Differential anti-inflammatory effects of large and small particle size inhaled corticosteroids in asthma

BACKGROUND: Extra-fine particle formulations of hydrofluoroalkane-134a beclometasone dipropionate (HFA-BDP) exhibit clinical effects comparable with conventional particle formulations of chlorofluorocarbon beclometasone dipropionate (CFC-BDP) at half the dose. There is little data comparing their effects on inflammation. We have evaluated the effects of HFA-BDP and CFC-BDP on pulmonary and systemic markers of asthmatic inflammation. METHODS: A double-blind randomized crossover trial was undertaken comparing the anti-inflammatory effects of HFA-BDP (100 and 400 microg/day) and CFC-BDP (200 and 800 microg/day). Treatment with montelukast was evaluated as add-on to the higher dose of BDP. RESULTS: Compared with baseline after withdrawal of usual asthma therapy, 100 microg of HFA-BDP significantly attenuated serum eosinophilic cationic protein levels (0.61-fold change, 95% CI 0.49-0.77; a 39% reduction, P < 0.001), but 200 microg of CFC-BDP did not (0.87-fold change, 95% CI 0.63-1.23; P = 1). A dose of 800 microg of CFC-BDP and 400 microg of HFA-BDP led to reductions in exhaled nitric oxide (0.57-fold change, 95% CI 0.44-0.73; a 43% reduction, P < 0.001 and 0.65-fold change, 95% CI 0.47-0.91; a 35% reduction, P = 0.008, respectively); and peripheral eosinophils (-74 cells/microl, 95% CI -146 to -2; P = 0.020 and -77 cells/microl, 95% CI -140 to -14; P = 0.012, respectively). Montelukast further reduced exhaled nitric oxide (0.81-fold change, 95% CI 0.66-0.98; P = 0.028) with 400 microg HFA-BDP and eosinophils (-44 cells/microl, 95% CI -80 to -8; P = 0.012) with 800 microg CFC-BDP, but not vice versa. CONCLUSION: Chlorofluorocarbon beclometasone dipropionate and HFA-BDP have differential effects on pulmonary and systemic inflammation, which dictate the additive effects of montelukast.     

On the Production of Chitosan-Coated Polycaprolactone Nanoparticles in a Confined Impinging Jet Reactor

This work is focused on the synthesis of polycaprolactone nanoparticles, coated with chitosan, in a confined impinging jet reactor using the solvent displacement method. The role of the various reacting species was investigated, evidencing that a biocompatible polymer, for example, polycaprolactone, is required to support chitosan to obtain a monomodal particle size distribution, with low particle diameters. A surfactant is required to reduce the nanoparticle size (down to a mean diameter of about 260 nm) and obtain a positive zeta potential (about +31 mV), perfectly suitable for pharmaceutical applications. Different surfactants were tested, and Poloxamer 388 appeared to be preferable to polyvinyl alcohol. The effect of the concentration of Poloxamer 388 (in the range 0.5-5 mg mL^?1) and of chitosan (in the range 1.5-5 mg mL^?1) on both the mean particle size and zeta potential was also investigated, evidencing that chitosan concentration has the strongest effect on both parameters. Finally, the effect of solvent evaporation, quenching and feed flow rate was investigated, showing that the evaporation stage does not affect particle characteristics, quenching is required to avoid particle aggregation, and a minimum liquid flow rate of 80 mL min^?1 is required in the considered reactor to minimize the particle size.     

自制双层盐袋固定袋应用于永久起搏器植入术后压迫的效果分析

摘要 目的：探讨自制双层盐袋固定袋在永久起搏器植入术后患者切口压迫中的效果。方法： 2015年1月～2016年6月间在心内科行永久起搏器植入术的患者,随机进行分组。对照组患者术后使用两个500g普通盐袋压迫12～24 h,观察组患者术后采用自制的双层盐袋固定袋压迫切口6～12 h。观察患者术后并发症、心理、睡眠状况、舒适度,患者和护士对压迫工具的满意度。结果：观察组与对照组相比,观察组患者术后并发症少、患者心理、睡眠状况及术后舒适度更好,患者和护士的满意度高（P＜0.05）。结论：使用自制的双层盐袋固定袋压迫切口处,临床使用效果满意,有效降低术后并发症,提高患者的睡眠质量。 关键词 盐袋;永久起搏器;切口压迫;并发症;舒适度     

Characterization of the innate stimulatory capacity of plant-derived virus-like particles bearing influenza hemagglutinin

Cell-mediated immunity is an important component of immediate and long-term anti-viral protection. Dendritic cells (DCs) are essential for the induction of cell-mediated immunity by instructing the activation and differentiation of antigen-specific T cell responses. Activated DCs that express co-stimulatory molecules and pro-inflammatory cytokines are necessary to promote the development of type 1 immune responses required for viral control. Here we report that plant-derived virus-like particles (VLPs) bearing influenza hemagglutinins (HA) directly stimulate mouse and human DCs. DCs exposed to H1- and, to a lesser extent, H5-VLPs in vitro rapidly express co-stimulatory molecules and produce pro-inflammatory cytokines including IL-12, IL-6 and TNFα. Furthermore, these VLPs support the activation and differentiation of antigen-specific T cell responses. Mechanistically, H1-VLPs stimulate the activation of kinases typically activated downstream of pattern recognition receptors including AKT, p38, and p42/44 ERK. In vivo, immunization with plant-derived VLPs induce the accumulation of both cDC1s and cDC2 in the draining lymph node and a corresponding increase in T and B cells. VLPs devoid of HA protein activate DCs, suggesting they are intrinsically immunostimulatory. Together, the results demonstrate that these candidate plant-derived VLP vaccines have an inherent and direct stimulatory effect on DCs and can enhance the ability of DCs to promote Type 1 immune responses.     

PVC材质一次性输注泵在常用局麻药应用中的安全性研究

目的考察一次性使用输注泵与常用局麻药的相容性,评定其在临床常用局麻药物使用中的安全性。方法3种常用局麻药分别与2种液体（生理盐水及乳酸林格氏液）按临床使用浓度配伍,在不同时间点分别采用LC-MS／MS法、光阻法、高效液相色谱法测定邻苯二甲酸二-（2-乙基己基）酯（DEHP）含量、不溶性微粒和药物浓度。结果DEHP含量低于LC-MS／MS测定方法定量下限（0．072gg·mL^-1）,更低于考核标准静脉晶体溶液输注成年人（70kg）DEHP剂量上界估算值（0．005mg·kg^-1·d^-1）;48h内各实验药物在一次性使用输注泵中药物含量相对0h均〉96．0％,受试输注泵与各种药物在48h内未见明显吸附;输注泵中溶液稳定,0h每1mL粒子直径≥10μm粒子数（n=30）（35．13±14．4）粒;每1mL粒子直径≥25μm粒子数（n=30）（0．61±0．49）粒,符合中国药典2010版标准。结论研究表明本一次性使用输注泵应用于3种常用局麻药物较为稳定,其DEHP溶出、不溶性微粒及药物吸附性等方面符合安全使用要求。     

Optimisation of Shrinkage and Strength on Thick Plate Part Using Recycled LDPE Materials

Achieving good quality of products from plastic injection moulding processes is very challenging, since the process comprises many affecting parameters. Common defects such as warpage are hard to avoid, and the defective parts will eventually go to waste, leading to unnecessary costs to the manufacturer. The use of recycled material from postindustrial waste has been studied by a few researchers. However, the application of an optimisation method by which to optimise processing parameters to mould parts using recycled materials remains lacking. In this study, Response Surface Methodology (RSM) and Particle Swarm Optimisation (PSO) methods were conducted on thick plate parts moulded using virgin and recycled low-density polyethylene (LDPE) materials (100:0, 70:30, 60:40 and 50:50; virgin to recycle material ratios) to find the optimal input parameters for each of the material ratios. Shrinkage in the x and y directions increased in correlation with the recycled ratio, compared to virgin material. Meanwhile, the tensile strength of the thick plate part continued to decrease when the recycled ratio increased. R30 (70:30) had the optimum shrinkage in the x direction with respect to R0 (100:0) material where the shrinkage increased by 24.49% (RSM) and 33.20% (PSO). On the other hand, the shrinkage in the y direction for R30 material increased by 4.48% (RSM) and decreased by 2.67% (PSO), while the tensile strength of R30 (70:30) material decreased by 0.51% (RSM) and 2.68% (PSO) as compared to R0 (100:0) material. Validation tests indicated that the optimal setting of processing parameter suggested by PSO and RSM for R0 (100:0), R30 (70:30), R40 (60:40) and R50 (50:50) was less than 10%.     

A Novel Method for Assessing Respiratory Deposition of Welding Fume Nanoparticles

Welders are exposed to high concentrations of nanoparticles. Compared to larger particles, nanoparticles have been associated with more toxic effects at the cellular level, including the generation of more reactive oxygen species activity. Current methods for welding-fume aerosol exposures do not differentiate between the nano-fraction and the larger particles. The objectives of this work are to establish a method to estimate the respiratory deposition of the nano-fraction of selected metals in welding fumes and test this method in a laboratory setting. Manganese (Mn), Nickel (Ni), Chromium (Cr), and hexavalent chromium (Cr(VI)) are commonly found in welding fume aerosols and have been linked with severe adverse health outcomes. Inductively coupled plasma mass spectrometry (ICP-MS) and ion chromatography (IC) were evaluated as methods for analyzing the content of Mn, Ni, Cr, and Cr(VI) nanoparticles in welding fumes collected with nanoparticle respiratory deposition (NRD) samplers. NRD samplers collect nanoparticles at deposition efficiencies that closely resemble physiological deposition in the respiratory tract. The limits of detection (LODs) and quantitation (LOQs) for ICP-MS and IC were determined analytically. Mild and stainless steel welding fumes generated with a robotic welder were collected with NRD samplers inside a chamber. LODs (LOQs) for Mn, Ni, Cr, and Cr(VI) were 1.3 μg (4.43 μg), 0.4 μg (1.14 μg), 1.1 μg (3.33 μg), and 0.4 μg (1.42 μg), respectively. Recovery of spiked samples and certified welding fume reference material was greater than 95%. When testing the method, the average percentage of total mass concentrations collected by the NRD samplers was ～30% for Mn, ～50% for Cr, and ～60% for Ni, indicating that a large fraction of the metals may lie in the nanoparticle fraction. This knowledge is critical to the development of toxicological studies aimed at finding links between exposure to welding fume nanoparticles and adverse health effects. Future work will involve the validation of the method in workplace settings.

[Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resource: Digestion, extraction, and analysis procedures for nylon mesh screens.]     

Long‐term retention of avulsed maxillary permanent incisors replanted after prolonged non‐physiological storage

Ankylosis and external replacement resorption (ERR) are two typical biological responses to delayed replantation of avulsed teeth in cases where adequate root canal treatment is performed. The patient's growth stage affects the progression of root resorption and the long‐term outcome of the affected teeth. This case report describes the long‐term outcome of an 18.5‐year‐old patient following an accident in which both of his maxillary central incisors were avulsed and replanted after four hours of non‐physiological storage. ERR and ankylosis of teeth 11 and 21 were detected clinically and radiographically during the second year of follow‐up. Sixteen years after replantation, replacement resorption was progressing very slowly, enabling functional tooth retention with favorable esthetics. Young adults, with delayed replantation of avulsed teeth, may benefit from tooth retention with slow ERR.