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Öğe Examination of antimicrobial effect of fluoxetine in experimental sepsis model: An in vivo study(Wiley, 2023) Çakır, Ahsen; Bozali, Kübra; Çelikten, Mert; Güler, Eray Metin; Şahan, Ebru; Durdu, Bülent; Sümbül, Bilge; Koçyiğit, AbdurrahimSince most infectious diseases can develop into sepsis, it is still a major medical problem. Some in-vivo studies showed promising properties of fluoxetine in the treatment of infections. This study aims the antimicrobial effect of fluoxetine on the inflammatory process used in the treatment of sepsis-modeled rats. Besides, to investigate the efficacy of fluoxetine on modifying the antibiotic effect of imipenem in the inflammatory response. An experimental sepsis model was divided into negative control, positive control, fluoxetine 5 mg/kg, imipenem 60 mg/kg, and combined (fluoxetine; imipenem). Procalcitonin (PCT), high-sensitivity C-reactive protein (hs-CRP), lactate, myeloperoxidase activity (MPO), the inflammation markers interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alfa (TNF-alpha), and monocyte chemoattractant protein-1 (MCP-1) levels were measured by enzyme-linked immunosorbent assay method. Oxidative stress markers, total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), and native thiol (NT) were measured using photometric methods. Oxidative stress index (OSI) was calculated according to TAS and TOS levels. The statistical analysis was performed by Statistical Package for Social Sciences version 22.0. After treatment with fluoxetine, imipenem, and combined groups, IL-1 beta, IL-6, TNF-alpha, MPO activity, MCP-1, hs-CRP, PCT, lactate, and the oxidative stress markers OSI, and disulfide levels were decreased (p < 0.05). The TT, NT, and TAS levels significantly statistically increased (p < 0.05). This research demonstrates that fluoxetine has effects as anti-inflammatory and antioxidant, and the combined treatment with antibioticum imipenem indicates positive synergistic effects in the experimental sepsis model.Öğe Modeling and simulation of the "IL-36 cytokine" and CAR-T cells interplay in cancer onset(World Scientific, 2022) Al-Utaibi, Khaled Abdul-Aziz; Nutini, Alessandro; Sohail, Ayesha; Arif, Robia; Tunç, Sümeyye; Sait, Sadiq M.Background: CAR-T cells are chimeric antigen receptor (CAR)-T cells; they are target-specific engineered cells on tumor cells and produce T cell-mediated antitumor responses. CAR-T cell therapy is the "first-line" therapy in immunotherapy for the treatment of highly clonal neoplasms such as lymphoma and leukemia. This adoptive therapy is currently being studied and tested even in the case of solid tumors such as osteosarcoma since, precisely for this type of tumor, the use of immune checkpoint inhibitors remained disappointing. Although CAR-T is a promising therapeutic technique, there are therapeutic limits linked to the persistence of these cells and to the tumor's immune escape. CAR-T cell engineering techniques are allowed to express interleukin IL-36, and seem to be much more efficient in antitumoral action. IL-36 is involved in the long-term antitumor action, allowing CAR-T cells to be more efficient in their antitumor action due to a "cross-talk" action between the "IL-36/dendritic cells" axis and the adaptive immunity. Methods: This analysis makes the model useful for evaluating cell dynamics in the case of tumor relapses or specific understanding of the action of CAR-T cells in certain types of tumor. The model proposed here seeks to quantify the action and interaction between the three fundamental elements of this antitumor activity induced by this type of adoptive immunotherapy: IL-36, "armored" CAR-T cells (i.e., engineered to produce IL-36) and the tumor cell population, focusing exclusively on the action of this interleukin and on the antitumor consequences of the so modified CAR-T cells. Mathematical model was developed and numerical simulations were carried out during this research. The development of the model with stability analysis by conditions of Routh-Hurwitz shows how IL-36 makes CAR-T cells more efficient and persistent over time and more effective in the antitumoral treatment, making therapy more effective against the "solid tumor". Findings: Primary malignant bone tumors are quite rare (about 3% of all tumors) and the vast majority consist of osteosarcomas and Ewing's sarcoma and, approximately, the 20% of patients undergo metastasis situations that is the most likely cause of death. Interpretation: In bone tumor like osteosarcoma, there is a variation of the cellular mechanical characteristics that can influence the efficacy of chemotherapy and increase the metastatic capacity; an approach related to adoptive immunotherapy with CAR-T cells may be a possible solution because this type of therapy is not influenced by the biomechanics of cancer cells which show peculiar characteristics.Öğe Preliminary findings on the role of high-frequency (5Hz) rTMS stimulation on M1 and pre-SMA regions in Parkinson's disease(Elsevier Ireland Ltd, 2020) Hanoğlu, Lütfü; Sarıcaoğlu, Mevhibe; Toprak, Güven; Helvacı Yılmaz, Nesrin; Yuluğ, BurakIt has been already shown that the motor symptoms of the Parkinson's Disease (PD) have been improved with high frequency rTMS although there is no consensus on the most suitable target brain localization for a maximal therapeutic efficacy. Here, we aimed to compare the therapeutic effect of high frequency (5Hz) rTMS stimulation on primary motor cortex (M1) and pre-supplementary (pre SMA) regions in patients with PD who were still on pharmacological treatment. The study included right-hand dominant16 patients with PD (5 females, 11 males) with demographically and clinically similar characteristics which were randomly assigned to group 1 (n=8) and group 2 (n=8) and received left M1 and the left pre-SMA rTMS procedure, respectively. Total and sequential motor scores of the Unified Parkinson's Disease Rating Scale (UPDRSmotor) were applied to all patients at the baseline and the patients were re-evaluated under the same clinical conditions one week after the end of the sessions. Comparisons of the UPDRS-motor scores between two groups yielded significant improvements after the rTMS on pre-SMA compared to M1 (M1 p=0.14; pre-SMA p=0.01). which were especially significant for the bradykinesia (p=0.04) and axial score related items (p=0.01). This is the first study that shows the effect of rTMS on pre-SMA and it appears to be a promising option in the treatment of PD.Öğe Kinesiotaping reduces knee diameter but has no effect on differences pain and edema following knee artroscopy(Galen S.R.O., 2018) Gülenç, Barış; Kuyucu, Ersin; Biçer, Hüseyin; Genç, S.G.; Yalçın, Sercan; Erdil, Mehmet EminPURPOSE OF THE STUDY Investigating the efficacy of kinesiotaping for the reduction of postoperative pain and swelling after invasive knee arthroscopy, which tend to develop in almost every patient undergoing this procedure. MATERIALS AND METHODS Kinesiotaping or sham taping was performed in a total of 42 patients who underwent invasive knee arthroscopy. Pain intensities; mid-thigh, knee, mid-calf, and ankle diameters; and VAS (Visual Analogue Scale) were recorded preoperatively and postoperatively. RESULTS However knee diameter was significantly greater in the control group compared to the group there is no significant differences were observed between the two groups´ pain scores at the postoperative period. There were also no significant statistical differences between the two groups with respect to mid-thigh, calf, and ankle diameters. CONCLUSIONS Kinesiotherapy could be used as an effective treatment method to relieve knee effusion after knee arthroscopy. However, both groups did not have significant differences with respect to pain and edema levels.
