The ability of pharmacological preconditioning mimetics to confer long-lasting and sustained cardioprotection may be a logical criterion to develop a drug that can be used clinically for cardioprotection. We propose here that the use of long-acting phosphodiesterase-5 inhibitor, tadalafil, may confer sustained cardioprotection against ischemia. Tadalafil (5 mg/kg) was administered orally to male C57B/6J mice (n = 6 in each treatment subgroup at each time point studied). Hearts were isolated and subjected to 40 min of ischemia and 30 min of reperfusion on Langendorff's apparatus at 1, 12, 24, 36, 48, 60, 72, and 108 h after tadalafil administration. In 1- to 48-h subgroups, tadalafil was given once at 0 h only. In 60- and 72-h subgroups, tadalafil was given twice at 0 and 36 h. Similarly, in the 108-h subgroup, tadalafil was administered at 0, 36, and 72 h. In the same subgroups, wortmannin (15 microg/kg ip), an inhibitor of phosphatidylinositol 3-kinase or 5-hydroxydecanoic acid (5 mg/kg ip), an inhibitor of mitochondrial ATP-sensitive K(+) channels, was given together with tadalafil, and the hearts were subjected to ischemia-reperfusion at 36 h to determine whether the effect of tadalafil on ischemia-reperfusion injury was abolished. As a result, tadalafil treatment reduced left ventricular end-diastolic pressure and increased left ventricular developed pressure as well as reduced lactate dehydrogenase release. This protection remained till 36-40 h, and thereafter it vanished. The readministration of tadalafil at 36 and 72 h restored the protection till 108 h. Tadalafil treatment accelerated Akt phosphorylation in cardiac tissue and decreased myocyte apoptosis. The administration of wortmannin abolished the beneficial effects of tadalafil on hemodynamic parameters and myocyte apoptosis, together with significantly reduced Akt phosphorylation. 5-Hydroxydecanoic acid also abolished the antiapoptotic effect of tadalafil. It is concluded that tadalafil treatment induces the long-term protection of ischemic myocardium via phosphatidylinositol 3-kinase/Akt signaling pathway.

Psoriasis is a chronic autoimmune skin disorder that can vary in severity and extent of disease. While localized disease can be managed with topical medications, widespread disease often requires systemic therapy including biologics. This medication class targets different components of the immune system and thus modulates disease activity. The biologic secukinumab is a human monoclonal antibody against

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A patient diagnosed with tumid lupus erythematosus (TLE) was subsequently found to have systemic lupus erythematosus (SLE) after presenting to a tertiary care medical centre with shortness of breath and oedema. In this commentary, we discuss this patient’s presentation and the association between TLE and SLE.