0
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      A Case Report of Exacerbation of Leg Ulcers Associated with Acute High-dose Acetylsalicylic Acid in a Patient with Klinefelter Syndrome

      case-report
      1 , 2 , 3 , 4 , 1 ,
      ,
      Cureus
      Cureus
      acetylsalicylic acid, testosterone, klinefelter syndrome, leg ulcers

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Klinefelter syndrome (KS) is the most frequent type of congenital sex-chromosomal disorder caused by at least one extra X chromosome and commonly treated with lifetime testosterone therapy. Ulcerative lesions on lower extremities may occur as a complication of KS. The pathogenesis of ulcers in KS patients has not been clarified on a molecular level. Here we present a case of leg ulcers exacerbation associated with the administration of a high dose of acetylsalicylic acid in a 63-year-old KS patient with karyotype 47,XXY undergoing testosterone replacement therapy for the last 20 years. The appearance of the ulcer on the patient's leg occurred during one week of high oral acetylsalicylic acid intake (1.2 g daily). The patient was advised to return to his standard daily dose of 0.1 g of acetylsalicylic acid and significant improvement of his leg ulcer was observed after two weeks. We hypothesize that testosterone-mediated nitric oxide balance in KS patient is perturbed under the condition of acute high-dose acetylsalicylic acid administration. We propose that small standard doses of approximately 0.1 g/day of acetylsalicylic acid have no apparent effect on nitric oxide status, whereas higher doses may cause dysregulation of nitric oxide production and/or utilization, creating conditions which may cause the appearance of leg ulcers in the KS patients.

          Related collections

          Most cited references19

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism

          Klinefelter Syndrome (KS) is characterized by an extreme heterogeneity in its clinical and genetic presentation. The relationship between clinical phenotype and genetic background has been partially disclosed; nevertheless, physicians are aware that several aspects concerning this issue are far to be fully understood. By improving our knowledge on the role of some genetic aspects as well as on the KS, patients’ interindividual differences in terms of health status will result in a better management of this chromosomal disease. The aim of this review is to provide an update on both genetic and clinical phenotype and their interrelationships.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Correction to: 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines

            (2019)
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Androgen receptor-dependent activation of endothelial nitric oxide synthase in vascular endothelial cells: role of phosphatidylinositol 3-kinase/akt pathway.

              The mechanisms of testosterone-induced vasodilatation are not fully understood. This study investigated the effect of testosterone on nitric oxide (NO) synthesis and its molecular mechanism using human aortic endothelial cells (HAEC). Testosterone at physiological concentrations (1-100 nm) induced a rapid (15-30 min) increase in NO production, which was associated with phosphorylation and activation of endothelial NO synthase (eNOS). Then, the involvement of the androgen receptor (AR), which is abundantly expressed in HAEC, was examined. The effect of testosterone on eNOS activation and NO production were abolished by pretreatment with an AR antagonist nilutamide and by transfection with AR small interference RNA. In contrast, testosterone-induced eNOS phosphorylation was unchanged by pretreatment with an aromatase inhibitor or by transfection with ERalpha small interference RNA. 5alpha-Dihydrotestosterone, a nonaromatizable androgen, also stimulated eNOS phosphorylation. Next, the signaling cascade that leads to eNOS phosphorylation was explored. Testosterone stimulated rapid phosphorylation of Akt in a time- and dose-dependent manner, with maximal response at 15-60 min. The rapid phosphorylation of eNOS or NO production induced by testosterone was inhibited by Akt inhibitor SH-5 or by phosphatidylinositol (PI) 3-kinase inhibitor wortmannin. Co-immunoprecipitation assays revealed a testosterone-dependent interaction between AR and the p85alpha subunit of PI3-kinase. In conclusion, testosterone rapidly induces NO production via AR-dependent activation of eNOS in HAEC. Activation of PI3-kinase/Akt signaling and the direct interaction of AR with p85alpha are involved, at least in part, in eNOS phosphorylation.
                Bookmark

                Author and article information

                Journal
                Cureus
                Cureus
                2168-8184
                Cureus
                Cureus (Palo Alto (CA) )
                2168-8184
                23 December 2019
                December 2019
                : 11
                : 12
                : e6449
                Affiliations
                [1 ] Biochemistry, University of Belgrade - Faculty of Chemistry, Belgrade, SRB
                [2 ] Chemistry, Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Belgrade, SRB
                [3 ] Psychiatry, Institute of Mental Health, University of Belgrade - Faculty of Medicine, Belgrade, SRB
                [4 ] Physiology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Belgrade, SRB
                Author notes
                Article
                10.7759/cureus.6449
                6929241
                31893193
                a4603d36-59fc-42d1-b718-0baa06a78fed
                Copyright © 2019, Arizanovic et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 15 April 2019
                : 20 December 2019
                Funding
                The work was supported by the Ministry of Education, Science and Technological Development, Republic of Serbia [Grant numbers 172035 and 173014].
                Categories
                Dermatology
                Genetics
                Miscellaneous

                acetylsalicylic acid,testosterone,klinefelter syndrome,leg ulcers

                Comments

                Comment on this article