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Öğe Effect of U-92032, T-Type Ca(2+)Channel Blocker, on Rats with Genetic Absence Epilepsy(Karger, 2020) Yananlı, Hasan Raci; Demirkapu, Mahluga Jafarova; Sakallı, Halil Eren; Gülhan, Rezzan; Onat, Filiz YılmazIntroduction:Absence epilepsy is associated with diffuse spike-and-wave discharges (SWD) on the electroencephalogram (EEG). Recent studies have demonstrated that the primary somatosensory cortex is also implicated in the generation of the SWDs.Objective:This study investigated the effects of systemic and local administrations of U-92032 into the brain of Genetic Absence Epilepsy Rats from Strasbourg (GAERS).Methods:GAERS animals underwent stereotaxic surgery for the placement of EEG recording electrodes and guide cannulas for U-92032 administration into the lateral ventricle (intracerebroventricular [i.c.v.]), upper lips area (S1Ulp) or barrel field area (S1B) of primary somatosensory cortex. Following 7 days of recovery, electrical activity was recorded continuously for 1 h before and 6 h after intraperitoneal (0.25; 1; 5 mg/kg i.p.) or local U-92032 or dimethyl sulfoxide (DMSO) injections.Results:No changes were detected in the cumulative duration, mean duration, and number of SWDs following i.p. U-92032 injections. Local i.c.v. injections of U-92032 caused a significant decrease in the cumulative duration (i.c.v., 50 and 100 nmol/L), mean duration (i.c.v., 50, 100, and 250 nmol/L), and the number (i.c.v., 250 nmol/L) of SWDs compared to DMSO groups. Intra-cortical (S1Ulp and S1B) U-92032 injections caused a significant decrease in all 3 parameters compared to DMSO groups, as well.Conclusion:Intra-cortical injection of U-92032 caused almost complete removal of SWDs in GAERS and i.c.v. administration resulted in a significant reduction. However, systemic i.p. administration did not cause a significant change with the applied -doses.Öğe Effects of acute topiramate administration on post-traumatic stress disorder in rats(Cukurova Univ, Fac Medicine, 2022) Demirkapu, Mahluga Jafarova; Doğan, Furkan Cuma; Karabağ, Sevil; Yılmaz, Ahsen; Çelikkol, Aliye; Yananlı, Hasan RaciPurpose: The aim of this study was to investigate the effects of acute systemic topiramate administration on anxiety index and freezing time, plasma estrogen and progesterone levels, and salivary gland immunoglobulin A in a post-traumatic stress disorder rat model. Materials and Methods: A total of eighteen female Wistar rats used in the study were exposed to predatory odor stress. One week later, saline was administered to the control group and 15 mu M and 30 mu M topiramate to the treatment groups, after which the animals were exposed to the trauma reminder and their behavior was monitored in the elevated plus maze. At the end of the experiment, blood samples were taken, animals were sacrificed, salivary glands were removed immediately after. Results: Topiramate suppressed anxiety index and freezing time in rats with post-traumatic stress disorder at both 15 mu M and 30 mu M doses compared to the control group. A positive correlation was observed between plasma estrogen level and anxiety index in the control group, and topiramate suppressed this correlation in a dose-dependent manner. Topiramate did not change the plasma progesterone level, but suppressed the salivary gland immunoglobulin A level at the low dose. Conclusion: These findings obtained in our study indicate that topiramate may be effective in the treatment of post-traumatic stress disorder.Öğe Effects of Chronic Oral Monosodium Glutamate Consumption on Naloxane-Induced Morphine Withdrawal in Infant Rats(2022) Yananlı, Hasan Raci; Yıldız, Merve; Temel, Hasan; Kılınç, Melih; Özen, Berna; Demirkapu, Mahluga Jafarova; Kutluay, Sena NurAim: The aim of this study was to investigate chronic oral monosodium glutamate (MSG) consumption effects on symptoms of withdrawal, locomotor activity, and anxiety in morphine withdrawal syndrome induced by naloxone in infant rats. Materials and Methods: Twelve 21-day-old male Wistar rats used in the study. Infant rats were given unlimited access to saline (control group) or MSG (MSG group) added to drinking water for 32 days. Withdrawal was induced by naloxone in morphine-dependent rats. Evaluation of withdrawal symptoms and anxiety were performed simultaneously with locomotor activity measurements. Results: Withdrawal sings, such as jumping, wet dog shake, and weight loss; stereotypic, ambulatory, and vertical locomotor activity movements; central, peripheral, and total activities used in the assessment of anxiety in infant rats with naloxone-induced withdrawal syndrome that consumed oral MSG for 32 days were not different from the control group. Conclusion: These findings obtained in our study indicate that chronic consumption of oral MSG in infant rats whose blood-brain barrier has not yet developed does not affect morphine dependence and naloxone-induced withdrawal. Further studies are needed to investigate the mechanism of action of orally administered MSG.Öğe Potential drug-drug interactions in outpatient lung cancer patients in a university hospital(Karger, 2024) Demirkapu, Mahluga Jafarova; Cavdar, EyyupIntroduction: Concomitant use of drugs in the same or different indications can sometimes lead to undesirable interactions. The prevalence of drug interactions is high in cancer patients. In this study, we aimed to determine the frequency and clinical severity of drug interactions in outpatient lung cancer patients. Methods: The drugs used, kidney and liver blood analysis results of 160 outpatient lung cancer patients over the age of 18 who received chemotherapy between October 2020 and July 2021 were evaluated. The Lexi-Interact online database was used to identify the types of clinically significant drug interactions, frequently interacting drugs, and clinical outcomes predicted by the databases. Results: The average number of drugs per patient was 4.2 +/- 2.3. It was determined that there was a relationship between multi-drug use and comorbidity, and the number of drugs used increased as the number of diagnoses increased. A relationship was also found between potential drug-drug interactions (pDDI), which we observed in 52.5% of the patients, and the number of drugs used and age. The most common clinically significant C (36.9%), D (16.9%) and X (10.6%) type pDDI were detected between conventional paclitaxel-hydrochlorothiazide, conventional paclitaxel-carboplatin, and ipratropium-tiotropium, respectively. Conclusions: The use of frequently interacting drugs in outpatient lung cancer patients can lead to pDDI. In these patients, the application of therapy by observing the drug-drug interaction may improve the quality of life.Öğe Potential drug-drug interactions in university hospital medical intensive care unit patients in turkey(Verduci Editore s.r.l, 2021) Demirkapu, Mahluga Jafarova; Kara, Sonat PınarOBJECTIVE: Concomitant use of drugs not only enhances the therapeutic effect, but may also lead to undesirable interactions. Drug interactions are frequently seen in intensive care patients. In this study, we aimed to determine the frequency and clinical severity of drug interactions in Medical Intensive Care Unit (MICU) patients. PATIENTS AND METHODS: The ordered drugs and blood analysis results of 314 patients aged ?18 years who stayed in the MICU for at least 24 h between January and December 2020 were evaluated. Using the Lexi-Interact online database, clinically significant types of drug interactions, frequently interacting drug/ drug groups, and potential adverse reactions were identified. RESULTS: The average number of drugs in 314 patients was 8.98±5.19. It was determined that polypharmacy was associated with comorbidity and the amount of drug used increased as the number of diagnoses increased. Potential drugdrug interactions were observed in 69.7% of the MICU patients, and it was determined that the amount of interactions increased as the amount of drug used increased. The most common X, D, and C type potential drug-drug interactions, were found between furosemide and salbutamol, enoxaparin and acetylsalicylic acid, ipratropium and potassium chloride, respectively. CONCLUSIONS: Use of frequently interacting drugs in the treatment of critically MICU patients may lead to potential drug-drug interactions and adverse reactions. Daily monitoring and updating of drug therapy can improve patient's quality of life by preventing or reducing potential drugdrug interactions. © 2021 Verduci Editore s.r.l. All rights reserved.Öğe Potential drug-drug interactions in University Hospital Medical Intensive Care Unit patients in Turkey(Verduci Publisher, 2021) Demirkapu, Mahluga Jafarova; Kara, Sonat PınarOBJECTIVE: Concomitant use of drugs not only enhances the therapeutic effect, but may also lead to undesirable interactions. Drug interactions are frequently seen in intensive care patients. In this study, we aimed to determine the frequency and clinical severity of drug interactions in Medical Intensive Care Unit (MICU) patients. PATIENTS AND METHODS: The ordered drugs and blood analysis results of 314 patients aged >= 18 years who stayed in the MICU for at least 24 h between January and December 2020 were evaluated. Using the Lexi-Interact online database. clinically significant types of drug interactions, frequently interacting drug/drug groups, and potential adverse reactions were identified. RESULTS: The average number of drugs in 314 patients was 8.98 +/- 5.19. It was determined that polypharmacy was associated with comorbidity and the amount of drug used increased as the number of diagnoses increased. Potential drug-drug interactions were observed in 69.7% of the MICU patients, and it was determined that the amount of interactions increased as the amount of drug used increased. The most common X, D, and C type potential drug-drug interactions, were found between furosemide and salbutamol, enoxaparin and acetylsalicylic acid, ipratropium and potassium chloride, respectively. CONCLUSIONS: Use of frequently interacting drugs in the treatment of critically MICU patients may lead to potential drug-drug interactions and adverse reactions. Daily monitoring and updating of drug therapy can improve patient's quality of life by preventing or reducing potential drug-drug interactions.Öğe Pre-emptive analgesia with preoperative oral gabapentin and pregabalin in lumbar narrow canal surgery(Pharmamed Mado Ltd, 2024) Mordeniz, Cengiz; Ozdemir, Fatma; Karaarslan, Numan; Yıldırım, Ilker; Demirkapu, Mahluga Jafarova; Arar, Makbule CavidanThe success of pre-emption depends on the strategy pertaining to the choice of agent and when and how, to use. This study was aimed to evaluate the efficacy of preemptive analgesia regarding the postoperative pain management in lumbar spinal stenosis surgery. The oral gabapentin 800 mg or pregabalin 225 mg or placebo were administered 1 h before surgery. The pain and sedation scores were measured through Visual Analogue Scale (VAS) and Ramsay Sedation Scale (RSS). Three groups of 30 patients each were included in the study. Group 1 was administered with gabapentin 800 mg, Group 2 with pregabalin 225 mg, and Group 3 with placebo 1 hour before the surgery. VAS scores at the 1st, 2nd, 4th, 6th, 8th, 10th, 12th, 14th, 16th, 18th, 20th, 22nd and 24th hours of surgery, and RSS scores and analgesic drug usage in the 1st to 24 hours of surgery were recorded. There were statistically significant differences between the 1st, 2nd and 4th hour VAS score averages. RSS scores changed among the three groups in postoperative period. The total analgesics employed in gabapentin and pregabalin groups were lower than those in placebo group. Pre-emptive analgesia of oral pregabalin or gabapentin minimized the postoperative pain in patients undergoing lumbar stenosis surgery. © 2024 The Author(s).Öğe The effect of acute topiramate administration on morphine withdrawal syndrome and brain-derived neurotrophic factor in central nervous system(Taylor & Francis Ltd, 2023) Ozkula, Songul; Demirkapu, Mahluga Jafarova; Yananli, Hasan Raci; Aydin, Banu; Nacar, Cevdet; Cabadak, HulyaObjectivesNucleus accumbens plays an important role in opioid addiction. Topiramate, increases postsynaptic gamma-aminobutyric acid receptor activity and antagonizes glutamatergic activity. Brain-derived neurotrophic factor (BDNF), which plays a key role in synaptic plasticity, is produced from proBDNF. The aim of this study is to investigate the effects of 100 mu M topiramate applied into the lateral ventricle or nucleus accumbens on naloxone-induced morphine withdrawal and the BDNF/proBDNF ratio in the frontal cortex.MethodsIn the study, 36 adult male Wistar rats weighing 250-350 g were used. Morphine dependence was created with morphine pellets following guide cannula implantations. Withdrawal findings were evaluated in naloxone-induced morphine withdrawal syndrome following topiramate administration, and locomotor activity measurements were performed simultaneously. The brains of sacrificed animals were removed for determination of BDNF/proBDNF ratio.ResultsTopiramate administered by either route significantly suppressed the number of jumps in morphine withdrawal. Topiramate applied into the nucleus accumbens significantly reduced stereotypical behavior in morphine withdrawal, but did not cause any changes in other locomotor activity behaviors. Topiramate applied into the lateral ventricle significantly decreased the BDNF/proBDNF ratio, whereas administered into the nucleus accumbens significantly increased this ratio.ConclusionThe findings of this study indicate that topiramate administered into the lateral ventricle and nucleus accumbens reduces naloxone-induced morphine withdrawal symptoms, stereotypical locomotor activity, and changes the BDNF/proBDNF ratio.Öğe The effect of oral administration of monosodium glutamate on epileptogenesis in infant rats(John Libbey, 2020) Demirkapu, Mahluga Jafarova; Yananlı, Hasan Raci; Akşahin, E.; Karabiber, C.; Günay, P.; Kekilli, A.; Topkara, B.Aim: Glutamate is an excitatory neurotransmitter that is widely distributed throughout the brain. An increase in glutamate concentration or sensitivity of glutamate receptors triggers neurodegenerative diseases, epilepsy in particular. Monosodium glutamate is a substance added to foods to enhance flavour. We investigated the effect of monosodium glutamate on epileptogenesis, as well asheight and weight, in rats that were just weaned. Methods: Twenty-four male and female 21-day-old Wistar Albino rats were divided into two groups: one with monosodium glutamate added to the drinking water, and a control in which NaCl was added to the drinking water. The electrical stimulation threshold values were determined in animals to which the hippocampal kindling process was applied, and the stimulations at these threshold values were invariably applied to the animals until they were kindled. Results: The electrical stimulation threshold values of the monosodium glutamate group did not statistically change, whereas the number of required stimulations for kindled rats was significantly lower compared with the control group. Conclusion: These results reveal that long-term oral administration of glutamate salts causes an increase in excitability in the central nervous system during ontogenetic development. © 2020 Epileptic DisordersÖğe The effect of telmisartan, an angiotensin receptor blocker, on alcohol consumption and alcohol-induced dopamine release in the nucleus accumbens(Elsevier Inc., 2021) Tezcan, Kutluhan; Yananli, Hasan Raci; Demirkapu, Mahluga Jafarova; Gören, M. Zafer; Sakalli, H. Eren; Colombo, Giancarlo; Gülhan, RezzanAlcohol use disorder remains a major health problem. The mesocorticolimbic dopaminergic system, including the nucleus accumbens region and multiple neural circuits, is involved in its complex underlying mechanism. For instance, alcohol intake stimulates the central and peripheral renin-angiotensin system and increases angiotensin II levels, which predominantly affect angiotensin 1 receptors both in the periphery and in the brain. In this study, we aimed to investigate the effects of the intracerebroventricularly-administered angiotensin 1 receptor blocker telmisartan on the alcohol consumption of male Sardinian alcohol-preferring (sP) rats and on the alcohol-induced dopamine levels in the nucleus accumbens region in Wistar rats. Acute intracerebroventricular administration of telmisartan (100 nM) reduced the alcohol intake for 24 hours without affecting food and water consumption in sP rats. Acute intracerebroventricular injection of the opioid receptor antagonist naloxone (75 nM), tested as a reference compound, also reduced the alcohol consumption in sP rats; however, naloxone's effect lasted only for 30 minutes. In microdialysis experiments, telmisartan administered intracerebroventricularly did not change dopamine levels in the nucleus accumbens that had been induced by acute intraperitoneal alcohol administration in Wistar rats. According to these results, further studies are needed to elucidate the role of the renin-angiotensin system on alcohol use disorder pathophysiology. © 2021 Elsevier Inc.Öğe The Effects of Fentanyl on Testicular Ischemia-Reperfusion Injury(2021) Mordeniz, Cengiz; Demirkapu, Mahluga Jafarova; Akgül, Murat; Karabağ, Sevil; Çelikkol, Aliye; Yananlı, Hasan RaciObjective: Testicular torsion is a condition that often occurs as a result of the rotation of the spermatic cord in childhood and adolescence in men, manifests with acute pain and causes infertility in the future even if emergency intervention is performed. The aim of this study is to investigate the protective and preventive effects of fentanyl, a potent analgesic agent frequently used in anaesthesia practice, on testicular ischemia–- reperfusion injury, which manifests through acute pain. Methods: A total of 16 adult male Wistar rats, weighing 200-250 g, were used in this study. They were divided into two groups, consisting of eight animals in each group. Torsion was created in all rats by rotating left testicles 720 clockwise on the day of the experiment. 3 mM of fentanyl was applied intraperitoneally 30 minutes before detorsion to the fentanyl group. Following an hour of ischemia, the left testicle was reinstated, and tissues were repaired according to their physiology. Following 24 hours of reperfusion, the animals were euthanised after taking left testes and blood samples. Results: Fentanyl, administered prior to testicular detorsion, significantly suppressed germ cell damage in torsioned tissue, catalase activity and malondialdehyde levels in blood samples taken from the heart. No significant differences were observed in plasma total thiol concentration, histological score, Leydig cell counts, percentage of necrosis and tubule rupture. Conclusion: These findings show that fentanyl administered before detortion creates a protective effect by preventing testicular ischemia–- reperfusion injury leading to infertility in the future.Öğe The Effects of L-Name and Agmatine in the Nucleus Accumbens Core Region on Morphine Withdrawal Syndrome(2020) Demirkapu, Mahluga Jafarova; Yananlı, Hasan Raci; Mammadov, Elmar; Dervishi, Ina; Kırbaş, Ali; Yaşar, Şafak Recep; Topkara, BetilayAim: The mesocorticolimbic dopaminergic system, especially the nucleus accumbens, is an important region in opioid dependence and withdrawal. Studies have shown that nitric oxide synthase inhibitors modulate the development of tolerance to opioids, opioid dependence, and withdrawal. In this study, we aimed to investigate the effects of local injections of L-NAME and agmatine into the nucleus accumbens core (NAcc), one of the nucleus accumbens subregions on withdrawal signs and locomotor activity behavior during naloxone-induced withdrawal in morphine-dependent rats. Materials and Methods: Twenty-four adult Sprague-Dawley rats were used in the study. Morphine dependence was developed in all animals after guide cannula implantation into the NAcc region. On the last day of experiment, following bilateral L-NAME, agmatine or artificial cerebrospinal fluid (aCSF, control group) microinjections morphine withdrawal was induced by naloxone. Results: Local administration of agmatine and L-NAME into the NAcc significantly suppressed the jumping number during naloxone induced withdrawal. Local agmatine treatment significantly suppressed the score of teeth chattering, although the L-NAME did not change. No significant difference was observed in withdrawal symptoms such as wet dog shakes and defecation after local agmatine and L-NAME treatment. Agmatine increased stereotypic movements, but did not change locomotor activity behaviors such as ambulatory activity and total covered distance. Local administration of L-NAME into the NAcc did not increase stereotypic and ambulatory movements, and total covered distance during naloxone-induced withdrawal. Conclusion: These results suggest that inhibition of nitric oxide synthesis in NAcc plays a role in morphine withdrawal symptoms, but it is not responsible alone.Öğe The Effects of Topiramate Applied to the Nucleus Accumbens Region on Morphine Withdrawal Syndrome(2020) Özkula, Songül; Yananlı, Hasan Raci; Gülhan, Rezzan; Dündar, Oya Helin; Erol, Selçuk; Bakar, Ramazan; Demirkapu, Mahluga JafarovaAim: Nucleus accumbens, one of the nuclei of the basal ganglia, and dopamine, the neurotransmitter play a critical role in opioiddependence and withdrawal. In opioid withdrawal, the importance of neurotransmitters such as glutamate and gamma aminobutyric acid(GABA), as well as dopamine, is known. In this study, we aimed to investigate the effects of local injections of topiramate, anantiepileptic agent affecting GABAergic and glutamatergic pathways, into the nucleus accumbens on withdrawal signs and locomotoractivity during naloxone-induced withdrawal in morphine-dependent rats.Materials and Methods: Twenty male Sprague-Dawley rats were divided in topiramate treatment and control groups. All animalsreceived morphine pellets and guide cannulas were placed bilaterally in the nucleus accumbens regions by stereotaxic surgery. On thelast day of the experiment, following the bilateral topiramate or saline (control group) microinjections, morphine withdrawal was triggeredby naloxone.Results: Topiramate microinjections into the nucleus accumbens region significantly suppressed the signs of naloxone-inducedmorphine withdrawal such as number of jumpings and weight loss. No significant difference was observed in wet dog shakes, one of thewithdrawal signs, after local topiramate treatment. Although topiramate microinjections increased stereotypical activity it did not changelocomotor activity behavior such as vertical and ambulatory activity, and total covered distance.Conclusion: These findings show that local microinjection of topiramate into the nucleus accumbens is effective in preventing opioiddeprivation symptoms without significant effect on locomotor activity.
