Objectif The results would open up new avenues to the understanding of Raynaud's phenomenon seen in miners and steel workers suffering from Vibration White Finger syndrome, and will be of fundamental importance in understanding the regulatory mechanisms of cutaneous blood flow and the potential abnormality in these manual workers.The pharmacological studies will increase understanding of the molecular and intracellular mechanisms regulating synthesis and responsiveness of the cutaneous microvascular endothelium to ET-1 and EDRF thus leading to the identification of sites for pharmacological intervention and new treatments for Raynaud's phenomenon and Vibratory White Finger. METHODS AND MEANS BY WHICH THE AIMS ARE TO BE ACHIEVEDTissue Skin biopsies will be taken from the dorsum of the finger and processed for different investigative techniques. Immunocytochemistry Light microscopical studies will be carried out using the indirect immunofluorescence technique. Quantification by computer image analysis Quantification will be carried out using a low light video camera mounted on a Vanox fluorescence microscope, and linked to a VIDAS image analyzer to assess different parameters. Confocal microscopy The distribution of immunoreactive nerves will be studied using confocal scanning laser microscopy linked to an image analyzer to obtain a precise 3-dimensional localisation of the innervation in skin and of the changes in pathological specimens. Receptor binding studies The technique, combined with image analysis, allows the mapping of putative receptors to precise anatomical regions and their pharmacological characterization using appropriate analogues and antagonist. In vitro pharmacological studies The experiments will utilize human dermal microvascular endothelial cells (HDMEC) cultured from neonatal foreskin obtained at circumcision. mRNA expression for ET-1 and ET-1 receptor will be investigated by in situ hybridization and Northern blot analysis, cellular immunoreactive protein will be localised by immunocytochemistry and measurement of released immunoreactive protein by radioimmunoassay. Programme(s) ECSC-MEDRES 5C - Fifth medical research programme (ECSC) "Protection of workers against risks arising from work in the coal and steel industries", 1988-1992 Thème(s) Data not available Appel à propositions Data not available Régime de financement CSC - Cost-sharing contracts Coordinateur Royal Postgraduate Medical School Contribution de l’UE Aucune donnée Adresse Du Cane Road W12 0NN London Royaume-Uni Voir sur la carte Coût total Aucune donnée
