleral stiffening experiments using human donor eyes. These findings demonstrate the importance of scleral material properties on the biomechanical deformation response of the cornea in air-puff induced deformation.Conclusion: The results of an air-puff induced deformation are often considered to be solely due to IOP and corneal properties. The current study showed that the stiffer the sclera, the greater will be the limitation on corneal deformation, separately from IOP. This may have important clinical implications to interpreting the response of the cornea under air-puff loading in pathologic conditions

Our Taz

In memory of Professor Andrew Taslit

Detection of Keratoconus With a New Biomechanical Index

To evaluate the ability of a new combined biomechanical index called the Corvis Biomechanical Index (CBI) based on corneal thickness profile and deformation parameters to separate normal from keratoconic patients

The association between benign prostatic hyperplasia and chronic kidney disease in community-dwelling men

The association between benign prostatic hyperplasia and chronic kidney disease in community-dwelling men.BackgroundBenign prostatic hyperplasia (BPH) and chronic kidney disease are important public health problems in older men. Previous referral-based studies disagree on whether BPH is associated with chronic kidney disease. The objective of this study was to determine the community-based association between clinical measures of BPH and chronic kidney disease.MethodsA community-based sample of 2115 white men (ages 40–79 years) was randomly selected from the Olmsted County, Minnesota population (55% participation rate) in 1990. A random subsample (N = 476) had a detailed clinical evaluation. This evaluation included a questionnaire with similar queries to the International Prostate Symptom Score (IPSS), peak urinary flow rates (uroflowmeter), postvoid residual urine volume (ultrasound), prostate volume (ultrasound), serum prostate specific antigen (PSA), and serum creatinine.ResultsAfter adjustment for age, hypertension, diabetes, leukocyte esterase positive (possible urinary tract infection), and smoking, chronic kidney disease [serum creatinine ≥133 μmol/L (1.5 mg/dL)] was associated with diminished peak urinary flow rate (<15 mL/sec) by an odds ratio (OR) = 2.96 (95% CI 1.30–7.01), moderate-severe lower urinary tract symptoms (IPSS >7) by an OR = 2.91 (95% CI 1.32–6.62), and chronic urinary retention (postvoid residual >100 mL) by an OR = 2.28 (95% CI 0.66–6.68). There was no association with a prostate volume >30 mL by an OR = 0.56 (95% CI 0.22–1.37) or PSA >1.4 ng/mL by an OR = 1.17 (95% CI 0.47–2.81).ConclusionThere was a cross-sectional association between signs and symptoms of bladder outlet obstruction and chronic kidney disease in community-dwelling men. Prostatic enlargement was not associated with chronic kidney disease

A New Stiffness Parameter in Air Puff Induced Corneal Deformation Analysis

OCULUS Optikgerate GmbHOhio State Univ, Ophthalmol & Visual Sci & Biomed Engn, Columbus, OH 43210 USAOhio State Univ, Mech & Aerosp Engn, Columbus, OH 43210 USAUniv Liverpool, Sch Engn, Liverpool, Merseyside, EnglandUniv Insubria, Div Ophthalmol, Varese, ItalyHumanitas Clin & Res Ctr, Ctr Eye, Rozzano, ItalyVincieye Clin, Milan, ItalyRio de Janeiro Corneal Tomog & Biomech Study Grp, Rio De Janeiro, BrazilUniv Fed Sao Paulo, Ophthalmol, Rio De Janeiro, BrazilUniv Fed Sao Paulo, Ophthalmol, Rio De Janeiro, BrazilWeb of Scienc

Characterization of cone size and centre in keratoconic corneas

A novel method to locate the centre of keratoconus (KC) and the transition zone between the pathological area and the rest of the corneal tissue is proposed in this study. A spherical coordinate system was used to generate a spherical height map measured relative to the centre of the optimal sphere fit, and normal to the surface. The cone centre was defined as the point with the maximum height. Second derivatives of spherical height were then used to estimate the area of pathology in an iterative process. There was mirror symmetry between cone centre locations in both eyes. The mean distance between cone centre and corneal apex was 1.45 ± 0.25 mm (0.07–2.00), the mean cone height normal to the surface was 37 ± 23 µm (2–129) and 75 ± 45 µm (5–243) in the anterior and posterior surfaces, respectively. There was a significant negative correlation between the cone height and the radius of the sphere of optimal fit (p < 0.05 for both anterior and posterior surfaces). On average, posterior cone height was larger than the corresponding anterior cone height by 37 ± 24 µm (0–158). The novel method proposed can be used to estimate the cone centre and area, and explore the changes in anterior and posterior corneal surfaces that take place with KC progression. It can help improve understanding of keratoconic corneal morphology and assist in developing customized treatments

Erratum to: How Can Psychological Science Inform Research About Genetic Counseling for Clinical Genomic Sequencing?

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147141/1/jgc40372.pd