Person: GÜLHAN, REZZAN
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GÜLHAN
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REZZAN
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Publication Metadata only The relationship between age-related development of spike-and-wave discharges and the resistance to amygdaloid kindling in rats with genetic absence epilepsy(ACADEMIC PRESS INC ELSEVIER SCIENCE, 2008) ONAT, FİLİZ; Carcak, Nihan; Aker, Rezzan Guelhan; Oezdemir, Osman; Demiralp, Tamer; Onat, Filiz YilmazGenetic Absence Epilepsy Rats from Strasbourg (GAERS) are resistant to amygdaloid kindling. Since in GAERS the characteristics of spike-and-wave discharges (SWDs) change with age, we have studied the relation between SWD maturation and the development of kindling resistance. Non-epileptic Wistar rats and GAERS were stimulated in basolateral amygdala with 400 mu A at 20 min intervals until they reached stage 5 seizures or for a maximum of 36 stimulations. All of the Wistar rats, the postnatal (PN) day 20 GAERS and the (kindling-prone) subgroups of GAERS at PN30 and PN60 reached stage 5 seizures; at PN20, PN30 and PN60 kindling rates were significantly slower in GAERS compared to Wistar rats. At PN30 and PN60, 41% and 69% of GAERS, respectively, showed no stage 3, 4 or 5 seizures after 36 stimulations (kindling-resistant subgroups). The SWD maturation involves changes in spectral patterns and correlate with age-related increases in kindling resistance in GAERS. (C) 2008 Elsevier Inc. All rights reserved.Publication Metadata only Plasma lamotrigine levels of patients with polymorphic UGT1A4 enzymes(2010-06-27) GÜLÇEBİ İDRİZ OĞLU, MEDİNE; GÖREN, MEHMET ZAFER; GÜLHAN, REZZAN; ONAT, FİLİZ; GÜLÇEBİ İDRİZ OĞLU M., ÖZKAYNAKÇI A., GÖREN M. Z. , ÖZKARA Ç., GÜLHAN R., ONAT F.Publication Metadata only The relationship between UGT1A4 polymorphism and serum concentration of lamotrigine in patients with epilepsy(ELSEVIER, 2011) ONAT, FİLİZ; Gulcebi, Medine Idrizoglu; Ozkaynakci, Aydan; Goren, Mehmet Zafer; Aker, Rezzan Gulhan; Ozkara, Cigdem; Onat, Filiz YilmazLamotrigine (LTG) which has a widespread use in epilepsy treatment as an antiepileptic agent is metabolized by UDP-glucuronosyl transferase (UGT) enzymes. In this study, single nucleotide polymorphisms, P24T and L48V, of the UGT1A4 enzyme have been investigated in a Turkish population of patients with epilepsy (n=131) by comparing serum levels of LTG of wild type and polymorphic subjects. High performance liquid chromatography (HPLC) was used to measure serum concentrations of LTG. The P24T and L48V polymorphisms of the UGT1A4 enzyme were analyzed with a matrix assisted laser desorption-time of flight (MALDI-TOF) mass spectrometry method. The frequencies of the heterozygous alleles for L48V or P24T polymorphisms were 22.4% and 3.8%, respectively. L48V polymorphism was found to decrease the serum concentration of LTG in patients on monotherapy or polytherapy. The LTG levels of non smoking monotherapy patients were 52% lower for the L48V polymorphism than for wild type alleles. Also the LTG levels were significantly lower for non smoking or smoking polymorphic alleles than for normal. The high frequency of the L48V polymorphism detected in the Turkish population indicates that LTG dose adjustments in patients with the UGT1A4 L48V polymorphic enzyme should be taken into account. (c) 2011 Elsevier B.V. All rights reserved.Publication Metadata only The neuroprotective effect of regular swimming exercise programme on the dopaminergic neurons localized in the striatum of Parkinsonian rat models(2016-09-05) BORACI, HATİCE; KİRAZLI, ÖZLEM; GÜLHAN, REZZAN; YILDIZ, SERCAN DOĞUKAN; ŞEHİRLİ, ÜMİT SÜLEYMAN; BORACI H., KİRAZLI Ö., GÜLHAN R., YILDIZ S. D., ŞEHİRLİ Ü. S.Publication Metadata only Cardiovascular regulation through hypothalamic GABA(A) receptors in a genetic absence epilepsy model in rat(BLACKWELL PUBLISHING INC, 2002) ONAT, FİLİZ; Aker, RG; Onat, FYPurpose: gamma-Aminobutyric acid (GABA) plays a vital role in both central cardiovascular homeostasis and pathogenesis of epilepsy. Epilepsy affects autonomic nervous system functions. In this study, we aimed to clarify the role of GABA(A) receptors in hypothalamic cardiovascular regulation in a genetically determined animal model of absence epilepsy. Methods: Nonepileptic Wistar rats and genetic absence epilepsy rats from Strasbourg (GAERS) were instrumented with a guide cannula for drug injection and extradural electrodes for EEG recording. After a recovery period, iliac arterial catheters were inserted for direct measurement of mean arterial pressure and heart rate. Bicuculline, a GABA(A)-receptor antagonist, was injected into the dorsomedial (DMH) or posterior (PH) hypothalamic nuclei of nonepileptic control rats or GAERS. Blood pressure, heart rate, and EEG recordings were performed in conscious unrestrained animals. Results: Bicuculline injections into the hypothalamus produced increases in blood pressure and heart rate of both control rats and GAERS. The DMH group of GAERS showed a twofold increase in the blood pressure and the heart rate compared with those of control rats. Pressor responses to bicuculline, when microinjected into the PH, were similar in the nonepileptic animals and GAERS. Conversely, the amplitude of tachycardic responses to the administration of bicuculline into the PH was significantly higher in GAERS compared with those of control rats. Conclusions: The bicuculline-induced increases in blood pressure and heart rate were more prominent when given in the DMH of GAERS. These results indicate an increased GABA(A) receptor-mediated cardiovascular response through the DMH in conscious rats with absence epilepsy.Publication Metadata only Cerebellar connections to the dorsomedial and posterior nuclei of the hypothalamus in the rat(WILEY, 2001) ONAT, FİLİZ; Cavdar, S; San, T; Aker, R; Sehirli, U; Onat, FThe stimulation or ablation of cerebellar structures has produced a variety of visceral responses, indicating a cerebellar role in visceral functions. Studies using anterograde and retrograde tracing methods have revealed connections between the hypothalamus and cerebellar structures. The aim of this study is to investigate the cerebellar connections of the dorsomedial (DMH) and posterior hypothalamic nuclei using retrograde axonal transport of horseradish peroxidase (HRP). In the present study, micro-injection of HRP restricted within the borders of the DMH showed that the projections of this nucleus are not uniform throughout its extent. The posterior DMH receives projections from the cerebellum whereas the anterior DMH does not. These projections were from the (greatest to least concentration) lateral (dentate), anterior interposed (emboliform), and medial (fastigial) cerebellar nuclei. In addition, both the anterior and posterior DMH receive projections from various areas of the brainstem which confirms earlier studies and provides detailed descriptions. This study also demonstrates the distribution of labelled neurons to cerebellar and brainstem nuclei following HRP injection into the posterior hypothalamic nucleus. It provides clear evidence for a direct cerebellar nuclei-posterior DMH and cerebellar nuclei-posterior hypothalamic nucleus connections. We suggest that the brainstem reticular nuclei and other connections, such as the solitary, trigeminal and vestibular nuclei, of both DMH and posterior hypothalamus may contribute to the indirect cerebellohypothalamic connections. These observations offer a new perspective on the question of how the cerebellum may influence autonomic activity.Publication Metadata only Extracellular concentrations of catecholamines and amino acids in the dorsomedial hypothalamus of kindled rats - A Microdialysis Study(KARGER, 2003) ONAT, FİLİZ; Goren, MZ; Aker, R; Yananli, HR; Onat, FYEpilepsy affects homeostasis and autonomic nervous system functions. It has been thought that the dysfunction in the autonomic neural mechanisms could be a cause of sudden unexpected death in patients with epilepsy. The kindling model of epilepsy is considered to be an animal model for complex partial seizures with secondary generalization. The objectives of this study were to investigate the extracellular gamma-aminobutyric acid (GABA), glutamate, noradrenaline and dopamine levels in the dorsomedial nucleus of the hypothalamus in nonepileptic and kindled epileptic rats and to explain some of the cardiovascular changes in the kindling model of epilepsy. Stimulation electrodes were stereotaxically implanted into the basolateral amygdala and electrical stimulation was applied 3 times a day at a constant current. The rats were then kindled to full stage 5 seizures. Microdialysis experiments were performed to demonstrate the neurotransmitter levels in the dorsomedial nucleus of the hypothalamus 3-5 days after being kindled. Decreases in noradrenaline and dopamine levels in the dorsomedial nucleus were detected in the conscious kindled animals. This finding is in agreement with prior findings that the noradrenergic system has a negative role in the process of kindling. The basal level of glutamic acid and GABA remained unchanged in the kindled group when compared to non-epileptic animals, and similarly, neither blood pressure nor heart rate responses to bicuculline or N-methyl-D-aspartate were affected by the acute kindled state. These findings suggest that the autonomic changes in kindling require further studies. Copyright (C) 2003 S. Karger AG, Basel.Publication Metadata only p353 Evalution of antiepileptic drug use in the pregnant patients with epilepsy in a university hospital in Istanbul(2014-07-03) GÜLÇEBİ İDRİZ OĞLU, MEDİNE; GÜLHAN, REZZAN; KARAALP, ATİLA; GÖREN, MEHMET ZAFER; ONAT, FİLİZ; GÜLÇEBİ İDRİZ OĞLU M., Küçükibrahimoğlu E., JAFAROVA DEMİRKAPU M., GÜLHAN R., KARAALP A., GÖREN M. Z., ONAT F.Publication Metadata only Frequency and type of synthetic cannabinoids analyzed in the council of forensic medicine istanbul narcotic department Turkey(2011-09-25) GÜLHAN, REZZAN; GÜRDAL F., KORKUT Ş., GÖÇER Y., KÜÇÜKİBRAHİMOĞLU E. E., GÜLHAN R., AŞIRDİZER M.Objectives: In recent years, synthetic cannabinoids are frequently observed in seized materials all over the world. These new generation designer drugs, also known as “Spice” or “Legal Highs,” can easily be obtained via the internet and are in sold mixed with herbal substances. In this study, we aimed to evaluate the type and detection frequency of synthetic cannabinoids sent to be analyzed in our laboratory over a 10-month period between August 2010 and April 2011. Materials and methods: Herbal materials sent by judicial authorities to The Council of Forensic Medicine-Istanbul Narcotic Department between August 2010 and April 2011, were analyzed in the study. All materials were analyzed by physical examination, thin layer chromatography and GC-MS (Agilent 6890GC/5973MS inert, with 30m HP-5MS column). Results: A total of 1171 herbal substances were analyzed during the 10-month investigation period and 1156 of them (98.7%) contained synthetic cannabinoids. We found both JWH-018 and JWH-081 in 760 (65.7%) samples out of 1156; JWH-018 alone in 382 (33%); CP47,497 (C8) in 5 (0.4%); both CP47,497 (C8) and JWH-018 in 7 (0.6%) samples; JWH-250 alone in 2 (0.2%) samples. Samples material had different package names such as “Bonzai Aromatic Potpori” (n=755), “Bonzai” (n=313), “Heaven” (n=14), “Aromatic Incense,” (n=6), “Yukatan Fire” (n=7), “Tribal Warrior Ultimate” (n=5), “Jamaican Gold” (n=43) and “Jamaican Sprit” (n=5). All Bonzai packages (n=313) contained JWH-018 while 2 samples contained JWH-250. JWH-018 along with JWH-081 was detected in “Bonzai Aromatic Potpori” (n=755) and in “Jamaican Spirit” (n=5). All “Yukatan Fire” packages contained JWH-018 with CP47,497 (C8). “Tribal Warrior Ultimate” packages had CP47,497(C8) (n=5). The rest of packages with different names had JWH-018. Conclusions: JWH-018 was the most frequent type of synthetic cannabinoids (detected in 98.7% of 1156 samples). “Bonzai” and “Bonzai Aromatic Potpori” were the most common product name amongst the herbal products sent to our laboratory (n=1068). Although some of these synthetic cannabinoid compounds are banned by law, there is not an “analogue or derivative” clause established in Turkey yet. The increase use of different derivatives, lack of analytical data and reference standards for analysis, lack of information on metabolism and metabolites for toxicological analysis in human subjects are important problems that need to be solved.Publication Metadata only GABA(A) receptor mediated transmission in the thalamic reticular nucleus of rats with genetic absence epilepsy shows regional differences: Functional implications(ELSEVIER SCIENCE BV, 2006) ONAT, FİLİZ; Aker, Rezzan Gulhan; Ozyurt, Hazan B.; Yananli, Hasan R.; Cakmak, Yusuf Ozgur; Ozkaynakci, Aydan E.; Sehirli, Umit; Saka, Erdinc; Cavdar, Safiye; Onat, Filiz YimazThe aim of the present study was to investigate the effect of local injections of the GABA(A) receptor antagonist, bicuculline, into the rostral and caudal parts of the thalamic reticular nucleus (TRN), on the generation of spike-and-wave discharges in Genetic Absence Epilepsy Rats from Strasbourg (GAERS). Spike-and-wave discharges are important in the pathophysiology of absence epilepsy and generated by the cortico-thalamo-cortical pathway, where GABA has a significant role, particularly in the TRN. Artificial cerebrospinal fluid or bicuculline was administered to rostral or caudal parts of TRN of GAERS through a stereotaxically placed guide cannula. Administration of bicuculline produced opposite effects according to the injection site. Administration into the caudal TRN produced statistically significant increases in the duration of spike-and-wave discharges, whereas injections into the rostral TRN produced significant decreases. Correspondingly, distinct patterns of afferent connections have been demonstrated with the wheat-germ-agglutinin horseradish peroxidase (WGA-HRP) retrograde tracing method in control non-epileptic rats and GAERS for the rostral and caudal parts of the TRN. Injection of WGA-HRP tracer showed no detectable difference regarding the rostral and caudal connections between GAERS and Wistar animals. Rostral parts of TRN have thalamic and cortical connections that are primarily motor and limbic whereas for the caudal parts these connections are primarily sensory. Further, the rostral parts receive inputs from the substantia nigra pars reticularis and the ventral pallidum that the caudal part lacks. The extent to which these connectional differences may be responsible for the functional differences demonstrated by the bicucculine injections remains to be explored. (c) 2006 Elsevier B.V. All rights reserved.