28 results on '"AKOKAY, P."'
Search Results
2. Effects of rivaroxaban and apixaban on intimal hyperplasia in rabbits
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Mustafa Baris Kemahli, Tugra Gencpinar, Huseyin Dursun, Cagatay Bilen, Pinar Akokay, Serdar Bayrak, and Abidin Cenk Erdal
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rivaroxaban ,apixaban ,intimal hyperplasia ,thromboprophylaxis ,factor xa inhibitor ,Surgery ,RD1-811 ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Aim: Intimal hyperplasia causes vascular occlusion and its optimal treatment is unknown. In this study, we evaluated the effectiveness of Apixaban and Rivaroxaban treatment for preventing intimal hyperplasia in rabbits. Material and Methods: The rabbits (n = 15) were randomly divided into three groups. Reanastomoses are applied to the carotid artery. All groups received 100 U/kg heparin sodium during the operation period. Group A (n = 5) as a control group had no medication. Group B (n = 5) was given Rivaroxaban 3 mg/kg/day. In-group C (n = 5) Apixaban was administered per orally 10 mg/kg. At the end of the treatment on the 28th day, carotid artery specimens were excised and evaluated histologically. Results: Increased intima thickness was observed in the control group than the drug groups (P=0.019, P=0.007). It was found that there was no difference between groups in terms of lumen diameter, lumen area, tunica media area and tunica media thickness. There was difference between groups in terms of caspase 3 or TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining (p [Turk J Vasc Surg 2022; 31(3.000): 148-56]
- Published
- 2022
3. Angiotensin receptor-neprilysin inhibition by sacubitril/valsartan attenuates doxorubicin-induced cardiotoxicity in a pretreatment mice model by interfering with oxidative stress, inflammation, and Caspase 3 apoptotic pathway
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Ferhat Dindaş, Hüseyin Güngör, Mehmet Ekici, Pınar Akokay, Füsun Erhan, Mustafa Doğduş, and Mehmet Birhan Yılmaz
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2021
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4. Effect of bivalirudin on neointimal hyperplasia and endothelial proliferation in rabbit
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Gencpinar, Tugra, Bayrak, Serdar, Bilen, Cagatay, Kemahli, Baris, Akokay, Pinar, Baris, Mustafa, and Erdal, Cenk
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- 2021
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5. Reply to Letter to the Editor: 'Can ARNI Prevent Doxorubicin-Induced Cardiotoxicity?'
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Ferhat Dindaş, Hüseyin Güngör, Mehmet Ekici, Pınar Akokay, Füsun Erhan, Mustafa Doğduş, and Mehmet Birhan Yılmaz
- Subjects
Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2022
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6. Epigenetic Programming Through Breast Milk and Its Impact on Milk-Siblings Mating
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Hasan Ozkan, Funda Tuzun, Serpil Taheri, Peyda Korhan, Pınar Akokay, Osman Yılmaz, Nuray Duman, Erdener Özer, Esra Tufan, Abdullah Kumral, and Yusuf Özkul
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breast milk ,epigenetic regulatory mechanisms ,miRNA ,transgenerational inheritance ,cross-fostering ,life span ,Genetics ,QH426-470 - Abstract
BackgroundThe epigenetic effects of transmission of certain regulatory molecules, such as miRNAs, through maternal milk on future generations, are still unknown and have not been fully understood yet. We hypothesized that breastfeeding regularly by adoptive-mother may cause transmission of miRNAs as epigenetic regulating factors to the infant, and the marriage of milk-siblings may cause various pathologies in the future generations.ResultsA cross-fostering model using a/a and Avy/a mice had been established. F2 milk-sibling and F2 control groups were obtained from mating of milk-siblings or unrelated mice. Randomized selected animals in the both F2 groups were sacrificed for miRNA expression studies and the remainings were followed for phenotypic changes (coat color, obesity, hyperglycemia, liver pathology, and life span). The lifespan in the F2 milk-sibling group was shorter than the control group (387 vs 590 days, p = 0.011) and they were more obese during the aging period. Histopathological examination of liver tissues revealed abnormal findings in F2 milk-sibling group. In order to understand the epigenetic mechanisms leading to these phenotypic changes, we analyzed miRNA expression differences between offspring of milk-sibling and control matings and focused on the signaling pathways regulating lifespan and metabolism. Bioinformatic analysis demonstrated that differentially expressed miRNAs were associated with pathways regulating metabolism, survival, and cancer development such as the PI3K-Akt, ErbB, mTOR, and MAPK, insulin signaling pathways. We further analyzed the expression patterns of miR-186-5p, miR-141-3p, miR-345-5p, and miR-34c-5p and their candidate target genes Mapk8, Gsk3b, and Ppargc1a in ovarian and liver tissues.ConclusionOur findings support for the first time that the factors modifying the epigenetic mechanisms may be transmitted by breast milk and these epigenetic interactions may be transferred transgenerationally. Results also suggested hereditary epigenetic effects of cross-fostering on future generations and the impact of mother-infant dyad on epigenetic programming.
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- 2020
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7. Impact of postnatal nutrition on neurodevelopmental outcome in rat model of intrauterine growth restriction.
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BAYSAL, B., MIÇILI, S., ENGÜR, D., AKOKAY, P., KARABULUT, A. R., KESKINOĞLU, P., YILMAZ, O., and KUMRAL, A.
- Abstract
OBJECTIVE: There are limited data on nutritional management of infants with intrauterine growth restriction (IUGR). Postnatal protein supplementation for promoting growth is a common clinical practice in neonatology. The present study aims to investigate the consequences of protein supplementation on long-term growth, brain and body weight, brain histology and behavioral outcome in a rat model of IUGR. MATERIALS AND METHODS: Twenty-four IUGR-formed rat puppies and 12 healthy puppies were included in the study. IUGR model was established by low (10%) protein diet throughout pregnancy together with intraperitoneal injection of lipopolysaccharide (LPS). Pups were started to be fed with either standard protein (SP), or high protein (HP) diet until postnatal day (PN) 35. Puppies in the control group were given SP diet for 35 days. Six pups from each group were sacrificed at PN7, remaining six were evaluated by Morris water maze test between PN 30 to 35 days and then sacrificed at PN35. Histologic evaluation of brain tissue was performed at PN7 and PN35. RESULTS: IUGR group displayed lower body and brain weights at PN7 when compared with control. At PN35, SP group achieved similar brain/body weight ratios with control, whereas HP group displayed lowest brain/body weight ratio. The number of TUNEL positive cells was significantly higher and myelin basic protein and oligodendrocyte marker O4 immunoreactivity were significantly lower in HP group when compared with SP at PN35. Neuronal density in prefrontal cortex and hippocampus at PN7 were similar among SP and HP groups, but significantly lower in HP group when compared with SP at PN35. SP group displayed better results in the Morris water maze test when compared with HP group. CONCLUSIONS: Although postnatal HP support is associated with increase in body weight at PN35, it did not result in better brain/body weight ratios in the rat model of IUGR. In IUGR rats, HP diet was associated with increased apoptosis in brain tissue with lower neuronal density and decreased myelination when compared to SP. Furthermore, better neurodevelopmental scores were achieved by SP diet rather than HP support in IUGR. [ABSTRACT FROM AUTHOR]
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- 2022
8. The effect of lipoic acid on wound healing in a full thickness uterine injury model in rats
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Micili, Serap Cilaker, Goker, Asli, Sayin, Oya, Akokay, Pinar, and Ergur, Bekir Uğur
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- 2013
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9. The healing effect of topical tea tree oil on pressure ulcers in a rat model
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Oran, Nazan Tuna, Alan, Nurten, Akokay, Pinar, Büyükçoban, Sibel, and Ugur Ergür, Bekir
- Abstract
Objective:The effects of topical tea tree oil (TTO) on the healing of pressure ulcers (PUs) in an animal model was evaluated.Method:To induce PUs, ischaemia-reperfusion cycles were performed by the external application of magnetic plates, with an ischaemic period of eight hours and a reperfusion period of 16 hours. Male and female Wistar rats were divided into three equally sized groups (n=20): one group received topical glycerin twice daily, another group received topical 10% (volume/volume (v/v)) TTO in glycerin twice daily; and the remaining group was untreated. The animals were assessed after one, four, seven and 14 cycles of ischaemia-reperfusion by thermal camera imaging, and then euthanised and sampled to investigate the degree of inflammation, collagen synthesis and apoptosis in the PUs.Results:Although topical glycerin alone suppressed local inflammation and apoptosis, this suppressive effect was accentuated at all timepoints by the application of topical TTO + glycerin. Similarly, an increase in collagen synthesis was observed in the glycerin group and this was accentuated by TTO at all timepoints. Parallel to the histological findings, the local temperature had decreased significantly on days 4 and 7 for both treatment groups (glycerin and TTO+glycerin).Conclusion:In this study, treatment with 10% (v/v) TTO in glycerin effectively suppressed skin inflammation and apoptosis, while it increased collagen synthesis during PU formation.
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- 2023
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10. Effects of resveratrol on alpha-amanitin-induced nephrotoxicity in BALB/c mice
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Arici, MA, primary, Sahin, A, additional, Cavdar, Z, additional, Ergur, BU, additional, Ural, C, additional, Akokay, P, additional, Kalkan, S, additional, and Tuncok, Y, additional
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- 2019
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11. Effects of resveratrol on alpha-amanitin-induced nephrotoxicity in BALB/c mice.
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Arici, MA, Sahin, A, Cavdar, Z, Ergur, BU, Ural, C, Akokay, P, Kalkan, S, and Tuncok, Y
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NEPHROTOXICOLOGY ,CULTIVATED mushroom ,OXIDANT status ,ANTIDOTES ,HEPATOTOXICOLOGY ,RESVERATROL ,MICE - Abstract
Alpha-amanitin (α-AMA), the primary toxin of Amanita phalloides, is known to cause nephrotoxicity and hepatotoxicity. Resveratrol is an antioxidant that has shown efficacy in many nephrotoxicity models. The aim of this study was to investigate the effects of resveratrol against the early and late stages of α-AMA-induced nephrotoxicity, compared to those of silibinin, a well-known antidote for poisoning by α-AMA-containing mushrooms. Mice kidney tissues were obtained from five groups: (1) α-AMA + NS (simultaneous administration of α-AMA and normal saline), (2) α-AMA + SR (simultaneous administration of α-AMA and resveratrol), (3) α-AMA + 12R (resveratrol administration 12 h after α-AMA administration), (4) α-AMA + 24R (resveratrol administration 24 h after α-AMA administration), and (5) α-AMA + Sil (simultaneous administration of α-AMA and silibinin). Histomorphological and biochemical analyses were performed to evaluate kidney damage and oxidant–antioxidant status in the kidney. Scores of renal histomorphological damage decreased significantly in the early resveratrol treatment groups (α-AMA + SR and α-AMA + 12R), compared to those in the α-AMA + NS group (p < 0.05). Catalase levels increased significantly in the α-AMA + SR group, compared to those in the α-AMA + NS group (p < 0.001). Early resveratrol administration within 12 h after α-AMA ingestion may reverse the effects of α-AMA-induced nephrotoxicity, partly through its antioxidant action, thereby suggesting its potential as a treatment for poisoning by α-AMA-containing mushrooms. [ABSTRACT FROM AUTHOR]
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- 2020
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12. Effect of magnesium sulfate on renal ischemia-reperfusion injury in streptozotocin-induced diabetic rats.
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AKAN, M., OZBILGIN, S., BOZTAS, N., CELIK, A., OZKARDESLER, S., ERGUR, B. U., GUNELI, E., SISMAN, A. R., AKOKAY, P., and MESERI, R.
- Abstract
OBJECTIVE: Ischemia/reperfusion (I/R) injury is a major cause of acute organ dysfunction and I/R related acute renal failure is a common clinical problem. Diabetes mellitus is defined as a risk factor for the development of acute renal injury as diabetic nephropathy compromises the renal tolerance to ischemia. The aim of this study was to investigate the protective effect of magnesium sulfate in a diabetic rat renal I/R injury model. MATERIALS AND METHODS: Diabetes mellitus was induced using streptozotocin. Thirty-five rats were divided into five groups: Group I: Nondiabetic sham group; Group II: Diabetic sham group; Group III: Diabetic I/R group; Group IV: Diabetic I/R + prophylactic (preischemic) MgSO
4 ; and Group V: Diabetic I/R + therapeutic (following reperfusion) MgSO4 group. MgSO4 was administered 200 mg/kg intraperitoneally. Renal I/R (45 min ischemia + 4 h reperfusion) was induced in both kidneys. Histomorphological, immunohistochemical (caspase-3 and iNOS) and biochemical (BUN, Creatinine) methods were performed to assess the blood and tissue samples. RESULTS: Histomorphological injury scores and immunostaining intensities (for both caspase-3 and iNOS) were significantly lower in the MgSO4 administered groups (prophylactic and therapeutic) than in the Diabetic IR group. There were no significant differences in biochemical parameters (BUN, Cr) between the MgSO4 administered groups and the Diabetic IR group. CONCLUSIONS: In the present study, it was demonstrated by histomorphological and immunohistochemical methods that magnesium sulfate administration before ischemia or following reperfusion significantly reduced renal I/R injury in a diabetic rat model. [ABSTRACT FROM AUTHOR]- Published
- 2016
13. Effect of magnesium sulfate on renal ischemia-reperfusion injury in streptozotocin-induced diabetic rats
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Mert Akan, Ozbilgin, S., Boztas, N., Celik, A., Ozkardesler, S., Ergur, B. U., Guneli, E., Sisman, A. R., Akokay, P., and Meseri, R.
- Abstract
OBJECTIVE: Ischemia/reperfusion (I/R) injury is a major cause of acute organ dysfunction and I/R related acute renal failure is a common clinical problem. Diabetes mellitus is defined as a risk factor for the development of acute renal injury as diabetic nephropathy compromises the renal tolerance to ischemia. The aim of this study was to investigate the protective effect of magnesium sulfate in a diabetic rat renal I/R injury model.
14. PP-021 A SPECIAL STUDY MODULE IN MEDICAL EDUCATION: THE INVESTIGATION OF POSSIBLE PROTECTIVE EFFECTS OF LIPOIC ACID ON P38 MAPK SIGNALING PATHWAY AGAINST CISPLATIN INDUCED TESTICULAR DAMAGE IN RATS
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Sifil, Sedenay, Sezer, Beyza, Çakırlar, Hatice, Tunga, Elif Ekin, Ural, Cemre, Koçak, Ayşe, Akokay, Pınar, Harmancı, Duygu, Pekçetin, Çetin, and Çavdar, Zahide
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- 2018
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15. PP-01 AN EXAMPLE OF A SPECIAL STUDY MODULE IN DOKUZ EYLUL SCHOOL OF MEDICINE: THE PROTECTIVE EFFECTS OF LIPOIC ACID VIA PI3K/AKT SIGNALING PATHWAY AGAINST ON CISPLATIN INDUCED TESTICULAR INJURY
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Kayataş, Arda, Gül, Büşra, Yıldız, Ezgi, Karabacak, Can Ahmet, Emik, İbrahim, Koçak, Ayşe, Akokay, Pınar, Harmancı, Duygu, Pekçetin, Çetin, and Çavdar, Zahide
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- 2018
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16. The effect of edoxaban on apoptosis in an abdominal aortic aneurysm model in rats.
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Gencpınar T, Bilen C, Kemahli B, Sayarer C, Akokay P, Bayrak S, and Erdal C
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Background: This study aimed to evaluate the effects of edoxaban, which is used in venous thrombosis, systemic embolism, and stroke, on an aortic aneurysm model and to demonstrate the pharmacokinetic and molecular effects of edoxaban through the induction of apoptosis., Methods: In this double-blind experimental study, 21 Wistar albino male rats (mean weight: 290 g; range, 280 to 300 g) were divided into three groups: the sham group (n=7), the abdominal aortic aneurysm (AAA) group (n=7), and the AAA-edoxaban group (n=7). Edoxaban 10 mg/kg was given to the AAA-edoxaban group by oral gavage daily for 30 days. At the end of 30 days, the aneurysmal aorta was surgically removed and histologically examined. The abdominal aorta was surgically exposed and wrapped with a calcium chloride (0.5 mol/L) sponge for 10 min., Results: Immunohistochemically, aortic sections were marked with caspase-3 and caspase-9 antibodies. It was observed that the pathways that trigger apoptosis (caspase-3 and caspase-9; p <0.004 and p <0.005, respectively) were significantly reduced in the AAA-edoxaban group compared to the AAA group. In the AAA-edoxaban group, it was observed that the expansion in aortic diameter and the deterioration in the elastic fibril structure in the aortic aneurysm were decreased as a result of edoxaban treatment. Edoxaban treatment was observed to reduce cell death in both the tunica intima and tunica media., Conclusion: This study provided strong evidence of the protective effect of edoxaban on aortic aneurysm-related vascular damage by reducing apoptosis and mitophagy., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2024, Turkish Society of Cardiovascular Surgery.)
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- 2024
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17. Histomorphological Investigation of Microfracture Location in a Rabbit Osteochondral Defect Model.
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Kilic AI, Hapa O, Ozmanevra R, Pak T, Akokay P, Ergur BU, and Kosay MC
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- Rabbits, Animals, Aggrecans, Fibrocartilage, Collagen Type I, Collagen Type II, Fractures, Stress, Intra-Articular Fractures
- Abstract
Background: Microfracture is the most common treatment for cartilage defects of the knee. In microfracture surgery, holes are randomly drilled into the subchondral bone. The effect of the hole's location on its interaction with the cartilage defect site and its influence on the healing process is currently uncertain ., Purpose: To investigate the effects of different microfracture locations on healing in a rabbit knee osteochondral defect model., Study Design: Controlled laboratory study., Methods: A total of 29 adult New Zealand White rabbits were divided into 5 groups. In the healthy cartilage control group (n = 5), no surgical procedure was performed. Cylindrical full-thickness cartilage defects (5 × 3 mm) were created in the patellar groove of the remaining 24 rabbits. In the defect control group (n = 6), only the defect was created. A microfracture was performed at the 12-o'clock position (group peripheral single; n = 6), centrally (group central; n = 6), and at the 12- and 6-o'clock positions (group peripheral double; n = 6) of the defect. The animals were sacrificed after 8 weeks. Cartilage healing was evaluated by International Cartilage Regeneration & Joint Preservation Society (ICRS) score, modified O'Driscoll score, immunohistochemical analysis (type 1 collagen, type 2 collagen, and aggrecan), and scanning electron microscopy analysis., Results: In group peripheral double, better cartilage healing was observed in all parameters compared with the other groups ( P < .05). Group peripheral double had the greatest amount of filling, with 79% of the defect area filled with fibrocartilage repair tissue. Group peripheral single demonstrated filling of 73% of the defect area, group central 56%, and the defect control group 45%. The ICRS score was significantly higher in group peripheral single compared with group central and the defect control group. Type 2 collagen and aggrecan immunoreactivity were significantly stronger in group central than group peripheral single and the defect control group ( P < .05)., Conclusion: Microfracture performed at the peripheral margin of the defect had better filling characteristics in a rabbit model. This study suggests that interaction of pluripotent cells released from the microfracture site with the intact cartilage may enhance the quality of the repair tissue., Clinical Relevance: The location of microfracture holes in relation to the peripheral border of the osteochondral defect (to the intact cartilage) is important in both the quality and the quantity of the newly formed repair tissue.
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- 2023
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18. Effects of rivaroxaban on myocardial mitophagy in the rat heart.
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Gencpinar T, Bilen C, Kemahli B, Kacar K, Akokay P, Bayrak S, and Erdal C
- Abstract
Background: This study aims to demonstrate the efficacy of rivaroxaban's pharmacokinetic effects on myocardial mitophagy in rats by inducing apoptosis., Methods: In this double-blind experiment, Wistar albino male rats were randomly divided into three groups for an experimental ischemia model: the sham group (Group 1; n=7), the control group (Group 2; n=7), and the drug group (Group 3; n=7). Rivaroxaban was perorally administered with gavage at 2 mg/ kg/day for 28 days in Group 3. The heart was surgically exposed, and ischemia was achieved by compressing the vessel around the proximal part of the left anterior descending coronary artery for 10 min. The heart tissue was then transected, removed, and morphologically and immunohistochemically examined under a light microscope., Results: Heart sections were immunohistochemically marked with caspase 3, caspase 9, APAF1, and Bcl-2 antibodies. Group 1 was compared to the rivaroxaban-treated group, and the pathways inducing apoptosis was increased (caspase 3, caspase 9, APAF1; p<0.015, p<0.004, and p<0.01, respectively) and Bcl-2, the molecule that inhibits apoptosis, was decreased (p<0.01) in Group 3., Conclusion: The present study provides an evidence that the mitophagy response is less in rivaroxaban-treated rats, showing the protective effect of rivaroxaban against acute ischemia. Rivaroxaban-treated rats may have reduced cell death in cardiomyocytes during myocardial infarction and thus have reduced damage to the heart tissue caused by myocardial infarction., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2023, Turkish Society of Cardiovascular Surgery.)
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- 2023
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19. Loofah-chitosan and poly (-3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) based hydrogel scaffolds for meniscus tissue engineering applications.
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Baysan G, Colpankan Gunes O, Akokay P, Husemoglu RB, Ertugruloglu P, Ziylan Albayrak A, Cecen B, and Havitcioglu H
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- Tissue Engineering methods, Hydrogels pharmacology, Tissue Scaffolds chemistry, 3-Hydroxybutyric Acid, Polyesters chemistry, Hydroxybutyrates, Chitosan chemistry, Luffa, Meniscus
- Abstract
The meniscus is a fibrocartilaginous tissue that is very important for the stability of the knee joint. However, it has a low ability to heal itself, so damage to it will always lead to articular cartilage degeneration. The goal of this study was to make a new type of meniscus scaffold made of chitosan, loofah mat, and PHBV nanofibers, as well as to describe hydrogel composite scaffolds in terms of their shape, chemical composition, mechanical properties, and temperature. Three different concentrations of genipin (0.1, 0.3, and 0.5 %) were used and the optimal crosslinker concentration was 0.3 % for Chitosan/loofah (CL) and Chitosan/loofah/PHBV fiber (CLF). Scaffolds were seeded using undifferentiated MSCs and incubated for 21 days to investigate the chondrogenic potential of hydrogel scaffolds. Cell proliferation analyses were performed using WST-1 assay, GAG content was analyzed, SEM and fluorescence imaging observed morphologies and cell attachment, and histological and immunohistochemical studies were performed. The in vitro analysis showed no cytotoxic effect and enabled cells to attach, proliferate, and migrate inside the scaffold. In conclusion, the hydrogel composite scaffold is a promising material for engineering meniscus tissue., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)
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- 2022
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20. Fabrication of 3D Printed poly(lactic acid) strut and wet-electrospun cellulose nano fiber reinforced chitosan-collagen hydrogel composite scaffolds for meniscus tissue engineering.
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Gunes OC, Kara A, Baysan G, Bugra Husemoglu R, Akokay P, Ziylan Albayrak A, Ergur BU, and Havitcioglu H
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- Animals, Rabbits, Cellulose, Collagen, Hydrogels chemistry, Iridoids, Polyesters chemistry, Printing, Three-Dimensional, Tissue Engineering, Tissue Scaffolds chemistry, Water, Chitosan chemistry, Meniscus
- Abstract
The main goal of the study was to produce chitosan-collagen hydrogel composite scaffolds consisting of 3D printed poly(lactic acid) (PLA) strut and nanofibrous cellulose for meniscus cartilage tissue engineering. For this purpose, first PLA strut containing microchannels was incorporated into cellulose nanofibers and then they were embedded into chitosan-collagen matrix to obtain micro- and nano-sized topographical features for better cellular activities as well as mechanical properties. All the hydrogel composite scaffolds produced by using three different concentrations of genipin (0.1, 0.3, and 0.5%) had an interconnected microporous structure with a swelling ratio of about 400% and water content values between 77 and 83% which is similar to native cartilage extracellular matrix. The compressive strength of all the hydrogel composite scaffolds was found to be similar (∼32 kPa) and suitable for cartilage tissue engineering applications. Besides, the hydrogel composite scaffold comprising 0.3% (w/v) genipin had the highest tan δ value (0.044) at a frequency of 1 Hz which is around the walking frequency of a person. According to the in vitro analysis, this hydrogel composite scaffold did not show any cytotoxic effect on the rabbit mesenchymal stem cells and enabled cells to attach, proliferate and also migrate through the inner area of the scaffold. In conclusion, the produced hydrogel composite scaffold holds great promise for meniscus tissue engineering.
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- 2022
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21. Reply to Letter to the Editor: "Can ARNI Prevent Doxorubicin-Induced Cardiotoxicity?"
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Dindaş F, Güngör H, Ekici M, Akokay P, Erhan F, Doğduş M, and Yılmaz MB
- Published
- 2022
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22. Angiotensin receptor-neprilysin inhibition by sacubitril/valsartan attenuates doxorubicin-induced cardiotoxicity in a pretreatment mice model by interfering with oxidative stress, inflammation, and Caspase 3 apoptotic pathway.
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Dindaş F, Güngör H, Ekici M, Akokay P, Erhan F, Doğduş M, and Yılmaz MB
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- Aminobutyrates, Angiotensins, Animals, Biphenyl Compounds, Caspase 3 metabolism, Doxorubicin, Inflammation, Mice, Oxidative Stress, Receptors, Angiotensin, Valsartan, Cardiotoxicity, Neprilysin
- Abstract
Objective: Doxorubicin (DOX) is a well-known cardiotoxic agent, whereas sacubitril/valsartan (Sac/Val) is an effective treatment option in heart failure. In this study, we aimed to evaluate the effect of Sac/Val on DOX-induced cardiotoxicity in pretreatment mice model., Methods: A total of 24 mice were equally classified into 4 groups; control group, DOX (20 mg/kg; fifth day), Sac/Val (80 mg/kg), and Sac/Val+DOX (Sac/Val was given from day one of the study before doxorubicin administration). Electrocardiography parameters, including durations of QRS, ST, QT, PP segment, and QT/PQ index were measured. Total antioxidant status (TAS), total oxidant status (TOS), tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), IL-6, NT-proBNP concentrations, and Caspase 3 activity were evaluated., Results: At the end of the 9-day study duration, QRS, ST, QT intervals, QT/PQ index and TAS, TOS, TNF-α, IL-1β, IL-6 levels were significantly higher in the DOX group than in the control group (p<0.001). Moreover, there were significant differences only in the PP interval when comparing the Sac/Val+DOX and control groups (p<0.001). QRS, ST, QT intervals, and QT/PQ index, TAS, TOS, TNF-α, IL-1β, IL-6 levels were significantly lower in the Sac/Val+ DOX group compared with the DOX group (p<0.001). Furthermore, NT-proBNP levels were lower in the Sac/Val+DOX group compared with the DOX group along with less Caspase 3 apoptosis., Conclusion: Sac/Val seems to be cardioprotective against DOX-induced cardiotoxicity in pretreatment mice model. These findings can be attributed to the antiarrhythmic, anti-inflammatory, antioxidant, and antiapoptotic effects of Sac/Val as shown in this study.
- Published
- 2021
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23. Epigenetic Programming Through Breast Milk and Its Impact on Milk-Siblings Mating.
- Author
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Ozkan H, Tuzun F, Taheri S, Korhan P, Akokay P, Yılmaz O, Duman N, Özer E, Tufan E, Kumral A, and Özkul Y
- Abstract
Background: The epigenetic effects of transmission of certain regulatory molecules, such as miRNAs, through maternal milk on future generations, are still unknown and have not been fully understood yet. We hypothesized that breastfeeding regularly by adoptive-mother may cause transmission of miRNAs as epigenetic regulating factors to the infant, and the marriage of milk-siblings may cause various pathologies in the future generations., Results: A cross-fostering model using a/a and A
vy /a mice had been established. F2 milk-sibling and F2 control groups were obtained from mating of milk-siblings or unrelated mice. Randomized selected animals in the both F2 groups were sacrificed for miRNA expression studies and the remainings were followed for phenotypic changes (coat color, obesity, hyperglycemia, liver pathology, and life span). The lifespan in the F2 milk-sibling group was shorter than the control group (387 vs 590 days, p = 0.011) and they were more obese during the aging period. Histopathological examination of liver tissues revealed abnormal findings in F2 milk-sibling group. In order to understand the epigenetic mechanisms leading to these phenotypic changes, we analyzed miRNA expression differences between offspring of milk-sibling and control matings and focused on the signaling pathways regulating lifespan and metabolism. Bioinformatic analysis demonstrated that differentially expressed miRNAs were associated with pathways regulating metabolism, survival, and cancer development such as the PI3K-Akt, ErbB, mTOR, and MAPK, insulin signaling pathways. We further analyzed the expression patterns of miR-186-5p, miR-141-3p, miR-345-5p, and miR-34c-5p and their candidate target genes Mapk8, Gsk3b, and Ppargc1a in ovarian and liver tissues., Conclusion: Our findings support for the first time that the factors modifying the epigenetic mechanisms may be transmitted by breast milk and these epigenetic interactions may be transferred transgenerationally. Results also suggested hereditary epigenetic effects of cross-fostering on future generations and the impact of mother-infant dyad on epigenetic programming., (Copyright © 2020 Ozkan, Tuzun, Taheri, Korhan, Akokay, Yılmaz, Duman, Özer, Tufan, Kumral and Özkul.)- Published
- 2020
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24. Efficiency of Minimized Circuits of a Heart Roller Pump on Systemic Inflammatory Response Syndrome and Multiorgan Effects in a Rat Model.
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Bayrak S, Gencpinar T, Akkaya G, Bilen Ç, Akokay P, Dereli N, Yılmaz O, and Metin K
- Subjects
- Animals, Disease Models, Animal, Equipment Design, Male, Myocardial Ischemia diagnosis, Myocardial Ischemia etiology, Rats, Rats, Wistar, Systemic Inflammatory Response Syndrome complications, Systemic Inflammatory Response Syndrome diagnosis, Cardiopulmonary Bypass instrumentation, Myocardial Ischemia prevention & control, Myocardium pathology, Systemic Inflammatory Response Syndrome therapy
- Abstract
Background: The aim of this study is to compare the effects of tubing length on systemic inflammatory response syndrome and myocardial protection in a rat model of cardiopulmonary bypass (CPB) from a histological standpoint., Methods: Twelve adult male Wistar Albino rats weighing >180 g were randomly selected and divided into 2 groups. In 1 group, the pump lines were kept 1 m shorter than standard. The right jugular vein and tail artery were cannulated using a 16-gauge catheter. Animals received 500 IU/kg intravenous heparin. Cardiac index and rectal temperature were set at 2.4 mL and 36°C, respectively. Total line volume was maintained at 8 mL. A roller pump was adjusted to supply a blood flow of 6 to 28 mL/min (mean 10 mL/min), similar to the typical cardiac output of rats. CPB duration was 15 minutes throughout the experiment. After sacrifice, tissue samples were collected from heart, liver, and kidney for histomorphologic examination., Results: All histochemical and histomorphologic analyses, performed by 2 blinded researchers, revealed band loss in cardiomyocytes, mononuclear (MNL) cell infiltration, and impaired fibrillar organization in the standard-line group. Additionally in that group, sinusoidal dilatation in the liver, low-level congestion, focal necrosis, and periportal MNL infiltration were noted. In the shorter-line group, on the other hand, MNL cell infiltration, band loss in myofibrils, and cardiomyocyte degeneration were rarely observed. Higher liver congestion and lower MNL cell infiltration were observed in the shorter-line group. No significant differences were found in kidney samples., Conclusion: In a shorter-line roller pump test model, less multiorgan damage and fewer systemic inflammatory responses were observed. It may be applicable to keep CPB lines as close to the table as possible, especially in pediatric cardiac surgery cases., (2020 Forum Multimedia Publishing, LLC)
- Published
- 2020
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25. Effects of carbon dioxide insufflation on anastomosis remodeling at a carotid artery site in rabbits.
- Author
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Gençpınar T, Akkaya G, Bilen Ç, Akokay P, Yılmaz O, and Çatalyürek H
- Abstract
Introduction: Use of carbon dioxide (CO
2 ) insufflation (CDI) on the surgical field during heart surgery has become widespread, and in some units routine., Aim: To assess the effects of CDI on endothelial dysfunction in a carotid artery model in rabbits., Material and Methods: Twelve randomly selected rabbits were divided into two groups. Right carotid arteries of the animals were transected and sutured with running suture technique. Then, 1 l/min CO2 insufflation was initiated with a 45° angle. In the control group, the anastomotic field was irrigated with 0.1 ml/s flow of 0.9% saline. At day 28, the carotid artery segments were removed and prepared for histological specimens., Results: In the cross-sections of the control group vessel samples, thickening of the tunica intima was observed. Scoring the quantity of endothelial nitric oxide synthase (e-NOS) and α-smooth muscle actin (α-SMA) positive staining revealed a nonsignificant difference between the experimental groups ( p = 0.07). In the CO2 group, the intimal hyperplasia ( p = 0.2) and the thickness of the tunica media ( p = 0.2) were indistinguishable when compared to the control group. The mean luminal diameters and luminal areas of the experimental groups were all evaluated by histomorphometry and a significant differences was found between luminal areas ( p = 0.016). On the other hand, no significant difference was found between mean luminal diameters ( p = 0.055)., Conclusions: Our study indicated that CDI can affect endothelial cell damage and the mean luminal diameters.- Published
- 2018
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26. Effects of rivaroxaban on intimal hyperplasia and smooth muscle cell proliferation at the carotid artery anastomosis site in rabbits.
- Author
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Akkaya G, Bilen Ç, Gençpınar T, Akokay P, and Uğurlu B
- Subjects
- Anastomosis, Surgical, Animals, Disease Models, Animal, Factor Xa Inhibitors administration & dosage, Male, Myocytes, Smooth Muscle drug effects, Rabbits, Rivaroxaban administration & dosage, Tunica Intima drug effects, Carotid Arteries pathology, Cell Proliferation drug effects, Factor Xa Inhibitors pharmacology, Hyperplasia prevention & control, Rivaroxaban pharmacology
- Abstract
Objective: This study aimed to assess the effect of new generation oral, direct factor Xa inhibitor rivaroxaban on intimal hyperplasia and smooth muscle cell proliferation at the carotid artery anastomosis site of rabbits., Methods: In total, 14 New Zealand male rabbits weighing 3-3.5 kg were randomized into two groups. Group A (7 rabbits) served as the control group and received no medication. Rivaroxaban was perorally administered to group B (7 rabbits) mg/kg/day for 28 days. Following anesthesia induction, carotid arteries were dissected through a right neck incision. following heparinization at 100 IU/kg, vertical full thickness arteriotomy was performed, then was repaired continuously with 8-0 polypropylene. At day 28, all rabbits were sacrificed and the anastomosed carotid artery segments were analyzed using light microcopy. Hematoxylin-eosin and Masson's trichrome stained images were analyzed using a digital image analysis program, and lumen diameter, lumen area, intimal and medial thickness, and media areas were measured and results were compared., Results: In the serial sections, the average lumen diameter of group B was higher than that of group A (p=0.001). The lumen areas of group B were also higher than those of group A (p=0.004). The intimal thickness of group B was lower than that of group A (p=0.001). When the section series were evaluated for media thickness, the thickness of group B was lesser than that of group A; the difference was statistically significant (p=0.002)., Conclusion: This study may imply a potential midterm benefit of rivaroxaban following arterial anastomosis by reducing intimal proliferation and restenosis.
- Published
- 2017
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27. The effects of α-lipoic acid on aortic injury and hypertension in the rat remnant kidney (5/6 nephrectomy) model.
- Author
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Ergür BU, Çilaker Mıcılı S, Yılmaz O, and Akokay P
- Subjects
- Administration, Oral, Animals, Antioxidants pharmacology, Aorta, Abdominal injuries, Blood Pressure drug effects, Dietary Supplements, Disease Models, Animal, Hypertension etiology, Hypertension pathology, Kidney drug effects, Male, Rats, Rats, Wistar, Thioctic Acid pharmacology, Vascular System Injuries prevention & control, Antioxidants administration & dosage, Aorta, Abdominal drug effects, Hypertension drug therapy, Kidney Failure, Chronic prevention & control, Thioctic Acid administration & dosage
- Abstract
Objective: The present study was designed to investigate the effects of α-lipoic acid on the abdominal aorta and hypertension in a remnant kidney model histomorphometrically, immunohistochemically, and ultrastructurally., Methods: We surgically reduced the renal tissue mass to 5/6 by applying a remnant kidney model. The rats were divided into 4 groups: Group 1- control group, Group 2- lipoic acid group, Group 3- 5/6 nephrectomy group, and Group IV: 5/6 nephrectomy+lipoic acid-treated group. Lipoic acid solution 100 mg/kg was administered by oral gavage for 8 weeks to Groups II and IV. At the end of the experiment, systemic mean blood pressure was monitored. Then, aortic tissues were removed and fixed. After routine histological procedures, tissue sections were examined histochemically, immunohistochemically (type I angiotensin receptor, vascular endothelial growth factor, alpha-smooth muscle actin), and ultrastructurally., Results: The blood pressure measurements in 5/6 nephrectomy group were significantly higher compared to other groups. In the 5/6 nephrectomy+lipoic acid group, measured blood pressure values and tunica media thickness were significantly lower than in the 5/6 nephrectomy group. In the 5/6 nephrectomy+lipoic acid group, decreased aortic wall thickness, regularity in the structure of elastic fibrils, and more organized elastic lamellae were seen. The expression of type I angiotensin receptor, vascular endothelial growth factor, alpha-smooth muscle actin in the 5/6 nephrectomy+lipoic acid group was decreased compared to the 5/6 nephrectomy group., Conclusion: In the present study, we found that α-lipoic acid could be a favorable agent for the target organ effects of secondary hypertension.
- Published
- 2015
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28. Lipoic acid decreases peritoneal adhesion formation in a rat uterine scar model.
- Author
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Mıcılı SC, Göker A, Sayın O, Akokay P, and Ergür BU
- Abstract
Objective: To investigate the effects of lipoic acid in the prevention of postoperative pelvic adhesions by a visual scoring system and immunohistochemistry in a rat uterine horn model with full thickness injury., Material and Methods: Twenty-eight female Wistar albino rats were randomised into four groups: uterine trauma control, 15 days and 30 days, and uterine trauma + lipoic acid, 15 days and 30 days. A full thickness defect was established by incising a segment of approximately 1.0 cm in length from each uterine horn, leaving the mesometrium intact. Extension and severity of the adhesions in each group were scored by a visual scoring system and evaluated immunohistochemically., Results: Adhesion scores were 2.00±0.81, 2.14±0.69 0.71±0.75, and 0.85±0.69 for extent and 2.28±0.48, 2.14±0.69, 0.85±0.69, and 1.14±0.69 for severity in Groups 1, 2, 3 and 4, respectively. Adhesion extent and severity were significantly less for groups treated by lipoic acid but no difference was observed between long and short administration. Both Vitronectin and u-PAR staining were significantly increased in treatment groups when compared to the control group., Conclusion: Lipoic acid was found to be effective in reducing postoperative adhesion formation in a rat model.
- Published
- 2013
- Full Text
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