Candesartan restores pressure-induced vasodilation and prevents skin pressure ulcer formation in diabetic mice

BACKGROUND: Angiotensin II type 1 receptor (AT1R) blockers have beneficial effects on neurovascular complications in diabetes and in organ’s protection against ischemic episodes. The present study examines whether the AT1R blocker candesartan (1) has a beneficial effect on diabetes-induced alteration of pressure-induced vasodilation (PIV, a cutaneous physiological neurovascular mechanism which could delay the occurrence of tissue ischemia), and (2) could be protective against skin pressure ulcer formation. METHODS: Male Swiss mice aged 5–6 weeks were randomly assigned to four experimental groups. In two groups, diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ, 200 mg.kg(−1)). After 6 weeks, control and STZ mice received either no treatment or candesartan (1 mg/kg-daily in drinking water) during 2 weeks. At the end of treatment (8 weeks of diabetes duration), C-fiber mediated nociception threshold, endothelium-dependent vasodilation and PIV were assessed. Pressure ulcers (PUs) were then induced by pinching the dorsal skin between two magnetic plates for three hours. Skin ulcer area development was assessed during three days, and histological examination of the depth of the skin lesion was performed at day three. RESULTS: After 8 weeks of diabetes, the skin neurovascular functions (C-fiber nociception, endothelium-dependent vasodilation and PIV) were markedly altered in STZ-treated mice, but were fully restored by treatment with candesartan. Whereas in diabetes mice exposure of the skin to pressure induced wide and deep necrotic lesions, treatment with candersartan restored their ability to resist to pressure-induced ulceration as efficiently as the control mice. CONCLUSION: Candesartan decreases the vulnerability to pressure-induced ulceration and restores skin neurovascular functions in mice with STZ-induced established diabetes

Focus on 1,25-Dihydroxyvitamin D3 in the Peripheral Nervous System

In this review, we draw attention to the roles of calcitriol (1,25-dihydroxyvitamin D3) in the trophicity of the peripheral nervous system. Calcitriol has long been known to be crucial in phosphocalcium homeostasis. However, recent discoveries concerning its involvement in the immune system, anti-cancer defenses, and central nervous system development suggest a more pleiotropic role than previously thought. Several studies have highlighted the impact of calcitriol deficiency as a promoting factor of various central neurological diseases, such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson’s disease, and Alzheimer’s disease. Based on these findings and recent publications, a greater role for calcitriol may be envisioned in the peripheral nervous system. Indeed, calcitriol is involved in myelination, axonal homogeneity of peripheral nerves, and neuronal-cell differentiation. This may have useful clinical consequences, as calcitriol supplementation may be a simple means to avoid the onset and/or development of peripheral nervous-system disorders

Étude de la vasodilatation cutanée induite par la pression au cours d'un diabète expérimental avec ou sans neuropathie

Une altération de la réponse vasodilatatrice cutanée à une pression progressive et non douloureuse (PIV : Pressure-Induced-Vasodilation) appliquée localement a été observée chez des patients diabétiques de type 1. Le but de cette thèse a été d'évaluer l'atteinte de la PIV dans différents contextes de durée de diabète expérimental chez la souris. Dans les mêmes contextes de durée de diabète, nous avons étudié les effets d'inhibiteurs pharmacologiques sur l'atteinte de la PIV. Une prévention de l'atteinte de la PIV par l'acide alpha-lipoïque a été observée dans un diabète précoce n'exprimant qu'une microangiopathie. Une restauration de la PIV par le sorbinil a été observée dans un diabète tardif exprimant une neuropathie sévère associée à une microangiopathie. Ces études ouvrent des perspectives thérapeutiques intéressantes pour prévenir et améliorer les complications microcirculatoires cutanées liées à la pression chez les patients diabétiques.Pressure-induced vasodilation (PIV) is a mechanism whereby skin blood flow increases in response to progressive locally applied pressure. PIV decreases early in diabetic patients as a result of vascular and/or neural impairment. This work was designed to determine the effect of vascular changes and neurovascular changes on PIV in streptozotocin-induced diabetic mice. We determined whether the diabetes-induced PIV alteration could be prevented or restored by pharmacological agents in these different terms of diabetes. Alpha-lipoïc acid treatment was able to preserve PIV response in diabetic mice in short-term diabetes without neuropathy. Sorbinil treatment restored PIV response in a long-term diabetes with severe neuropathy. Alpha-lipoic acid and sorbinil treatments by preserving and by restoring the cutaneous PIV response respectively should preserve the normal reaction to pressure strain, which might limit the risk of pressure-induced ulcer in diabetic patients.ANGERS-BU Médecine-Pharmacie (490072105) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Pathologies cutanées courantes chez le cheval et thérapeutiques officinales

LIMOGES-BU Médecine pharmacie (870852108) / SudocLYON1-BU Santé (693882101) / SudocSudocFranceF

TRPV1 dans les neuropathies douloureuses

Depuis le clonage du gène codant pour TRPV1 (transient receptor potential vanilloid type 1) en 1997, les études fonctionnelles et structurales de ce récepteur ont conduit à améliorer notre compréhension des mécanismes qui sont impliqués dans la transduction des stimulus nociceptifs thermiques et mécaniques véhiculés par les fibres sensitives de faible diamètre. Le rôle de TRPV1 dans les processus inflammatoires et la transmission de la douleur fait de ce récepteur une cible thérapeutique d’intérêt dans le traitement des douleurs neuropathiques. Des modèles animaux de neuropathie des petites fibres ont été développés, et plusieurs laboratoires ont progressé dans la conception d’agents interagissant avec TRPV1. Des agonistes et antagonistes sont en développement clinique et de nouvelles molécules dites modulatrices de TRPV1, présentant moins d’effets secondaires, font actuellement l’objet d’études précliniques

Approche médicamenteuse de l’insuffisance veineuse

International audienceSome medications may be offered in pharmacy as an adjunctive therapy for mild pathologies related to venous insufficiency. These treatments are very useful in summer, when medical compression can be difficult to bear.Certains médicaments peuvent être proposés à l’officine en tant que thérapeutique d’appoint pour les pathologies légères en lien avec l’insuffisance veineuse. Ces traitements sont très utiles en période estivale, quand la compression médicale peut s’avérer difficile à supporter