Inflammation and remodelling patterns in early stage chronic rhinosinusitis.

BACKGROUND: A distinct set of inflammatory and remodelling factors have been found elevated in chronic rhinosinusitis. OBJECTIVE: The investigation of their expression in early stage disease may reveal early events in this common disease. METHODS: Sinonasal mucosal samples from nine patients with early stage CRSsNP were taken from the inferior and middle turbinates, the uncinate process, maxillary sinus, anterior ethmoid, bulla ethmoidalis and the posterior ethmoid and measured for TGF-beta 1 and it's receptors, MPO protein as well as pro-inflammatory cytokines (TNF-alpha and IL-1beta) and the Th1 cell signature (IFN-gamma and T-bet). As outcome parameter for TGF-beta signalling collagen deposition was analysed. Inferior turbinates from patients undergoing (rhino-) septoplasty were collected as controls. RESULTS: TGF-beta 1 protein concentrations were significantly increased in the maxillary sinuses (P = 0.006), the uncinate process (P = 0.01), the anterior ethmoid including the bulla ethmoidalis (P = 0.005) and the posterior ethmoid (P = 0.037) when compared to the inferior and middle turbinates. Collagen deposition was significantly increased in the maxillary sinus when compared to the inferior turbinates (P = 0.008). In contrast, mRNA for TGF-beta receptors, Th1 related markers (IFN-gamma and T-bet), pro-inflammatory cytokines (IL-1 beta and TNF-alpha), and MPO protein as neutrophil marker were expressed at all locations but showed no significant differences between the various locations. TGF-beta 1 mRNA expression in inferior turbinates of CRSsNP was significantly higher when compared to inferior turbinates of controls (P = 0.017). The pro-inflammatory cytokines and Th1-related cytokines did not show an upregulation in inferior turbinates of CRSsNP when compared to controls. CONCLUSIONS: In early stage chronic sinus disease, TGF-beta protein is expressed in significantly higher concentrations within the paranasal sinuses when compared to turbinates, whereas pro-inflammatory, neutrophilic and Th1 markers did not show any difference. These findings suggest that TGF-beta plays a central role in the initiation of CRSsNP, and represents a major target for further research and future intervention.

Important research questions in allergy and related diseases: 3-chronic rhinosinusitis and nasal polyposis - a GALEN study.

Chronic rhinosinusitis is one of the most common health care challenges, with significant direct medical costs and severe impact on lower airway disease and general health outcomes. The diagnosis of chronic rhinosinusitis (CRS) currently is based on clinical signs, nasal endoscopy and CT scanning, and therapeutic recommendations are focussing on 2 classes of drugs, corticosteroids and antibiotics. A better understanding of the pathogenesis and the factors amplifying mucosal inflammation therefore seems to be crucial for the development of new diagnostic and therapeutic tools. In an effort to extend knowledge in this area, the WP 2.7.2 of the GA(2)LEN network of excellence currently collects data and samples of 1000 CRS patients and 250 control subjects. The main objective of this project is to characterize patients with upper airway disease on the basis of clinical parameters, infectious agents, inflammatory mechanisms and remodeling processes. This collaborative research will result in better knowledge on patient phenotypes, pathomechanisms, and subtypes in chronic rhinosinusitis. This review summarizes the state of the art on chronic rhinosinusitis and nasal polyposis in different aspects of the disease. It defines potential gaps in the current research, and points to future research perspectives and targets.

Non destructive analysis of the wax layer of apple (Malus domestica Borkh.) by means of confocal laser scanning microscopy.

Confocal laser scanning microscopy (CLSM) was used to non-destructively analyse the changes in the structure and thickness of the cuticle during storage of apples (Malus domestica Borkh.). Interpretation of the confocal images was performed by comparison with scanning electron microscopy and environmental scanning electron microscopy images. The natural reflectance of the wax and the auto-fluorescence of the underlying cells made it possible with CLSM to distinguish the wax from the underlying layers without any pretreatment of the fruit. The thickness of the consecutive layers (wax, cutin, cells) could be estimated from measurements of the reflection and fluorescence intensities as a function of the number of pixels. The mean wax-layer thickness measured in this way amounted to 2.58 microm, 3.41 microm or 4.14 microm for the cultivars Jonagold, Jonagored and Elstar, respectively. Changes in the wax structure and cells of the same important Belgian apple cultivars as mentioned above were monitored during nine months of storage in ultra low oxygen and after exposure to ambient conditions. The changes in the wax ultrastructure and cell morphology are likely related to water losses and specific protection of the apple cultivars against water losses during storage and shelf life.

Four-dimensional imaging and computer-assisted track analysis of nuclear migration in root hairs of Arabidopsis thaliana.

Nuclear migration is a fundamental mechanism necessary for the proper growth and development of many eukaryotic organisms. In this study root hairs of Arabidopsis thaliana were used as a research model to gain insight into the dynamics of nuclear migration. Root hairs are long tubular outgrowths of epidermal cells and are responsible for the uptake of water and nutrients. During the development of root hairs, the nucleus migrates into the hair after the bulge is formed. The position of the nucleus relative to the tip plays an essential role in the growth process. However, what is happening to the nucleus in full-grown root hairs is still unclear. To study nuclear dynamics in living root hair cells, stably transformed plants with the fusion proteins Histone2B-YFP and NLS-GFP-GUS were used. Four-dimensional confocal laser scanning microscopy made it possible to monitor the exact position of the nucleus in different root hairs. To analyse the sequential positions of the nuclei in the root hairs, a new computer-assisted method was developed. After track analysis a number of parameters could be extracted from the movies, such as the average speed, the amplitude, direction factor and the range of movement in the root hairs. Our results show that nuclei do not reach a final position in full-grown root hairs and this sustained movement seems to be more similar in root hairs lying close to each other. Moreover, with this methodology it could be quantitatively demonstrated that the integrity of actin is necessary for nuclear movement.