Intravenous fate of poly(2-(dimethylamino)ethyl methacrylate)-based polyplexes

The objective of this study was to assess the in vivo fate of poly(2-(dimethylamino)ethyl methacrylate) (pDMAEMA)-based polyplexes after intravenous administration into mice. Circulation kinetics and tissue distribution in terms of plasmid localization and transfection efficiency were assessed. To gain more insight into the observed biodistribution and gene expression profile, the interaction of pDMAEMA-based polyplexes with blood components (erythrocytes and albumin) was investigated in vitro. In the case of i.v. injection of positively charged polyplexes at a dose of 30 microg DNA most of the radioactivity was found in the lungs and the liver 60 min after injection. In the case of pDMAEMA/DNA polyplexes with a negative charge, uptake occurred mainly by the liver. Administration of positively charged complexes at a 30 microg DNA dose resulted in reporter gene expression primarily in the lungs. Injection of negatively charged complexes and naked plasmid did not result in luciferase expression in any of the organs examined. In vitro turbidity experiments showed the induction of a charge dependent aggregation process upon addition of albumin to the polyplexes pointing out to the involvement of aggregate formation in the dominant lung uptake of the positively charged polyplexes. Also, incubations of polyplexes after pre-incubation with a physiological concentration of albumin with washed erythrocytes confirmed that polyplexes induce the formation of extremely large structures. This paper underlines the need for the design of systems with reduced interaction with blood components to promote the delivery of DNA to target tissues outside the lungs.     

The cerebrospinal fluid transferrin/tau proteins. A study by two-dimensional polyacrylamide gel electrophoresis (2D) and agarose isoelectrofocusing (IEF) followed by double-antibody peroxidase labeling and avidin-biotin amplification

The cerebrospinal fluid (CSF) transferrin/Tau proteins were studied by two-dimensional polyacrylamide gel electrophoresis (2D) followed by immunoblotting and by agarose isoelectrofocusing (IEF), and subsequent double immunofixation, peroxidase staining and Avidin-Biotin Complex (ABC) amplification. The pattern of the Tau protein was similar but not equal to that of the transferrin (Tf). When a genetic variant of Tf was present in the serum, the same variant was also observed in the corresponding CSF Tf and in the Tau fraction. After neuraminidase treatment, both serum and CSF Tf moved to the Tau position on IEF and 2D. On 2D, no desialized precursors of the Tau proteins were detected, whereas the Tf precursors were always detected. No synthesis of the Tau globulin in the brain can, therefore, be inferred. In CSF not treated with neuraminidase, Tf is the only sialoglycoprotein clearly desialized, showing that the Tau fraction cannot be generated by neuraminidase action at CSF level. In fact, the treatment of serum and CSF proteins with neuraminidase produced a clear shift in the isoelectric mobility of all sialoglycoproteins. We clearly demonstrate that the Tau globulin is the result of neuraminidase activity not located in the CSF compartment. We suggest that Tf could be desialized by the action of neuraminidase at the brain level and then be "washed" into the CSF. Brain utilization of Tf, meeting the brain iron requirement, seems likely.     

强的松对大白鼠心肺肝脾肾影响的病理改变

为了解强的松对心肺肝脾肾影响的病理改变,应用正常Wistar大白鼠28只,分实验组及对照组各14只。实验组给予相当于人2mg/kg.d等效剂量的强的松片剂溶入当日饮水中,对照组饮自来水,共10周,之后解剖光镜见对照组心肺肝脾肾及实验组心肺均无异常。实验组肝肾轻度充血,脾充血明显,且见较多舍铁血黄素沉着,以红髓边缘明显。证实常规剂量的强的松对肝脾肾也有一定不良影响,应用激素时要注意及时调整剂量和给药方式与时间,尽量减少副作用。     

Effect of long-term exposure to nitrogen dioxide on lung glycoproteins level

Summary The influence of nitrogen dioxide on glycoprotein level in lung tissue of guinea pigs was studied after 180 days (8 h per day) of exposure at a concentration of 2 mg/m³.A long-term exposure induced a decrease of protein-hound hexosamines and an increase of sialic acid level in lungs.     

疏风解毒胶囊联合环丙沙星与维生素C治疗肺风粉刺的临床观察

目的 评价疏风解毒方联合环丙沙星与维生素C治疗肺风粉刺的临床疗效和愈后。方法 将60例痤疮中医辨证为肺经风热型的患者随机分成治疗组与对照组各30例，对照组给予外用盐酸环丙沙星和口服VitC，治疗组在对照组的基础上同时给予疏风解毒胶囊，两组疗程均为1个月。两组分别在治疗2、4周时评价系统症状（口干、便秘等）和皮损炎症好转情况、新发皮损情况、愈后（出现色素沉着和凹陷性瘢痕）情况、临床总有效率，同时考察两组不良反应以评价其安全性。结果 两组治疗后临床疗效对比，治疗组总有效率为96.67%高于对照组的76.67%（P<0.05）。治疗两周后，治疗组口渴、便秘等系统症状减轻例数、皮损处红肿消退例数分别为26例、24例，对照组为4例、7例，治疗组的症状减轻人数明显多于对照组，差异有显著统计学意义（P<0.01）；且两周后治疗组有新发皮损数明显少于对照组，差异有显著统计学意义（P<0.01）。结论 疏风解毒方联合环丙沙星与维生素C在治疗痤疮肺经风热证上疗效显著，愈后理想。     

Oral exposure to cadmium and mercury alone and in combination causes damage to the lung tissue of Sprague-Dawley rats

Environmental presence and human exposure to heavy metals in air and cigarette smoke has led to a worldwide increase in respiratory disease. The effects of oral exposure to heavy metals in liver and kidney structure and function have been widely investigated and the respiratory system as a target is often overlooked. The aim of the study was to investigate the possible structural changes in the lung tissue of Sprague-Dawley rats after oral exposure for 28 days to cadmium (Cd) and mercury (Hg), alone and in combination at 1000 times the World Health Organization’s limit for each metal in drinking water. Following exposure, the general morphology of the bronchiole and lungs as well as collagen and elastin distribution was evaluated using histological techniques and transmission electron microscopy. In the lungs, structural changes to the alveoli included collapsed alveolar spaces, presence of inflammatory cells and thickening of the alveolar walls. In addition, exposure to Cd and Hg caused degeneration of the alveolar structures resulting in confluent alveoli. Changes in bronchiole morphology included an increase in smooth muscle mass with luminal epithelium degeneration, detachment and aggregation. Prominent bronchiole-associated lymphoid tissue was present in the group exposed to Cd and Hg. Ultrastructural examination confirmed the presence of fibrosis where in the Cd exposed group, collagen fibrils arrangement was dense, while in the Hg exposed group, additional prominent elastin was present. This study identified the lungs as target of heavy metals toxicity following oral exposure resulting in cellular damage, inflammation and fibrosis and increased risk of respiratory disease where Hg showed the greatest fibrotic effect, which was further, aggravated in combination with Cd.     

Estimating normal lung weight measurement using postmortem CT in forensic cases

PurposeThe aim of this study is to estimate the lung weight using postmortem CT in well aerated lung autopsy cases. The correlation coefficients to the lung weight were also evaluated for the cadavers’ height, weight, whole body surface area (WBSA), body mass index, and estimated lung volume.Materials and methodsFrom October 2015 to July 2016, 31 cadavers (male 12, female 19, age 20–98 (mean 66.9) y.o., postmortem interval 0.3–75.0 (5.7) days) were compared as regards body weight, height, whole body surface area (WBSA), body mass index (BMI), lung volume on CT, and total lung volume classified into several CT number categories, with their lung weight in autopsy.ResultsThe lung weight (mean ± SE) was 284.9 ± 14.8 g in right lung and 249.3 ± 12.9 g in left lung. The %ALV was 79.9 ± 0.9 HU (mean ± standard error (SE)) in both lungs, 80.3 ± 1.3 HU in right lung, and 77.6 ± 2.0 HU in left lung. Using a simple linear regression test, there was no statistically significant correlation between the lung weight and the categories (R²: body height 0.234, weight 0.224, WBSA 0.309, BMI 0.046, lung volume 0.059). The volume for each individual CT density category showed no significant correlation, but the stepwise regression test yielded an excellent correlation coefficient (R² = 0.840).ConclusionThe well aerated lung weight was 284.9 ± 14.8 g in right lung and 249.3 ± 12.9 g in left lung, and the postmortem CT could estimate the lung weight with high correlation coefficient.     

Respiratory dendritic cells: mediators of tolerance and immunity

The respiratory tract is under constant bombardment from both innocuous and pathogenic material. The decision of how to respond to these challenges is mediated by a specialized set of antigen presenting cells within the lungs called dendritic cells (DC). Proper respiratory homeostasis requires that these respiratory DC (rDC) utilize both the local lung inflammatory environment as well as recognition of pathogen-specific patterns to determine whether to maintain homeostasis by either driving tolerance or immunity to the inhaled material. This review will focus on rDC and highlight how rDC regulate tolerance and immunity.