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Öğe Association of soluble ST2 Level with 6-month Mortality and/or Recurrent Cardiovascular-Related Hospitalization in Pulmonary Embolism(Arquivos Brasileiros Cardiologia, 2024) Gunes, Hakan; Gunes, Handan; Dagli, Musa; Kirisci, Mehmet; Ozbek, Meryem; Atilla, Nurhan; Yilmaz, Mehmet BirhanBackground: The association of soluble suppression of tumorigenesis-2 (sST2) levels with prognosis in pulmonary embolism (PE) is unknown. Objective: This study aimed to investigate the relationship between sST2 levels in patients with acute PE and 6 -month mortality and recurrent hospitalizations. Methods: This prospective study included 100 patients with acute PE. Patients were classified into two groups according to 6 -month mortality and the presence of recurrent Cardiovascular -Related hospitalizations. Two groups were compared. A p -value of 0.05 was considered statistically significant. Results: Soluble ST2 levels were significantly higher in the group with mortality and recurrent hospitalizations. (138.6 ng/mL (56.7-236.8) vs. 38 ng/mL (26.3-75.4); p<0.001) The best cut-off threshold for sST2 levels in the prediction of a composite outcome of 6 -month mortality and/or recurrent Cardiovascular -Related hospitalization was found to be >89.9 with a specificity of 90.6% and a sensitivity of 65.2%, according to the receiver operating characteristic curve (area under the curve = 0.798; 95% CI, 0.705-0.891; p <0.0001). After adjusting for confounding factors that were either statistically significant in the univariate analysis or for the variables correlated with the sST2 levels, sST2 level (OR = 1.019, 95% CI: 1.009-1.028, p 0.001) and C -reactive protein (CRP ) (OR = 1.010, 95% CI: 1.001-1.021, p = 0.046) continued to be significant predictors of 6 -month mortality and/or recurrent Cardiovascular -Related hospitalization in the multiple logistic regression model via backward stepwise method. Conclusion: Soluble ST2 level seems to be a biomarker to predict 6 -month mortality and/or recurrent CardiovascularRelated hospitalization in patients with acute PE.Öğe Determination of Vascular Endothelial Growth Factor (VEGF) and Tie-2 Levels in Patients with Primary Hypertension(ELSEVIER SCIENCE INC, 2013) Filiz, Ahmet Kemal; Gunes, Hakan; Ozdemir, Ercan; Gunes, Handan; Yilmaz, Mehmet Birhan…Öğe The Effect of Coenzyme Q10 on Absence Seizures and the Role of Nitric Oxide Pathway in this Effect(WILEY-BLACKWELL, 2016) Gunes, Handan; Ozdemir, Ercan; Gulturk, Sefa; Arslan, Gokhan…Öğe Effect of Pantoprazole, a Proton Pump Inhibitor, on Morphine Tolerance in Rats(Maik Nauka/Interperiodica/Springer, 2024) Sahin, Bilal; Gunes, HandanPantoprazole's neuroprotective effects and its role in altering processes linked to apoptosis, inflammation, and oxidative stress were demonstrated. Consequently, this study aimed to explore how pantoprazole influences the development of morphine tolerance and the associated mechanisms, including apoptosis, oxidative stress, and inflammation. Six groups of rats were created: saline, 10 mg/kg pantoprazole, 5 mg/kg morphine, morphine tolerance, morphine + pantoprazole, and morphine tolerance + pantoprazole. Hot plate and tail-flick tests were utilized to detect the analgesic effect. Following the analgesic tests, samples of the dorsal root ganglion (DRG) tissues were collected. Oxidative stress parameters (total oxidant status, total antioxidant status), inflammation parameters (Pro-IL-1 beta, IL-1 beta, NLRP-3), and apoptosis proteins (Caspase-1, Caspase-3, Capsape-9) were detected in dorsal root ganglions (DRG) tissues. Pantoprazole showed a weak but statistically significant analgesic activity when given alone. Furthermore, pantoprazole potentiated the antinociceptive effect of morphine and prevented the development of tolerance to morphine. Moreover, it increased total antioxidant status and decreased total oxidant status as well as caspase-1 when given with single-dose morphine and after tolerance induction. Furthermore, pantoprazole decreased Pro-IL-1 beta, IL-1 beta, Caspase-3 and Capsape-9 levels after tolerance development. Collectively, pantoprazole produces a weak analgesic activity and boosts the morphine's analgesic effect. On the other hand, pantoprazole can prevent tolerance development. These effects likely arise through the modulation of pathways associated with oxidative stress, inflammation and apoptosis pathways.Öğe Effect of The Cyclooxygenase-2 Inhibitor Tenoxicam on Pentylenetetrazole-Induced Epileptic Seizures in Rats(WILEY, 2017) Toptas, Hacer Aybike; Guney, Ozge; Kutlu, Rukiye; Gumus, Ekan; Gunes, Handan; Taskiran, Ahmet Sevki; Arslan, Gokhan…Öğe Effects of Oxytocin Receptor Antagonist Atosiban on Analgesia and Morphine Analgesia in Rats(WILEY, 2017) Taskiran, Ahmet Sevki; Erdem, Berat; Gunes, Handan; Ozdemir, Ercan…Öğe Effects of probiotics on GABA/glutamate and oxidative stress in PTZ-induced acute seizure model in rats(Elsevier, 2023) Ciltas, Arzuhan Cetindag; Toy, Cemal Erdem; Gunes, Handan; Yaprak, MeryemStudies conducted in recent years have indicated a relationship between epilepsy and gut microbiota. Ion channels, excitatory/inhibitory balance and regulatory systems play a role in the pathophysiology of epilepsy. In addition, gut dysbiosis is also involved in the pathophysiology of epilepsy. This research investigated the impacts of probiotic mixture on epileptic seizures, Gamma aminobutyric acid (GABA), glutamate, and TAS and TOS levels in hippocampal tissue in the PTZ-induced acute seizure model in rats. Four groups were formed with male Wistar albino rats. The first and second groups were given 1 ml/day saline solution, and the other groups were given 0.05 mg/1 ml/day vehicle or 109cfu/1 ml/day probiotic supplementation, respectively via gavage for 21 days. A single-dose PTZ (45 mg/kg) was administered to induce seizure. The stages of seizure were analyzed according to the Racine scale. While ELISA was used to determine GABA and glutamate levels in the hippocampus, an automated colorimetric method was utilized to measure oxidant/antioxidant biomarkers. It was found that by delaying the first myoclonic jerk (FMJ), and the onset of the generalized tonic-clonic seizures, the probiotic mixture demonstrated anticonvulsant effects against seizures. The probiotic mixture was found to increase the inhibitory neurotransmitter GABA. It was also found to decrease TOS levels and increase TAS concentration. The findings of this study showed that probiotic mixture reduced oxidative stress with its positive effects against PTZinduced epileptic seizures. Further studies are needed to reveal potentially related mechanisms.Öğe Inhibition of the TRPM2 cation channel attenuates morphine tolerance by modulating endoplasmic reticulum stress and apoptosis in rats(Elsevier Ireland Ltd, 2025) Ciltas, Arzuhan Cetindag; Ozdemir, Ercan; Gunes, Handan; Ozturk, AysegulOpioid drugs such as morphine are frequently preferred drugs for severe pain in cancer and chronic diseases, but long-term use causes opioid tolerance. The mechanism of tolerance to opioids is quite complex and not fully understood. Our aim in this study was to investigate the effects of TRPM2 cation channel antagonists N-(pamylcinnamoyl) anthranilic acid (ACA) and 2-aminoethoxydiphenyl borate (2-APB) on morphine analgesia and tolerance in rats. Forty-eight Wistar Albino male rats were included in the study and the rats were randomly divided into drug and control (saline) groups. To induce morphine tolerance, the rats were injected with 10 mg/ kg morphine intraperitoneally for 7 days. After thermal analgesia tests, dorsal root ganglion (DRG) and cortex tissues were isolated. Proapoptotic mediators caspase-3 and 9, total oxidant status (TOS) and total antioxidant status (TAS) and ER stress proteins GRP78/BiP, ATF-6, p-IRE1 and pERK levels were measured by biochemical analysis of tissue homogenates. The findings showed that there was a significant decrease in morphine tolerance in rats administered ACA and 2-APB (p<0.05). In addition, biochemical tests revealed a significant decrease in ER stress proteins, proapoptotic biomarkers and TOS levels and a significant increase in TAS levels in DRG, thalamus and sensory cortex tissues (p<0.05). In conclusion, inhibition of TRPM2 cation channel by ACA and 2APB reduces morphine tolerance by preventing ER stress and apoptosis. It may be possible to increase the analgesic potential of morphine by combined application with ACA and 2-APB in the clinic, but further experimental and molecular studies are needed.Öğe Modulatory effects of neuropeptides on pentylenetetrazol-induced epileptic seizures and neuroinflammation in rats(Assoc Medica Brasileira, 2019) Kilinc, Erkan; Gunes, HandanOBJECTIVE: We aimed to explore the effects of neuropeptides ghrelin, obestatin, and vasoactive intestinal peptide (VIP) on seizures and plasma concentrations of neuroinflammation biomarkers including calcitonin gene-related peptide (CGRP), substance-P (SP), and interleukin-1 beta (IL-1 beta) in pentylenetetrazol-induced seizures in rats. METHODS: Ghrelin (80 mu g/kg), obestatin (1 mu g/kg), VIP (25 ng/kg) or saline were administered to rats intraperitoneally 30 min before pentylenetetrazole (PTZ, 50 mg/kg) injections. Stages of epileptic seizures were evaluated by Racine's scale, and plasma CG RP, SP, and IL-1 beta concentrations were measured using ELISA. RESULTS: Both obestatin and VIP shortened onset-time of generalized tonic-clonic seizure, respectively, moreover VIP also shortened the onset-time of first myoclonic-jerk induced by PTZ. While PTZ increased plasma CG RP, SP and IL-1 beta concentrations, ghrelin reduced the increases evoked by PTZ. While VIP further increased PTZ-evoked CG RP levels, it diminished IL-1 beta concentrations. However, obestatin did not change CGRP, SR and IL-1 beta concentrations. CONCLUSION: Our results suggest that ghrelin acts as an anticonvulsant, obestatin acts as a proconvulsant, and VIP has dual action on epilepsy. Receptors of those neuropeptides may be promising targets for epilepsy treatment.Öğe Ondansetron and AS19 attenuate morphine tolerance by modulating serotonin 5-HT3 and 5-HT7 receptor expressions in rat dorsal root ganglia(Elsevier, 2023) Ozsoy, Seyma; Ozdemir, Ercan; Gunes, Handan; Gevrek, Fikret; Gulmez, KaderPurpose: Opioid drugs are frequently preferred drugs for severe pain, but their long-term use causes tolerance to their analgesic effects. However, the factors that contribute to the development of tolerance to opioids are diverse and not fully understood. In this study, our aim was to investigate the effects of 5-HT3 receptor antagonist ondansetron (ODN) and 5-HT7 receptor agonist AS19 on morphine analgesia and tolerance in rats. Material and methods: Eighty-four randomly selected Wistar Albino (230-260 g) male rats were included in the study. To induce morphine tolerance in rats, morphine (10 mg/kg) was administered subcutaneously twice daily for 7 days, and tolerance was assessed by thermal analgesia tests on day 8 for 120 min. After thermal analgesia tests, dorsal root ganglia (DRGs) at spinal L4-S5 level were isolated. 5-HT3 and 5-HT7 receptor expressions in DRGs were measured by immunohistochemical method. Results: The results show that co-administration of ODN or AS19 with morphine indicated a significant increase in analgesic effect compared to morphine alone In addition, the difference between the mean of ODN or AS19 combined with morphine and the morphine-tolerant group was statistically significant. H-score analysis significantly increased 5-HT3 receptor expressions in the morphine-tolerant rats, and administration of ODN prevented this. Similarly, 5-HT7 receptor expressions were significantly decreased in the morphine tolerant group, and the administration of AS19 increased this expression. Conclusion: These study results suggest that both ODN and AS19 alter the 5-HT3 and 5-HT7 receptor expressions in the DRG and possibly attenuate morphine tolerance in this way.Öğe Regulatory Neuropeptide Mechanisms in Pentylenetetrazol-Induced Epileptic Seizures in Rats(WILEY, 2018) Kilinc, Erkan; Gunes, Handan…Öğe Relation of Levels of Soluble ST2 with Clinic and Prognosis in Heart Failure Patients.(EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC, 2017) Gunes, Hakan; Zararsiz, Abdullah; Gul, Ibrahim; Gunes, Handan…Öğe The Anticonvulsant Effects of Adenosine A1 Agonist N6-Cyclopentyladenosine on Pentylenetetrazole-Induced Kindling Model of Epilepsy(Wiley, 2022) Ciltas, Arzuhan Cetindag; Ozdemir, Ercan; Gumus, Erkan; Arslan, Gokhan; Gunes, Handan[Abstract Not Available]Öğe The Anticonvulsant Effects of Alpha-2 Adrenoceptor Agonist Dexmedetomidine on Pentylenetetrazole-Induced Seizures in Rats(Springer/Plenum Publishers, 2022) Cetindag Ciltas, Arzuhan; Ozdemir, Ercan; Gumus, Erkan; Taskiran, Ahmet Sevki; Gunes, Handan; Arslan, GokhanAlpha2-adrenoreceptor (alpha(2)-AR) is a noradrenergic receptor that is frequently studied for modulation of seizure activity. However, the precise role of this receptor agonists in regulating seizure activity is still unclear. Our aim in this study was to investigate the effects of alpha(2)-AR agonist dexmedetomidine (DEX) and atipamezole (alpha(2)-AR antagonist, ATI) on seziures in rats. In the study, 32 adult male Wistar Albino rats (weighing 220-260 g) were used. To induce seizures in rats, pentylenetetrazole (PTZ, 35 mg/kg) was injected intraperitoneally (i.p.) and seizure stages were determined according to the Racine scale. After induction of seizures, DEX (0.1 mg/kg, i.p.) and ATI (1 mg/kg, i.p.) were administered to rats and their effects determined on seizures. GABA levels of the brain hippocampal tissue sample were measured using an ELISA kit and c-Fos positive cells of the dentate gyrus and hippocampal regions were quantitatively analyzed with Image J software. The results showed that DEX decreased the seizure stages according to the Racine scale, significantly prolonged the onset time of first myoclonic jerk (FMJ) and reduced the number of spikes and percentage seizure duration (p < 0.05). In contrast, ATI increased the seizure stage, the number of spikes and percentage seizure duration. The hippocampal GABA level was significantly decreased in rats with only PTZ injection (p < 0.05). In addition, DEX reduced the number of c-Fos positive cells in dentate gyrus and the hippocampal CA1 and CA3 regions. In conclusion, our findings showed that alpha 2-AR agonist DEX had a reducing activity on PTZ-induced seizure, while alpha 2-AR antagonist ATI facilitated seizure formation.Öğe The Effects of Proton Pump Inhibitors (Pantoprazole) on Pentylenetetrazole-Induced Epileptic Seizures in Rats and Neurotoxicity in the SH-SY5Y Human Neuroblastoma Cell Line(Springer/Plenum Publishers, 2021) Taskiran, Ahmet Sevki; Ergul, Mustafa; Gunes, Handan; Ozturk, Aysegul; Sahin, Bilal; Ozdemir, ErcanRecent studies have shown that proton pump inhibitors have positive effects on the nervous system. However, its effect on epileptic seizure and neuronal damage are still unclear. In this study, it was aimed to investigate the effect of pantoprazole on pentylenetetrazole-induced epileptic seizures in rats and neurotoxicity in the SH-SY5Y cell line. Animals were divided into three groups: control, saline (1 mL/kg serum physiologic), and pantoprazole (10 mg/kg). Pentylenetetrazole (45 mg/kg) was given to induce a seizure and a passive avoidance test trial was carried out to evaluate memory function. 8-hydroxy-2 '-deoxyguanosine (8-OHdG), caspase-3, and brain-derived neurotrophic factor (BDNF) levels were measured in the brain by commercial kits. SH-SY5Y cells were treated with saline or pantoprazole for one hour, and then pentylenetetrazole (30 mu m) was added to the medium to induce neurotoxicity. After 24 h, cell viability, total antioxidant, total oxidant status, and apoptosis were measured in SH-SY5Y cells. It was found that pantoprazole treatment postponed epileptic seizure onset, protected memory, reduced 8-OHdG, caspase-3, and also increased BDNF in the brain. In addition, it blocked pentylenetetrazole toxicity, apoptosis, increased antioxidant, and decreased oxidant status in SH-SY5Y cells. Pantoprazole significantly improved seizure, oxidative stress, and apoptosis. Thus, pantoprazole could be used as a supportive therapeutic agent in epilepsy.Öğe What is the most appropriate method for coronary sinus cannulation? The telescopic method or the electrophysiologic method?(PUBLIC LIBRARY SCIENCE, 2018) Gunes, Hakan; Aksu, Ekrem; Nacar, Huseyin; Kerkutluoglu, Murat; Gunes, Handan; Ozgul, SamiObjectives The most challenging stage of cardiac resynchronization therapy (CRT) is coronary sinus cannulation (CS). The aim of this study was to compare coronary sinus cannulation techniques using electrophysiology catheters and coronary angiography catheters. Methods In this observational, retrospective and non-randomized study, 87 patients who were eligible for CRT device implantation were screened at Kahramanmaras Sutcu Imam University Hospital between March 2014 and March 2018. Seventy-two patients who met the inclusion criteria were enrolled in the study. The study population was divided into 2 groups: the first group consisted of 36 patients whose coronary sinuses were cannulated via electrophysiology (EP) catheters and the second group included 36 patients who received coronary angiography catheters for coronary sinus cannulation. Results The two groups were similar in terms of the baseline characteristics of the patients. The total fluoroscopy time was less with cannulation using coronary angiography catheters. There were no differences between the two groups in terms of the amount of contrast material and the success of the operations. Conclusions Coronary sinus catheterization using coronary angiography catheters significantly reduces fluoroscopy time in patients undergoing CRT.
