Browsing by Author "Tuglu, MI"

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    The Effect of Centrifuge Duration on Fat Graft Survival
    Demirel, O; Karakol, P; Bozkurt, M; Tuglu, MI
    Background Although fat grafts are widely used for reconstruction and aesthetic purposes, their survival rates differ significantly. Centrifugation is one of the methods used to increase the survival of fat grafts. However, experimental studies examining the long-term outcomes of centrifugation duration are currently limited. Thus, in the present study, the effects of centrifugation duration on the survival of fat grafts were assessed using an animal model. Methods Thirty Sprague Dawley rats were included in the study and fat grafts were obtained from each specimen by excision from inguinal fat pads. Preparation protocols were administered as an en-bloc fat graft in Group 1, minced fat graft in Group 2, and fat graft centrifuged at 1,054 xg for 2 minutes, 3 minutes, and 4 minutes in Group 3, 4, and 5, respectively. After 12 weeks of follow-up, grafts were harvested and were subjected to histopathological evaluation based on an established scoring system. Results En-block fat grafts were associated with necrosis, fibrosis, inflammation, vacuole formation, and alterations in adipocyte morphology. Among the three centrifugation groups, Group 3 demonstrated the best adipocyte viability and vascularity. However, graft weights decreased in all experimental groups. Conclusion The centrifugation process may have positive effects on adipocyte survival by means of purifying the fat graft and increasing adipocyte concentration. When the centrifugal durations were compared, 3-minute centrifuge yielded the most favorable results.
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    Design of Pulsed Electromagnetic Field Generator and Applicator and the Effect of Wound Healing
    Kaya, A; Tuglu, MI; Kaya, D
    Today, biomedical devices have become an issue where system manufacturers are working intensively. At present, many domestic and foreign biomedical companies offer various EMA products. Electromagnetic fields (EMF) has a significant impact on our body. These fields are being used for bone problems, cartilage regeneration, and pain removal for physiotherapy purposes. Lately, EMFs are often used in in vitro and in vivo assays. In this study, in vivo test results of the applied pulsed electromagnetic fields (PEMF) with our designed Helmholtz coil array system are given. The skin wound healing conducted in rats as an experimental model provides important information for evaluating the efficacy and mechanism of these kind of treatments. For this purpose, effectiveness of PEMF compared to control groups on experimental skin healing effect was examined macroscopically. Compared with the control groups a faster wound healing process was followed by PEMF application at 75 Hz frequency.
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    Effects of Electromagnetic Fields Application on Experimental Varicocele Model in Rats
    Gülbagça, F; Sal, DH; Saygili, S; Sönmez, PK; Aydemir, I; Özkut, M; Öztürk, S; Gümüsay, M; Kaya, A; Tuglu, MI
    Varicocele is the most clinical condition which can be treated by surgery. The frequency in male is 20%. The half of infertile patient has this pathology which there is dilatation in plexus pampiniformis veins of testes. Varicocele causes increase of heat or increse of oxidative stres in seminifer tubules where they produce pathology for spermatogenesis. Low frequency magnetic fields are useful for the treatment of many area where they become important role. In this study the effect of low frequency magnetic fields on the experimental varicocele model of rat testes was investigated. The parameters for oxidative stres suggest eNOS and iNOS with apoptosis were evaluated by immunohistochemical staining. There was increaese in eNOS, iNOS and apoptosis by the varicocele experiment where there was testicular damage and low frequency magnetic fields caused decrease in oxidative stress and apoptosis. Application of magnetic fields can help the clinical varicocele pathologies either with treatment or supportive effect.
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    Effects of adipose tissue derived mesenchymal stem cells and conditioned medium on experimental premature ovarian insufficiency model
    Sen Halicioglu, B; Tuglu, MI
    Purpose: The aim of this study was to investigate the effects of adipose tissue derived mesenchymal stem cells (ADMSC) and conditioned medium (CM), which can be recommended for the treatment of chemotherapy-induced premature ovarian insufficiency (POI), on oxidative stress and apoptosis. Materials and Methods: In the study, adult female Wistar albino rats were divided into 4 groups; Control, POI, POI+ADMSC, POI+CM. H&E staining was performed for histopathological evaluations in the ovary and all ovarian follicles were counted. iNOS and Caspase3 expressions were shown immunohistochemically as markers of oxidative stress and apoptosis. Results: Follicular cell degenerations and vacuolization were observed in the ovaries of the POI group, while significant decreases were observed in these degenerations in the ADMSC and CM groups. Increased iNOS and Caspase3 expressions in the POI group were statistically significant decreased in both the ADMSC and CM groups. Conclusion: Mesenchymal stem cells and cell-free conditioned medium, which are increasingly used in the field of regenerative medicine, can be an alternative treatment strategy for POI by reducing apoptosis and oxidative stress, which are the main mechanisms of the disease.
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    Effects of various electromagnetic field applications on the aggressiveness of breast cancer line
    Gümüsay, M; Saygili, S; Aydemir, I; Kaya, A; Tuglu, MI
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    Design of Coils Driven by Pulsed Electromagnetic Field Generator and the Effect of Wound Healing in Rats
    Gümüsay, M; Gülbagça, F; Saygili, S; Aydemir, I; Kaya, A; Tuglu, MI
    Chronic wound healing is an important problem especially in diabetic and the elderly which is needed development of the current treatment methods. Electromagnetic fields (EMF) has a significant impact on our body. These fields are being used for bone problems, cartilage regeneration, and pain removal for physiotherapy purposes. Lately, EMFs are often used in in vitro and in vivo assays. In this study, in vivo test results of the applied pulsed electromagnetic fields (PEMF) with our designed Helmholtz coil array system are given. The skin wound healing conducted in rats as an experimental model provides important information for evaluating the efficacy and mechanism of these kind of treatments. For this purpose, effectiveness of PEMF compared to control groups on experimental skin healing effect was examined macroscopically. Compared with the control groups a faster wound healing process was followed by PEMF application at 75 Hz frequency.
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    Design of Antenna-Applicator for Electromagnetic Field Applications and Excitation Model for Rat and Heat Transfer Analysis
    Gümüsay, M; Gülbagça, F; Aydemir, I; Saygili, S; Kaya, A; Tuglu, MI
    There has been only a few technical progress which contribute to wound healing in the last century. Despite these advances wound healing is very hard issue to study because of its subjectivity, diversity and complexity of the wound healing process and diversity of patients. Molecules are insufficient in the chronic wound and unlike other cells multiplying endothelial cells interrupt the healing process. To restart this process, cells can be excitated by pulsed electromagnetic fields stimulation method. When a suitable frequency and waveform electromagnetic field (EMF) signal is applied to the target tissue with the help of a coil or applicator physiological effects occurs at the cellular size. Low-frequency electromagnetic fields are non-ionizing part of the EM spectrum and they are used as adjunct therapy in soft tissue injuries. In this study, an antenna-applicator design was performed and the effect of non-thermal pulsed radio frequency energy (PRFE) system to the wound created rat skin was examined.
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    The cytotoxic, neurotoxic, apoptotic and antiproliferative activities of extracts of some marine algae on the MCF-7 cell line
    Kurt, O; Özdal-Kurt, F; Tuglu, MI; Akçora, CM
    We investigated the cytotoxic, neurotoxic, apoptotic and antiproliferative effects of extracts from Petalonia fascia, Jania longifurca and Halimeda tuna on the MCF-7 breast cancer cell line. J. longifurca extracts were more toxic than those of P. fascia and H. tuna. The algal extracts showed significant toxic effects at different dilutions. The toxic effects were due to increased oxidative stress and resulted in apoptosis. Algal toxicity may exert negative effects through the food chain or by direct interaction. Algal toxicity also has potential for cancer therapy. The toxic effects that we observed may be especially important for therapy for breast tumors.
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    The relationship of 4-vinylcyclohexene diepoxide toxicity with cell death, oxidative stress, and gap junctions in female rat ovaries
    Sen Halicioglu, B; Saadat, KASM; Tuglu, MI
    Purpose It was aimed to investigate the damage caused by VCD toxicity in the ovary, which women working in the industrial field are frequently exposed to, and to show the relationship between gap junction protein, oxidative stress, and apoptosis, which is thought to be effective in the emergence of this damage. Methods Rats were divided into three groups as control, sham, and VCD. Histological stainings were performed for histopathological evaluations in ovary. Serum AMH level was measured with the ELISA. Then, iNOS, caspase 3, connexin 43 protein, and mRNA expression levels were analyzed by immunohistochemistry and RT-qPCR methods. Results As a result of the analyses, different amounts of degenerations such as hemorrhage, vacuolization, and fibrosis were observed in the ovary. VCD group AMH level decreased compared to control. In VCD group, iNOS and caspase 3 expressions increased, while connexin 43 expression decreased. Conclusions It was shown that VCD caused damage to all ovarian tissue. Also, it was revealed for the first time that VCD triggered apoptosis by increasing oxidative stress in the ovary and suppressed connexin 43 which was also effective in the survival of granulosa cells. The devastating effect of exposure to occupational chemicals such as VCD on fertility was demonstrated in this study.
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    Effect of geldanamycin on the expression of the matrix molecules and angiogenetic factors in a gastric cancer cell line
    Gürpinar, T; Kosova, F; Kurt, FO; Cambaz, SU; Yücel, AT; Umur, N; Tuglu, MI
    Angiogenesis is the formation of new blood vessels. Angiogenesis affects cancer growth and is a useful target for cancer therapeutics. The effects of geldanamycin on angiogenesis in cases of gastric cancer are poorly understood. We investigated the effects of different doses of 17-allylamino-17-demethoxygeldanamycin (17-AGG), a semi-synthetic derivative of geldanamycin, on the interactions between cellular matrix proteins and angiogenesis factors in a gastric cancer cell line. We examined cancer cells on laminin and collagen I coated surfaces to determine their response to the angiogenic effect of these matrix molecules. We also evaluated the expression levels of VEGF, MMP-9, ES and TSP-1 using ELISA. We found that application of 17-AAG to the gastric cancer cell line on culture dish plastic decreased VEGF, TSP-1, ES and MMP-9 expression, whereas of all of these proteins were increased by laminin and collagen coating. 17-AAG currently is in clinical trial phase 2 and may be a promising drug for treatment of gastric cancer.
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    In-Vitro Evaluation of Immunomodulation Effects of Mesenchymal Stem Cell-Derived Exosomes in Refractory Chronic Spontaneous Urticaria
    Ozdemir, AT; Kirmaz, C; Ozgul Ozdemir, RB; Oztatlici, M; Kilicarslan Sonmez, P; Tuglu, MI
    Objective: Approximately half of chronic spontaneous urticaria (CSU) patients are thought to have an autoimmune pathology, and they are resistant to current treatment approaches. Mesenchymal stem cells (MSCs) are adult cells that have been shown to be useful in many autoimmune pathologies due to their immunomodulation properties. This study aimed to investigate the immunomodulatory effects of MSCs, and exosomes isolated from refractory CSU patients.Materials and Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 5 refractory CSU patients and 5 healthy volunteers. The effects of MSCs isolated from CSU patients and healthy MSCs were compared. Co-culture experiments were performed to evaluate the efficacy of Mesenchymal Stem Cells and exosomes on PBMCs of CSU patients and healthy volunteers. To compare the resulting effects, changes in IFN-gamma, IL-4, IL-10, IL-17a, and TGF-(3 cytokines were detected by the ELISA method. Cell proliferations were detected with the CCK-8 kit.Results: The effects of autologous and allogeneic MSCs on IFN-gamma expressions were similar, both providing significant suppression at all cell ratios. However, IL-4 and IL-10 expression of PBMCs co-cultured with allogeneic MSCs significantly decreased while IL-17a and TGF-(3 expression increased significantly. In addition, our findings indicated that exosomes were capable of significant suppression at low PBMC ratios, regardless of autologous or allogeneic origin, but MSCs were more effective as the number of PBMCs increased.Conclusion: These preliminary findings from in-vitro experiments suggested that allogeneic MSC, or high-dose exosome administration may be a potential approach for treatment in CSU patients, most of whom are regarded as suffering from an autoimmune disease and resistant to current treatments. However, our findings need to be supported by clinical studies.
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    The effects of hypoxia on cancer stem cells in mouse neuroblastoma cell line
    Uluer, ET; Onal, T; Tuglu, MI; Ozbilgin, K; Vatansever, HS
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    Adipose-Derived Mesenchymal Stem Cell Transplantation in Chemotherapy-Induced Premature Ovarian Insufficiency: the Role of Connexin and Pannexin
    Sen Halicioglu, B; Saadat, KASM; Tuglu, MI
    In women undergoing chemotherapy, it is inevitable that infertility risk will increase because of impaired reproductive functions. Premature ovarian insufficiency (POI), which occurs as a devastating result of chemotherapy, is the complete depletion or dysfunction of ovarian follicles. Adipose-derived mesenchymal stem cells (ADMSCs) transplantation is among the alternative treatment methods for POI, which currently do not have an effective treatment method. Apoptosis of granulosa cells in POI is seen as the main mechanism of the disease. It is also reported that in addition to molecules directly associated with apoptosis, connexins, and pannexins are also potential effector molecules in apoptosis. The roles of these molecules in POI, which are known to play a role in many important mechanisms in the ovary, are unknown. In this study, it was aimed to analyze the expressions of Connexin43 and Pannexin1, which are thought to be effective in the formation of POI, and to show the relationship between the antiapoptotic effects of ADMSCs transplantation and these molecules in POI. For this purpose, Caspase3, Connexin43, Pannexin1 proteins, and mRNA expressions were analyzed by immunohistochemistry and RT-qPCR, and AMH levels were measured by ELISA. It was determined that Pannexin1, Caspase3 proteins, and mRNA levels increased in the POI, while Pannexin1 and Caspase3 expressions decreased in the ADMSCs treated group. While Connexin43 level decreased in POI, Connexin43 protein and mRNA levels increased in ADMSCs group. Consequently, this study demonstrated for the first time that Connexin43 and Pannexin1 were associated with apoptosis in POI. In addition, it was revealed that ADMSCs transplantation could produce antiapoptotic effects by modulating these molecules.
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    Comprassion of the Effect of Pulsed Electromagnetic Field and Pulsed Radio Frequency Energy on Wound Healing in Rats
    Gümüsay, M; Gülbagça, F; Saygili, S; Aydemir, I; Kaya, A; Tuglu, MI
    Delayed or not sufficiently good wound healing is a significant problem in medical treatment is needed to support in order to improve healing. Low frequency electromagnetic field (EMF) applications are seems to give this support. Disturbed vascularization, connective tissue formation, matrix exchange, and inflammation process in the wound environment are modified after EMF applications compared with control groups. Deteriorations in these factors which can be returned with the electrical impulses, DNA synthesis, transcription and transforms of protein synthesis, increasing of fibroblasts and endothelial cell proliferation indicate the presence of EMF mechanisms. Since the application and ambient conditions are kept constant but the type of the application has been changed in our study, it was provided that pulsed radio frequency energy (PRFE) is more effective and has more long-term improvement compared to pulsed electromagnetic fields (PEMF). The effects of these applications on cells and understanding of the mechanisms of the behavior will be much more significant and meaningful contribute to the treatment
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    The Histologic Evaluation of Atorvastatin and Melatonin Treatment on Oxidative Stress and Apoptosis of Diabetic Rat Pancreas
    Gürpinar, T; Ekerbiçer, N; Uysal, N; Barut, T; Tarakçi, F; Tuglu, MI
    In the diabetic state, there is an enhanced oxidative stress due to excessive production of reactive oxygen compounds and decreased bioavailability of nitric oxide. Antioxidant treatment has been used to prevent oxidative damage in diabetes. The objective of the present study was to explore the effects of atorvastatin (AT) and melatonin (MLT) on oxidative stress in diabetic rat pancreas. We also assessed nitric oxide synthase (NOS) activity and apoptosis. Diabetes was induced by an alkylating agent steptozotocin (STZ, 55 mg/kg, IP). Six weeks later rats were divided into five groups: STZ-induced diabetic group received atorvastatin (STZ+AT), STZ-induced diabetic group received melatonin (STZ+MLT) and STZ-induced diabetic group received atorvastatin and melatonin (STZ+AT+MLT). The vehicle-treated non-diabetic (CT) and diabetic group (STZ-CT) served as normoglycemic and diabetic controls. AT was given 8 mg/kg orally and MLT was given 10 mg/kg/IP once a day for 2 weeks beginning from the sixth week. Pancreatic tissue was examined by immunohistochemical methods. Although no significant difference was observed with respect to antioxidant status, NOS activity was tended to be higher in the untreated diabetic rats than in the treated rats. We observed that AT and MLT treatment improved the histopathological changes including apoptosis and oxidative stress in diabetic pancreas.
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    Development of Electromagnetic Field System for Providing Wound Healing on Created Wound Model Rat Skin and Sensor Application
    Gümüsay, M; Gülbagça, F; Aydemir, I; Saygili, S; Kaya, A; Tuglu, MI
    Electromagnetic field (EMF) radiation are formed by the acceleration of electric charge. Electric charges produce electric and magnetic energy in space when they move. These waves have different frequencies and wavelengths and when they interact with an object they can be refracted, reflected or absorbed. When a suitable frequency and waveform EM signal is applied to the target tissue with the help of a coil or applicator physiological effects will occur at the cellular size. Today studies revealed significant molecular mechanisms occurring during wound healing. Nonionizing part of the EM spectrum is low-frequency electromagnetic fields are used as adjunct therapy in soft tissue injuries. In this study, the main goal is development of systems which will give better results compared with conventional treatment methods taking into account the effect on rat skin. To achieve this, some improvements in output power, increased gain, versatility, easy adjustments are provided for the spiral and planar antenna-applicator design.
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    Histological investigations on thymus of male rats prenatally exposed to bisphenol A
    Aydemir, I; Kum, S; Tuglu, MI
    Bisphenol A is called as a endocrine-distrupting chemical because of the its steroid-like activity and it used in the construction of plastic containing materials. It is indicated that bisphenol A can pass the human serum, urine, follicular fluid, placenta and umblical cord as a result of the use of substances containing this agent. In this study, we aimed to investigate the effects of bisphenol A on the development of the thymus, a primary lymphoid organ which plays an important role in the specific immunity. The adult pregnant female rats were administered orally with bisphenol A (for 21 days) and postnatal thymus samples were obtained on day 21, 45 and 90 and were performed for histochemical and immunohistochemical staining for CD3, CD4, CD8 and CD79a and TUNEL assay for the apoptotic cells. Evaluation of all groups, CD3, CD4, CD8 and CD79a stainings were decreased in the experimental groups compared with control group. The apoptotic cells were determined in the all groups on day 90 as a result of the thymus involution. It is noted that there was not any histological and morphological damages in the rats prenatally exposed the bisphenol A. The effect of the bisphenol A is unknown in the future, but there is no problem in the adult rats. (C) 2018 Elsevier Ltd. All rights reserved.
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    Therapeutic effects of Lacosamide in a rat model of traumatic brain injury: A histological, biochemical and electroencephalography monitoring study
    Mete, M; Alpay, S; Aydemir, I; Unsal, UU; Collu, F; Özel, HF; Duransoy, YK; Kutlu, N; Tuglu, MI
    Objective: Traumatic Brain Injury (TBI) is a major cause of death and disability worldwide, especially in children and young adults. TBI can be classified based on severity, mechanism or other features. Inflammation, apoptosis, oxidative stress, and ischemia are some of the important pathophys-iological mechanisms underlying neuronal loss after TBI. Lacosamide (LCM) is an anticonvulsant compound approved for the adjunctive treatment of partial-onset seizures and neuropathic pain. This study aimed to investigate possible neuroprotective effects of LCM in a rat model of TBI. Material and methods: Twenty-eight adult male, Wistar albino rats were used. The rats were divided into 4 groups. Group 1 was the control group (n=7). Group 2 was the trauma group (n=7) where rats were treated with 100 mg/kg saline intraperitoneally (IP) twice a day. Groups 3 and 4, rats were treated with 6 (group 3, n=7) or 20 (group 4, n=7) mg/kg Lacosamide IP twice a day. For each group, brain samples were collected 72 hours after injury. Brain samples and blood were evaluated with histopathological and biochemical methods. In addition, electroencephalograpy monitoring results were compared. Results: The immunoreactivity of both iNOS and eNOS (oxidative stress markers) were decreased with LCM treatment compared to trauma group. The results were statistically significant (*** P<0.001). The treatments of low (56,17 +/- 9,69) and high-dose LCM (43,91 +/- 9,09) were decreased the distribution of HIF-1 alpha compared to trauma group (P<0.01). The number of apoptotic cells were decreased with LCM treatment the difference between the trauma group and 20mg/kg LCM treated group (9,55 +/- 1,02) was statistically significant (***P<0.001). Malondialdehyde level was reduced with LCM treatment. MDA level was significantly higher in trauma group compared to LCM treated groups (*** P<0.001). The level of Superoxide dismutase in the trauma group was 1,86 U/ml, whereas it was 36,85 U/ml in 20mg/kg LCM treated group (*** P<0.001). Delta strength of EEG in 20mg/kg LCM treated group were similar to control group values after LCM treatment. Conclusion: No existing study has produced results suggesting that different doses of LCM has therapeutic effect against TBI, using EEG recording in addition to histological and biochemical evaluations in rats. (C) 2021 Elsevier Ltd. All rights reserved.
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    The Contribution of Differentiated Bone Marrow Stromal Stem Cell-Loaded Biomaterial to Treatment in Critical Size Defect Model in Rats
    Tuglu, MI; Özdal-Kurt, F; Koca, H; Sarac, A; Barut, T; Kazanç, A
    Mandibular fractures present a challenge in maxillo-facial surgery due to difficulties in healing and complications. In recent years, advances in bio-engineering as well as stem-cell studies suggest that it may be possible to treat these fractures by stem cell treatment with biomaterials. In the present study, we explored the efficacy of differentiated stem cells placed on biomaterials on fracture treatment and its relation with oxidative stress and apoptosis. A 4 mm circular defect was made on the mandibulae of 20 adults Wistar rats. Hydroxyapatite gel (control, n=5) and bone marrow stromal cells differentiated into osteoblast-seeded hydroxyapatite gel (n=5) were implanted within these defects. We were also used empty cavities (n=5) and cavities filled with only cells (n=5) for negative controls. Animals were sacrificed after a 6-week healing period and samples were examined blindly by histological, immunohistochemical, radiological and morphometric methods. Compared to the control cavities that underwent no procedure or filled with just cells, there were significant (P<0.001) healings in both groups. Hydroxyapatite gel with differentiated stem cells on, however, yielded significantly (P<0.05) better new bone formation and osteoid production decreased fibrous tissue and increased cellular activity. Differentiated stromal cells combined with biomaterial accelerated the treatment in defects of critical volume within a 6-week period of healing, activated and resulted in significant formation of bone of higher quality. Promotion of bone formation by the helps of bioengineering and stromal cells has gained importance in the treatment and reconstruction of fractures.
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    Effects of alcohol during secondary neurulation in chick embryos
    Mete, M; Aydemir, I; Ünsal, ÜÜ; Özbilgin, K; Tuglu, MI; Gürcü, B
    Objective: Alcohol continues to be consumed even though its harmful effecs are well established. One of the most common damage of alcohol consumption is fetal alcohol syndrome, characterized by craniofacial anomalies, cardiac anomalies and neural tube defects. Therefore, understanding the molecular mechanisms underlying the alcohol-induced toxicity that occur with time and dose dependent manner is very important., Most of the studies in order to understand the effects of alcohol have been carried out on early neurulation, however its effects on late neurulation are still unknown. Therefore in this study, effects of alcohol on secondary neurulation were investigated in chick embryos. Methods: Leghorn breed of embryonic chicken eggs were used. At 50 h of incubation, 100 mu L 50% ethanol solution was injected. Depending on the period of exposure to alcohol, varying degrees of pathological disorders were detected in E3, E7 and E10 days. Results: Developmental delay, structural abnormalities, morphological abnormalities in the heart and face and especially presence of two spinal cord cavities were found. In addition, we also detected delays in the closure of the neural tube, cellular deformities and the structural abnormalities in notochord. While eNOS, iNOS, and TUNEL levels increased, while laminin levels decreased. Conclusion: In this study during late development, significant alcohol-induced morphological and histopathological changes were observed. We also determined Increased level of oxidative stress caused by alcohol was accompanied with the changes in matrix composition. Better understanding of these mechanisms which affect the cell behavior is important and will allow learning of harmful effects of alcohol.