Person: GÖREN, MEHMET ZAFER
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GÖREN
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MEHMET ZAFER
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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 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 The change in plasma GABA, glutamine and glutamate levels in fluoxetine- or S-citalopram-treated female patients with major depression(SPRINGER HEIDELBERG, 2009) GÖREN, MEHMET ZAFER; Kucukibrahimoglu, Esra; Saygin, Melek Z.; Caliskan, Mecit; Kaplan, Okan K.; Unsal, Cuneyt; Goren, M. ZaferObjective The aim of this study was to investigate the relationship between plasma glutamate, glutamine and gamma-aminobutyric acid (GABA) levels in female patients with major depression treated with S-citalopram or fluoxetine. Methods The patients were assigned into S-citalopram (10 mg/day) or fluoxetine (20 mg/day) groups (n= 15 per group). The Hamilton and Beck Depression Inventory Scales were performed on all study participants, and blood samples were collected. The same procedures were repeated 10 days following the onset of therapy. Fifteen female healthy volunteers were also included in the study for the evaluation of normal plasma levels. Results The plasma GABA levels of the healthy volunteers were higher whereas those for glutamate and glutamine were lower than the day zero samples of the patients. An increase in plasma GABA levels and a decrease in glutamate and glutamine levels were observed on the 10th day of treatment. No difference was detected between the drug treatments. Conclusion Our findings may suggest that GABA, glutamate and glutamine play a role in depression and that plasma GABA may be used as a biomarker for treatment control.Publication Metadata only Studies on Some 3-Oxo-5-benzylidene-6-methyl-(4H) -2-substitutedpyridazines with Antinociceptive and Antiinflammatory Activities(2003-03-01) GÖREN, MEHMET ZAFER; Balkan A., Özkanli F., ÜNSAL TAN O., GÖREN M. Z., TERZİOĞLU BEBİTOĞLU B.In this study, some new 3-oxo-5-benzylidene-6-methyl-(4H)-2-substituted pyridazine derivatives have been prepared by the reaction of 5-substituted benzylidene-6-methyl-(4H)-pyridazin-3-one with several substituted benzoyl-methyl bromides. The structures of the compounds have been elucidated by IR, 1H-NMR and elemental analysis. Antinociceptive (only for compound IIIa) and anti-inflammatory activity studies were evaluated by using in vivo tests. The anti-inflammatory activity was studied by means of the \"carrageenan paw edema\", whereas the \"acetic acid writhing\" test was used to assess the antinociceptive activity. Qualitatively, compound IIIa was shown to exert anti-inflammatory effect as potent as phenylbutazone and antinociceptive effect similar to acetylsalicylic acid.Publication Metadata only Prediction of cyclosporine A blood levels: an application of the adaptive-network-based fuzzy inference system (ANFIS) in assisting drug therapy(SPRINGER HEIDELBERG, 2008) ONAT, FİLİZ; Goeren, Sezer; Karahoca, Adem; Onat, Filiz Y.; Goeren, M. ZaferObjective Therapeutic drug monitoring (TDM) is a procedure in which the levels of drugs are assayed in various body fluids with the aim of individualizing the dose of critical drugs, such as cyclosporine A. Cyclosporine A assays are performed in blood. Methods We proposed the use of the Takagi and Sugeno-type adaptive-network-based fuzzy inference system (ANFIS) to predict the concentration of cyclosporine A in blood samples taken from renal transplantation patients. We implemented the ANFIS model using TDM data collected from 138 patients and 20 input parameters. Input parameters for the model consisted of concurrent use of drugs, blood levels, sampling time, age, gender, and dosing intervals. Results Fuzzy modeling produced eight rules. The developed ANFIS model exhibited a root mean square error (RMSE) of 0.045 with respect to the training data and an error of 0.057 with respect to the checking data in the MATLAB environment. Conclusions ANFIS can effectively assist physicians in choosing best therapeutic drug dose in the clinical setting.Publication Metadata only Muscarinic receptor-mediated nitric oxide release in a K562 erythroleukaemia cell line(2009) AYDIN OMAY, BANU; Cabadak H., Küçükibrahimoǧlu E., Aydin B., Kan B., Gören M.Z.1 In the present study we have investigated the expression of muscarinic receptors in K562 erythroleukaemic cells and the effects of muscarinic agonist and antagonists on extracellular citrulline levels in these cells, as a marker of nitric oxide (NO) generation. 2 Muscarinic acetylcholine receptors (M 1-M5) play key roles in regulating many diverse physiological processes. Recent studies suggest that muscarinic receptors mediate some cellular events in haematopoietic cells. Multiple subtypes of muscarinic receptors are expressed in different human cells. NO, a free radical and a signaling molecule, is involved in the regulation of many physiological functions and derived from certain nitric oxide synthases (NOS), which are related to muscarinic receptors. 3 In this study, the presence of M2, M3 and M4 subtypes in K562, an erythroleukaemic cell line, was demonstrated by using the reverse transcriptase-polymerase chain reaction. Moreover, the generation of NO induced by carbachol, a non-selective muscarinic agonist, was investigated by using high-performance liquid chromatography to measure changes in extracellular l-citrulline levels. 4 We found that carbachol enhanced l-citrulline production in K562 erythroleukaemic cells. The effect of carbachol on l-citrulline production was antagonized by atropine and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP), while tropicamide had little effect. These results suggest that the muscarinic receptor M 3 subtype may mediate NO signaling in K562 erythroleukaemic cells. © 2009 Blackwell Publishing Ltd.Publication Metadata only Synthesis and evaluation of the anticonvulsant activities of some 5-(4-substitutedbenzylidene)-6-methyl-4,5-dihydropyridazine-3(2H)-ones(2004-12-01) GÖREN, MEHMET ZAFER; ÜNSAL TAN O., Balkan A., Aypak C., TERZİOĞLU BEBİTOĞLU B., GÖREN M. Z.In this study, starting from 3-benzylidene-4-oxopentanoic add derivatives (1a-e), having 5-benzylidene-6-methyl-4,5-dihydropyridazine-3(2H)-one (2a-e) structure and their ester (3a-e), hydrazide (4a-e) and acetic acid (5a-e) derivatives were synthesized. The physical properties and UV absorptions of the five starting compounds (1a-e) and twenty target compounds (2a-5e) were determined. Their chemical structures were achieved by IR and 1H-NMR spectral data. Additionally, elemental analysis data of the new compounds (1b, 2b, 3b, 4b, 5b, 3c, 4c, 5c, 2e, 3e, 4e and 5e) were done to identify the structures. Anticonvulsant activities of the target compounds (2a-5e) were screened by pentylenetetrazole seizure model. It was observed that compound 2a showed an anticonvulsant effect similar to ethosuximide concerning the seizure grade.