Cellular uptake and localization of inhaled gold nanoparticles in lungs of mice with chronic obstructive pulmonary disease

Background: Inhalative nanocarriers for local or systemic therapy are promising. Gold nanoparticles (AuNP) have been widely considered as candidate material. Knowledge about their interaction with the lungs is required, foremost their uptake by surface macrophages and epithelial cells. Diseased lungs are of specific interest, since these are the main recipients of inhalation therapy. We, therefore, used Scnn1b-transgenic (Tg) mice as a model of chronic obstructive pulmonary disease (COPD) and compared uptake and localization of inhaled AuNP in surface macrophages and lung tissue to wild-type (Wt) mice. Methods: Scnn1b-Tg and Wt mice inhaled a 21-nm AuNP aerosol for 2 h. Immediately (0 h) or 24 h thereafter, bronchoalveolar lavage (BAL) macrophages and whole lungs were prepared for stereological analysis of AuNP by electron microscopy. Results: AuNP were mainly found as singlets or small agglomerates of ≤ 100 nm diameter, at the epithelial surface and within lung-surface structures. Macrophages contained also large AuNP agglomerates (> 100 nm). At 0 h after aerosol inhalation, 69.2±4.9% AuNP were luminal, i.e. attached to the epithelial surface and 24.0±5.9% in macrophages in Scnn1b-Tg mice. In Wt mice, 35.3±32.2% AuNP were on the epithelium and 58.3±41.4% in macrophages. The percentage of luminal AuNP decreased from 0 h to 24 h in both groups. At 24 h, 15.5±4.8% AuNP were luminal, 21.4±14.2% within epithelial cells and 63.0±18.9% in macrophages in Scnn1b-Tg mice. In Wt mice, 9.5±5.0% AuNP were luminal, 2.2±1.6% within epithelial cells and 82.8±0.2% in macrophages. BAL-macrophage analysis revealed enhanced AuNP uptake in Wt animals at 0 h and in Scnn1b-Tg mice at 24 h, confirming less efficient macrophage uptake and delayed clearance of AuNP in Scnn1b-Tg mice. Conclusions: Inhaled AuNP rapidly bound to the alveolar epithelium in both Wt and Scnn1b-Tg mice. Scnn1b-Tg mice showed less efficient AuNP uptake by surface macrophages and concomitant higher particle internalization by alveolar type I epithelial cells compared to Wt mice. This likely promotes AuNP depth translocation in Scnn1b-Tg mice, including enhanced epithelial targeting. These results suggest AuNP nanocarrier delivery as successful strategy for therapeutic targeting of alveolar epithelial cells and macrophages in COPD

State of green infrastructure in the GCR

July 2013This State of Green Infrastructure report is both an assessment of the set of natural and manmade landscape features in the Gauteng City-Region (GCR) and an interrogation into how the services provided by these assets are perceived, understood and valued. Inspiration is drawn from the conceptual and planning framework of ‘green infrastructure’, through which ecological systems, green spaces and other landscape features are regarded as providing services to society in the same way as those offered by traditional ‘hard’ infrastructure.written by Alexis Schäffler et al. for GCR

Improving insect conservation management through insect monitoring and stakeholder involvement

In recent years, the decline of insect biodiversity and the imminent loss of provided ecosystem functions and services has received public attention and raised the demand for political action. The complex, multi-causal contributors to insect decline require a broad interdisciplinary and cross-sectoral approach that addresses ecological and social aspects to find sustainable solutions. The project Diversity of Insects in Nature protected Areas (DINA) assesses insect communities in 21 nature reserves in Germany, and considers interactions with plant diversity, pesticide exposure, spatial and climatic factors. The nature reserves border on agricultural land, to investigate impacts on insect diversity. Part of the project is to obtain scientific data from Malaise traps and their surroundings, while another part involves relevant stakeholders to identify opportunities and obstacles to insect diversity conservation. Our results indicate a positive association between insect richness and biomass. Insect richness was negatively related to the number of stationary pesticides (soil and vegetation), pesticides measured in ethanol, the amount of area in agricultural production, and precipitation. Our qualitative survey along with stakeholder interviews show that there is general support for insect conservation, while at the same time the stakeholders expressed the need for more information and data on insect biodiversity, as well as flexible policy options. We conclude that conservation management for insects in protected areas should consider a wider landscape. Local targets of conservation management will have to integrate different stakeholder perspectives. Scientifically informed stakeholder dialogues can mediate conflicts of interests, knowledge, and values to develop mutual conservation scenarios

Spin dynamics in semiconductors

This article reviews the current status of spin dynamics in semiconductors which has achieved a lot of progress in the past years due to the fast growing field of semiconductor spintronics. The primary focus is the theoretical and experimental developments of spin relaxation and dephasing in both spin precession in time domain and spin diffusion and transport in spacial domain. A fully microscopic many-body investigation on spin dynamics based on the kinetic spin Bloch equation approach is reviewed comprehensively.Comment: a review article with 193 pages and 1103 references. To be published in Physics Reports

Size and surface charge of gold nanoparticles determine absorption across intestinal barriers and accumulation in secondary target organs after oral administration

It is of urgent need to identify the exact physico-chemical characteristics which allow maximum uptake and accumulation in secondary target organs of nanoparticulate drug delivery systems after oral ingestion. We administered radiolabelled gold nanoparticles in different sizes (1.4-200 nm) with negative surface charge and 2.8 nm nanoparticles with opposite surface charges by intra-oesophageal instillation into healthy adult female rats. The quantitative amount of the particles in organs, tissues and excrements was measured after 24 h by gamma-spectroscopy. The highest accumulation in secondary organs was mostly found for 1.4 nm particles; the negatively charged particles were accumulated mostly more than positively charged particles. Importantly, 18 nm particles show a higher accumulation in brain and heart compared to other sized particles. No general rule accumulation can be made so far. Therefore, specialized drug delivery systems via the oral route have to be individually designed, depending on the respective target organ

Improvement of Type 2 Diabetes Mellitus and Attenuation of NAFLD Are Associated with the Success of Obesity Therapy

Obesity and type 2 diabetes mellitus (T2D) represent important comorbidities of the metabolic syndrome, which are associated with non-alcoholic fatty liver disease (NAFLD)-related hepatic fibrosis. In total, 160 morbidly obese patients—81 following a low-calorie formula diet (LCD) program and 79 undergoing bariatric surgery (Roux-en-Y gastric bypass, RYGB)—were examined for anthropometric and metabolic parameters at base-line and during 12 months of weight loss, focusing on a putative co-regulation of T2D parameters and liver fibrosis risk. High NAFLD fibrosis scores (NFS) before intervention were associated with elevated HbA1c levels and T2D. Loss of weight and body fat percentage (BFL) were associated with improved glucose and lipid metabolism and reduced risk of NAFLD-related fibrosis, with particularly beneficial effects by RYGB. Both T2D improvement and NFS decrease were positively associated with high BFL. A highly significant correlation of NFS reduction with BFL was restricted to male patients while being absent in females, accompanied by generally higher BFL in men. Overall, the data display the relation of BFL, T2D improvement, and reduced NAFLD-related fibrosis risk during weight loss in morbidly obese individuals induced by diet or RYGB. Furthermore, our data suggest a considerable sexual dimorphism concerning the correlation of fat loss and improved risk of liver fibrosis