Browsing by Author "Akay, Alaaddin"

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Effects of Sacral Neuromodulation on Isolated Urinary Bladder Function in a Rat Model of Spinal Cord Injury
(2015) Kumsar, Sukru; Keskin, Ulya; Akay, Alaaddin; Bilgilisoy, Ugur Taylan; Erdem, S. Remzi; Peskircioglu, C. Levent; Ozkardes, Hakan; 0000-0002-7277-449X; 24917133; AAH-1052-2020
IntroductionSacral neuromodulation has been considered as an effective treatment option for various types of chronic voiding dysfunction, but the mechanism of action has not been well understood. The aim of this study was to evaluate the effect of chronic sacral neuromodulation on isolated bladder functions in a rat model of spinal cord injury. Materials and MethodsFemale Sprague-Dawley rats (250-300g; N = 20) were assigned to four groups as follows: 1) control group (N = 6); 2) spinal cord transection group (SCT; N = 5); 3) spinal cord transection + sacral neuromodulation group (SCT + SNM; N = 5); 4) sham (spinal cord transection + electrode wire implantation without sacral neuromodulation; N = 4). The rats in the SCT, SCT + SNM, and sham groups were anesthetized with ketamine (60mg/kg, i.p.) and xylazine (7mg/kg, i.p.). The spinal cord was completely transected at T8-T9 level in SCT and SCT + SNM groups. Electrode wires were implanted into S3 dorsal foramina in both sham and SNM groups, but only the SNM group was subjected to electrical stimulation for four hours a day for three weeks. Twenty-one days later, the rats were sacrificed via anesthetic overdose, and isolated longitudinal bladder strip preparations were placed in organ baths for the investigation of their isometric responses to pharmacological agents. ResultsIn isometric contraction experiments, SCT was found to increase the contraction responses of the bladder strips to muscarinic stimulation, and SNM could not prevent this increase. In isometric relaxation experiments, SCT caused a decrease in -adrenergic relaxation responses, and SNM augmented the bladder's -adrenergic relaxation responses. Nitric oxide did not affect the relaxation responses. ConclusionIn our rat model of SCT, SNM seemed to alter adrenergic receptor function in the urinary bladder. Further studies are required to clarify the mechanism of these alterations at the level of bladder receptors following sacral neuromodulation.
Expression of maspin in testis tumors with germ cells and its relation with angiogenesis factors
(2016) Celik, Huseyin; Turunc, Tahsin; Bal, Nebil; Hasirci, Eray; Akay, Alaaddin; Pekircioglu, Cetin Levent; 27513425
Background/aim: We aimed to evaluate the importance of maspin expression in testicular tumors with germ cells, its effect on prognosis, and the relation with angiogenesis factors. Materials and methods: The paraffin blocks of the orchiectomy materials of 32 patients who had undergone orchiectomy due to testicular tumors were taken within the scope of the study. The specimens of the cases included in the study group were reexamined under light microscope. Results: While just one maspin-positive sample was found in the seminoma cases, maspin stained positively in 6 of the nonseminoma germ cell tumors (NSGCTs). No statistical difference was found between maspin and tumor stage, size, alpha fetoprotein values, vascular endothelial growth factor, Ki-67, and CD31. A statistically positive correlation was only determined between maspin and p53 (P < 0.001). Conclusion: Maspin protein, whose expression in some tumors is accepted as a poor prognostic factor, is also expressed in testicular tumors with germ cells. However, according to our study, it is difficult to say whether this protein is a favorable or poor prognostic factor in testicular tumors and to understand how the effect mechanism works. The positive correlation between maspin and p53 in the NSGCTs makes us think that maspin might have displayed an effect on the p53 pathway.
Sıçan izole vajen ve mesane dokularında rho-kinaz inhibisyonuna yaşlılık ve cerrahi menopozun etkileri
(Başkent Üniversitesi Tıp Fakültesi, 2009) Akay, Alaaddin; Peşkircioğlu, Levent; Erdem, Remzi
Menopoz sonrası genitoüriner sistemde en sık karsılasılan sorunlar iritatif üriner yakınmalar ve kadın cinsel fonksiyon bozukluklarıdır. Bu yakınmaların olusmasında düzeyleri değisen seks steroidlerinin mesane ve vajen düz kaslarında meydana getirdikleri fizyolojik değisimler oldukça önemlidir. Düz kas kasılmasında kalsiyum-bağımlı yolaktan baska son zamanlarda kalsiyumdan bağımsız bir yolak olan Rho-kinaz yolağı önem kazanmıstır. Bu çalısmada Rho-kinaz yolağının sıçan izole mesane ve vajen düz kasındaki fizyolojik etkisini ve seks steroidlerindeki değisimin bu yolakla olan iliskisinin arastırılması hedeflendi. Bu amaçla östrojen düzeyinin düstüğü fizyolojik menopoz (yaslılık) ve hem östrojen hem de testosteron düzeyinin azaldığı cerrahi menopoz (ooferektomi) grupları kontrol gruplarıyla karsılastırıldı. Çalısmaya, 18’i genç eriskin (7-9 aylık), 6’sı yaslı (18 ay ve üzeri) olmak üzere 24 adet eriskin disi Wistar albino sıçan dahil edildi. Sıçanlar dört gruba ayrıldı. Bunlar; 1. Kontrol grubu (7-9 ay), 2. Kontrol cerrahi (sham) grubu, 3. Cerrahi menapoz (bilateral ooferektomi) grubu ve 4. Đleri yas (18 ay ve üzeri) grubu, olarak belirlendi. Cerrahi menopoz grubundaki sıçanlara bilateral ooferektomi yapılırken, kontrol cerrahi grubunda ise overler gözlendi ancak herhangi bir girisim yapılmaksızın batın tekrar kapatıldı. Cerrahi menopoz ve sham gruplarının 4 haftalık takibinden sonra tüm sıçanlar sakrifiye edildi. Vajen ve mesane dokularından izole edilen düz kas preparatlarında, Rho-kinaz antagonisti Y-27632 ve çesitli farmakolojik ajanların etkileri izole organ banyosu sisteminde incelendi. Vajen seritlerine, mesane seritlerinden farklı olarak elektriksel alan uyarımı uygulanarak sinirsel aracılı uyarımının fizyolojik yanıtları arastırıldı. Prekontrakte vajen ve mesane düz kaslarında Y-27632 ile konsantrasyon-bağımlı gevseme yanıtları gözlendi. Her iki dokuda da genç, sham ve yaslı gruplar arasında gevseme yanıtlarında anlamlı fark görülmezken, cerrahi menopoz grubu ile genç grubu arasında yüksek konsantrasyonlarda daha belirgin olmak üzere anlamlı fark gözlendi. Sempatik, parasempatik ve nitrerjik yolakların blokajı sonrası Y-27632 ile olusturulan gevseme yanıtları genç, sham ve yaslı gruplarda vajende bir miktar artarken mesanede azaldı. Her iki dokuda ooferektomi grubunda değisiklik gözlenmedi. Vajen dokusunda elektriksel alan uyarımı(EAU) yanıtlarını trifazik olarak gözlemlendi. Öncesinde gevseme, ardından bir kasılma ve “off” yanıtı gözlendi. Vajen dokusunda EAU genç grupta yaslı ve cerrahi menopoz gruplarına göre daha fazla gevseme olusturdu. Fakat tüm gruplarda benzer kasılma yanıtlarına neden oldu. Bu bulgular vajen ve mesane dokusunda Ca2+’dan bağımsız kasılmaya yol açan Rho-kinaz aktivitesinin varlığını düsündürmektedir. Bu çalısmada elde edilen ve Rho-kinaz aktivitesinin fizyolojik menepoz durumunda değismediğini, oysa cerrahi menopoz durumunda arttığını isaret eden bulgular, testosteronun Rho-kinaz üzerinde baskılayıcı yönde tonik bir etkisinin olabileceğini düsündürdü. Seks steroidlerinin yanı sıra mesanede nitrik oksit (NO) düzeyinin azalması da Rho-kinaz aktivitesinin artısına yol açarken, vajende NO Rho-kinaz yolakları arasında böyle bir etkilesim görülmemistir. Bu çalısmadan elde edilen bulguların ileri deneysel ve klinik çalısmalarda desteklenmesi halinde spesifik Rho-kinaz inhibitörü Y-27632 kullanılarak veya testosteron düzeyi düsük hastalarda testosteron replasmanı yapılıp, Rho-kinaz aktivitesi azaltılarak, iritatif üriner semptomlarda ve cinsel disfonksiyonda düzelme olabileceği söylenebilir. Irritative urinary complaints and female sexual dysfunction are the most common genitourinary problems in the postmenopausal period. Physiological changes in the bladder and vaginal smooth muscles which occur due to alterations in the levels of sex steroids are very important causative factors for these complaints. In recent years, beside the calciumdependent pathway, a calcium-independent pathway named as “Rho-kinase pathway”- gained importance in smooth muscle contraction. In this study, the aim was to investigate the physiological effect of Rho-kinase pathway in isolated bladder and vaginal smooth muscles of rat and to show the relationship between this pathway and alterations of the the levels of sex-steroids. For this purpose, physiological menopause (elderly) group in which estrogen levels decrease and surgical menopause (ooferectomy) groups in which both estrogen and testosterone levels decrease are compared with control groups. In this study 24 adult female Wistar albino rats were involved. Eighteen of them were young adults (7-9 months of age) and 6 of them were elderly (18 months of age and older). Rats were divided into four groups; as: 1. Control group (7-9 months), 2. Control surgery (sham) groups, 3. Surgical menopause (bilateral ooferectomy), 4. Advanced age group (18 months and older). Bilateral ooferectomy was performed to surgical menopause group and only ovaries were exposed without any intervention and then abdomen was closed in the control surgery group. All rats were sacrificed after a follow-up of 4 weeks in the sham and surgical menopause groups. The effects of Y-27632 which is a Rho-kinase antagonist and other pharmacological agents on smooth muscle slides isolated from vagina and bladder tissues were investigated in isolated organ bath. Physiological responses of neuronal mediated stimulation were also studies by electrical field stimulation application in vaginal bands, but not in bladder bands. Concentration-dependent relaxation responses to Y-27632 was observed in pre-contracted vaginal and bladder smooth muscles. There was statistically no significant difference in relaxation responses between young, sham and elderly groups in both tissues; where as, the difference was significant between surgical menopause and young groups, more prominent in higher concentrations. After the blockage of sympathetic, parasympathetic and nitrergic pathways, relaxation responses induced by Y-27632 while increasing in vagina a bit, decreased in bladder in young, sham and elderly groups. There was no difference in ooferectomy group in both tissues. We observed the electrical field stimulation (EFS) responses in vaginal tissue as triphasic. Relaxation at the beginning, followed by a contraction and an “off response” were observed. In vaginal tissue, EFS produced more relaxation in young group compared to elderly and surgical menopause groups. But it caused similar contraction responses in all groups. These findings give rise to the thought of presence of Rho-kinase activity, causing Ca2+- independent contraction in vaginal and bladder tissues. The results of this study implying that Rho-kinase activity does not change in physiological menopause, where as increases in surgical menopause pointed a suppressive tonic effect of testosterone on Rho-kinase. Beside sex steroids, decrease in nitric-oxide (NO) levels improved Rho-kinase activity in bladder, but such an interaction couldn’t be determined between NO and Rho-kinase pathways in vagina. If the findings of this study are supported by further experimental and clinical studies, improvement in irritative urinary symptoms and sexual dysfunction could be achieved by using the specific Rho-kinase inhibitor Y-27632 or by testosterone replacement in patients with low testosterone levels.