In nature, organisms living in extreme environmental conditions produce antifreeze proteins (AFPs) that prevent the growth of ice crystals and depress the freezing point of body fluids. In this study, three different peptides derived from the N-terminal sequence of the helical type I AFP HPLC6, along with a stapled derivative produced via on-resin microwave-assisted copper(I)-catalyzed azide-alkyne cycloaddition, were conjugated to gold nanoparticles. The aim of decorating the surface of the nanoparticles with multiple copies of the peptides was to combine the ice-binding capability of the peptides with the size of a nanoparticle, thus, mimicking the protein bulkiness to enhance the peptide antifreeze activity.
View Article and Find Full Text PDFComput Methods Programs Biomed
November 2024
Background: Chronic obstructive pulmonary disease (COPD) is characterised by airway obstruction with an increase in airway resistance (R) to airflow in the lungs. An extreme case of expiratory airway resistance is expiratory flow limitation, a common feature of severe COPD. Current analyses quantify expiratory R with linear model-based methods, which do not capture non-linearity's noted in COPD literature.
View Article and Find Full Text PDFIn everyday life during terrestrial locomotion our body interacts with two media opposing the forward movement of the body: the ground and the air. Whereas the work done to overcome the ground reaction force has been extensively studied, the work done to overcome still air resistance has been only indirectly estimated by means of theoretical studies and by measurements of the force exerted on puppets simulating the geometry of the human body. In this study, we directly measured the force exerted by still air resistance on eight male subjects during walking and running on an instrumented treadmill with a belt moving at the same speed of a flow of laminar air facing the subject.
View Article and Find Full Text PDFAcute dyspnea represents one of the most frequent symptoms leading to emergency room evaluation. Its significant prognostic value warrants a careful evaluation. The differential diagnosis of dyspnea is complex due to the lack of specificity and the loose association between its intensity and the severity of the underlying pathological condition.
View Article and Find Full Text PDFRespir Physiol Neurobiol
February 2022
Chronic obstructive pulmonary disease (COPD) patients often experience tidal expiratory flow-limitation (tEFL), a condition causing respiratory and cardiovascular detrimental effects. As the appearance of tEFL should increase expiratory (Rexp) relative to inspiratory (Rins) resistance, we hypothesized that Rexp/Rins can be used to detect tEFL. Rexp/Rins was measured with a commercial plethysmograph in 109 healthy subjects and, before and after bronchodilation (BD), in 64 COPD patients, 36 with and 28 without tEFL according to the NEP technique.
View Article and Find Full Text PDFDiscovered some 40 years ago, the I current has since been known as the "pacemaker" current due to its role in the initiation and modulation of the heartbeat and of neuronal excitability. But this is not all, the funny current keeps entertaining the researchers; indeed, several data discovering novel and uncanonical roles of f/HCN channel are quickly accumulating. In the present review, we provide an overview of the expression and cellular functions of HCN/f channels in a variety of systems/organs, and particularly in sour taste transduction, hormones secretion, activation of astrocytes and microglia, inhibition of osteoclastogenesis, renal ammonium excretion, and peristalsis in the gastrointestinal and urine systems.
View Article and Find Full Text PDFSince its introduction in the clinical practice, body plethysmography has assisted pneumologists in the diagnosis of respiratory diseases and patients' follow-up, by providing easy assessment of absolute lung volumes and airway resistance. In the last decade, emerging evidence suggested that estimation of alveolar pressure by electronically-compensated plethysmographs may contain information concerning the mechanics of the respiratory system which goes beyond those provided by the simple value of airway resistance or conductance. Indeed, the systematic study of expiratory alveolar pressure-flow loops produced during spontaneous breathing at rest has shown that the marked expansion of expiratory loops in chronic obstructive pulmonary disease patients mainly reflects the presence of tidal expiratory flow-limitation.
View Article and Find Full Text PDFSepsis is the life-threatening organ dysfunction arising from a dysregulated host response to infection. Although the specific mechanisms leading to organ dysfunction are still debated, impaired tissue oxygenation appears to play a major role, and concomitant hemodynamic alterations are invariably present. The hemodynamic phenotype of affected individuals is highly variable for reasons that have been partially elucidated.
View Article and Find Full Text PDFWe investigated the effects of heliox administration (80% helium in O) on tidal inspiratory flow limitation (tIFL) occurring in supine anesthetized spontaneously breathing rabbits, regarded as an animal model of obstructive apnea-hypopnea syndrome. 22 rabbits were instrumented to record oro-nasal mask flow, airway opening, tracheal and esophageal pressures, and diaphragm and genioglossus electromyographic activities while breathing either room air or heliox, and, in 12 rabbits, also during the application of continuous positive airway pressure (CPAP; 6 cmHO). For the group, heliox increased peak inspiratory flow, ventilation (18 ± 11%), peak inspiratory tracheal and dynamic transpulmonary pressures, but in no animal eliminated tIFL, as instead CPAP did in all.
View Article and Find Full Text PDFDuring spontaneous breathing at rest, the alveolar pressure (P)-flow (V̇) relation exhibits a prominent expiratory loop in many chronic obstructive pulmonary disease (COPD) patients. Among the possible determinants of the loop, tidal expiratory flow limitation (tEFL) may be the main responsible. To compare the characteristics of the expiratory loop in COPD patients with flow limitation (FL) and without flow limitation (NFL), tEFL was assessed with the negative expiratory pressure technique in stable mild to very severe COPD patients undergoing body plethysmography before and after bronchodilation (BD), an intervention that is able to reduce mechanical heterogeneity, recruitment/derecruitment, and gas trapping but rarely abolishes tEFL.
View Article and Find Full Text PDFCOPD and asthma have different risk factors and pathogenesis, but they share a pathophysiologic hallmark characterized by small airways disease. Although difficult to explore and measure, modifications of distal airways' pathophysiology and biology represent an early sign of obstructive disease and should be researched and assessed in everyday clinical practice. In the last 15 years, computed microtomography scans have shed light on the anatomy and physiology of the so-called silent zone, and research devoted to investigate the effect of inhaled treatments on small airway pathophysiology has been increasing.
View Article and Find Full Text PDFA growing body of evidence implicates the human microbiome as a potentially influential player actively engaged in shaping the pathogenetic processes underlying the endotypes and phenotypes of chronic respiratory diseases, particularly of the airways. In this article, we specifically review current evidence on the characteristics of lung microbiome, and specifically the bacteriome, the modes of interaction between lung microbiota and host immune system, the role of the "lung-gut axis", and the functional effects thereof on asthma pathogenesis. We also attempt to explore the possibilities of therapeutic manipulation of the microbiome, aiming at the establishment of asthma prevention strategies and the optimization of asthma treatment.
View Article and Find Full Text PDFThe airway epithelium stretches and relaxes during the normal respiratory cycle, and hyperventilation exaggerates this effect, resulting in changes in lung physiology. In fact, stretching of the airways influences lung function and the secretion of airway mediators, which in turn may cause a potentially injurious inflammatory response. This aim of the present narrative review was to illustrate the current evidence on the importance of mechanical stress in the pathophysiology of lung diseases with a particular focus on chronic obstructive pulmonary disease (COPD) and to discuss how this may influence pharmacological treatment strategies.
View Article and Find Full Text PDFWorld J Crit Care Med
January 2019
Expiratory flow limitation (EFL), that is the inability of expiratory flow to increase in spite of an increase of the driving pressure, is a common and unrecognized occurrence during mechanical ventilation in a variety of intensive care unit conditions. Recent evidence suggests that the presence of EFL is associated with an increase in mortality, at least in acute respiratory distress syndrome (ARDS) patients, and in pulmonary complications in patients undergoing surgery. EFL is a major cause of intrinsic positive end-expiratory pressure (PEEPi), which in ARDS patients is heterogeneously distributed, with a consequent increase of ventilation/perfusion mismatch and reduction of arterial oxygenation.
View Article and Find Full Text PDFIn 9 anesthetized, paralyzed dogs lung and chest-wall standard (viscous resistance, Rint, and quasi-static elastance, Est) and viscoelastic parameters (resistance, Rvel, and time constant, τvel) were measured in the supine posture before and after rib-cage block, after application of an expiratory threshold load, and after 75° head-up tilting before and after wide chest opening. Lung and chest-wall τvel were the same under all conditions. Rvel was independent of volume and posture, and greater for the lung.
View Article and Find Full Text PDFPlethysmographic alveolar pressure-flow (-) loops contain potentially relevant information about the pathophysiology of chronic obstructive pulmonary disease (COPD), but no quantitative analysis of these loops during spontaneous breathing has ever been performed. The area of the loop's inspiratory () and expiratory portion (), and the difference between the end-expiratory and end-inspiratory alveolar pressure (Δ) were measured in 20 young, 20 elderly healthy subjects, and 130 stable COPD patients. and Δ increased by 55 and 78% from young to elderly subjects, and by 107 and 122% from elderly subjects to COPD patients, reflecting changes in mechanical heterogeneity, lung-units recruitment/derecruitment, and possibly air trapping occurring with aging and/or obstructive disease.
View Article and Find Full Text PDFIntroduction: Exercise intolerance is the most predominant symptom in patients with COPD. Nevertheless, it is unclear whether walking economy and gait variability are altered in these patients. Thus, our main objective was to compare the cost of transport and gait variability as a function of speed, including the self-selected walking speed, in subjects with COPD relative to healthy subjects.
View Article and Find Full Text PDFSmall airways represent the key factor of chronic obstructive pulmonary disease (COPD) pathophysiology. The effect of different classes of bronchodilators on small airways is still poorly understood and difficult to assess. Hence the acute effects of tiotropium (18 µg) and indacaterol (150 µg) on closing volume (CV) and ventilation inhomogeneity were investigated and compared in 51 stable patients (aged 70 ± 7 yr, mean ± SD; 82% men) with moderate to very severe COPD.
View Article and Find Full Text PDFPurpose: To determine whether the analysis of the slow expiratory transpulmonary pressure-volume (P-V) curve provides an alternative to the single-breath nitrogen test (SBN) for the assessment of the closing volume (CV).
Methods: SBN test and slow deflation P-V curve were simultaneously recorded in 40 healthy subjects and 43 COPD patients. Onset of phase IV identified CV in SBN test (CV), whereas in the P-V curve CV was identified by: a) deviation from the exponential fit (CV), and b) inflection point of the interpolating sigmoid function (CV).
Background: Lung diffusing capacity (DLCO) and lung volume distribution predict exercise performance and are altered in COPD patients. If pulmonary rehabilitation (PR) can modify DLCO parameters is unknown.
Objectives: To investigate changes in DLCO and ventilation inhomogeneity following a PR program and their relation with functional outcomes in patients with COPD.
To verify the hypothesis that by enmeshing lubricants, microvilli reduce the coefficient of kinetic friction (μ) of pleural mesothelium, μ was measured during reciprocating sliding of rabbit's visceral against parietal pleura before and after addition of hyaluronan, and related to the morphological features of the microvillar network. Because no relation was found between μ or μ changes after hyaluronan and microvillar characteristics, the latter are not determinants of the frictional forces which oppose sliding of normal mesothelial surfaces under physiological conditions, nor of the effects of hyaluronan. Addition of hyaluronan increased μ slightly but significantly in normal specimens, probably by altering the physiological mix of lubricants, but decreased μ of damaged mesothelia, suggesting protective, anti-abrasion properties.
View Article and Find Full Text PDFBackground: In COPD patients, reversibility is currently evaluated from the changes of forced expiratory volume at 1s (ΔFEV1) and forced vital capacity (ΔFVC). By lowering peripheral airway smooth muscle tone, bronchodilators should decrease dynamic hyperinflation, gas trapping, and possibly dyspnea at rest. Hence, we hypothesize that specific airway resistance changes (ΔsRAW) should better characterize the acute response to bronchodilators.
View Article and Find Full Text PDFBackground: Recent studies in healthy mice and rats have reported that positive pressure ventilation delivered with physiological tidal volumes at normal end-expiratory volume worsens lung mechanics and induces cytokine release, thus suggesting that detrimental effects are due to positive pressure ventilation per se. The aim of this study in healthy animals is to assess whether these adverse outcomes depend on the mode of mechanical ventilation.
Methods: Rats were subjected to 4 h of spontaneous, positive pressure, and whole-body or thorax-only negative pressure ventilation (N = 8 per group).