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Öğe Alpha lipoic acid decreases neuronal damage on brain tissue of STZ-induced diabetic rats(Pergamon-Elsevier Science Ltd, 2022) Tanbek, Kevser; Ozerol, Elif; Yilmaz, Umit; Yilmaz, Nesibe; Gul, Mehmet; Colak, CemilNeuropathy that develops due to diabetic complications causes cognitive impairment due to functional and structural damage. The aim of this study was to evaluate the biochemical, histological and physiological effects of Alpha Lipoic Acid (ALA) against brain tissue damage caused by diabetes. Fourty male Wistar albino rats were separated into four groups as control, diabetes mellitus (DM), ALA and DM+ALA. Single dose of 50 mg/kg intraperitonal streptozotocin (STZ) was used to induce DM. For six weeks, ALA (100 mg/kg/day) was administered to the ALA and DM+ALA groups. At the end of the six week rats were sacrificed by collecting blood samples and collected brain tissues (hippocampus, cortex, hippotalamus and striatum) were histologically evaluated in addition to the oxidant-antioxidant parameters. ALA administration showed significant improvement in cognitive functions evaluated by MWM in rats with diabetes mellitus (p < 0.05). SOD, CAT, GSH-Px activities, which were decreased in the DM group compared to the control group, increased statistically significantly in rats in DM+ALA group (p < 0.05). While MDA and PC levels increased in the DM group, they decreased statistically significantly in the DM+ALA group (p < 0.05). According to the histological examinations made by light and electron microscopies, it was determined that the ultrastructural damage and degeneration findings observed in the sections of the DM group were significantly ameliorated in the sections of rats in the DM+ALA group. ALA may be effective in restoring cell damage and cognitive functions in brain tissue with its antioxidant and neuroprotective effects without showing antidiabetic effects.Öğe APC Gene Expression Levels in Tumor and Adjacent Normal Tissues of Colorectal Cancer Patients(Wiley, 2017) Yilmaz, Nesibe; Yilmaz, Umit; Ergen, Arzu; Aksakal, Nihat; Zeybek, Umit[Abstract Not Available]Öğe Apc gene expression levels in tumor and adjacent normal tissues of colorectal cancer patients(Wıley, 111 rıver st, hoboken 07030-5774, nj usa, 2017) Yilmaz, Nesibe; Yilmaz, Umit; Ergen, Arzu; Aksakal, Nihat; Zeybek, UmitÖğe A case-control study on effects of the ATM, RAD51 and TP73 genetic variants on colorectal cancer risk(Walter De Gruyter Gmbh, 2019) Yazici, Merve; Yilmaz, Umit; Yilmaz, Nesibe; Celik, Faruk; Isikoren, Ece Gizem; Celikel, Burcu; Ergen, ArzuAim: ATM, RAD51 and TP73 are genes that take part in DNA repair pathways. The aim of this prospective case-control study was to determine the genotype and allele distributions of the ATM 5'-UTR G/A, RAD51 135 G/C and TP73 GC/AT polymorphisms and their relationship with clinical parameters in Turkish colorectal cancer (CRC) patients. Material and methods: One hundred and four CRC patients and 113 healthy individuals were included in this study as control. The polymerase chain reaction-restriction fragment length polymorphism techniques were used. Results: The ATM 5'-UTR G/A polymorphism GG (p = 0.001) and AA (p = 0.0001) genotypes were found higher in the patient group, while the GA genotype (p = 0.0001) and A allele (p= 0.001) were significantly higher in the control group. Moreover, the GG genotype (p = 0.042) was higher among patients with advanced-stage cancer and, while GA genotype (p = 0.047) was increased in patients without perineural invasion. The RAD51 135 G/C polymorphism GC genotype (p= 0.0001) and C allele (p = 0.0001) were significantly higher in the patient group, while CC genotype (p= 0.0001) was higher in the control group. No statistical significance was observed between the TP73 GC/AT polymorphism genotype and allele distribution and the clinical parameters. Conclusion: In the Turkish population, the ATM 5'-UTR GG and AA genotypes, and the RAD51 135 G/C GC genotype and the C allele presence may be risk factors for CRC.Öğe Effect of Intracerebroventricular Administration of Apelin-13 on the Hypothalamus-Pituitary-Thyroid Axis and Peripheral Uncoupling Proteins(Springer, 2018) Erden, Yavuz; Tekin, Suat; Tekin, Cigdem; Ozyalin, Fatma; Yilmaz, Umit; Onalan, Ebru Etem; Cigremis, YilmazApelin, a ligand for G protein-coupled APJ receptor, is a peptide hormone. Although apelin and APJ receptors are determined in hypothalamus and thyroid gland its role in the hypothalamus-pituitary-thyroid (HPT) axis and mechanism of action on energy metabolism is not clear. This suggests that apelin may play a role in the HPT axis and energy metabolism. This study was designed to determine possible effects of centrally administered apelin-13 on the HPT axis and energy metabolism. A total of 40 adult male Sprague Dawley rats were divided into four groups (n=10 each group). Intact rats served as control group while the sham group received vehicle of apelin. Apelin-13 was injected intracerebroventricularly at the doses of 1 and 10nmol, for 7 days in the rats in the experimental group. At the end of the experimental protocol, animals were decapitated and brain, blood, white and brown adipose tissues samples were collected. There was no significant difference between the groups in terms of hypothalamic TRH mRNA levels. Serum TSH levels were significantly higher in all groups compared to the control group (p<0.05). Serum fT3 and fT4 levels were significantly lower in apelin-13 administered groups (p<0.05). Moreover, apelin-13 administered groups had lower levels of UCP1 mRNA in white and brown adipose tissues. UCP3 mRNA expression in muscle tissue was also lower in apelin-13 treated groups (p<0.05). These results indicates that apelin-13 exhibits a decreasing effect on energy consumption through a mechanism involving the peripheral rather than central arms of the HPT axis.Öğe The Effect of Melatonin on the Alzheimer's Disease: Relationship with FEZ1 Gene Expression(Wiley-Blackwell, 2016) Demir, Mehmet; Yilmaz, Umit; Sandal, Suleyman; Colak, Cemil; Cigremis, Yilmaz[Abstract Not Available]Öğe Effect of ıntracerebroventricular administration of apelin-13 on the hypothalamus-pituitary-thyroid axis and peripheral uncoupling proteins(Internatıonal journal of peptıde research and therapeutıcs, 2018) Erden, Yavuz; Tekin, Cigdem; Ozyalin, Fatma; Yilmaz, Umit; Tekin, SuatApelin, a ligand for G protein-coupled APJ receptor, is a peptide hormone. Although apelin and APJ receptors are determined in hypothalamus and thyroid gland its role in the hypothalamus-pituitary-thyroid (HPT) axis and mechanism of action on energy metabolism is not clear. This suggests that apelin may play a role in the HPT axis and energy metabolism. This study was designed to determine possible effects of centrally administered apelin-13 on the HPT axis and energy metabolism. A total of 40 adult male Sprague Dawley rats were divided into four groups (n=10 each group). Intact rats served as control group while the sham group received vehicle of apelin. Apelin-13 was injected intracerebroventricularly at the doses of 1 and 10nmol, for 7 days in the rats in the experimental group. At the end of the experimental protocol, animals were decapitated and brain, blood, white and brown adipose tissues samples were collected. There was no significant difference between the groups in terms of hypothalamic TRH mRNA levels. Serum TSH levels were significantly higher in all groups compared to the control group (p<0.05). Serum fT3 and fT4 levels were significantly lower in apelin-13 administered groups (p<0.05). Moreover, apelin-13 administered groups had lower levels of UCP1 mRNA in white and brown adipose tissues. UCP3 mRNA expression in muscle tissue was also lower in apelin-13 treated groups (p<0.05). These results indicates that apelin-13 exhibits a decreasing effect on energy consumption through a mechanism involving the peripheral rather than central arms of the HPT axis.Öğe Effects of central FGF21 infusion on the glucose homeostasis in rats (brain-pancreas axis)(Taylor & Francis Ltd, 2023) Tanbek, Kevser; Yilmaz, Umit; Gul, Mehmet; Koc, Ahmet; Sandal, SuleymanIntroductionGlucose homeostasis is a physiological process mediated by a variety of hormones. Fibroblast growth factor (FGF) 21 is a protein expressed in the liver, adipose tissue, muscle and pancreas and exerts actions in multiple targets including adipose, liver, pancreas and hypothalamus. The aim of this study was to examine the possible involvement of FGF21 in pancreatic and central control of glucose by measuring reflective changes in the release of insulin and glucagon.MethodsThirty adult male Wistar Albino rats were divided; Control, PD + aCSF, PD + FGF21 groups (n = 10). Effects of intracerebroventricular (icv) FGF21 administration to pancreatic denervated (PD) rats. Agouti-related protein (AgRP), Pro-opiomelanocortin (POMC) levels and blood glucose homeostasis were investigated.ResultsAdministration of FGF21 to 3rd ventricle increased food consumption but body weight didn't change significantly. AgRP level increased, pancreatic insulin levels increased, and glucagon level decreased.ConclusionCentral FGF21 administration is effective in regulating blood glucose homeostasis by increasing the amount and efficiency of insulin and changing glucose use.Öğe Effects of central FGF21 infusion on the hypothalamus-pituitary-thyroid axis and energy metabolism in rats(Bmc, 2018) Yilmaz, Umit; Tekin, Suat; Demir, Mehmet; Cigremis, Yilmaz; Sandal, SuleymanThe aim of this study was to evaluate the impact of intracerebroventricular chronic fibroblast growth factor 21 (FGF21) infusion on hypothalamic-pituitary-thyroid (HPT) axis, energy metabolism, food intake and body weight. Thirty male Wistar albino rats were used and divided into three groups including control, sham (vehicle) and FGF21 infused groups (n = 10). Intracerebroventricularly, FGF21 and vehicle groups were infused for 7 days with FGF21 (0.72 mu g/day) and artificial cerebrospinal fluid, respectively. During the experimental period, changes in food intake and body weight were recorded daily. Serum thyroid stimulating hormone (TSH), Triiodothyronine (T3) and thyroxine (T4) levels were measured using ELISA. TRH and uncoupling protein 1 (UCP1) gene expressions were analyzed by using RT-PCR in hypothalamus and adipose tissues, respectively. Chronic infusion of FGF21 significantly increased serum TSH (p < 0.05), T3 (p < 0.05) and T4 (p < 0.001) levels. Additionally, hypothalamic TRH (p < 0.05) and UCP1 gene expressions (p<0.05) in white adipose tissue were found to be higher than in the vehicle and control groups. While FGF21 infusion did not cause a significant change in food consumption, it caused a reduction in the body weight of rats (p < 0.05). Our findings indicate that FGF21 may have an effect on energy metabolism via the HPT axis.Öğe Effects of central FGF21 infusion on the hypothalamus-pituitary-thyroid axis and energy metabolism in rats(Journal of physıologıcal scıences, 2018) Yilmaz, Umit; Tekin, Suat; Demir, Mehmet; Cigremis, Yilmaz; Sandal, SuleymanThe aim of this study was to evaluate the impact of intracerebroventricular chronic fibroblast growth factor 21 (FGF21) infusion on hypothalamic-pituitary-thyroid (HPT) axis, energy metabolism, food intake and body weight. Thirty male Wistar albino rats were used and divided into three groups including control, sham (vehicle) and FGF21 infused groups (n = 10). Intracerebroventricularly, FGF21 and vehicle groups were infused for 7 days with FGF21 (0.72 mu g/day) and artificial cerebrospinal fluid, respectively. During the experimental period, changes in food intake and body weight were recorded daily. Serum thyroid stimulating hormone (TSH), Triiodothyronine (T3) and thyroxine (T4) levels were measured using ELISA. TRH and uncoupling protein 1 (UCP1) gene expressions were analyzed by using RT-PCR in hypothalamus and adipose tissues, respectively. Chronic infusion of FGF21 significantly increased serum TSH (p < 0.05), T3 (p < 0.05) and T4 (p < 0.001) levels. Additionally, hypothalamic TRH (p < 0.05) and UCP1 gene expressions (p<0.05) in white adipose tissue were found to be higher than in the vehicle and control groups. While FGF21 infusion did not cause a significant change in food consumption, it caused a reduction in the body weight of rats (p < 0.05). Our findings indicate that FGF21 may have an effect on energy metabolism via the HPT axis.Öğe Effects of Central FGF21 Infusion on TRH and TSH Levels(Wiley-Blackwell, 2016) Yilmaz, Umit; Tekin, Suat; Demir, Mehmet; Sandal, Suleyman; Cigremis, Yilmaz[Abstract Not Available]Öğe Effects of Cerebral Glucagon Administration on Blood Glucose Homeostasis in Rats(Wiley, 2023) Tanbek, Kevser; Yilmaz, Umit; Gul, Mehmet; Koc, Ahmet; Sandal, Suleyman[Abstract Not Available]Öğe Effects of Glucagon on Central Nervous System in Regulating Glucose Homeostasis in Rats(Wiley, 2022) Tanbek, Kevser; Yilmaz, Umit; Gul, Semir; Koc, Ahmet; Gul, Mehmet; Sandal, Suleyman[Abstract Not Available]Öğe Expression Levels of Micrornas Related to Autophaphy Pathway in Tumor and Adjacent Normal Tissues of Colorectal Cancer Patients(Wiley, 2017) Yilmaz, Umit; Yilmaz, Nesibe; Ergen, Arzu; Aksakal, Nihat; Zeybek, Umit[Abstract Not Available]Öğe Intracerebroventricular BDNF infusion may reduce cerebral ischemia/reperfusion injury by promoting autophagy and suppressing apoptosis(Wiley, 2024) Yilmaz, Umit; Tanbek, Kevser; Gul, Semir; Koc, Ahmet; Gul, Mehmet; Sandal, SuleymanHere, it was aimed to investigate the effects of intracerebroventricular (ICV) Brain Derived Neurotrophic Factor (BDNF) infusion for 7 days following cerebral ischemia (CI) on autophagy in neurons in the penumbra. Focal CI was created by the occlusion of the right middle cerebral artery. A total of 60 rats were used and divided into 4 groups as Control, Sham CI, CI and CI + BDNF. During the 7-day reperfusion period, aCSF (vehicle) was infused to Sham CI and CI groups, and BDNF infusion was administered to the CI + BDNF group via an osmotic minipump. By the end of the 7th day of reperfusion, Beclin-1, LC3, p62 and cleaved caspase-3 protein levels in the penumbra area were evaluated using Western blot and immunofluorescence. BDNF treatment for 7 days reduced the infarct area after CI, induced the autophagic proteins Beclin-1, LC3 and p62 and suppressed the apoptotic protein cleaved caspase-3. Furthermore, rotarod and adhesive removal test times of BDNF treatment started to improve from the 4th day, and the neurological deficit score from the 5th day. ICV BDNF treatment following CI reduced the infarct area by inducing autophagic proteins Beclin-1, LC3 and p62 and inhibiting the apoptotic caspase-3 protein while its beneficial effects were apparent in neurological tests from the 4th day.Öğe Intracerebroventricular prokineticin 2 infusion may play a role on the hypothalamus-pituitary-thyroid axis and energy metabolism(Pergamon-Elsevier Science Ltd, 2024) Yilmaz, Umit; Tanbek, KevserAim: The hypothesis of this study is to determine the effects of intracerebroventricular (icv) prokineticin 2 infusion on food consumption and body weight and to elucidate whether it has effects on energy expenditure via the hypothalamus-pituitary-thyroid (HPT) axis in adipose tissue. Material and Methods: A total of 40 rats were used in the study and 4 groups were established: Control, Sham, Prokineticin 1.5 and Prokineticin 4.5 (n=10). Except for the Control group, rats were treated intracerebroventricularly via osmotic minipumps, the Sham group was infused with aCSF (vehicle), and the Prokineticin 1.5 and Prokineticin 4.5 groups were infused with 1.5 nMol and 4.5 nMol prokineticin 2, respectively. Food and water consumption and body weight were monitored during 7-day infusion in all groups. At the end of the infusion, the rats were decapitated and serum TSH, fT4 and fT3 levels were determined by ELISA. In addition, PGC-1 alpha and UCP1 gene expression levels in white adipose tissue (WAT) and brown adipose tissue (BAT), TRH from rat hypothalamic tissue were determined by real-time PCR. Results: Icv prokineticin 2 (4.5 nMol) infusion had no effect on water consumption but reduced daily food consumption and body weight (p<0.05). Icv prokineticin 2 (4.5 nMol) infusion significantly increased serum TSH, fT4 and fT3 levels when compared to Control and Sham groups (p<0.05). Also, icv prokineticin 2 (4.5 nMol) infusion increased the expression of TRH in the hypothalamus tissue and expression of PGC-1 alpha UCP1 in the WAT and BAT (p<0.05). Conclusion: Icv prokineticin 2 (4.5 nMol) infusion may suppress food consumption via its receptors in the hypothalamus and reduce body weight by stimulating energy expenditure and thermogenesis in adipose tissue through the HPT axis.Öğe Investigation of the Effect of Astaxanthin on Oxidative Stress in Renal Ischemia-Reperfusion Modeled Rats(Wiley, 2022) Kisaoglu, Aysegul; Kose, Evren; Yilmaz, Nesibe; Tanbek, Kevser; Yilmaz, Umit; Ozbag, Davut[Abstract Not Available]Öğe Is there Any Relationship Between Obesity and FGF21?(Wiley-Blackwell, 2016) Yilmaz, Umit; Tekin, Suat; Demir, Mehmet; Sandal, Suleyman[Abstract Not Available]Öğe Melatonin Attenuates Cerebral Ischemia/Reperfusion Injury Through Inducing Autophagy(Karger, 2023) Yilmaz, Umit; Tanbek, Kevser; Gul, Semir; Gul, Mehmet; Koc, Ahmet; Sandal, SuleymanIntroduction: The aim of this study was to investigate how melatonin administration for 3 days or 7 days following cerebral ischemia injury (CI/R) would affect autophagy, and therefore, survival in neurons of the penumbra region. Moreover, it was also aimed to determine how this melatonin treatment would affect the neurological deficit score and rotarod and adhesive removal test durations.Methods: Focal CI (90 min) was achieved in a total of 105 rats utilizing a middle cerebral artery occlusion model. After the start of reperfusion, the groups were treated with melatonin (10 mg/kg/day) for 3-days or 7-days. On all groups, neurological deficit scoring, rotarod and adhesive removal test were executed during reperfusion. Infarct areas were determined by TTC (2,3,5-triphenyltetrazolium chloride) staining at the end of the 3rd and 7th days of reperfusion. Beclin-1, LC3, p62 and caspase-3 protein levels were assessed using Western blot and immunofluorescence methods in the brain tissues. Moreover, penumbra areas were evaluated by transmission electron microscopy (TEM).Results: Following CI, it was observed that melatonin treatment improved the rotarod and adhesive removal test durations from day 5 and reduced the infarct area after CI. It also induced autophagic proteins Beclin-1, LC3 and p62 and suppressed the apoptotic protein cleaved caspase-3. According to TEM findings, melatonin treatment partially reduced the damage in neurons after CI.Conclusion: Melatonin treatment following CI reduced the infarct area and induced the autophagic proteins Beclin-1, LC3 and p62 via inhibiting the apoptotic caspase-3 protein. The functional reflection of melatonin treatment on neurological tests scores was became significant from the 5th day onward.Öğe Neurotransmitters Levels in Experimentally Produced Alzheimer Model in Rats(Wiley-Blackwell, 2016) Demir, Mehmet; Yilmaz, Umit; Sandal, Suleyman; Colak, Cemil; Ozyalin, Fatma[Abstract Not Available]