Modulation of endotoxin-induced neutrophil transendothelial migration by alveolar epithelium in a defined bilayer model.

Within the alveolus, epithelial cells, due to their close association with endothelial cells, can potentially influence endothelial cell responsiveness during inflammation and their interaction with leukocytes. To investigate this, three lung epithelial cell lines (A549, Calu-3, or NCI-H441) were grown with endothelium on opposing surfaces of Transwell filters and the formation and stability of bilayers was rigorously evaluated. All epithelial lines disrupted endothelial monolayer formation on filters with 3- or 5-microm pores by breaching the filter, and this occurred regardless of seeding density, matrix composition, or duration of culture. Endothelial disruption was not detectable by ele…

The toxic effect of monodisperse amorphous silica particles studied on an in vitro model of the human air–blood barrier

Development and in vitro Evaluation of Antigen-Loaded Poly(amidoamine) Nanoparticles for Respiratory Epithelium Applications

A poly(amidoamine) with disulfide linkages in the main chain and 4-hydroxybutyl and ω-carboxy-PEG groups (9:1 ratio) as side chains was prepared by Michael addition polymerization of cystamine bisacrylamide with 4-hydroxybutylamine and ω-carboxy-PEG-amine. To develop therapeutic protein formulations for improved delivery of antigen via the intranasal route, nanoparticles were prepared from this polymer by self-assembly with p24 or ovalbumin as the model proteins and CpG as the adjuvant. The nanoparticles incorporated the antigens and adjuvant from the feed solution with high efficiency (∼90 %) and have sizes of 112 and 169 nm, respectively, with low positive surface charge (∼+2 mV). Formula…

PO-58 - Cardiovascular risk profile in survivors of adult cancer - results from the general population study.

The advancements in cancer treatment and detection of early cancer have resulted in steady increase of adult cancer survivors over the years. However, due to the long term toxic effects of chemotherapy and radiotherapy, the incidence of cardiovascular diseases (CVD) is increasing in survivors. Identifying risk factors and interventions to reduce the excess burden of CVD in this vulnerable population is urgently needed.To investigate the cardiovascular risk factors (CVRFs), inflammation and coagulation profile in cancer survivors from a large population-based study.Presence of CVRFs and laboratory markers have been compared in individuals with (n=1,359) and without (n=13,626) history of canc…

Nitrogen mustard (melphalan) exposure of an in vitro coculture model in the human proximal respiratory system

Thrombin generation in cardiovascular disease and mortality – results from the Gutenberg Health Study

Thrombin generation may be a potential tool to improve risk stratification for cardiovascular diseases. The aim of this study was to explore the relation between thrombin generation and cardiovascular risk factors, cardiovascular diseases, and total mortality. For this study, 5,000 subjects from the population-based Gutenberg Health Study were analyzed in a highly standardized setting. Thrombin generation was assessed by the Calibrated Automated Thrombogram method at 1 and 5 pM tissue factor triggers in platelet-poor plasma. Lag time, endogenous thrombin potential, and peak height were derived from the thrombin generation curve. Sex-specific multivariable linear regression analysis adjusted…

Physiology and cell biology of the endothelium: a dynamic interface for cell communication.

This manuscript presents a brief overview of the physiology and cell biology of the endothelium, which is the basis for understanding the role of endothelial cells in pathological processes as diverse as atherosclerosis, tumour intravasation and multiple organ failure. Following consideration of general aspects of endothelial function in regulating haemostasis, vascular tone and growth, special emphasis will be placed on endothelial regulation of the inflammatory response, which centres on the microcirculation. A particular role in inflammation is played by cell adhesion molecules (CAM), expressed both on endothelial and blood cells. Cell and molecular biological methods to investigate the …

The Development of Novel Approaches to the Identification of Chemical and Protein Respiratory Allergens

In October 2006, the European Centre for theValidation of Alternative Methods (ECVAM) spon-sored and hosted a three-day workshop to consideropportunities and challenges in the development ofalternative methods for the identification and char-acterisation of chemical respiratory allergens. Theproceedings, conclusions and recommendations ofthat workshop were subsequently made available asECVAM Workshop Report 60 (1).In April 2008, a second meeting was convenedby ECVAM to consider what progress has beenmade in the light of the recommendations derivedfrom the 2006 Workshop and the publishedreport. This meeting had as a second objective —to consider whether new opportunities for theidentificatio…

Cell Culture Systems for Studying Biomaterial Interactions with Biological Barriers

The human body has numerous physical barriers that prevent most harmful or foreign compounds from entering the body. These barriers are formed by unique cell types, which through their location-specific biological cell characteristics prevent compounds from passing between or through them or selectively allow only specific compounds to move across the barrier that they form. Multiple cell types are involved that together form the functioning barrier in a particular organ or tissue. In many cases, in vitro human multicellular culture systems have been developed. These in vitro cell culture models have been extremely valuable in determining the toxic effects of novel compounds on cellular fun…