Person: GÜLHAN, REZZAN
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GÜLHAN
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REZZAN
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Publication Open Access The effects of partial bilateral lesioning of substantia nigra in a genetic absence epilepsy rat model(2002-04-01) GÜLHAN, REZZAN; ONAT, FİLİZ; GÖREN, MEHMET ZAFER; GÖREN M. Z., GÜLHAN R., ONAT F., Ergün A.Objective: \"Genetic Absence Epilepsy Rats from Strasbourg\" (GAERS), an inbred Wistar strain, serve as an experimental venue. These rats generate spontaneous spike-and-wave discharges (SWD) and have increased γ-aminobutyric acid (GABA) levels in the ventrolateral thalamus (VLT). Recently, substantia nigra pars reticulata (SNpr) was reported to act as an endogeneous inhibitory mechanism in the generation, onset and maintenance of various types of seizures. The presence of tonic control exerted by SNpr in absence seizures should also be tested in GAERS. Methods: In this current study, GABA and L-glutamic acid release in VLT of GAERS with partial bilateral electrolytic lesions of SNpr was evaluated by using microdialysis technique with fluorescent detection. Results: GABA levels in VLT were 0.12±0.04 μM and 0.24±0.08 μM in sham-lesioned and SNpr-lesioned GAERS, respectively. L-glutamic acid level was found to be 0.41 5±0.150 μM in sham-lesioned group and 0.324±0.094 μM in SNpr-lesioned GAERS. Statistical analysis revealed no significant difference between sham-lesioned and SNpr-lesioned rats. The number and the duration of SWD were also similar in two groups. Conclusion: These findings show that SNpr does not exert a tonic control in GAERS and we assume that intact SNpr acts as a site that may exert an inhibition on target structures when activated in GAERS.Publication Metadata only Sıçanlarda parkinson hastalığına bağlı oluşan bellek disfonksiyonuna farklı egzersiz uygulamalarının etkileri(2022-05-12) KOYUNCUOĞLU, TÜRKAN; ÖZKAN YENAL, NAZİYE; KASIMAY ÇAKIR, ÖZGÜR; GÜLHAN, REZZAN; YÜKSEL, MERAL; Koyuncuoğlu T., Erol G., Çulpan Y., Gülhan R., Yüksel M., Özkan Yenal N., Kasımay Çakır Ö.Giriş: Parkinson hastalığı (PH) Alzheimer hastalığından sonra en yaygın görülennörodejeneratif hastalıktır.1 PH’da motor semptomların yanı sıra bellek disfonksiyonugörülmektedir. Yüksek anksiyete seviyeleri bellek fonksiyonlarını olumsuz etkilemektedir.2Amaç: İstemli tekerlek çevirme egzersizi, direnç egzersizi ve kombine egzersizuygulamalarının anksiyete düzeyleri ile bellek üzerindeki etkilerinin araştırılması ve alttayatan mekanizmaların ortaya konulması amaçlanmıştır.Yöntem: Çalışmada Wistar Albino erkek sıçanlarda (n=50) taklit cerrahi ve Parkinsongrupları oluşturulduktan sonra sedanter ve 3 farklı egzersiz protokolünün uygulandığı istemli(İE), rezistans (RE) ve kombine (KE: İE+RE) grupları oluşturuldu. Egzersizler 6 haftaboyunca (3 gün/hafta) uygulandı. PH modeli oluşturmak için sıçanlarda sağ mediyal önbeyine 6-OHDA (0.5 μl/dk) enjeksiyonu yapıldı. Taklit cerrahili gruplara 6-OHDA’nınçözücüsü verildi. Apomorfin uygulamaları sonrası rotasyon hareketi ile Parkinson modelideğerlendirildi. Obje tanıma testi ve delikli levha testleri sıçanlarda bellek fonksiyonlarını veanksiyete düzeylerini değerlendirmek için yaptırıldı. Beyin dokusunda antioksidan glutatyon(GSH) ve lipid peroksidasyonu belirteci malondialdehit (MDA) ve nötrofil infiltrasyonugöstergeci miyeloperoksidaz (MPO) aktivitesi, oksidan radikallerin belirteci luminol velusigenin ölçüldü. Verilerin analizinde tek yönlü ANOVA ardından Tukey-Kramer testi ilestudent’s t testi kullanıldı. Bulgular: Her 3 egzersiz ile Parkinsona bağlı gerileyen bellek fonksiyonu düzelmiştir(p<0.05-0.01). Sedantere kıyasla PH oluşturulmuş KE grubunda rotasyon hareketi azalırken,İE grubunda arttı (p<0.05-0.01). PH oluşturulmasıyla luminol ve lusigenin düzeyleri artarken,İE ile luminol azalmıştır (p<0.05-0.001). MPO aktivitesinin PH oluşturulmasıyla sedantergrubunda yükseldiği, ancak İE ve RE gruplarında baskılandığı gözlenmiştir (p<0.01-0.001).Her 3 egzersiz ile GSH düzeylerinin arttığı (p<0.05-0.01), KE ile MDA düzeylerinin düştüğübulundu (p<0.05). PH oluşturulmasıyla sedanter grupta azalmış bulunan bakılan delik sayısıve şahlanma sayısı (p<0.01-0.001), RE ve KE gruplarında artmıştır (p<0.05-0.01). Sedanterve İE gruplarında artan donma süresi, KE ile azalmıştır (p<0.05-0.001).Tartışma ve Sonuç: KE lipid peroksidasyonunu baskılamış, İE ve RE nötrofilinfiltrasyonunu azaltmıştır. RE ve KE anksiyeteyi hafifletmiştir. PH’da oluşan bellekdisfonksiyonunda farklı egzersiz uygulamalarının koruyucu etki gösterdikleri ortayakonmuştur.Anahtar Sözcükler: Egzersiz, Parkinson, Anksiyete, Bellek, AntioksidanPublication Metadata only Wistar ve genetik absans epilepsili (GAERS) sıçanlarda dendrit morfolojisinin incelenmesi(2021-11-21) YAZI, SEVDENUR; ŞEHİRLİ, ÜMİT SÜLEYMAN; GÜLHAN, REZZAN; KİRAZLI, ÖZLEM; Yazı S., Şehirli Ü. S., Gülhan R., Onat F., Kirazlı Ö.Publication Open Access Alterations in the kinetic activity of aromatlc-L-amino acid decarboxylase and preliminary 2-DE investigation of the brains in a 6-OHDA induced Parkinson's disease rat model(2003-07-01) OGAN, AYŞE; ONAT, FİLİZ; GÜLHAN, REZZAN; Günel A., OGAN A., ONAT F., GÜLHAN R.Objective: The aim of this study was to isolate and purify the aromatic-L-amino acid decarboxylase (AADC,EC 4.1.1.28) enzyme rats from Parkinson\"s Disease (PD) induced and the healthy control group rat brains and compare the alterations in the kinetic activities of the isolated enzyme. The protein spots displaying on the 2-DE patterns of the diseased and the healthy control group crude rat brain homogenates were evaluated. Medhods: In this study, the Parkinson\"s Disease model was induced by injecting 6-hydroxydopamine into the brains of the rats. The PD model formation was successful in two rats out of three. Results: The AADC decarboxylase was isolated and partially purified by DEAE-Sephacel ion exchange chromatography from the brains of PD induced and healthy control animals to compare the kinetic activity of the enzyme. The kinetic activity of the enzyme was reduced 70% in the PD group compared to controls. In order to determine and correlate the alterations with PD, and the distribution of the proteins displayed by the crude brain homogenates of the diseased and the healthy control group both were investigated. Polyacrylamide gel electrophoresis (PAGE) of the crude brain homogenates under the native and denaturizing conditions displayed matching bands for both of the groups, while two dimensional electrophoresis (2-DE) patterns of the crude brain homogenates of the diseased and the control group displayed considerable differences. Conclusion: The results of this study confirm the power of 2-DE-PAGE technique of the proteome analysis. Currently only the proteome analysis enables the identification of disease correlated proteins.Publication Open Access Plasma concentration-time profile of a single dose of enteric-coated omeprazole in male and female healthy volunteers(2000-01-01) GÖREN, MEHMET ZAFER; AKIN, ŞEHNAZ; GÜLHAN, REZZAN; ONAT, FİLİZ; Iskender E., ASLAN N., GÖREN M. Z., Tellioglu T., Akin S., Erin N., GÜLHAN R., ONAT F., Berkman K., Oktay S.O b je c tiv e : T h e b io a vaila b ility of a single dose (20 m g) o f tw o e n te ric -c o a te d o m e p ra z o le fo rm u la tio n s, m arketed in T urkey, given 10-15 m in b e fo re b reakfast, w as studied in 12 healthy vo lu n te e rs (6 m ales and 6 fem ales) in a d o u b le blind, cro s s o v e r design. M e th o d s : B lood sam ples w ere collected prior to and at 10 tim e points w ithin 12 hrs. after dosing. P la s m a o m e p ra z o le c o n c e n tra tio n s w e re m easured by H P LC te ch n iq u e in our laboratory. R e s u lts a n d C o n c lu s io n s : T he tw o products w ere found to be b io e q u iva le n t in term s of extent of a b s o rp tio n (th e a re a u n d e r the p la s m a c o n c e n tra tio n -tim e cu rve s). M u ltip e a k p la sm a co n ce n tra tio n pro file s w e re seen in m ost of the su b je cts w ith both products. T im e to the e a rlie r peaks w as 1-2 hrs. and those peaks w ere low er in a m p litu d e th a n th e p e a ks re a ch e d a p p ro x im a te ly 4 .5 hrs. a fte r the a p p lica tio n . In te re stin g ly, the m u ltip e a k profile w as m ore fre q u e n t and the e a rlie r peaks w ere sig nificantly higher in fe m a le su b je cts than in m ales. The reason fo r th is g e n d e r d iffe re n ce in m ultipeak p la s m a c o n c e n tra tio n - tim e p ro file of oral o m e p ra zo le needs fu rth e r investigation.Publication Metadata only Pentilentetrazol ile oluşturulan deneysel epilepsi modelinde farklı egzersiz tiplerinin kognitif fonksiyona etkileri(2022-05-12) KOYUNCUOĞLU, TÜRKAN; ÖZKAN YENAL, NAZİYE; KASIMAY ÇAKIR, ÖZGÜR; GÜLHAN, REZZAN; Erol G., Koyuncuoğlu T., Çulpan Y., Gülhan R., Yüksel M., Özkan Yenal N., Kasımay Çakır Ö.Giriş: Epilepsi, nöbetlerle seyreden bozukluktur. Egzersizin beyin sağlığına olumlu etkileribilinmekteyken, farklı egzersiz tiplerinin nöroprotektif etkileri merak konusudur.Amaç: Çalışmada pentilentetrazol (PTZ) ile oluşturulan kindling epilepsi modelinde; farklıegzersiz türlerinin kognitif fonksiyon üzerine etkileri ve altta yatan mekanizmalarınaraştırılması amaçlanmıştır.Yöntem: Erkek Wistar-Albino sıçanlar (n=48) kontrol ve epilepsi olarak iki ana gruba veardından sedanter, istemli egzersiz (İE: günlük ritim ölçer tekerleği), rezistans egzersiz (RE:ağırlıklı merdiven çıkma) ve kombine egzersiz (KE: tekerlek+ağırlıklı merdiven çıkma)olmak üzere alt gruplara ayrıldı. Egzersiz gruplarına 6 hafta boyunca haftada 3 gün egzersizyaptırılırken, sedanter gruplar kafeslerinde tutuldular. PTZ’nin (30 mg/kg; intraperitoneal)kronik enjeksiyonu ile deneysel kindling epilepsi modeli oluşturuldu. Epileptik nöbetlerindeğerlendirilmesinde Racine’nin skorlaması kullanıldı. Kognisyonu değerlendirmek için objetanıma testi, anksiyete düzeylerini değerlendirmek için delikli levha ve artı labirent testlerikullanıldı. Beyin dokularında biyokimyasal ve histolojik değerlendirmeler yapıldı.Bulgular: Epileptik nöbetlerde İE’e kıyasla RE ile grade 3’e ulaşmak için gereken toplamenjeksiyon sayısı azalmıştır (p<0.05). Epilepsi ile artan lusigenin ve luminol düzeylerini (p<0.001), egzersiz uygulamaları baskılamıştır (p<0.05-p< 0.001). Epilepsi oluşturulmasıylahipokampusta nöron hücrelerinde büzülmeler ve piknotik nükleuslar ile karakterize belirgindejenerasyonlar görülmüş, İE ise CA3 bölgesinde bu nöron dejenerasyonu baskılamıştır.Epilepsi oluşturulmasıyla artan MPO aktivitesini İE ve RE baskılamıştır (p<0.01-0.001).MDA düzeyleri epileptik hayvanlarda kontrole göre artmış (p<0.05-0.001), RE ile azalmıştır(p<0.05). Kognitif fonksiyon epilepsi ile azalmış, RE ve KE gruplarında artmıştır (p<0.05-0.01). Kontrole kıyasla epileptik hayvanlarda artan anksiyete düzeyini İE ve KE uygulamaları nöbetleriyle artan inflamatuvar süreç İE ve RE ile baskılanmıştır. Tüm egzersiz uygulamalarıoksidan hasar radikallerini azaltmış ve antioksidan kapasiteyi arttırmıştır. Sonuçlarımız farklıegzersiz tiplerinin epilepsi oluşturulmuş sıçanlarda bozulan kognitif fonksiyonu inflamatuvarve oksidan süreci baskılayarak, anksiyete düzeylerini hafifleterek iyileştirdiğinidüşündürmektedir.Anahtar Sözcükler: Epilepsi, İstemli, Rezistans, Egzersiz, KognisyonPublication Open Access Duration of ciprofloxacin use is important in the development of abdominal aortic aneurysm in a rat model(2022-11-01) ÖZYILMAZ YAY, NAGEHAN; ERGELEN, RABİA; AKAKIN, DİLEK; GÜLHAN, REZZAN; Çulpan Y., Keçeci İ., Sandıkçı İ., Gökçe Ş., Göker H., ÖZYILMAZ YAY N., ERGELEN R., AKAKIN D., GÜLHAN R.BACKGROUND: Recent findings suggest that fluoroquinolones, most prescribed antibiotic to treat various infections, have increased abdominal aortic aneurysm formation. We aimed to investigate the relation of the development of abdominal aortic aneurysm and the duration of ciprofloxacin use. METHODS: Male Sprague-Dawley rats were divided into 2 groups to administer saline to the control groups and CaCl2 to the aneurysm groups. These groups were then divided into 3 subgroups: intraperitoneal saline, ciprofloxacin for 2 weeks, and ciprofloxacin for 4 weeks. At the end of 4 weeks, the diameter of abdominal aorta was determined by ultrasonography and animals were sacrificed to obtain abdominal aorta specimens. Elastic fiber fracture, tunica media layer thickness, and aortic tissue damage were evaluated histologically. RESULTS: Aortic diameter of control-saline (2.15 mm ± 0.06), control-2 weeks (2.25 mm ± 0.06), and control-4 weeks (3.31 mm ± 0.09) ciprofloxacin groups was significantly different (P .05). CONCLUSION: The study showed that ciprofloxacin caused injury in the aortic wall but not a significant change in the thickness of the aortic tunica media layer. The duration of ciprofloxacin use was important in the development of aneurysm and aneurysm severity.Publication Open Access Counterfeit products containing medical active ingredients İlaç etkin maddesi İçeren sahte ürünler(2013-01-01) GÜLHAN, REZZAN; Küçükibrahimoǧlu E. E., Durmaz Z. A., Berber N., Ersoy C., Ince H., Kaymakçioǧlu B., Aşirdizer M., GÜLHAN R.Objective: Counterfeit and illegal drug trafficking is a worldwide problem. The most important substances of this trade include phosphodiesterase 5 enzyme inhibitors (PD5EI) which are used for the treatment of penil erection dysfunction, and weight loss products. These products are generally manufactured at clandestine laboratories and marketed under inappropriate conditions. The aim of this study was to examine these types of products, which have been seized by the judicial authorities in Turkey and to draw attention on the subject. Material and Methods: Products, non-alcoholic beverages and pharmaceutical compounds in the form of capsule, tablet or cream containing unlabeled sibutramine, PD5EI, and also products which were sold with these compounds seized by legal authorities and sent to the Council of Forensic Medicine for analysis between July-December 2011 were examined in this study. Results: The analysis of seized products revealed that 9 (69.2%) pharmaceutical compounds contained sildenafil, 3 (23.1%) contained local anesthetics, 1 (7.7%) contained sibutramine and beverages contained thiosildenafil. All of the products were counterfeit and they did not have a licence of production from legal authorities in Turkey or other countries, or import permission on their packages. Conclusion: Especially, PD5Is or weight loss products containing sibutramine which are widely marketed all over the world are also sold by illegal ways in our country, and because of inappropriate manufacturing and transport conditions, they cause a serious threat to public health. © 2013 by Türkiye Klinikleri.Publication Open Access Fabrication of ethosuximide loaded alginate/polyethylene oxide scaffolds for epilepsy research using 3D-printing method(2023-01-01) ULAĞ, SONGÜL; GÜLHAN, REZZAN; US, ZEYNEP; GÜNDÜZ, OĞUZHAN; Karabulut H., Dutta A., Moukbil Y., Cisen Akyol A., ULAĞ S., Aydin B., GÜLHAN R., US Z., Kalaskar D. M., GÜNDÜZ O.Epilepsy is a medical condition that causes seizures and impairs the mental and physical activities of patients. Unfortunately, over one-third of patients do not receive adequate relief from oral Antiepileptic Drugs (AEDs) and continue to experience seizures. In addition to that, long term usage of Antiepileptic Drugs can cause a range of side effects. To overcome this problem, the precision of 3D printing technology is combined with the controlled release capabilities of biodegradable polymers, allowing for tailored and localized AED delivery to specific seizure sites. As a result of this novel technique, therapeutic outcomes can be enhanced, side effects of AEDs are minimized, and patient-specific dosage forms can be created. This study focused on the use of ethosuximide, an antiepileptic drug, at different concentrations (10, 13, and 15 mg) loaded into 3D-printed sodium alginate and polyethylene oxide scaffolds. The scaffolds contained varying concentrations (0.25%, 0.50%, and 0.75% w/v) and had varying pores created by 3D patterning sizes from 159.86 ± 19.9 µm to 240.29 ± 10.7 µm to optimize the releasing system for an intracranial administration. The addition of PEO changed the Tg and Tm temperatures from 65°C to 69°C and from 262°C to 267°C, respectively. Cytotoxicity assays using the human neuroblastoma cell line (SH-SY5Y) showed that cell metabolic activity reached 130% after 168 h, allowing the cells to develop into mature neural cells. In vitro testing demonstrated sustained ethosuximide release lasting 2 hours despite crosslinking with 3% CaCl2. The workpaves the way for the use of ethosuximide -loaded scaffolds for treating epilepsy.Publication Open Access Effect of methylglyoxal on Parkinson’s disease pathophysiology in the rotenone model(2024-05-31) YILMAZ, BETÜL; GÜLHAN, REZZAN; Culpan Y., Ozden L., Gozderesi Y., Kocak B., Baltaci Z. H., Denizli A., Karademir Yilmaz B., GÜLHAN R.Objective: Type 2 diabetes mellitus patients have been reported to have a higher incidence of Parkinson’s disease. This study aimed to explore the effect of advanced glycation end products precursor methylglyoxal (MGO) on the pathophysiology of Parkinson’s disease in a rotenone model. Materials and Methods: Adult female Wistar rats (n=42) were divided into four groups. Rotenone toxicity was assessed by daily weight measurements and mortality rates. Effect of MGO on blood glucose was evaluated. Locomotor activity, rearing, and rotarod tests were performed to evaluate motor functions, and for neurodegeneration, tyrosine hydroxylase immunoreactivity in the striatum and substantia nigra regions was assessed. Results: The mortality rate was 9% in the rotenone-applied rats. The mean weight, locomotor activity, rearing activity, and longest time spent on a rotarod were lower in the MGO+Rotenone group than in the Control group. Tyrosine hydroxylase immunoreactivity in the striatum rostral to the anterior commissure in the MGO+Rotenone group was lower than that in the Control and MGO groups. The number of tyrosine hydroxylase positive cells in the substantia nigra pars compacta was comparable among the groups. Conclusion: When nigrostriatal degeneration was triggered, MGO was found to worsen motor dysfunction and increase damage to dopaminergic neuron projections.