Effects of PDE5 inhibitors on vasculogenic ED Savas M et al. Several potential limitations of this study should be considered. First, is the cross-sectional design of this study. Usually, to assess the effect of any agent on a molecule the investigation should be based on a chronic treatment set-up but in this study the acute effect of the PDE5 inhibitor was investigated. To extend the findings of our study, assess- ment of serum prolidase activity in endothelial cells, and evaluation of the association of serum prolidase activity with the presence and extent of atherosclerosis in other regions of the arterial system would better clarify the pathophysiological role of prolidase activity in endothelial dysfunction. Evaluation of the association of serum proli- dase activity with the extent of endothelial ischemia would identify the role of endothelial ischemia in increased collagen turnover in patients with vasculogenic ED. Finally, measurement of serum oxidative status and prolidase enzyme activities after daily treatment with PDE5 inhibitor would have added to the value of this study, but this was beyond the scope of this present work. In conclusion, the results of this preliminary study confirm the beneficial acute effects of PD5 inhibitor in patients with ED by evaluating serum oxidative status and prolidase activity. However, further clinical long-term studies of this issue, particularly including groups at high risk, should be carried out. REFERENCES 1. Frajese GV, Pozzi F. New achievement and novel therapeutic applica- tions of PDE5 inhibithors in older males. J Endocrinol Invest. 2005;28: 45-50. 2. Brindis RG, Kloner RA. Sildenafil in patients with cardiovascular disease. Am J Cardiol. 2003;92:26-36, doi: 10.1016/S0002-9149(02)03368-4. 3. Turgut NH, Temiz TK, Bagcivan I, Turgut B, Gulturk S, Karadas B. The effect of sildenafil on the altered thoracic aorta smooth muscle responses in rat pre-eclampsia model. Eur J Pharmacol. 2008;589:180-7, doi: 10.1016/ j.ejphar.2008.04.034. 4. Zhu B, Strada SJ. The novel functions of cGMP-specific phosphodiester- ase 5 and its inhibitors in carcinoma cells and pulmonary/cardio- vascular vessels. Curr Top Med Chem. 2007;7:437-54, doi: 10.2174/ 156802607779941198. 5. Attina TM, Malatino LS, Maxwell SR, Padfield PL, Webb DJ. Phosphodiesterase type 5 inhibition reverses impaired forearm exer- cise-induced vasodilatation in hypertensive patients. J Hypertens. 2008; 26:501-7, doi: 10.1097/HJH.0b013e3282f382ff. 6. Eleuteri E, Magno F, Gnemmi I, Carbone M, Colombo M, La Rocca G, et al. Role of oxidative and nitrosamine stress biomarkers in chronic heart failure. Front Biosci. 2009;14:2230-7, doi: 10.2741/3375. 7. Hamilton SJ, Chew GT, Watts GF. Therapeutic regulation of endothelial dysfunction in type 2 diabetes mellitus. Diab Vasc Dis Res. 2007;4:89-102, doi: 10.3132/dvdr.2007.026. 8. Perk H, Armagan A, Nazirog˘ lu M, Soyupek S, Hoscan MB, S u¨tc u¨ R, et al. Sildenafil citrate as a phosphodiesterase inhibitor has an antioxidant effect in the blood of men. J Clin Pharm Ther. 2008;33:635-40, doi: 10. 1111/j.1365-2710.2008.00962.x. 9. Bivalacqua TJ, Sussan TE, Gebska MA, Strong TD, Berkowitz DE, Biswal S, et al. Sildenafil inhibits superoxide formation and prevents endothelial CLINICS 2010;65(12):1311-1314 dysfunction in a mouse model of secondhand smoke induced erectile dysfunction. J Urol. 2009;181:899-906, doi: 10.1016/j.juro.2008.10.062. 10. Savas M, Yeni E, Celik H, Ciftci H, Utangac M, Oncel H, et al. The association of serum prolidase activity and erectile dysfunction. J Androl. 2010;31:146-54, doi: 10.2164/jandrol.109.008631. 11. Demirbag R, Yildiz A, Gur M, Yilmaz R, Elc¸i K, Aksoy N. Serum prolidase activity in patients with hypertension and its relation with left ventricular hypertrophy. Clin Biochem. 2007;40:1020-5, doi: 10.1016/j. clinbiochem.2007.05.015. 12. Altindag O, Erel O, Aksoy N, Selek S, Celik H, Karaoglanoglu M. Increased oxidative stress and its relation with collagen metabolism in knee osteoarthritis. Rheumatol Int. 2007;27:339-44, doi: 10.1007/s00296- 006-0247-8. 13. Surazynski A, Donald SP, Cooper SK, Whiteside MA, Salnikow K, Liu Y, et al. Extracellular matrix and HIF-1 signaling: the role of prolidase. Int J Cancer. 2008;122:1435-40, doi: 10.1002/ijc.23263. 14. Erel O. A new automated colorimetric method for measuring total oxi- dant status. Clin Biochem. 2005;38:1103-11, doi: 10.1016/j.clinbiochem. 2005.08.008. 15. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem. 2004;37:112-9, doi: 10. 1016/j.clinbiochem.2003.10.014. 16. Myara I, Cosson C, Moatti N, Lemonnier A. Human kidney prolidase purification, preincubation properties and immunological reactivity. Int J Biochem. 1994;26:207-14, doi: 10.1016/0020-711X(94)90147-3. 17. Chinard FP. Photometric estimation of proline and ornithine. J Biol Chem. 1952;199:91–5. 18. Burnett AL, Strong TD, Trock BJ, Jin L, Bivalacqua TJ, Musicki B. Serum biomarker measurements of endothelial function and oxidative stress after daily dosing of sildenafil in type 2 diabetic men with erectile dysfunction. J Urol. 2009;181:245-51, doi: 10.1016/j.juro.2008.09.005. 19. Singh U, Jialal I. Oxidative stress and atherosclerosis. Pathophysiology. 2006;13:129-42, doi: 10.1016/j.pathophys.2006.05.002. 20. Speranza L, Franceschelli S, Pesce M, Vinciguerra I, De Lutiis MA, Grilli A, et al. Phosphodiesterase type-5 inhibitor and oxidative stress. Int J Immunopathol Pharmacol. 2008;21:879-89. 21. Gonzalez-Cadavid NF. Mechanisms of penile fibrosis. J Sex Med. 2009;6 (suppl 3):353-62, doi: 10.1111/j.1743-6109.2008.01195.x. 22. Kovanecz I, Nolazco G, Ferrini MG, Toblli JE, Heydarkhan S, Vernet D, et al. Early onset of fibrosis within the arterial media in a rat model of type 2 diabetes mellitus with erectile dysfunction. BJU Int. 2009;103:1396- 404, doi: 10.1111/j.1464-410X.2008.08251.x. 23. Luo H, Goldstein I, Udelson D. A three-dimensional theoretical model of the relationship between cavernosal expandability and percent caverno- sal smooth muscle. J Sex Med. 2007;4:644–5, doi: 10.1111/j.1743-6109. 2007.00492.x. 24. Rajfer J, Rosciszewski A, Mehringer M. Prevalence of corporal venous leakage in impotent men. J Urol. 1988;140:69–71 25. Metro MJ, Broderick GA. Diabetes and vascular impotence: does insulin dependence increase the relative severity? Int J Impot Res. 1999;11:87–9, doi: 10.1038/sj.ijir.3900387. 26. Lue TF. Veno-occlusive dysfunction of corpora cavernosa: comparison of diagnostic methods. J Urol. 1996;155:786–7. 27. Verit FF, Geyikli I, Yazgan P, Celik A. Correlations of serum prolidase activity between bone turnover markers and mineral density in postmenopausal osteoporosis. Arch Gynecol Obstet. 2006;274:133-7, doi: 10.1007/s00404-006-0148-9. 28. Sienkiewicz P, Pałka M, Pałka J. Oxidative stress induces IGF-I receptor signaling disturbances in cultured human dermal fibroblasts. A possible mechanism for collagen biosynthesis inhibition. Cell Mol Biol Lett. 2004;9:643-50. 29. Yildiz A, Demirbag R, Yilmaz R, Gur M, Altiparmak IH, Akyol S, et al. The association of serum prolidase activity with the presence and severity of coronary artery disease. Coron Artery Dis. 2008;19:319-25, doi: 10.1097/MCA.0b013e32830042ba. 1314