Adsorption of Surfactant to Bronchial Epithelium: Possible Role of Receptor ‘Unmasking’ in Asthma

Background.?In a recent study in animals it has been shown how surface-active phospholipid (SAPL) in the form of a commercially available micronized (5 µmφ) dry powder (ALEC^T/Pumactant^T) was able to reduce afferent neural feedback to the brainstem in response to a methacholine challenge by the same order of magnitude as drugs commonly prescribed for asthma. The underlying theory assumed that adsorption of SAPL to bronchial epithelium masked irritant receptors eliciting the bronchoconstrictor reflex, thus providing a barrier to noxious stimuli entering the lungs. Objective.?To test the underlying assumption that SAPL was actually adsorbed (i.e., bound to bronchial epithelium), especially the major and most surface-active component of lung surfactant, namely dipalmitoyl phosphatidylcholine (DPPC). A secondary objective was to investigate any role of phosphatidylglycerol (PG) in promoting the adsorption of DPPC. Methods.?Radiolabeled DPPC dispersed ultrasonically in saline was used to incubate excised sections of porcine bronchial epithelium. The adsorbed DPPC was then quantified by rigorously rinsing the tissue of adhering fluid and then digesting it for β-scintillation counting. Each test (n = 8 runs) was repeated for ratios of DPPC:PG of 9:1, 7:3 (as per ALEC^T/Pumactant^T) and 1:1 for both dipalmitoyl PG (DPPG) and EggPG (as incorporated in ALEC^T/Pumactant^T). Results.?Despite rigorous rinsing postincubation, bronchial epithelium was found to adsorb DPPC at a level roughly equivalent to one close-packed monolayer; whereas both DPPG and EggPG promoted the adsorption of DPPC in a dose-dependent manner, reaching an approximate threefold increase for 7:3 DPPC:PG. Conclusion.?DPPC adsorbs to bronchial epithelium in amounts necessary for the masking of receptors, and this adsorption (probably chemisorption) is quite strongly promoted by PG either in its indigenous state (DPPG) or in the form (EggPG) used in ALEC^T to suppress the sensitivity of bronchial irritant receptors in our previous study and in clinical trials just completed.     

Protein Concentration and Hydrostatic Pressure in Subcutaneous Tissue of Rats in Hypoproteinemia

Protein concentration and hydrostatic pressure were measured in subcutaneous tissue of rats during development of aminonucleoside nephrosis. Samples of interstitial fluid for protein analysis were collected from subcutaneous tissue by a wick method, and hydrostatic pressure was measured by a modified Scholander technique. When the serum protein concentration was reduced from 6.1 to 4.8 g/100 ml, interstitial fluid protein concentration fell from 3.0 to 1.1 g/100 ml. This corresponds to a reduction of calculated oncotic pressures from 18.0 to 13.0 mm Hg and from 7.8 to 3.0 mm Hg in serum and interstitial fluid, respectively, thus leaving a nearly constant net transcapillary oncotic pressure. When serum protein concentration was further reduced to 3.8 g/100 ml, interstitial fluid protein concentration was reduced to 0.5 g/100 ml, reducing net transcapillary oncotic pressure by 2–3 mm Hg. The average hydrostatic pressure in subcutis was 1.0 mm Hg sub-atmospheric under control conditions and did not change during hypoproteinemia. The results indicate that a reduction of interstitial protein concentration is an important factor in preventing edema formation in hypoproteinemia.     

Neural tissue engineering: Adrenal chromaffin cell attachment and viability on chitosan scaffolds

Abstract

This study introduces chitosan-based matrices as cell substrates for bovine chromaffin cell attachment in transplantation procedures. Chitosan ([1 → ] linked 2-amino-2-deoxy-β-O-glucopyranose), having structural similarity to glycosaminoglycans, was modified using several proteins (collagen, albumin and gelatin) to increase surface area and improve biocompatibility. In vitro, collagen-blended chitosan (CC) matrices were found to attach more readily to chromaffin cells than to gelatin- or albumin-blended matrices. Morphological evidence showed that the chromaffin cells attached to CC substrates integrated well with the hydrogel matrix and survived for at least two weeks, under in vivo culture conditions. The chromaffin cells within chitosan scaffolds also survived for at least two weeks in vitro and after subarachnoid grafting to rats. [Neural Res 1998; 20: 648–654]     

Predictors of neutrophilic airway inflammation in young smokers with asthma

Introduction: Asthma is one of the most widespread chronic diseases worldwide. In spite of numerous detrimental effects on asthma, smoking is common among asthma patients. These smoking-induced aggravations of asthma may be attributed to changes in airway inflammation, which is characterized by a higher degree of neutrophilic inflammation than in non-smokers. A state of neutrophilic inflammation may lead to increased steroid resistance and an accelerated loss of lung function owing to tissue destruction. The aim of this study was to elucidate predictors of neutrophilic inflammation in young asthmatic smokers not on steroid treatment, including analysis of tobacco history and bacterial colonization. Methods: In a cross-sectional study, 52 steroid-free, current smokers with asthma were examined with induced sputum, fractional exhaled nitric oxide (FeNO), lung function, ACQ6 score, mannitol and methacholine challenge. A sample from the sputum induction was taken for bacterial analysis using 16S gene PCR technique and sequencing. Results: Using one-way analysis of variance and binary and linear regression models, only age and ACQ6 score were found to be significant predictors for airway neutrophilia. The investigation also included analysis for effect of pack years, current tobacco consumption, body mass index, lung function, FeNO; methacholine and mannitol responsiveness, atopy, gender, asthma history and presence of bacteria. The most common potentially pathogenic bacteria found were Streptococcus spp., Haemophilus spp. and Mycoplasma spp. Conclusion: In this study, no tobacco-related predictors of airway neutrophilia were found, indicating that in the younger years of asthma patients who smoke, the amount of tobacco smoked in life does not influence the degree of neutrophilia. Conversely, for asthmatic smokers, neutrophilia may be induced when a certain threshold of tobacco consumption is reached.     

Porphyria cutanea tarda and Sjogren's syndrome

Porphyria cutanea tarda is prevalent in connective tissue disease, common in systemic lupus erythematosus. However, the co-existence of primary sjogren''s syndrome and porphyria cutanea tarda is rare and poses diagnostic and therapeutic challenges. We report a case of porphyria cutanea tarda associated with primary sjogren''s syndrome.     

不同病理类型肺腺癌临床和影像特征及预后分析

目的:探讨不典型腺瘤样增生(atypical adenomatous hyperplasia，AAH)、原位腺癌(adenocarcinoma in situ，AIS)、微浸润性腺癌(minimally invasive adenocarcinoma，MIA)及浸润性腺癌(invasive adenocarcinoma，IAC)的临床、影像、病理特征及预后相关的影响因素。方法:回顾性选取自2012年01月至2019年01月我院行手术治疗且病理确诊的肺腺癌患者503例，根据病理类型分为AAH、AIS、MIA、IAC四组，对比四组患者的临床、影像、病理特征，并采用单因素方差分析和多因素Cox比例风险回归模型分析四组患者预后危险因素的相关性。结果:AAH、AIS、MIA、IAC四组患者在性别比例方面，女性多于男性；在年龄分布方面，青年阶段（≤45岁）和中老年阶段（61~75岁）的差异有统计学意义（P＜0.01，P＜0.01）。不同病理类型肺腺癌患者在结节大小、结节性质及手术方式上差异有统计学意义（P＜0.05）。单因素生存分析发现，不同结节性质肺腺癌患者在手术年龄、再次手术及死亡率方面差异有统计学意义（P＜0.05）。多因素分析发现，结节最长直径［HR=7.166，95%CI（1.011,50.823）］、N分期［HR=10.689,95%CI（2.276,50.200）］是肺腺癌患者预后的独立影响因素（P＜0.05）。结论:在AAH-AIS-MIA-IAC肿瘤演变过程中，结节最长直径、实性成分大小及N分期是肺腺癌患者预后的影响因素，肺腺癌国际新分类方法有助于肺腺癌患者预后评估。