Browsing by Author "Gök S."

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    Effects of a lipoxygenase inhibitor on digoxin-induced cardiac arrhythmias in the isolated perfused guinea-pig heart
    (1997) Gök S.; Ülker S.; Hüseyinov A.; Evinç A.
    1. The effects of a lipoxygenase inhibitor, BW A4C, on digoxin-induced arrhythmias and cardiac dynamics (contractile force, perfussion pressure, heart rate) were investigated in Langendorff perfused isolated guinea pig hearts. In the control group, arrhythmias were induced by 25 μg/ml digoxin at a perfusion rate of 0.5 ml/min. In the treated groups, BW A4C (1 and 0.3 μM) perfused continuously from 15 min prior to digoxin until cardiac arrest occurred. Digoxin exposure (μg/g wet weight of heart) for the occurrence of arrhythmias and cardiac arrest were the parameters evaluated to assess cardiotoxicity, 2. Digoxin caused a marked increase in leukotriene B4 release in the coronary effluent, and was collected during tachyarrhythmias. BW A4C markedly inhibited the digoxin induced elevation of LTB4. 3. BW A4C (1 and 0.3 μM) did not prevent the onset of ventricular fibrillation and ventricular tachycardia despite a slight delay in the occurrence of ventricular fibrillation and cardiac arrest at the 0.3 μM concentration. 4. Contractile force increased significantly after digoxin infusion which was concomitant with the time of onset of arrhythmias. In the presence of BW A4C, the contractile force increased, but not significantly. Perfusion pressure increased initially after digoxin infusion in the absence and the presence of BW A4C, but not significantly. 5. These findings show that the lipoxygenase inhibitor lacked any protective action on digoxin induced arrhythmias despite its effective suppression of digoxin induced elevation of LTB4 in coronary effluent.
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    Effect of vitamin E on vascular responses of thoracic aorta in rat experimental arthritis
    (1998) Çinar M.G.; Can C.; Ülker S.; Gök S.; Coker; Soykan N.; Koşay S.; Evinç A.
    1. Vascular contractile and relaxant responses were evaluated in isolated aortic rings of adjuvant induced arthritic rats in comparison with control rats, and the effect of an antioxidant treatment on the development of the arthritis was investigated by vitamin E administration (100 mg/kg/day, IM, for 26 days). 2. Arthritis was induced by an intradermal injection of Freund's complete adjuvant into rat paw. Vascular responses, arthritic lesions and serum copper levels were evaluated after 26 days from adjuvant inoculation. 3. Serum copper levels were significantly lower in arthritic rats than in the control, 4. The contractile response of aortic rings to phenylephrine (PE), but not to KCl, was increased in preparations from arthritic rats, which could be explained by an enhancement of intracellular calcium contents. 5. Acetylcholine (Ach)-mediated endothelium dependent and sodium nitroprusside (SNP)-mediated endothelium-independent relaxations were not changed significantly in vascular preparations from arthritic rats. 6. In arthritic rats, vitamin E treatment improved arthritic lesions with an increase in copper levels. Despite this ameliorating effect, vitamin E treatment caused an increase in contractile response to PE and a decrease in the relaxant response to Ach and SNP in arthritic rats. 7. These data show that vitamin E provides ameliorating effects in improving systemic signs of experimental arthritis, but it fails to restore abnormalities in vascular function, indicating that adjuvant-induced alterations in vascular function may include mechanisms other than oxygen-free radical formation.
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    The antinociceptive effect of leukotriene D4 receptor antagonist, MK- 571, in mice: Possible involvement of opioidergic mechanism
    (1999) Gök S.; Önal A.; Çinar M.G.; Evinç A.
    The effect of a leukotriene D4 receptor antagonist, (3-(3-(2-(7-chloro- 2-quinolinyl)ethenyl)phenyl(3-dimethyl amino-3-oxo propyl)thio)methyl)thio) propanoic acid (L-660,711; MK-571), was investigated on nociceptive responses in mice using three different assays: acetic-acid-induced abdominal constrictions, formalin response and tail-flick test. MK-571 (8-32 mg/kg, i.v.) produced dose-dependent protection against acetic-acid-induced abdominal constriction (ED50 = 30 mg/kg). The compound (10-80 mg/kg, i.p.) was also effective, in a dose-dependent manner, on the second phase of the formalin response (ED50 = 26 mg/kg). However, it had no effect on the first phase of the formalin response and in the tail-flick test. Naloxone (1 mg/kg, i.v.), an opioid antagonist, almost completely blocked the antinociceptive effect of MK-571 in both acetic-acid-induced abdominal constriction and the second phase of the formalin test. These results provide evidence for an antinociceptive action of MK-571 at peripheral sites and suggest that opioid mechanisms are involved.
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    Role of leukotrienes on coronary vasoconstriction in isolated hearts of arthritic rats: Effect of in vivo treatment with CI-986, a dual inhibitor of cyclooxygenase and lipoxygenase
    (S. Karger AG, 2000) Gök S.; Ülker S.; Hüseyinov A.; Hatip F.B.; Çinar M.G.; Evinç A.
    In this study, coronary perfusion pressure and force of contraction were investigated in isolated hearts removed from arthritic rats by using the Langendorff method. A strong coronary vasoconstriction was determined in arthritic hearts which was associated with elevated levels of arachidonate 5-lipoxygenase (5-LOX) products, leukotriene B4 (LTB4) and LTC4 in coronary effluents. In vivo treatment with the dual inhibitor of cyclooxygenase (COX) and LOX, CI-986 (2 and 10 mg/kg/day) on days 14-26 following adjuvant injection, prevented the coronary vasoconstriction and the increased production of LTB4 and LTC4. These results suggest that the coronary vasoconstriction in the isolated arthritic hearts is associated with an increased activity of the LOX system and CI-986 could have a preventive effect on constriction of coronary arteries.
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    Personalized and predictive medicine in Turkey: A symposium report of the Istanbul Working Group on Personalized Medicine, Istanbul, Turkey, September 10-12, 2009
    (Bentham Science Publishers, 2009) Hizel C.; Gök S.; Sardaş S.; Bernard-Gallon D.; Maugard C.; Genç E.
    Pharmacogenetics has its roots in the 1950s with pioneering studies of monogenic variations in drug metabolism and pharmacokinetics. With the availability of high-throughput genomics technologies and the completion of the Human Genome Project in 2003, we are now in the postgenomics era. This transition is increasingly marked with study of polygenic and multifactorial traits such as common complex human diseases as well as pharmacodynamic differences among populations. Changes that emerge from postgenomics medicine are not, however, limited to seismic shifts in scale and scope of pharmacogenetics research. Importantly, many low- and middle-income countries (LMICs) of the South, Asia-Pacific, Eastern Mediterranean and the Middle-East are becoming notable contributors with rapid globalization of science and increasing access to genomics technologies. This brings about, in parallel, an acute demand for regional capacity building in LMICs so that the future evaluation and implementation of postgenomics technologies in personalized medicine take place in an integrated, sustainable and equitable manner. With this overarching vision, we herein report the founding of the Istanbul Working Group in Personalized Medicine (IWG-PM, represented by the authors of this report) that was inaugurated as a component of the 2nd Symposium on Personalized and Predictive Medicine held in Istanbul, sponsored by the Yeditepe University, and the Turkish Scientific and Technological Research Council (TUB?TAK) (10-12 September, 2009). While highlighting the applications of personalized medicine in oncology, psychiatry, nutrition, infectious diseases, occupational health, genetic testing and systems biology, the symposium also raised challenging questions in the context of LMICs. How can we best evaluate the promises, intended and unintended impacts of personalized medicine and enabling technologies in the context of Turkey, and the LMICs more generally? IWG-PM is a small but significant and necessary step to initiate regional capacity building in Turkey. We trust that the IWG-PM initiative may also provide a constructive example to further develop capacity in other LMICs in the Eastern Mediterranean region. © 2009 Bentham Science Publishers Ltd.