α-Helical peptides on plasma-treated polymers promote ciliation of airway epithelial cells.

Airway respiratory epithelium forms a physical barrier through intercellular tight junctions, which prevents debris from passing through to the internal environment while ciliated epithelial cells expel particulate-trapping mucus up the airway. Polymeric solutions to loss of airway structure and integrity have been unable to fully restore functional epithelium. We hypothesised that plasma treatment of polymers would permit adsorption of α-helical peptides and that this would promote functional differentiation of airway epithelial cells. Five candidate plasma compositions are compared; Air, N2, H2, H2:N2 and Air:N2. X-ray photoelectron spectroscopy shows changes in at% N and C 1s peaks after plasma treatment while electron microscopy indicates successful adsorption of hydrogelating self-assembling fibres (hSAF) on all samples. Subsequently, adsorbed hSAFs support human nasal epithelial cell attachment and proliferation and induce differentiation at an air-liquid interface. Transepithelial measurements show that the cells form tight junctions and produce cilia beating at the normal expected frequency of 10-11 Hz after 28 days in culture. The synthetic peptide system described in this study offers potential superiority as an epithelial regeneration substrate over present "gold-standard" materials, such as collagen, as they are controllable and can be chemically functionalised to support a variety of in vivo environments. Using the hSAF peptides described here in combination with plasma-treated polymeric surfaces could offer a way of improving the functionality and integration of implantable polymers for aerodigestive tract reconstruction and regeneration.

From protons to OXPHOS supercomplexes and Alzheimer's disease: structure-dynamics-function relationships of energy-transducing membranes.

By the elucidation of high-resolution structures the view of the bioenergetic processes has become more precise. But in the face of these fundamental advances, many problems are still unresolved. We have examined a variety of aspects of energy-transducing membranes from large protein complexes down to the level of protons and functional relevant picosecond protein dynamics. Based on the central role of the ATP synthase for supplying the biological fuel ATP, one main emphasis was put on this protein complex from both chloroplast and mitochondria. In particular the stoichiometry of protons required for the synthesis of one ATP molecule and the supramolecular organisation of ATP synthases were examined. Since formation of supercomplexes also concerns other complexes of the respiratory chain, our work was directed to unravel this kind of organisation, e.g. of the OXPHOS supercomplex I(1)III(2)IV(1), in terms of structure and function. Not only the large protein complexes or supercomplexes work as key players for biological energy conversion, but also small components as quinones which facilitate the transfer of electrons and protons. Therefore, their location in the membrane profile was determined by neutron diffraction. Physico-chemical features of the path of protons from the generators of the electrochemical gradient to the ATP synthase, as well as of their interaction with the membrane surface, could be elucidated by time-resolved absorption spectroscopy in combination with optical pH indicators. Diseases such as Alzheimer's dementia (AD) are triggered by perturbation of membranes and bioenergetics as demonstrated by our neutron scattering studies.

Role of 2-[18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the early assessment of response to chemotherapy in metastatic breast cancer patients.

We investigated the role of 2-[18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the early evaluation of response to chemotherapy in metastatic breast cancer patients. Breast cancer patients who received an epirubicin/paclitaxel--containing regimen as first-line treatment for metastatic disease were included in this study. A PET study was performed within 1 week before the start of treatment, at day 8 after the first course, and at the end of the planned program of chemotherapy. Tumor response was determined clinically and radiographically every 2 courses of treatment. Thirteen patients with metastatic breast cancer who were referred for treatment protocols with gemcitabine/epirubicin/paclitaxel or epirubicin/paclitaxel chemotherapy regimens were included in this study. All metastatic sites were easily visualized on the baseline FDG-PET images, obtained 50 to 60 minutes after tracer injection. Nine patients who completed the planned courses of chemotherapy and the FDG-PET studies were available for analysis. In the six patients who achieved a response to treatment, median glucose standard uptake value (SUV) (semiquantitative analysis) was 7.65 (range, 3.4-12.3) at baseline, 5.7 (range, 2.8-7.6) at day 8 after the first course, and 1.2 (range, 0.99-1.3) at the end of the 6 planned courses of chemotherapy. Three patients who obtained a stable disease as best response had no significant decrease in tumor glucose SUV compared to baseline levels. Qualitative visual analysis in the six responding patients showed a decrease in delineation of tumor mass from background activity soon after the first course, while the nonresponding patients had no significant modification from basal levels. Semiquantitative FDG-PET scanning of metastatic breast cancer sites showed a rapid and significant decrease in tumor glucose metabolism soon after the first course of treatment in patients who achieved a response to first-line chemotherapy. On the contrary, no significant decrease was observed in nonresponding patients.