The Effect of Tasuldine, a Bronchosecretolytic Agent, on Mucus Rheology and Clearability and the Interaction with Acetylcholine in Ferrets

Tasuldine (Ts) is an orally active bronchosecretolytic agent shown to be clinically effective in human studies. Tasuldine decreases the sialomucin content of the mucus and, in animal studies, this modulation of the glycopeptide correlates with decreased mucus viscosity. The aim of this study was to evaluate the effect of tasuldine on mucus viscoelasticity and correlate the rheological changes to mucociliary and cough clearability. Tracheal mucus samples were collected from anaesthetized adult ferrets by a modification of the cytology brush technique. Mucus was collected prior to and following administration of either vehicle (normal saline) or Ts (10 mg/kg i.v.), and followed by acetylcholine (ACH) challenge (ca. 4 ml of 10⁻²M i.v., slow infusion). The analysis included magnetic microrheometry to measure the viscosity and elasticity of microlitre quantities of mucus. Mucociliary transportability (NFPTR) was measured by means of the frog palate assay and mucus collection rates (mg/min) were used as an indirect measure of secretion rate. The principal index of mucus rigidity, log G*, decreased with tasuldine infusion (P=0.014) and further decreased with ACH (P=0.002). In simple terms, the mucus became less rigid or more deformable with tasuldine administration, thus benefiting clearability based on predictions from model studies. The changes observed with acetylcholine alone were consistent with a classic secretagogue response—the outputting of a large volume of watery mucus. NFPTR increased with tasuldine treatment, and even further with acetylcholine; however, the combination of Ts and ACH resulted in a decrease in NFPTR close to baseline, which was likely due to the fact that the resulting mucus was too liquid for maximal mucociliary efficiency. The index of mucus flux (mg/min) was very much elevated with ACH compared with control; this was not the case with Ts. This indicates that tasuldine, despite improving the rheological properties of the mucus, did not stimulate hypersecretion, as was the case for acetylcholine. The changes in mucus rheology with infused tasuldine can be considered beneficial with respect to their effects on predicted mucociliary and cough clearability, supporting the clinical effectiveness of this type of mucolytic therapy in airway diseases such as chronic bronchitis. The study also illustrates the potential danger of overliquification of mucus.     

心脏舒张功能障碍的被动力学机制

心肌被动力学特性的改变在心脏舒张功能障碍中起着重要的作用。心肌被动力学的研究将为深入认识心脏舒张功能障碍的病理生理机制和舒张性心力衰竭的诊断、治疗提供实验依据和理论基础。     

Core-Shell-Structured Copolyaniline-Coated Polymeric Nanoparticle Suspension and Its Viscoelastic Response under Various Electric Fields

Semi-conducting poly(n-methylaniline) (PNMA)-coated poly(methyl methacrylate) (PMMA) composite nanoparticles were synthesized using cross-linked and grafted PMMA particles as a core, and then, the PNMA shell was coated via chemical oxidative polymerization on the surface of modified PMMA nanoparticles. Their electroresponsive electrorheological characteristics when dispersed in silicone were confirmed under applied electric fields using a rotational rheometer, focusing on their viscoelastic response. Using a frequency sweep test, the frequency dependence of both the storage and loss moduli was confirmed to increase upon increasing the electric field, with a stable plateau regime over the entire angular frequency range.     

Parameter Identification and Validation of Shape-Memory Polymers within the Framework of Finite Strain Viscoelasticity

Shape-Memory Polymers (SMPs) can be stretched to large deformations and recover induced strains when exposed to an appropriate stimulus, such as heat. This emerging class of functional polymers has attracted much interest and found applications in medicine and engineering. Nevertheless, prior to any application, their physical and mechanical properties must be thoroughly studied and understood in order to make predictions or to design structures thereof. In this contribution, the viscoelastic behavior of a polyether-based polyurethane (Estane) and its rate- and temperature-dependent behavior have been studied experimentally and by the mean of simulations. The model-inherent material parameters are identified with the assumption of the thermo-rheological complexity. Here, the numerical results of uni-axial stress relaxations were compared with the associated experiments in conjucation with the Levenberg-Marquard optimization method to determine the parameters of the Prony equation. The ability of the model to simulate the thermo-mechanical properties of Estane was evaluated by data-rich experimental observations on tension and torsion in various temperature ranges. Heterogeneous tests are included into the experimental program to cover a broader spectrum of loading scenarios.     

Age-associated changes in viscoelastic properties of the bovine temporomandibular joint disc

To test the hypothesis that compressive properties of the temporomandibular joint (TMJ) disc change with age, we investigated its viscoelastic properties and stress-relaxation behavior under compression. Compressive stress-relaxation tests were performed in different regions of bovine discs of various ages. For each disc, specimens were derived from three different regions (anterior, central, and posterior). For four strain levels (5, 10, 15, and 20%), a stress-relaxation test was conducted over a 5-min period. Values of the instantaneous modulus, E(0), appeared to be larger in the anterior than in the posterior region of the disc, irrespective of age. The E(0) value increased with age, especially in the central region. Values of the relaxed modulus, E(R), also increased significantly with age. There were no regional differences in values of the relaxed modulus. Under stress-relaxation, the relaxation time became longer with age, especially in the posterior region. The results suggest that the compressive properties, instantaneous and relaxed moduli, increase with age, while the relaxation time becomes longer. This implies that the TMJ disc becomes harder with age. Furthermore, the compressive properties of the TMJ disc are region-specific. As a result of the harder disc, it is likely that the TMJ becomes more vulnerable to secondary damage, such as fracture and tissue degradation.     

Effects of dexmedetomidine on respiratory mechanics and control of breathing in normal rats

Dexmedetomidine is a highly selective and specific alpha(2)-adrenergic agonist, with sedative, analgesic, and sympatholytic activities. The aim of the present study was to define the effects of DMED in respiratory mechanics in normal rats. In addition, lung morphometry was studied to determine whether the physiological changes reflected underlying morphological changes defining the sites of action of dexmedetomidine. Arterial blood gases were also determined. Twelve adult Wistar rats were randomly assigned to two groups of six animals each: PENTO and DMED. In PENTO group animals were sedated (diazepam, 5mg, i.p.) and anaesthetised with pentobarbital sodium (20mgkg(-1) i.p.). The rats of the DMED group received dexmedetomidine (250mugkg(-1) i.p. followed by intravenous infusion of 0.5mugkg(-1)h(-1)). In spontaneously breathing rats, minute ventilation, respiratory frequency, and neuromuscular inspiratory drive were lower in dexmedetomidine group, which also presented hypercapnia, whereas tidal volume, inspiratory, expiratory, and total respiratory cycle times were higher in dexmedetomidine group compared to the PENTO group. During mechanical ventilation, respiratory mechanical parameters were similar in both groups. These findings were supported by the absence of histological changes. In conclusion, under the conditions studied, dexmedetomidine did not change respiratory mechanical parameters and lung histology, but induced ventilatory depression.     

Viscoelastic measurements after vocal fold scarring in rabbits—short-term results after hyaluronan injection

Abstract

Conclusions. The scarring model resulted in significant damage and elevated viscoelasticity of the lamina propria. Hyaluronan preparations may alter viscoelasticity in scarred rabbit vocal folds. Objectives. Vocal fold scarring results in stiffness of the lamina propria and severe voice problems. The aims of this study were to examine the degree of scarring achieved in the experiment and to measure the viscoelastic properties after injection of hyaluronan in rabbit vocal folds. Materials and methods. Twenty-two vocal folds from 15 New Zealand rabbits were scarred, 8 vocal folds were controls. After 8 weeks 12 of the scarred vocal folds received injections with 2 types of cross-linked hyaluronan products and 10 scarred folds were injected with saline. After 11 more weeks the animals were sacrificed. After dissection, 15 vocal folds were frozen for viscoelastic measurements, whereas 14 vocal folds were prepared and stained. Measurements were made of the lamina propria thickness. Viscoelasticity was measured on intact vocal folds with a linear skin rheometer (LSR) adapted to laryngeal measurements. Results. Measurements on the digitized slides showed a thickened lamina propria in the scarred samples as compared with the normal vocal folds (p <0.05). The viscoelastic analysis showed a tendency to stiffening of the scarred vocal folds as compared with the normal controls (p =0.05). There was large variation in stiffness between the two injected hyaluronan products.     

低聚香豆胶交联凝胶体系

首次研究了微波辅助酸降解香豆胶过程及其影响因素，并与水浴酸降解过程进行对比，获得了低聚香豆胶。研究了低聚香豆胶与硼砂交联形成凝胶的过程，考察了低聚香豆胶浓度、硼砂浓度和pH值对形成凝胶体系的影响，获得了稳定的凝胶体系。进一步研究了低聚香豆胶凝胶体系的流变特性。结果表明：微波辅助酸降解法是快速降解香豆胶的新方法，降解速度显著高于水浴酸降解法。在适当的碱性条件下，低聚香豆胶可与硼砂形成较稳定的交联凝胶体系，该体系具有显著的粘弹性和剪切变稀特性。