Diabetes Mellitus’un yol açtığı erektil disfonksiyonda asetilsalisilik asit kullanımının koruyucu rolü olup olmadığının araştırılması
Bu çalışmanın amacı, diabetes mellitus gibi son organ komplikasyonunun çok olduğu bir patolojide, aspirin gibi bilinen, ulaşımı kolay ve vasküler sistemde etkileri sıkça tartışılan bir ilacın, erektil disfonksiyonda da koruyucu rolü olup olmadığının araştırılmasıdır.
8 haftalık diabet oluşturulmuş erkek Sprague-Dawley cinsi sıçanlara, kuyruk veninden verilen 40 mg/kg STZ ile diabet indüksiyonundan 4 gün sonra 100 mg/kg dozda asetilsalisilik asit (ASA, aspirin süspansiyonu), 8 hafta boyunca oral yolla verilmiştir. Denekler, kontrol (K), aspirin tedavili (K-ASA), diabetik (D) ve diabetik aspirin tedavili (D-ASA) olmak üzere dört gruba ayrılmış, in vivo ve in vitro çalışma sonuçları bu gruplar arasında karşılaştırılmıştır. In vivo deneylere alınan sıçanlarda, intrakavernozal basınç ölçümü, ortalama sistolik arteriyal basınca bölünerek hesaplanmıştır (ICP/MAP). D-ASA grubuna ait sıçanlarda elde edilen artmış intrakavernozal basınç değerleri istatistiksel olarak anlamlı bulunmuştur. In vitro çalışmalar dahilindeki elektriksel alan stimülasyonu, sodyum nitroprussit gevşeme yanıtlarında anlamlı fark gözlenmemiştir. Fenilefrin kasılma yanıtlarında da anlamlı farktan sözedilmemiştir. Moleküler çalışmalarda COX-1 ve nNOS mRNA ekspresyonları, PCR ile hesaplanmış, beta-aktine oranlarında anlamlı sonuç elde edilmemiştir.
Sonuç olarak değerlendirmemiz, oral yolla verilen aspirinin, kavernoz sinir üzerinde diabetin oluşturabileceği geri dönüşümsüz patolojilerden önce koruyucu etkisinin olabileceği, ASA tedavisi ile erektil fonksiyonların bozulmasının önlenebileceğini yönündedir. Ancak sonraki çalışmalarda yapılması gereken adımlar, gruplara ait n sayısının artırılması, NOS ve COX enzimlerine ait detaylı mekanizmalara yönelik in vitro ve in vivo çalışmaların yapılmasıdır.
Anahtar Sözcükler: Erektil disfonksiyon, korpus kavernozum, diabetes mellitus, asetilsalisilik asit, kavernozometri
SUMMARY
The possible protective effect of acetylsalicyclic acid on erectile dysfunction in Diabetes Mellitus
The aim of this study is, to investigate the possible protective effects of acetylsalicylic acid called Aspirin in generic, which is the most discussed drug on vascular system, on erectile dysfunction, one of the end-organ pathologies of diabetes mellitus.
Male Spraque Dawley rats were diabetic by injection of 40mg/kg streptozotocin via tail vein. The duration was 8 weeks. After 4 days of the incubation of diabetes, 100 mg/kg acetylsalicylic acid (ASA, as aspirin suspension) were given by orally during 8 weeks. Rats were divided into 4 groups as control (K), diabetic (D), aspirin treated (K-ASA), and diabetic aspirin treated (D-ASA), and all in vivo and in vitro studies were compared in these groups. For in vivo studies, intracavernosal pressure was measured and calculated by division into mean arterial blood pressure (ICP/MAP).
ICP/MAP results of D-ASA group were found significantly higher when compared with diabetics.
We did not find any significant results in in vitro studies as EFS, SNP relaxant responses and phenylephrine contractile responses. In molecular studies COX-1 and nNOS mRNA levels did not change compared with controls when divided into betaactin mRNA levels.
As result, we thought that orally given 100mg/kg aspirin, may protect cavernosal nerve from irreversible possible pathologies of diabetes, as a possible protective effect of ASA, before the dysfunction of erection. The next steps must be to increase the n number of experiments, and to study on the detailed mechanisms of NOS and COX enzymes in vivo and in vitro.
Key words: Erectile dysfunction, corpus cavernosum, diabetes mellitus, acetylsalicylic acid, cavernosometry
KAYNAKLAR
AKINGBA, A. G. & BURNETT, A. L. (2001) Endothelial nitric oxide synthase protein expression, localization, and activity in the penis of the alloxan-induced diabetic rat.
Molecular Urology 5, 189–197.
AKKUS E, KADIOGLU A, ESEN A, DORAN S, ERGEN A, ANAFARTA K, HATTAT H;
TURKISH ERECTILE DYSFUNCTION PREVALENCE STUDY GROUP. (2002) Prevalence and correlates of erectile dysfunction in Turkey: a population-based study. Eur Urol. Mar;41(3):298-304
AMARAL, S., OLIVEIRA, P. J. & RAMALHO-SANTOS, J. (2008) Diabetes and the impairment of reproductive function: possible role of mitochondria and reactive oxygen species. Current Diabetes Reviews 4, 46–54
ANAFARTAK, (2000). Penil ereksiyon ve empotans: Klinik Andrology, Ankara Üniversitesi Basımevi, Ankara, 337-373.
ANDERSSON KE.(2001). Pharmacology of erectile function and dysfunction. Urol Clin North Am. May;28(2):233-47
ARGIOLAS A, MELIS MR (2003). The neurophysiology of the sexual cycle. J Endocrinol Invest.;26(3 Suppl):20-2
ARGIOLAS A, MELIS MR. (2004). The role of oxytocin and the paraventricular nucleus in the sexual behaviour of male mammals.Physiol Behav. Nov 15;83(2):309-17.
AZADZOİ KM, KİM N, BROWN ML, GOLDSTEİN I, COHEN RA, SAENZ DE TEJADA I.
(1992). Endothelium-derived nitric oxide and cyclooxygenase products modulate corpus cavernosum smooth muscle tone. J Urol. Jan;147(1):220-5.
BETTERIDGE, D. J. (2000) What is oxidative stress? Metabolism 49, 3–8.
BIVALACQUA, T. J., CHAMPION, H. C., USTA, M. F., CELLEK, S., CHITALEY, K., WEBB, R. C., LEWIS, R. L., MILLS, T. M., HELLSTROM, W. J. & KADOWITZ, P. J. (2004a) RhoA ⁄ Rho-kinase suppresses endothelial nitric oxide synthase in the penis: a mechanism for diabetes-associated erectile dysfunction. Proceedings of the National Academy of Sciences of the United States of America 101, 9121–9126.
BIVALACQUA, T. J., USTA, M. F., CHAMPION, H. C., LEUNGWATTANAKIJ, S. &
DABISCH, P. A. (2004b) Effect of combination endothelial nitric oxide synthase gene therapy and sildenafil on erectile function in diabetic rats. International Journal of Impotence Research 16, 21–29.
BUVAT J (2003) Hyperprolactinemia and sexual function in men: a short review. Int J Impot Res. Oct;15(5):373-7.
CAI, H., GRIENDLING, K. K. & HARRISON, D. G. (2003) The vascular NAD(P)H oxidases as therapeutic targets in cardiovascular diseases. Trends in Pharmacological Sciences 24,471–478.
CELLEK, S., FOXWELL, N. A. & MONCADA, S. (2003) Two phases of nitrergic neuropathy in streptozotocin-induced diabetic rats. Diabetes 52, 2353–2362.
CHANG, S., HYPOLITE, J. A., VELEZ, M., CHANGOLKAR, A., WEIN, A. J., CHACKO, S.
& DISANTO, M. E. (2004) Downregulation of cGMP-dependent protein kinase-1 activity in the corpus cavernosum smooth muscle of diabetic rabbits. American Journal of Physiology 287, R950–R960
CHRIST G, DAY N, SANTIZO C, SATO Y, ZAHO W, SCLAFANI T, BAKAL R, SALMAN M, DAVIES K, MELMAN A. (2004). Intracorporal injection of hSlo cDNA restores erectile capacity in STZ-diabetic F-344 rats in vivo. Am J Physiol Heart Circ Physiol 287: H1544-H1553,.
CHRIST GJ, HODGES S. (2006). Molecular mechanisms of detrusor and corporal myocyte contraction: identifying targets for pharmacotherapy of bladder and erectile dysfunction, Br J Pharm, 147, S41-S55,
Circulation. 2002 Sep 3;106(10):1282-7
CYRUS T, SUNG S, ZHAO L, FUNK CD, TANG S, PRATİCÒ D.
DALEY JT, BROWN ML, WATKİNS T, TRAİSH AM, HUANG YH, MORELAND RB, DE TEJADA IS. (1996 a). Prostanoid production in rabbit corpus cavernosum: I.
regulation by oxygen tension.J Urol. Apr;155(4):1482-7.
DALEY JT, WATKİNS MT, BROWN ML, MARTİNEZ V, CUEVAS P, SAENZ DE TEJADA I.
(1996 b) Prostanoid production in rabbit corpus cavernosum. II. Inhibition by oxidative stress J Urol. Sep;156(3):1169-73.
DEAN R, LUE T, (2005). Physiology of penile erection and pathophysiology of erectile dysfunction, Urol Clin North Am. November ; 32(4): 379–v
DU Y, SARTHY VP, KERN TS. (2004)..Interaction between NO and COX pathways in retinal cells exposed to elevated glucose and retina of diabetic rats. Am J Physiol Regul Integr Comp Physiol. Oct;287(4):R735-41
Effect of low-dose aspirin on vascular inflammation, plaque stability, and atherogenesis in low-density lipoprotein receptor-deficient mice.
EL MELEGY NT, ALI ME, AWAD EM (2005). Plasma levels of endothelin-1, angiotensin II, nitric oxide and prostaglandin E in the venous and cavernosal blood of patients with erectile dysfunction. BJU Int. Nov;96(7):1079-86.
EL MİDAOUİ A, WU R, DE CHAMPLAİN J. Prevention of hypertension, hyperglycemia and vascular oxidative stress by aspirin treatment in chronically glucose-fed rats. J Hypertens. 2002 Jul;20(7):1407-12.,
EVGENOV, O. V. & LIAUDET, L. (2005) Role of nitrosative stress and activation of poly(ADP-ribose) polymerase-1 in cardiovascular failure associated with septic and hemorrhagic shock. Current Vascular Pharmacology 3, 293–299
FREDHOLM BB, ABBRACCHIO MP, BURNSTOCK G, DUBYAK GR, HARDEN TK, JACOBSON KA, SCHWABE U, WILLIAMS M. (1997). Towards a revised nomenclature for P1 and P2 receptors. Trends Pharmacol Sci. Mar;18(3):79-82.
GANONG WF Synaptic and junctional transmission. In Ganong WF(ed): (1999). Review of Medical Physiology, 19th ed. Stamford, Conn, Appleton&Lange ;80-112.
GANONG WF. Neural basis of instinctual behavior and emotions. In Ganong WF(ed):
(1999). Review of Medical Physiology, 19th ed. Stamford, Conn, Appleton&Lange,;244-254
GONZALEZ-CADAVID, N. F., IGNARRO, L. J. & RAJFER, J. (1999)Nitric oxide and the cyclic GMP system in the penis. Molecular Urology 3, 51–59.
Goodman and Gilman’s, 2001, bölüm 27
GUR S, KADOWITZ PJ, HELLSTROM WJG, A (2008). critical appraisal of erectile dysfunction in animal models of diabetes mellitus, Int J Andr, 1-22.
HEATON JP, MORALES A, ADAMS MA, JOHNSTON B, EL-RASHIDY R. (1995).
Recovery of erectilefunction by oral administration of apomorphine. Urology.
Feb;45(2):200-6.
HENNEKENS CH (2007). Aspirin in the treatment and prevention of cardiovascular disease: current perspectives and future directions..Curr Atheroscler Rep.
Nov;9(5):409-16. Review.
HENSLEY, K., ROBINSON, K. A., GABBITA, S. P., SALSMAN, S. & FLOYD, R. A. (2000) Reactive oxygen species, cell signaling, and cell injury. Free Radical Biological Medicine 28, 1456– 1462.
HUNTE, C., SOLMAZ, S. & LANGE, C. (2002) Electron transfer between yeast cytochrome bc1 complex and cytochrome c: a structural analysis (Abstract). Biochimica et Biophysica Acta 1555, 21–28.
IGNARRO, L. J., BUSH, P. A., BUGA, G. M., WOOD, K. S., FUKUTO, J. M. & RAJFER, J.
(1990) Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle. Biochemical Biophysics Research Communications 170, 843–850.
JEFFREYS D, (2004). Aspirin: Mucize İlacın Çarpıcı Öyküsü,. ISBN : 9758829712.
JEREMY JY, MORGAN RJ, MİKHAİLİDİS DP, DANDONA P. (1986). Prostacyclin synthesis by the corpora cavernosa of the human penis: evidence for muscarinic control and pathological implications. Prostaglandins Leukot Med. Aug;23(2-3):211-6
JEREMY, J. Y., JONES, R. A., KOUPPARIS, A. J., HOTSTON, M., PERSAD, R., ANGELINI, G. D. & SHUKLA, N. (2007) Reactive oxygen species and erectile dysfunction: possible role of NADPH oxidase. International Journal of Impotence Research 19, 265–280
JIN, L., LAGODA, G., LEITE, R., WEBB, R. C. & BURNETT, A. L. (2008) NADPH oxidase activation: a mechanism of hypertension-associated erectile dysfunction. Journal of Sexual Medicine 5, 544–551
Johansen JS, Harris AK, Rychly DJ, Ergul A.Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice. Cardiovasc Diabetol. 2005 Apr
KALYANI, R. R. & DOBS, A. S. (2007) Androgen deficiency, diabetes, and the metabolic syndrome in men. Current Opinion Endocrinology Diabetes Obesity 14, 226–234 KAPETANOVİC IM, BAUER KS, TESSİER DM, LİNDEBLAD MO, ZAKHAROV AD, LUBET
R, LYUBİMOV A. (2009). Comparison of pharmacokinetic and pharmacodynamic profiles of aspirin following oral gavage and diet dosing in rats. Chem Biol Interact.
May 15;179(2-3):233-9.
KEEGAN, A., COTTER, M. A. & CAMERON, N. E. (1999a) Effects of chelator treatment on aorta and corpus cavernosum from diabetic rats. Free Radicai Biological Medicine 27, 536–543.
KEEGAN, A., COTTER, M. A. & CAMERON, N. E. (1999b) Effects of diabetes and treatment with the antioxidant alpha-lipoic acid on endothelial and neurogenic responses of corpus cavernosum in rats. Diabetologia 42, 343–350
KHAN MA, CALVERT RC, SULLIVAN ME, THOMPSON CS, MUMTAZ FH, MORGAN RJ, MIKHAILIDIS DP. (2000). Normal and pathological erectile function: the potential clinical role of endothelin-1 antagonists Curr Drug Targets. Nov;1(3):247-60.
KNECHT, K., FEATHER, M. & BAYNES, J. (1992) Detection of 3-deoxyfructose and 3- deoxyglucosone in human urine and plasma: evidence for intermediate stage of the Maillard reaction in vivo. Archives Biochemistry Biophysics 294, 130–137
KODAMA M, YAMASAKİ Y, SAKAMOTO K, YOSHİOKA R, MATSUHİSA M, KAJİMOTO Y, KOSUGİ K, UEDA N, HORİ M. Antiplatelet drugs attenuate progression of carotid intima-media thickness in subjects with type 2 diabetes. Thromb Res. 2000 Feb 15;97(4):239-45.
KOJDA, G. & HARRISON, D. (1999) Interaction between NO and reactive oxygen species:
pathological importance in atherosclerosis, hypertension, diabetes and heart failure.
Cardiovascular Research 43, 562–571
LIN C, LIN G, LUE T, (2005). Cyclic Nucleotide Signaling in Cavernous Smooth Muscle, J Sex Med; 2:478-491.
LUE TF (2002). Physiology of penile erection and pathophysiology of erectile dysfunction and priapism. In Walsh PC (ed):Campell’s Urology, 8th ed.Saunders, Elsevier , p1591-1618.
LUE TF: (2000). Erectile dysfunction N Engl J Med. Jun 15;342(24):1802-13.
MALLICK HN, MANCHANDA SK, KUMAR VM. (1994) Sensory modulation of the medial preoptic area neuronal activity by dorsal penile nerve stimulation in rats.. J Urol.
Mar;151(3):759-62
MARSON L, PLATT KB, MCKENNA KE. (1993). Central Nervous System innervation of penis as revealed by transneuronal transport of pseudorabies virus. Neuroscience.
Jul;55(1):263-80.
MEDINA P, SEGARRA G, VILA JM, DOMENECH C, MARTÍNEZ-LEÓN JB, LLUCH S (2000). Effects of sildenafil human penile blood vessels Urology. Sep 1;56(3):539-43.
MİNHAS S, CARTLEDGE J, EARDLEY I. (2000). The role of prostaglandins in penile erection. Prostaglandins Leukot Essent Fatty Acids. Mar;62(3):137-46. Review.
MONTORSI F, PERANI D, ANCHISI D, SALONIA A, SCIFO P, RIGIROLI P, ZANONI M, HEATON JP, RIGATTI P, FAZIO F. (2003). Apomorphine-induced brain modulation during sexual stimulation: a new look at central phenomena related to erectile dysfunction Int J Impot Res. Jun;15(3):203-9
NUSBAUM MR, (2000). Erectile dysfunction: prevalence, etilogy and major risk factors. J Am Osteopath Assoc, 102: 1-6,
PIEPER, G. M. & DONDLINGER, L. A. (1997) Plasma and vascular tissue arginine are decreased in diabetes: acute arginine supplementation restores endothelium-dependent relaxation by augmenting cGMP production. Journal of Pharmacology and Experimental Therapeutics 283, 684–691
RADİ ZA. (2009). Pathophysiology of cyclooxygenase inhibition in animal models. Toxicol Pathol.;37(1):34-46. Review.
RAINA R, LAKIN MM, AGARWAL A, SHARMA R, GOYAL KK, MONTAGUE DK, KLEIN E, ZIPPE CD. (2003). Long-term effect of sildenafil citrate on erectile dysfunction after radical prostatectomy: 3-year follow-up. Urology. Jul;62(1):110-5.
RAJFER, J., ARONSON, W. J., BUSH, P. A., BUSH, P. A., DOREY, F. J.& IGNARRO, L. J.
(1992) Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic,noncholinergic neurotransmission. New EnglandJournal of Medicine 326, 90–94.
RYBALKIN, S. D., YAN, C., BORNFELDT, K. E. & BEAVO, J. A. (2003) Cyclic GMP phosphodiesterases and regulation of smooth muscle function. Circulation Research 93, 280–291
SAENZ DE TEJADA, I., GOLDSTEIN, I., AZADZOI, K., KRANE, R. J. & COHEN, R. A.
(1989) Impaired neurogenic and endotheliummediated relaxation of penile smooth muscle from diabetic men with impotence. New England Journal of Medicine 320, 1025–1030.
SHUKLA, N., JONES, R., PERSAD, R., ANGELINI, G. D. & JEREMY, J. Y. (2005) Effect of sildenafil citrate and a nitric oxide donating sildenafil derivative, NCX 911, on cavernosal relaxation and superoxide formation in hypercholesterolaemic rabbits.
European Journal of Pharmacology 517, 224–231
SZABO, C (1996). The pathophysiological role of peroxynitrite in shock, inflammation, and ischemia-reperfusion injury. Shock 6, 79–88
TAUSEEF M, SHAHİD M, SHARMA KK, FAHİM M.Basic. (2008).Antioxidative action of aspirin on endothelial function in hypercholesterolaemic rats. Clin Pharmacol Toxicol Oct;103(4):314-21.
TETSUKA T, DAPHNA-IKEN D, SRİVASTAVA SK, BAİER LD, DUMAİNE J, MORRİSON AR. (1994). Cross-talk between cyclooxygenase and nitric oxide pathways:
prostaglandin E2 negatively modulates induction of nitric oxide synthase by interleukin 1. Proc Natl Acad Sci U S A. Dec 6;91(25):12168-7.
TODA, N., AYAJIKI, K. & OKAMURA, T. (2005) Nitric oxide and penile erectile function.
Pharmacological Therapeutics 106, 233–266
TONG YC, BRODERICK G, HYPOLITE J VE LEVIN RM . (1992). Correlation of purinergic, cholinergic and functions in rabbit corporal cavernosal tissue. Pharmacology
;45:241-249
TRAISH, A. M., MUNARRIZ, R., O’CONNELL, L., CHOI, S., KIM, S. W., KIM, N. N., HUANG, Y. H. & GOLDSTEIN, I. (2003). Effects of medical or surgical castration on erectile function in an animal model. Journal of Andrology 24, 381–387
VASQUEZ-VIVAR, J., KALYANARAMAN, B., MARTASEK, P., HOGG, N., MASTERS, B. S.
& KAROUI, H. (1998) Superoxide generation by endothelial nitric oxide synthase:
the influence of cofactors. Proceedings of the National Academy of Sciences of the United States of America 95, 9220–9225
VERNET, D., CAI, L. & GARBAN, H. (1995) Reduction of penile nitric oxide synthase in diabetic BB ⁄WORdp (type I) and BBZ ⁄WORdp (type II) rats with erectile dysfunction. Endocrinology 136, 5709–5717
VIGNOZZI, L., MORELLI, A., FILIPPI, S., AMBROSINI, S., MANCINA, R., LUCONI, M. ET AL. (2007) Testosterone regulates RhoA ⁄ Rhokinase signaling in two distinct animal models of chemical diabetes. Journal of Sexual Medicine 4, 620–630
WILLIAMSON, J. R., CHANG, K., FRANGOS, M., HASAN, K. S., IDO, Y., KAWAMURA, T., NYENGAARD, J. R., VAN DEN ENDEN, M., KILO, C. & TILTON, R. G. (1993) Hyperglycemic pseudohypoxia and diabetic complications. Diabetes 42, 801–813 WOOLLARD AC, WOLFF SP, BASCAL ZA. Antioxidant characteristics of some potential
anticataract agents. Studies of aspirin, paracetamol, and bendazac provide support for an oxidative component of cataract. Free Radic Biol Med. 1990;9(4):299-305.
XIA, Y. & ZWEIER, J. L. (1997) Direct measurement of nitric oxide generation from nitric oxide synthase. Proceedings of the National Academy of Sciences of the United States of America 94, 12705–12710
YING, W., ALANO, C. C., GARNIER, P. & SWANSON, R. A. (2005) NAD+ as a metabolic link between DNA damage and cell death. Journal Neuroscience Research 79, 216–
223.
ZHANG, X.-H., FILIPPI, S., MORELLI, A., VIGNOZZI, L., LUCONI, M., DONATI, S., FORTI, G. & MAGGI, M. (2006) Testosterone restores diabetes-induced erectile dysfunction
and sildenafil responsiveness in two distinct animal models of chemical diabetes.
Journal of Sexual Medicine 3, 253–266
ZHENG L, HOWELL SJ, HATALA DA, HUANG K, KERN TS. (2007). Salicylate-based anti-inflammatory drugs inhibit the early lesion of diabetic retinopathy. Diabetes.
Feb;56(2):337-45
ZIPPE CD, JHAVERI FM, KLEIN EA, KEDIA S, PASQUALOTTO FF, KEDIA A, AGARWAL A, MONTAGUE DK, LAKIN MM. (2000). Role of Viagra after radical prostatectomy.
Urology. Feb;55(2):241-5 29;4(1):5. Review
ÖZGEÇMİŞ
Adı: Gaye
Soyadı: Hafez
Doğum Yeri ve Tarihi: Antakya, 2,02,1979
Uyruğu: TC
Medeni Durumu: Bekar
İletişim Adresi: 19. sok 32/3 Bahçelievler/Ankara
Telefon: 0312 213 86 06
Eğitimi: Yüksek lisans
Yabancı Dili: İngilizce, fransızca
1979’da Antakya’da doğdum. İlk, orta ve lise öğrenimimi Antakya’da tamamladım.
1997’de Marmara Üniversitesi Eczacılık Fakültesi’ne girdim ve 2001 Haziran’ında mezun oldum. Yüksek lisansımı Ankara Üniversitesi Eczacılık Fakültesi Farmakoloji Anabilim Dalı’nda “Diabetik ve non-diabetik sıçanlardan alınan idrar kesesi preparatlarında kolinerjik ve pürinerjik sistem yanıtlarına parsiyel obstrüksiyonun etkileri” başlıklı tez projemi 2003 Haziran ayında tamamladım. Yüksek lisans süresi içinde iki ay boyunca, onursal fellow olarak Royal Free & University College Medical School Autonomic Neuroscience Institute Londra’da Prof. Geoffrey Burnstock’un laboratuvarında bulundum. 2005’te Ada Eczanesi adında halen sahibi olduğum kendi eczanemi açtım. Beraberinde, 2004 yılından bu yana, Tepe International Sağlık Bilişim Sistemleri adlı şirkete, eczanelerce kullanılan ilaç veri tabanları oluşturulması konularında on-line danışmanlık hizmeti vermekteyim. Doktoramı yine
diabetes mellitus ve yol açtığı patolojiler ve bunların olası tedavileri üzerine, üroloji alanında yapmaktayım. İlgi duyduğum çalışma alanları ise, kanser, ağrı ve kök hücre çalışmalarıdır.
Yayın ve posterler:
2008, Kosan M, Tul M, Ozturk B, Hafez G, Inal G, Cetinkaya M, Alteration in contractile responses in human detrusor smooth muscle from obstructed bladders with overactivity. Urol Int. 80(2):193-200.
2005, Kosan M, Hafez G, Ozturk B, Ozgunes O, Gur S, Cetinkaya M, Effect of urothelium on bladder contractility in diabetic rats. Int J Urol. 12(7):677-82.
2005, Gur S, Dogan AU, Dogan M, Karahan ST, Can B, Hafez G, Ozgunes O, Kendirci M, Short-term effects of arsenic sulfur in deficits of contractile and relaxant responses on urinarybladder: pharmacological and structural changes. Urol Int.
74(3):272-5.
2005, Aki FT, Kosan M, Gonulalan U, Hafez G, Ozgunes O, Ozturk B, Gur S, Cetinkaya M, Contractile and relaxation properties of native bladder and ileal patch on ileal augmentation experimental model in rats. Poster presantation ESPU 2nd joint meeting section on urology
2004, Ozturk B, Gur S, Coskun M, Kosan M, Erdurak C, Hafez G, Ozgunes O, Cetinkaya M, Relaxant effect of ferulago syriaca root extract on human corpus cavernosum. Poster presantation Eur Urol Suppl. (3): 62.
2003, Hafez G, Gur S, Kosan M, Ozturk B, Cetinkaya M, Coexistence of diabetes and mild partial outlet obstruction on contractile responses of urinary bladder from