Chronic spontaneous urticaria (CSU) is a complex idiopathic disease of the skin with various cellular infiltrations. Although mast cells are key effector cells in the pathogenesis of CSU, CD4+ T helper 2 cells also have particular roles in the development and maintenance of CSU. Periostin is known as a downstream molecule of interleukin (IL)-4 and IL-13, key cytokines of type 2 immune responses. In this study, we examined periostin and IL-13 levels in the sera of patients with CSU (n=84) and healthy normal controls (NCs, n=43). Periostin levels were significantly lower in the CSU group than in NCs (71.4±21.8 vs 85.1±22.4 ng/mL, P=0.04). Periostin levels were also lower in the severe CSU group than those in mild CSU (59.7±18.0 vs 73.4±22.0 ng/mL, P=0.04). However, IL-13 levels were significantly higher in patients with CSU than in NCs (508.5±51.2 vs 200.7±13.3 pg/mL, P=0.001). In conclusion, periostin and IL-13 may be independently related to the pathogenesis of CSU.

itric oxide (NO) is an important regulator of cardiac function. 1,2 In patients with congestive heart failure (CHF) the concentrations of NO and tumor necrosis factor-increase in proportion to the severity of heart failure. 3,4 Previous studies have shown that inhibition of cardiac NO synthase (NOS) augments the positive inotropic response to -adrenergic receptor stimulation in human heart failure, suggesting that increased activity of myocardial NOS and NO attenuates -adrenergic responsiveness. [5][6][7] In patients with severe CHF, the increase in intracellular cyclic AMP and myocardial contractility in response toadrenergic receptor stimulation is reduced, 5 which reflects cardiac desensitization to -receptor agonists, 8 partly modulated by the increased production of NO in the myocardium. 5 Previous studies have shown that forskolin produces beneficial cardiac effects by directly stimulating adenylyl cyclase in the failed human heart, especially in those with a relative insensitivity to -adrenergic receptor stimulation. 9 Colforsin daropate (NKH477; 6-(3-dimethyl-aminopropionyl) forskolin hydrochloride) is a new water-soluble forskolin derivative, which experimental studies have shown to be able to generate positive inotropic and vasodilatory actions. 10,11 Furthermore, we previously reported that NKH477 might be a superior alternative to dobutamine for mechanical energy transduction in patients with left ventricular (LV) systolic dysfunction. 12 It remains to be clarified how NO modulates -adrenergic post-receptor signaling, such as adenylyl cyclase stimulation in the failing human heart. The objective of this study was to address the role of NO by evaluating the effects of cardiac NOS inhibition on LV hemodynamics and mechanoenergetics in response to adenylyl cyclase stimulation with colforsin daropate in patients with idiopathic cardiomyopathy (IDC). Methods Study SubjectsWe examined 13 patients (10 men, 3 women, mean age 56±13 years) who were undergoing diagnostic cardiac catheterization for the evaluation of heart failure on their first admission to hospital. All patients showed normal sinus rhythm and were diagnosed as IDC by the absence of coronary artery disease or other known causes of dilated cardiomyopathy. The patients were in New York Heart Association functional class II (n=8) or class III (n=5) with a LV ejection fraction (LVEF) of less than 40%. None of Background Increased nitric oxide (NO) in the failing heart attenuates the myocardial contractile response to -adrenergic receptor stimulation. However, the physiological effects of NO on the -adrenergic post-receptor signaling system are unknown. The objective of the present study was to examine the effects of cardiac NO synthase (NOS) inhibition on left ventricular (LV) hemodynamics and mechanoenergetics in response to adenylyl cyclase stimulation in human heart failure. Methods and ResultsThe study group comprised 13 patients with heart failure because of idiopathic cardiomyopathy (IDC). Emax was examined as an index of LV contractility, LV...

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