Développement de la iontophorèse comme axe thérapeutique des atteintes microcirculatoires dans la sclérodermie systémique

Abstract : Systemic scleroderma (ScS) is a rare disease that may be associated with a poor prognosis. The pathogenesis of the disease remains still unclear but comprises vascular abnormalities related to skin fibrosis. ScS disease treatment is difficult. No etiologic therapy is available and patient's management is rather centred on the treatments of the different organs failure symptoms. Skin iontophoresis is a non invasive technique, which allows a transcutaneous diffusion of molecules in solution thanks to an electrical stimulation. This technique was initially used as physiological test. Our objective is to test and to develop therapeutic iontophoresis, in particular with molecules possessing vasodilator properties. The final objective is to use it in therapeutic applications such as the treatment of ScS digital ulcerations. Three parts will be developed in the present work. The first part describes the association of two vasodilatator drugs (sildenafil used per os, associated with sodium nitroprusside used through cathodal iontophoresis. We studied the safety of the association and its effect on the skin vascular flow in healthy volunteers (INFLUX-VS study). The second part describes the screening of vasodilatator drugs delivered through cutaneous iontophoresis in rats (INFLUX-RAT study). The aim of the study was to select the more potent drugs in term of maximal rat skin vasodilatation. The more potent drugs were prostacyclins analogues. The third part describes the iontophoresis of prostacyclins analogues in healthy volunteers: the INFLUX-IT-VS study. The more potent cutaneous vasodilatation was observed with treprostinil, with a good skin and systemic tolerance. The last part decribes the reproducibility of the techniques used to quantify skin blood flow along with studies using these techniques in scleroderma patients. These are required to enable a reproducible evaluation of the effect of skin iontophoresis in patients with scleroderma
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Sciences agricoles. Université de Grenoble, 2011. Français. 〈NNT : 2011GRENS027〉
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Sophie Blaise. Développement de la iontophorèse comme axe thérapeutique des atteintes microcirculatoires dans la sclérodermie systémique. Sciences agricoles. Université de Grenoble, 2011. Français. 〈NNT : 2011GRENS027〉. 〈tel-00650040〉



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