Person: GÜLÇEBİ İDRİZ OĞLU, MEDİNE
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GÜLÇEBİ İDRİZ OĞLU
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Publication Open Access The pathways connecting the hippocampal formation, the thalamic reuniens nucleus and the thalamic reticular nucleus in the rat(WILEY, 2008-03) ONAT, FİLİZ; Cavdar, Safiye; Onat, Filiz Y.; Cakmak, Yusuf Oezguer; Yananli, Hasan R.; Gulcebi, Medine; Aker, RezzanMost dorsal thalamic nuclei send axons to specific areas of the neocortex and to specific sectors of the thalamic reticular nucleus; the neocortex then sends reciprocal connections back to the same thalamic nucleus, directly as well indirectly through a relay in the thalamic reticular nucleus. This can be regarded as a 'canonical' circuit of the sensory thalamus. For the pathways that link the thalamus and the hippocampal formation, only a few comparable connections have been described. The reuniens nucleus of the thalamus sends some of its major cortical efferents to the hippocampal formation. The present study shows that cells of the hippocampal formation as well as cells in the reuniens nucleus are retrogradely labelled following injections of horseradish peroxidase or fluoro-gold into the rostral part of the thalamic reticular nucleus in the rat. Within the hippocampal formation, labelled neurons were localized in the subiculum, predominantly on the ipsilateral side, with fewer neurons labelled contralaterally. Labelled neurons were seen in the hippocampal formation and nucleus reuniens only after injections made in the rostral thalamic reticular nucleus (1.6-1.8 mm caudal to bregma). In addition, the present study confirmed the presence of afferent connections to the rostral thalamic reticular nucleus from cortical (cingulate, orbital and infralimbic, retrosplenial and frontal), midline thalamic (paraventricular, anteromedial, centromedial and mediodorsal thalamic nuclei) and brainstem structures (substantia nigra pars reticularis, ventral tegmental area, periaqueductal grey, superior vestibular and pontine reticular nuclei). These results demonstrate a potential for the thalamo-hippocampal circuitry to influence the functional roles of the thalamic reticular nucleus, and show that thalamo-hippocampal connections resemble the circuitry that links the sensory thalamus and neocortex.Publication Metadata only EFFECTS OF KINDLING STIMULATIONS ON TYROSINE HYDROXYLASE IMMUNOREACTIVITY IN SUBSTANTIA NIGRA PARS RETICULATA OF GAERS AND WISTAR RATS(2013-06-27) GÜLÇEBİ İDRİZ OĞLU, MEDİNE; KARAMAHMUTOĞLU, TUĞBA; ONAT, FİLİZ; GÜLÇEBİ İDRİZ OĞLU M., AKMAN Ö., ÇARÇAK YILMAZ N., KARAMAHMUTOĞLU T., ONAT F.Publication Metadata only Electroencephalographic and behavioral effects of intracerebroventricular injection of grayanotoxin in adult Wistar rats(2011-08-28) KARAMAHMUTOĞLU, TUĞBA; GÜLÇEBİ İDRİZ OĞLU, MEDİNE; ONAT, FİLİZ; HALAÇ H. M. , TEMİZ G., KURU P., TORUN M., İSKENDER E., KARAMAHMUTOĞLU T., GÜLÇEBİ İDRİZ OĞLU M., ONAT F.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 Potential drug-drug interactions in a medical intensive care unit of a university hospital(TUBITAK SCIENTIFIC & TECHNICAL RESEARCH COUNCIL TURKEY, 2016) KARAALP, ATİLA; Gulcebi Idriz Oglu, Medine; Kucukibrahimoglu, Esra; Karaalp, Atila; Sarikaya, Ozlem; Demirkapu, Mahluga; Onat, Filiz; Goren, Mehmet ZaferBackground/aim: Drug-drug interactions (DDIs) can impact patient safety. Occurrence of clinically important DDIs is higher for intensive care unit (ICU) patients. This observational study aimed to evaluate the potential DDIs in medical ICU patients of a university hospital. Materials and methods: The Medical Pharmacology Department organized consultation reports for ICU patients in order to detect the DDIs. To focus on clinically important DDIs, interactions in the C, D, or X risk rating categories of the Lexi-Interact online database were analyzed. Frequency and clinical risk rating categories of DDIs were detected. Relationship between number of prescriptions and DDIs were assessed. The most frequent drug/drug groups were identified. Results: Of 101 ICU patients, 45.5% were found to have DDIs. We detected 125 C (72.2%), 37 D (21.4%), and 11 X (6.4%) risk category interactions. A statistically significant increase in the number of DDIs was shown with the number of prescriptions (P = 0.002). The most frequent DDIs were between agents acting on the cardiovascular system and corticosteroids (12.8%). Conclusion: Results of this study show that pharmacological consultation plays a critical role in the recognition of DDIs for improvement of medication management and effective therapeutic endpoints without any adverse or toxic reactions.Publication Open Access The role of the substantia nigra pars reticulata in kindling resistance in rats with genetic absence epilepsy(WILEY, 2015-11) ONAT, FİLİZ; Akman, Ozlem; Gulcebi, Medine I.; Carcak, Nihan; Ozatman, Sema Ketenci; Eryigit, Tugba; Moshe, Solomon L.; Galanopoulou, Aristea S.; Onat, Filiz YilmazObjectiveGenetic Absence Epilepsy Rats from Strasbourg (GAERS) show a resistance to secondary generalization of focal limbic seizures evoked by kindling. The substantia nigra pars reticulata (SNR) is involved in the propagation and modulation of seizures in kindling. We first examined the role of the SNRanterior and SNRposterior subregions in the resistance to the development of kindling in GAERS. Subsequently, to determine whether kindling resistance relates to differential sensitivity of -aminobutyric acid -aminobutyric acid (GABA)ergic or dopaminergic SNR neurons to kindling, we studied the effects of kindling-inducing stimulations on parvalbumin (PRV; GABAergic neuron marker) or tyrosine hydroxylase (TH; dopaminergic neuron marker) immunoreactivity (ir), respectively, in GAERS and in nonepileptic control (NEC) Wistar rats that lack kindling resistance. MethodsAdult male GAERS were implanted with a stimulation electrode in the amygdala, and bilateral injection cannulas for lidocaine or saline injection (30 min before each kindling stimulation until the animals reached three stage 5 seizures or the 22 stimulations) into the SNRanterior or SNRposterior. In another experiment, PRV-ir in SNRanterior and SNRposterior and TH-ir in SNRposterior only were densitometrically compared in GAERS-SHAM, NEC-SHAM GAERS-STIM, and NEC-STIM animals (6 kindling stimulations). ResultsBilateral SNRposterior infusions of lidocaine eliminated the kindling resistance and resulted in stage 5 generalized motor seizures in all kindled rats. Bilateral lidocaine infusions in the SNRanterior failed to alter the kindling resistance in GAERS. PRV-ir in the SNRposterior was unaltered in GAERS-STIM but increased in NEC-STIM group. Cellular TH-ir in the SNRposterior significantly increased by kindling stimulations in both NEC-STIM and GAERS-STIM groups. SignificanceThe kindling resistance in GAERS is mediated by the SNRposterior in a lidocaine-sensitive manner. The insensitivity to kindling stimulation of PRV-ir in SNRposterior of GAERS but not NEC rats, implicate GABAergic SNRposterior neurons in kindling resistance. In contrast, the observed stimulation-specific increase in TH-ir in the SNRposterior is unrelated to kindling resistance.Publication Metadata only Topographical connections of the substantia nigra pars reticulata to higher-order thalamic nuclei in the rat(PERGAMON-ELSEVIER SCIENCE LTD, 2012) ONAT, FİLİZ; Gulcebi, Medine Idrizoglu; Ketenci, Sema; Linke, Rudiger; Hacioglu, Husniye; Yanali, Hasan; Veliskova, Jana; Moshe, Solomon L.; Onata, Filiz; Cavdar, SafiyeThe substantia nigra pars reticulata (SNR) is the ventral subdivision of the substantia nigra and contains mostly GABAergic neurons. The present study explores whether the SNR relates to all dorsal thalamic nuclei equally or just to a particular group of nuclei, such as first or higher-order nuclei. Injections of biotinylated dextran amine (BDA) were made into the SNR of 10 male adult rats. The distribution of anterogradely labelled axon terminals in the thalamic nuclei was documented. The projections of the SNR to the thalamic nuclei were exclusively to some motor higher-order, but not to first-order thalamic relays. There were bilateral projections to the ventromedial (VM), parafascicular (PF), centromedian (CM) and paracentral (PC) nuclei and unilateral projections to the centrolateral (CL), mediodorsal (MD) and thalamic reticular nucleus (Rt). Labelled axon terminals in the thalamic nuclei ranged from numerous to sparse in VM, PF, CM, CL, PC, MD and Rt. Further, injections into the SNR along its rostral-caudal axis showed specific topographical connections with the thalamic nuclei. The rostral SNR injections showed labelled axon terminals of VM, PF, CL, PC, CM, MD and Rt. Caudal SNR injections showed labelling of VM, PF, PC, CM and MD. All injections showed labelled axons and terminals in the zona incerta. The nigrothalamic GABAergic neurons can be regarded as an important system for the regulation of motor activities. The SNR is in a position to influence large areas of the neocortex by modulating some of the motor higher-order thalamic nuclei directly or indirectly via Rt. (C) 2011 Elsevier Inc. All rights reserved.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 Open Access The effect of serum levetiracetam concentrations on therapeutic response and IL1-beta concentration in patients with epilepsy(ELSEVIER SCIENCE BV, 2018-12) ONAT, FİLİZ; Gulcebi, Medine I.; Kendirli, Tansel; Turgan, Zehra Asik; Patsalos, Philip N.; Onat, Filiz YilmazObjective: Assessment of the relevance between serum drug concentration to its therapeutic response is a valid monitoring strategy for the clinical efficacy of antiepileptic drugs (AEDs). Levetiracetam (LEV) is a broad spectrum AED with a possible anti-inflammatory effect. We aimed to determine the relationship between LEV concentrations and its therapeutic response, and the effect of LEV on IL1-beta concentrations in patients with epilepsy. Methods: Patients on monotherapy (n = 7) or polytherapy (n = 15) with LEV for their seizures management were included. Blood samples of each patient were collected: just before LEV intake, 1 h, 2 h, 4 h and 8 h following the last dose. Serum LEV concentrations were measured by liquid chromatography mass spectrometry and IL1-beta concentrations by chemiluminescent immunometric assay. Concentration to dose (C/D) ratio values was used for analyses. LEV concentrations were compared between responders (<= 1 seizure/month) and non responders (> 1 seizure/month) and patients with or without adverse reactions. IL1-beta concentrations before and at 2 h following LEV ingestion were compared in order to detect the effect of the increase in serum LEV concentration on IL1-beta. Results: Although there was no change in LEV (C/D) ratio or LEV maximum concentration (Cmax)/D ratio of the responders and non-responders, the C/D ratio following 1 h of LEV intake (2.17 +/- 0.59 kg.day/L) and Cmax/D ratio (2.25 +/- 0.56 kg.day/L) in the patients with adverse effects was significantly higher than for the patients without adverse effects (1.09 +/- 0.12 kg.day/L and 1.49 +/- 0.14 kg.day/L respectively). A statistically significant decrease was found in the IL1-beta concentration to LEV (C/D) ratio with the increase in LEV concentration in patients on LEV monotherapy. Conclusion: The possible relationship between LEV Cmax and its therapeutic response or IL1-beta concentrations may be an importance indication of LEV antiepileptic efficacy. Consequently, monitoring LEV Cmax values may enhance LEV adherence because patients would be less likely to develop adverse effects.