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Genotoxicity profiles in exfoliated human mammary cells recovered from lactating mothers in Istanbul; relationship with demographic and dietary factors

Yılmaz, B. | Sandal, S. | Ayvaci, H. | Tug, N. | Vitrinel, A.

Article | 2012 | Mutation Research - Genetic Toxicology and Environmental Mutagenesis749 ( 01.02.2020 ) , pp.17 - 22

We have investigated the presence of DNA damage in human mammary epithelial cells collected from healthy lactating mothers (age, 20-35 years) who were resident in the Istanbul area. Breast milk (10. ml) was collected from 30 women between one and two weeks post-. partum. Demographic information (parity, breast cancer, occupation, duration of residency in Istanbul, consumption of fish, beef and poultry) was also obtained. Milk samples were diluted 1:1 with RPMI 1640 medium and centrifuged to collect cells. The cells were re-suspended and cell viability was determined by use of 0.4% trypan blue. DNA damage was assessed by use of the c . . .omet assay (alkaline single-cell gel electrophoresis). Fifty cells per slide and two slides per sample were scored to evaluate DNA damage. The cells were visually classified into four categories on the basis of extent of migration: undamaged (UD), lightly damaged (LD), moderately damaged (MD) and highly damaged (HD). Total comet scores (TCS) were calculated as: 1× UD. +. 2× LD. +. 3× MD. +. 4× HD. Exfoliated mammary cells of the donors showed high (TCS. ? 150. a.u.), moderate and low DNA damage in 10 (33.3%), 8 (26.7%) and 12 (40%) mothers, respectively. There was no significant correlation between TCS for DNA damage and the duration of previous breastfeeding, parity or age. None of the mothers was vegetarian, smoker or on any medication. Meat and chicken consumption did not significantly correlate with the TCS values. Fish consumption was significantly correlated with TCS results (Spearman's rho = 0.39, Daha fazlası Daha az

Effects of apelin on reproductive functions: relationship with feeding behavior and energy metabolism

Tekin, S. | Erden, Y. | Sandal, S. | Etem Onalan, E. | Ozyalin, F. | Ozen, H. | Yılmaz, B.

Article | 2017 | Archives of Physiology and Biochemistry123 ( 1 ) , pp.9 - 15

Apelin is an adipose tissue derived peptidergic hormone. In this study, 40 male Sprague–Dawley rats were used (four groups; n = 10). Apelin-13 at three different dosages (1, 5 and 50 µg/kg) was given intraperitoneally while the control group received vehicle the same route for a period of 14 days. In results, apelin-13 caused significant decreases in serum testosterone, luteinizing hormone and follicle-stimulating hormone levels (p < 0.05). Administration of apelin-13 significantly increased body weights, food intake, serum low-density lipoprotein and total cholesterol levels (p < 0.05), but caused significant decreases in high-dens . . .ity lipoprotein levels (p < 0.05). Serum glucose and triglyceride levels were not significantly altered by apelin-13 administration. Significant decreases in both uncoupling protein (UCP)-1 levels in the white and brown adipose tissues and UCP-3 levels in the biceps muscle (p < 0.05) were noted. The findings of the study suggest that apelin-13 may not only lead to obesity by increasing body weight but also cause infertility by suppressing reproductive hormones. © 2016 Informa UK Limited, trading as Taylor & Francis Group Daha fazlası Daha az

Salmon calcitonin ameliorates migraine pain through modulation of CGRP release and dural mast cell degranulation in rats

Kilinc, E. | Dagistan, Y. | Kukner, A. | Yılmaz, B. | Agus, S. | Soyler, G. | Tore, F.

Article | 2018 | Clinical and Experimental Pharmacology and Physiology45 ( 6 ) , pp.536 - 546

The exact mechanism of migraine pathophysiology still remains unclear due to the complex nature of migraine pain. Salmon calcitonin (SC) exhibits antinociceptive effects in the treatment of various pain conditions. In this study, we explored the mechanisms underlying the analgesic effect of salmon calcitonin on migrane pain using glyceryltrinitrate (GTN)-induced model of migraine and ex vivo meningeal preparations in rats. Rats were intraperitoneally administered saline, GTN (10 mg/kg), vehicle, saline + GTN, SC (50 µg/kg) + GTN, and SC alone. Also, ex vivo meningeal preparations were applied topically 100 µmol/L GTN, 50 µmol/L SC, . . .and SC + GTN. Calcitonin gene-related peptide (CGRP) contents of plasma, trigeminal neurons and superfusates were measured using enzyme-immunoassays. Dural mast cells were stained with toluidine blue. c-fos neuronal activity in trigeminal nucleus caudalis (TNC) sections were determined by immunohistochemical staining. The results showed that GTN triggered the increase in CGRP levels in plasma, trigeminal ganglion neurons and ex vivo meningeal preparations. Likewise, GTN-induced c-fos expression in TNC. In in vivo experiments, GTN caused dural mast cell degranulation, but similar effects were not seen in ex vivo experiments. Salmon calcitonin administration ameliorated GTN-induced migraine pain by reversing the increases induced by GTN. Our findings suggested that salmon calcitonin could alleviate the migraine-like pain by modulating CGRP release at different levels including the generation and conduction sites of migraine pain and mast cell behaviour in the dura mater. Therefore salmon calcitonin may be a new therapeutic choice in migraine pain relief. © 2018 John Wiley & Sons Australia, Lt Daha fazlası Daha az

Effects of memantine and melatonin on signal transduction pathways vascular leakage and brain injury after focal cerebral ischemia in mice

Kilic, U. | Yılmaz, B. | Reiter, R.J. | Yüksel, A. | Kilic, E.

Article | 2013 | Neuroscience237 , pp.268 - 276

Because of their favorable action profiles in humans, both memantine and melatonin are particularly interesting candidates as neuroprotectants in acute ischemic stroke. Until now, the signaling mechanisms mediating memantine's neuroprotective actions remained essentially uninvestigated. In addition, we have combined memantine with melatonin, which is a well-known neuroprotective molecule. Herein, we examined the effects of memantine (20. mg/kg, i.p.) administered alone or in combination with melatonin (4. mg/kg, i.p.) on the activation of signaling transduction pathways, IgG extravasation and ischemic injury in mice submitted to 90. . . . min of intraluminal middle cerebral artery occlusion, followed by 24. h of reperfusion. In these studies, both agents reduced ischemic injury and the density of DNA-fragmentation. Notably, melatonin/memantine combination reduced ischemic injury further as compared with memantine treatment, which was associated with reduced IgG extravasation, indicating vascular leakage in the brain. Animals receiving memantine exhibited elevated ERK-1/2 and decreased p21 and p38/MAPK activations, while it had no significant effect on phosphorylated Akt and SAPK/JNK1/2 in the ischemic brain. However, melatonin increased the activation of Akt and reduced the activations of ERK-1/2, p21, p38/MAPK and SAPK/JNK1/2 significantly. Synergistic effects of memantine and melatonin were observed in the inactivation of p21, p38/MAPK and SAPK/JNK1/2 pathways. Moreover, memantine reversed the effects of melatonin on the activation of ERK-1/2 pathway. Here, we provide evidence that free radical scavenger melatonin potentiates the effects of memantine on ischemic brain injury via inactivations of p21 and stress kinases p38/MAPK and SAPK/JNK1/2 pathways. © 2013 IBRO Daha fazlası Daha az

Genotoxic effects of PCB 52 and PCB 77 on cultured human peripheral lymphocytes

Sandal, S. | Yılmaz, B. | Carpenter, D.O.

Article | 2008 | Mutation Research - Genetic Toxicology and Environmental Mutagenesis654 ( 1 ) , pp.88 - 92

Polychlorinated biphenyls (PCBs) are known to be carcinogenic, but the mechanisms of this action are uncertain. Most, but not all, studies have concluded that PCBs are not directly mutagenic, and that much if not all of the carcinogenic activity resides in the fraction of the PCB mixture that contains congeners with dioxin-like activity. The present study was designed to determine genotoxic effects of an ortho-substituted, non-coplanar congener, 2,2',5,5'-tetrachlorobiphenyl (PCB 52), and a non-ortho-substituted coplanar congener with dioxin-like activity, 3,3',4,4'-tetrachlorobiphenyl (PCB 77) on cultured human peripheral lymphocyt . . .es. DNA damage was assessed by use of the comet assay (alkaline single-cell gel electrophoresis). After cell cultures were prepared, test groups were treated with different concentrations of PCB 52 (0.2 and 1 µM) and PCB 77 (1 and 10 µM) for 1 h at 37 °C in a humidified carbon dioxide incubator, and compared to a DMSO vehicle control group. The cells were visually classified into four categories on the basis of extent of migration such as undamaged (UD), low damage (LD), moderate damage (MD) and high damage (HD). The highest concentration of PCBs 52 and 77 significantly increased DNA breakage in human lymphocytes (p < 0.001). Our results indicate that both the non-coplanar PCB 52 and coplanar PCB 77 cause DNA damage, and that the ortho-substituted congener was significantly more potent than the dioxin-like coplanar congener. © 2008 Elsevier B.V. All rights reserved Daha fazlası Daha az

Effects of the gonadotropin-releasing hormone antagonist cetrorelix in the early postimplantation period on rat pregnancy

Tug, N. | Uslu, U. | Cumbul, A. | Eyuboglu, S. | Cam, C. | Karateke, A. | Yılmaz, B.

Article | 2011 | European Journal of Obstetrics and Gynecology and Reproductive Biology155 ( 2 ) , pp.166 - 170

Objective: The effect of cetrorelix given in the early implantation period on rat pregnancy was investigated. Study design: Forty-nine virgin Sprague-Dawley rats were randomized into six groups. At the 4th or 8th days of sperm plug, groups received 15, 75, 150 µg/kg cetrorelix or saline. Three subjects were randomly selected from each group and sacrificed at 11th gestational day for histomorphometric analysis. The remaining subjects were allowed to complete their pregnancy period. Volumes of total conceptus, labyrinth zone, transitional zone, giant cell zone, and exocoelomic cavity were calculated according to Cavalieri's principle. . . . Results: Subjects receiving cetrorelix at 15 or 150 µg doses at the 4th day (D4) and those receiving cetrorelix at 150 µg dose at the 8th day (D8) of pregnancy delivered later than the controls. On necropsy examination at the 11th day, mean embryo weights of the cetrorelix 15 D4, 150 D4, 15 D8 and 75 D8 groups were found to be significantly lower than that of the controls (p < 0.05). On histomorphometric evaluation, volumes of the fetuses and the amniotic sacs were decreased by cetrorelix at all doses studied dose dependently. Gross congenital anomalies were observed in the pups of three rats of the cetrorelix 150 D4 and D8 groups. Conclusion: The results of this study suggest that cetrorelix in the early post-implantation period may lead to serious side effects in the rat. © 2010 Elsevier Ireland Ltd Daha fazlası Daha az

Nesfatin-1 and irisin levels in response to the soccer matches performed in morning, afternoon and at night in young trained male subjects

Ozcelik, O. | Algul, S. | Yılmaz, B.

Article | 2018 | Cellular and molecular biology (Noisy-le-Grand, France)64 ( 10 ) , pp.130 - 133

This study aimed to investigate the potential effects of acute soccer matches performed in morning, afternoon and at night on both nesfatin-1 and irisin levels in trained subjects. Total of 20 male subjects performed in soccer matches at three different times of day: morning, afternoon, and night. Pre- and post-match venous blood samples were taken, and levels of both nesfatin-1 and irisin were analysed using the enzyme-linked immunosorbent assay (ELISA). Following all matches, the subjects' irisin levels increased significantly in all subjects (p < 0.0001). Nesfatin-1 levels were also increased after the matches; however, the in . . .crease was statistically significant for morning (P=0.01) and night-time (p=0.009). The subjects' nesfatin-1 levels did not increase in all subjects and decrease of nesfatin-1 levels observed in some subjects after matches. This study finds that soccer matches performed different workout times have strong stimulatory effects on irisin levels in all subjects but nesfatin-1 response varied among the subjects and it did not change significantly in afternoon match Daha fazlası Daha az

Melatonin elicits protein kinase C-mediated calcium response in immortalized GT1-7 GnRH neurons

Kelestimur, H. | Ozcan, M. | Kacar, E. | Alcin, E. | Yılmaz, B. | Ayar, A.

Article | 2012 | Brain Research1435 , pp.24 - 28

Melatonin is suggested to have effects on hypothalamic-pituitary-gonadal (HPG) axis. The pulsatile pattern of GnRH release, which results in the intermittent release of gonadotropic hormones from the pituitary, has a critical importance for reproductive function but the factors responsible from this release pattern are not known. Calcium is a second messenger involved in hormone release. Therefore, investigation of the effects of melatonin on intracellular free calcium levels ([Ca 2+] i) would provide critical information on hormone release in immortalized GnRH neurons. The pattern of melatonin-induced intracellular calcium signalin . . .g was investigated by fluorescence calcium imaging using the immortalized GnRH-secreting GT1-7 hypothalamic neurons. Melatonin caused a significant increase in [Ca 2+] i, which was greatly blocked by luzindole, a melatonin antagonist, or attenuated by pre-treatment with protein kinase C inhibitor. This study suggests that melatonin seems to have a direct effect on GnRH neurons. © 2011 Elsevier B.V. All rights reserved Daha fazlası Daha az

Thermodynamic assessment of information transmission in squid’s giant axon may explain why squid populations thrive with global warming

Yalçınkaya, B.H. | Yılmaz, B. | Özilgen, M.

Article | 2019 | International Journal of Global Warming19 ( 3 ) , pp.233 - 250

Thermodynamic analyses are performed to determine the effects of global warming on information transmittance in the squid giant axon. Squids are cold-blooded animals and their body temperature is the same as that of the environment. Modelling showed that at 6.3°C energy cost, exergy destruction and entropy generation were 1.77 × 10–10 kJ/cm2, 3.49 × 10–9 kJ/cm2, and 1.25 × 10–11 kJ/K cm2, respectively. Entropy generation decreased with temperature increase, implying that living became easier for the squid. Thermodynamic analyses performed in this study may help to explain why the squid populations thrive with global warming. Copyrig . . .ht © 2019 Inderscience Enterprises Ltd Daha fazlası Daha az

Effects of letrozole on hippocampal and cortical catecholaminergic neurotransmitter levels, neural cell adhesion molecule expression and spatial learning and memory in female rats

Aydin, M. | Yılmaz, B. | Alcin, E. | Nedzvetsky, V.S. | Sahin, Z. | Tuzcu, M.

Article | 2008 | Neuroscience151 ( 1 ) , pp.186 - 194

We have investigated effects of letrozole, an aromatase inhibitor, on spatial learning and memory, expression of neural cell adhesion molecules (NCAM) and catecholaminergic neurotransmitters in the hippocampus and cortex of female rats. In the intact model, adult Sprague-Dawley rats were divided into four groups (n=8). Control received saline alone. Letrozole was administered to the animals in the second and third groups by daily oral gavage at 0.2 and 1 mg/kg doses, respectively, for 6 weeks. Another group of letrozole-treated rats was allowed to recover for 2 weeks. In the second model, 24 rats were ovariectomized (ovx) and the fi . . .rst group served as control. The second group received letrozole (1 mg/kg) for 6 weeks. Ovx rats in the third group were given letrozole (1 µg/kg) plus estradiol (E2) (10 µg/rat). At the end, all rats were tested in a spatial version of the Morris water maze. Then they were decapitated and the brains rapidly removed. Catecholamine concentrations were determined by high performance liquid chromatography with electrochemical detection. NCAM 180, 140 and 120 isoforms were detected by Western blotting. Uterine weights were significantly reduced by letrozole in a dose-dependent manner (P<0.01) which returned to control values following 2 weeks of recovery (P<0.05). Serum E2 levels followed a similar course (P<0.01). Although improvement in spatial learning performance of letrozole-treated rats was not statistically significant, the high-dose letrozole-treated group remained significantly longer in the target quadrant compared with the control (P<0.05). Administration of letrozole to ovx animals significantly reduced the latency (P<0.001) and increased the probe trial performance compared with ovx controls (P<0.05). Letrozole increased expression of NCAM 180 and NCAM 140 in both hippocampus and cortex of intact rats. In the cortex samples of ovx animals, NCAM 180 was overall lower than the intact control values (P<0.05). Noradrenaline, dopamine and their metabolites were decreased in the hippocampus of the letrozole-treated group (P<0.01). Letrozole had differential effects on noradrenaline and dopamine content in the cortex. It appears that inhibition of estrogen synthesis in the brain may have beneficial effects on spatial memory. We suggest that structural changes such as NCAM expression and catecholaminergic neurotransmitters in the hippocampus and prefrontal cortex may be the neural basis for estrogen-dependent alterations in cognitive functions. © 2008 IBRO Daha fazlası Daha az

Effects of raloxifene and estradiol on bone turnover parameters in intact and ovariectomized rats

Canpolat, S. | Tug, N. | Seyran, A.D. | Kumru, S. | Yılmaz, B.

Article | 2010 | Journal of Physiology and Biochemistry66 ( 1 ) , pp.23 - 28

This study was designed to investigate effects of raloxifene (RLX) and estradiol on bone formation and resorption in intact and ovariectomized (ovx) rat models. In the intact model, a total of 24 adult female rats were divided into three groups: Controls subcutaneously received saline alone. RLX (2 mg/kg) and estradiol (30 µg/kg) were injected to two groups of animals for a period of 6 weeks at two daily intervals. In the second model, rats (n=24) were ovx and allowed to recover for a period of at least 3 weeks. Control group received vehicle alone. Remaining rats were divided into two groups and injected with RLX (2 mg/kg) and estr . . .adiol (30 µg/kg) for 6 weeks. Urine samples were collected from all animals 24 h after the last drug administration. Urinary deoxypyridinoline (DPD) was measured by ELISA. Serum parathyroid hormone (PTH), calcitonin, and osteocalcin levels were measured by immunoradiometric method. Serum concentrations of alkaline phosphatase (ALP), Ca, and inorganic phosphate were determined by enzymatic- colorimetric method. Lumbar vertebrae (L2) of all animals were dissected out and processed for histopathological evaluation. Removal of ovaries significantly elevated urinary DPD levels ( Daha fazlası Daha az

Effects of erythropoietin on spontaneous and oxytocin induced myometrial contractions in the nonpregnant rat

Tug, N. | Ayvaci Tasan, H. | Sargin, M.A. | Dogan Taymur, B. | Ayar, A. | Kilic, E. | Yılmaz, B.

Article | 2017 | European Review for Medical and Pharmacological Sciences21 ( 2 ) , pp.5028 - 5033

OBJECTIVE: Erythropoietin (EPO) is a glycoprotein hormone that regulates erythropoiesis. EPO activity has also been detected in a variety of tissue including the nervous system, and female and male reproductive organs. It has been shown that EPO causes relaxation in vascular smooth muscle. In the present study, we have investigated effects of EPO on spontaneous and oxytocin-induced contractions of non-pregnant rat myometrium. MATERIALS AND METHODS: Myometrial stripes were obtained from adult Wistar rats at the oestrous stage. The samples were placed in an isolated organ chamber under physiological conditions and 1 g passive tension. . . . Epoetin beta (rEPO) was added cumulatively at 0.1, 1 and 10 IU/ml concentrations to the myometrial samples showing regular spontaneous contractions for periods of 30 min. Frequency and amplitude of contractions were electrophysiologically recorded and analyzed by using a BIOPAC data acquisition system. RESULTS: rEPO inhibited both area under curve and frequency of spontaneous contractions (ANOVA, n1, 2 = 9, f1 = 20.938, f2 = 20.492, p1,2 = 0.000). The inhibitory effect was insignificant at 0.1 mIU/ml rEPO level (Tukey HSD, p1 = 0.051, p2 = 0.581). In the oxytocin treated myometrial samples, a single dose of 1 IU/ml rEPO was studied. The area under curve and frequency values of these samples were inhibited by rEPO (Student's t-test, n = 9, t1 = 4.776, p1 = 0.000; t2 = 2.835, p2 = 0.012, respectively). CONCLUSIONS: rEPO inhibited spontaneous and oxytocin-induced rat myometrial contractions at 1 and 10 IU/ml concentrations. It appeared that the effect was dose-dependent. © 2017 Verduci Editore s.r.l. All rights reserved Daha fazlası Daha az

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