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      Effect of the dual endothelin receptor antagonist bosentan on untreatable skin ulcers in a patient with diabetes: a case report

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          Abstract

          Introduction

          Refractory skin ulcers are a major burden in patients with diabetes. Their pathogenesis is multifactorial, and data increasingly implicate endothelin as a mediator of diabetic macro- and microvasculopathy. Here we describe the first reported case of an endothelin receptor antagonist being used to successfully treat refractory skin ulcers in a patient with diabetes.

          Case presentation

          An 85-year-old Caucasian man with a 30-year history of type 2 diabetes developed multiple skin ulcerations, including a right heel ulcer. Despite appropriate treatment, the ulcer showed little improvement and the risk of amputation was high. The patient was treated with the dual endothelin receptor antagonist bosentan. After three weeks of treatment, major improvements were observed, and after 21 weeks, all ulcers had healed. No abnormalities were observed during monitoring of blood pressure, erythrocyte sedimentation rate or serum aminotransferase levels.

          Conclusion

          In patients with refractory ulceration associated with diabetes, bosentan may be of real benefit, especially in terms of amputation prevention. This case supports the proposed role for endothelin in the pathogenesis of skin ulceration in diabetes and is suggestive of a potential benefit of bosentan in this patient type. This case report is of interest to diabetologists and dermatologists.

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          Most cited references14

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          The dysvascular foot: a system for diagnosis and treatment.

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            The importance of endothelin-1 for microvascular dysfunction in diabetes

            Most of the late diabetic complications such as retinopathy, nephropathy, and neuropathy, have their basis in disturbed microvascular function. Structural and functional changes in the micro-circulation are present in diabetes mellitus irrespective of the organ studied, and the pathogenesis is complex. Endothelial dysfunction, characterized by an imbalance between endothelium-derived vasodilator and vasoconstrictor substances, plays an important role in the pathogenesis of diabetic microangiopathy. Increased circulating levels of endothelin-1 (ET-1), a potent vasoconstrictor peptide, has been found in patients with diabetes, and a positive correlation between plasma ET-1 levels and microangiopathy in patients with type 2 diabetes has been demonstrated. In addition to its direct vasoconstrictor effects, enhanced levels of ET-1 may contribute to endothelial dysfunction through inhibitory effects on nitric oxide (NO) production. Vascular endothelial dysfunction may precede insulin resistance, although the feature of insulin resistance syndrome includes factors that have negative effects on endothelial function. Furthermore, ET-1 induces a reduction in insulin sensitivity and may take part in the development of the metabolic syndrome. In the following, the mechanisms by which ET-1 contributes to the development of diabetic microangiopathy and the potentially beneficial effect of selective ETA receptor antagonists are discussed.
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              Increased activity of endogenous endothelin in patients with type II diabetes mellitus.

              Endothelial dysfunction may contribute to the risk of premature atherosclerosis in patients with diabetes. Endothelin (ET-1) may be involved in this process by activating smooth muscle cell mitogenesis and leukocyte adhesion. We sought to assess the activity of endogenous ET-1 in a group of patients with type II diabetes mellitus with the use of antagonists of ET-1 receptors. Forearm blood flow (FBF) responses (strain gauge plethysmography) to intraarterial infusion of a selective blocker of ET(A) receptors (BQ-123) and, on a different occasion, to ET-1, were measured in 15 patients with diabetes and 12 healthy controls. In addition, 5 patients with diabetes received coinfusion of BQ-123 and BQ-788 (a selective blocker of ET(B) receptors). In normal subjects, BQ-123 did not significantly modify FBF from baseline (P=0.16). In contrast, BQ-123 administration resulted in a significant vasodilator response in patients with diabetes (P<0.001). Infusion of exogenous ET-1 resulted in lower vasoconstrictor responses in patients with diabetes than in controls (P=0.001), whereas the vasoconstrictor response to norepinephrine was similar in the 2 groups (P=0.78). In patients with diabetes, the vasodilator response to selective ET(A) blockade was not significantly modified by nonselective blockade of ET-1 receptors obtained by coinfusion of BQ-123 and BQ-788. The activity of endogenous ET-1 on ET(A) receptors is enhanced in the resistance vessels of patients with diabetes, whereas their sensitivity to exogenous ET-1 is blunted. This abnormality may participate in the pathophysiology of vascular complications associated with diabetes.
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                Author and article information

                Journal
                J Med Case Reports
                Journal of Medical Case Reports
                BioMed Central
                1752-1947
                2011
                16 April 2011
                : 5
                : 151
                Affiliations
                [1 ]Service of Rheumatology, Hospital Universitario Nuestra Señora de la Candelaria, ES-38010 Santa Cruz de Tenerife, Spain
                Article
                1752-1947-5-151
                10.1186/1752-1947-5-151
                3097146
                21496286
                23b9f6c9-0346-4f5c-88c3-1a4c47cb31ed
                Copyright ©2011 Álvarez et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 March 2010
                : 16 April 2011
                Categories
                Case Report

                Medicine
                Medicine

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