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Öğe Effects of PON1 QR192 genetic polymorphism and paraoxonase, arylesterase activities on deep vein thrombosis(Walter De Gruyter Gmbh, 2023) Akbalik, Hasim; Polat, Muhammet Fevzi; Müderrisoğlu, Ahmet; Er, Zafer Cengiz; Caniklioğlu, Ayşen; Ekim, Meral; Ekim, HasanObjectives: We aimed to evaluate PON1 QR192 polymorphism's (rs662) effects on levels of triglyceride, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, glucose, and c-reactive protein, and paraoxonase-arylesterase activities among deep vein thrombosis patients and healthy subjects. Methods: Forty-five deep vein thrombosis patients and 45 healthy subjects participated in the study. Genetic analysis was performed by using polymerase chain reaction and sequencing. Paraoxonase and arylesterase enzyme activities were determined by a spectrophotometer. Serum levels of triglyceride, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, glucose, and c-reactive protein were measured by a similar method. Results: There were no statistically significant differences between patients and controls regarding the frequency of variant allele for the PON1 QR192 polymorphism, activities of paraoxonase-arylesterase, and level of high-density lipoprotein-cholesterol. Triglyceride, total cholesterol, low-density lipoprotein-cholesterol, glucose, and c-reactive protein levels were significantly higher in patients compared to controls (p values were 0.005, 0.0002, 0.009, 0.0009, <0.0001, respectively.) Paraoxonase activity was found to be associated with PON1 QR192 genetic polymorphism (p<0.0001). However, we observed no association of PON1 QR192 polymorphism with arylesterase activity and, levels of triglyceride, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, glucose, and c-reactive protein. Conclusions: There was no statistically significant difference between deep vein thrombosis patients and healthy subjects regarding variant allele frequency for the PON1 QR192 genetic polymorphism. In addition, paraoxonase and arylesterase activities were similar among the groups. These results indicate that PON1 QR192 genetic polymorphism and activity levels of paraoxonase-arylesterase have no effect on the development of deep vein thrombosis.Öğe The Physiological And Dna Damage Response Of In The Lichen Hypogymnia Physodes To Uv And Heavy Metal Stress(CORVINUS UNIV BUDAPEST, 2020) Hamutoolu, R.; Derici, M. K.; Aras, E. S.; Aslan, A.; Cansaran-Duman, D.This work aims to determine the response of Hypogymnia physodes (L.) Nyl. (hooded tube lichen) collected in an unpolluted site (Yenice Forest in Karabiik, Turkey) to stress conditions. In the present study, the effect of exposure to different heavy metals (Cd+2, Pb+2, and Cr+6) for different durations and UV radiations dosages on lichen was examined at the physiological and molecular levels. The effects of stress conditions were determined in the case of different parameters concerning heavy metal, protein, chlorophyll, and carotenoid contents and changes in the DNA profiles. According to the results obtained that exposure to heavy metals and UV radiations leads to a physiological response in a concentration and dose-dependent manner through differences in chlorophyll, protein content in heavy metals and UV treated lichen specimen. Furthermore, changes in RAPD assay and DNA methylation analysis showed that homologous nucleotide sequences in the genome from untreated and stress conditions treated lichen specimen showed different band patterns and methylation under heavy metals and UV stress. The results determined that lichen specimen suggest as a possible bioindicator able to measure the biological effects of heavy metal pollution and damage to UV radiation.Öğe Role of silymarin (Silybum marianum) in the prevention of colistin-induced acute nephrotoxicity in rats(TAYLOR & FRANCIS LTD, 2020) Dumludag, Burak; Derici, Mehmet Kursat; Sutcuoglu, Osman; Ogut, Betul; Pasaoglu, Ozge Tugce; Gonul, Ipek Isik; Derici, UlverSilymarin (Silybum marianum) has some protective effects against drug toxicity (cisplatin, acetaminophen, adriamycin, gentamicin etc.). Colistin is a strong antimicrobial, which is frequently used in the treatment of resistant gram-negative bacterial infections in recent years although it has nephrotoxic potential. This study was aimed to determine the role of silymarin against colistin-induced acute nephrotoxicity (CIN). Rats were randomly divided into four groups. The control group was treated with tap water whereas groups 2 and 3 received silymarin (orally, 100 mg/kg/day) and colistin (intraperitoneally, 750.000 IU/kg/day) for seven days, respectively. Group 4 received both 750,000 IU/kg/day colistin and 100 mg/kg/day silymarin for seven days. After euthanasia, histopathological and biochemical examinations were completed for the kidney tissue specimens and blood samples. All parameters of the control and silymarin groups were similar. Severe weight loss was seen in the groups receiving colistin (groups 3 and 4). Silymarin significantly increased glutathione peroxidase and superoxide dismutase levels when administered with colistin in group 4 only. Acute tubular injury, tubular necrosis, meduller congestion, interstitial inflammation and apoptotic indices of colistin group were significantly higher than the control group. The administration of colistin with silymarin (group 4) was able to make some improvements in tubular necrosis and significant increase in antioxidant capacity. Silymarin increased antioxidant enzyme activity only when used in combination with colistin. The effects of silymarin may become more pronounced when used at higher doses or with a longer duration of treatment and may prevent nephrotoxicity.Öğe Relationship between Serum Adipocyte Fatty Acid-Binding Protein Levels and Systemic Inflammation in Hemodialysis Patients(AVES, 2020) Korucu, Berfu; Derici, Mehmet Kursat; Deger, Serpil Muge; Cokay, Abdurrahman; Helvaci, Ozant; Elbeg, Sehri; Derici, UlverObjective: Adipocyte fatty acid-binding protein (A-FABP) is expressed in adipose tissue and macrophages. It regulates cholesterol trafficking and is involved in atherosclerosis formation. A-FABP levels are associated with cardiovascular diseases (CVDs) in patients with or without chronic kidney disease. In this study, we evaluated A-FABP levels in healthy controls and hemodialysis (HD) patients and compared the results with C-reactive protein (CRP) and interleukin-6 (IL-6) levels to determine their relationship with systemic inflammation. Materials and Methods: The study comprised 23 healthy controls and 70 HD patients, excluding individuals with an active infection, malignancy, anorexia, obesity, and hypo- or hyperthyroidism. Demographic features, laboratory findings, A-FABP levels, and levels of inflammatory markers were evaluated between and within the groups. Results: Levels of A-FABP and inflammatory markers were significantly higher in HD patients. In the HD group, 20% of the patients had documented CVD. Levels of A-FABP and inflammatory markers were similar in nondiabetic and diabetic HD patients. Age was negatively correlated with A-FABP levels. Presence of diabetes was not correlated with A-FABP. Serum CRP and IL-6 levels were significantly correlated with A-FABP levels (r=0.354, p=0.003 and r=0.393, p=0.001, respectively). Conclusion: A-FABP levels are elevated in HD patients. Systemic inflammation is significantly related to A-FABP levels in both nondiabetic and diabetic HD patients and decreases with age. Findings of this study support the adverse cardiovascular effects of systemic inflammation in HD patients.Öğe Effects of medium cut-off dialysis membranes on inflammation and oxidative stress in patients on maintenance hemodialysis(SPRINGER, 2020) Yeter, Hasan Haci; Korucu, Berfu; Akcay, Ömer Faruk; Derici, Kürşat; Derici, Ülver; Arinsoy, TurgayPurpose Medium cut-off membranes were developed for providing increased clearance of larger middle-molecule uremic toxins. We compared the effect of low-flux, medium cut-off, and high-flux membranes on chronic inflammation and oxidative stress in patients with maintenance hemodialysis. Methods A total of 42 patients were enrolled in this study. Total antioxidant status, total oxidant status, paraoxonase-1, ischemia-modified albumin, total Thiol, disulfide bond, and native Thiol were measured to determine oxidative stress. C-reactive protein was measured to define inflammation. Results 37% of the total patients were females, and the mean age was 52.9 +/- 16 years. Serum albumin and Kt/V were similar between groups during the study period. We did not find any significant difference at baseline in the 3rd and 6th months of the study when we compared the inflammatory marker and oxidative indicator levels between three hemodialysis membranes in the whole study group. In the subgroup analysis of 19 patients with a high C-reactive protein level, we found that the medium cut-off membrane significantly reduced serum C-reactive protein level, when compared to low-flux and high-flux membrane [2.8 mg/L vs. 13.7 mg/L and 6.1 mg/L, respectively,p = 0.05]. However, we did not find a significant change in oxidative stress indicators in patients with high C-reactive protein levels between the three dialysers. Conclusion The medium cut-off membrane has favorable effects on inflammation in patients with maintenance hemodialysis. However, this positive effect could not be demonstrated in oxidative stress.Öğe Effects of Genetic Polymorphisms of Drug Transporter ABCB1 (MDR1) and Cytochrome P450 Enzymes CYP2A6, CYP2B6 on Nicotine Addiction and Smoking Cessation(FRONTIERS MEDIA SA, 2020) Müderrisoğlu, Ahmet; Babaoğlu, Elif; Korkmaz, Elif Tuğçe; Ongun, Mert C.; Karabulut, Erdem; İskit, Alper B.; Emri, SalihObjectives To determine the effects of genetic polymorphisms of ABCB1 (MDR1), CYP2A6, CYP2B6 on smoking status, and clinical outcomes of smoking cessation therapies in a Turkish population. Methods 130 smokers and 130 non-smokers were recruited. Individuals who never smoked were described as non-smokers. 130 smokers were treated with nicotine replacement therapy (NRT) (n = 40), bupropion (n = 47), bupropion + NRT (n = 15), and varenicline (n = 28). Smokers were checked by phone after 12 weeks of treatment whether they were able to quit smoking or not. Genotyping and phenotyping were performed. Results Cessation rates were as follows; 20.0% for NRT, 29.8% for bupropion, 40.0% for bupropion + NRT, 57.1% for varenicline (p = 0.013). The frequency of ABCB1 1236TT-2677TT-3435TT haplotype was significantly higher in non-smokers as compared to smokers (21.5% vs. 10.8, respectively; p = 0.018). Neither smoking status nor smoking cessation rates were associated with genetic variants of CYP2A6 (p = 0.652, p = 0.328, respectively), or variants of CYP2B6 (p = 0.514, p = 0.779, respectively). Conclusion Genetic variants of the drug transporter ABCB1 and the 1236TT-2677TT-3435TT haplotype was significantly associated with non-smoking status. Neither ABCB1 nor CYP2A6, CYP2B6 genetic variants were associated with smoking cessation rates at the 12th week of drug treatment.Öğe Differential expressions and functions of phosphodiesterase enzymes in different regions of the rat heart(Elsevier Science Bv, 2019) Derici, Mehmet Kursat; Sadi, Gokhan; Cenik, Basar; Guray, Tulin; Demirel-Yilmaz, EminePhosphodiesterase enzymes (PDEs) are responsible for the adjustment of cyclic nucleotide levels. Alterations in PDE expressions in different tissues cause conflicts between functional and clinical effects of PDE inhibitors. Therefore, the aim of this study was to investigate the gene and protein expressions and the functional role of PDEs in atrium and ventricle of rat heart The expressions of PDEs were examined in cardiac intact tissues and enzymatically isolated cells. The effects of PDE1-5 inhibitors (vinpocetine, EHNA, milrinone, rolipram, sildenafil, and IBMX) on basal and isoprenaline-stimulated contractions and sinus rate were recorded in the isolated spontaneously beating right atrium and electrically stimulated left papillary muscles. The mRNA and protein levels of PDEs were significantly different in atrial and ventricular intact tissues and isolated myocytes. Atrial contractions were increased with vinpocetine while suppressed by EHNA, milrinone, rolipram, sildenafil and IBMX. Milrinone, sildenafil and IBMX increased the heart rate whereas vinpocetine caused negative chronotropy. Papillary muscle contractions have been increased only with the vinpocetine and IBMX. Both the expression and the action of PDE-1-5 show atrial and ventricular differences. Therefore, these differences should be taken into account in the experimental or therapeutic approaches of the heart.Öğe A Case-Control Study on the Oxidative Status in Women with Polycystic Ovary Syndrome Treated with Clomiphene Citrate(Int Scientific Information, Inc, 2019) Yildirim, Engin; Derici, Mehmet KursatBackground: Polycystic ovary syndrome (PCOS) is associated with infertility or subfertility due to impaired ovulation. Clomiphene citrate is a first-line treatment option for the induction of ovulation in women with PCOS. The study aimed to compare markers of oxidative stress or the total oxidative status (TOS), total antioxidant status (TAS), and levels of paraoxonase-1 (PON-1) before and after day 21 of the menstrual cycle in women with PCOS treated with clomiphene citrate to induce ovulation. Material/Methods: The study included 75 women who were divided into a control group (n=25) that included healthy untreated women, untreated women with PCOS (n=24) who had spontaneous ovulation, and women with PCOS who were treated with clomiphene citrate for subfertility or infertility (n=26) (the PCOS-CC group). The study group was treated for five days with clomiphene citrate (50 mg/day). Peripheral venous blood was sampled on day 3 and day 21 of the menstrual cycle from women in all three groups, and TAS, TOS, and PON-1 levels were measured. Results: In all three groups, TAS and PON levels were significantly reduced and TOS values were significantly increased on day 21 of the menstrual cycle. Comparison of TAS, TOS, and PON-1 levels between the three study groups on day 3 and day 21 of the menstrual cycle showed no significant difference (p=0.600, p=0.223, p=0.956, respectively). Conclusions: This study showed that spontaneous ovulation occurs in association with an oxidative state in healthy women and women with PCOS, and women with PCOS following treatment with clomiphene citrate.Öğe Skin-homing T-cell responses associated with Demodex infestation and rosacea(Wiley, 2019) Gazi, Umut; Gureser, Ayse Semra; Oztekin, Aynure; Karasartova, Djursun; Kosar-Acar, Nezahat; Derici, Mehmet Kursat; Taylan-Ozkan, AysegulAims Our aim was to investigate the skin-homing T-cell immune responses triggered in patients with Demodex infestation and/or rosacea. Methods Collected whole blood samples were divided into four groups: control subjects; nonrosacea patients with Demodex infestation (Demodex group); papulopustular rosacea (PPR) patients without Demodex infestation (Rosacea group); and PPR patients with Demodex infestation (Rosacea/Demodex group). Following ex vivo activation, skin-homing CLA+CD4+ T-cell subset levels were monitored by flow cytometry. Results When compared with control subjects, among skin-homing CD4+ T-cell subsets analysed, Demodex patients had higher T(H)9 and T-reg cell levels; Rosacea subjects displayed elevated T(H)1 cell levels; and Rosacea/Demodex patients exhibited increased frequencies of T(H)9 and T(H)22 cells. In contrast to Rosacea subjects, Rosacea/Demodex group members displayed higher T(H)2 cell levels; and when compared with Demodex groups, they had higher T(H)1 and T(H)2 but lower T-reg cell levels. Demodex group members also exhibited higher T-reg but lower T(H)1 and T(H)22 levels than Rosacea/Demodex group subjects. Conclusions The skin-homing T-cell responses associated with Demodex infestation and rosacea formation seem to influence each other. The present as well as future studies could contribute to the development of effective treatment strategies for demodicosis and rosacea.Öğe Is it possible to prevent contrast-induced nephropathy with dexpanthenol?(Springer, 2019) Sutcuoglu, Osman; Derici, Mehmet Kursat; Pasaoglu, Ozge Tugce; Dumludag, Burak; Helvaci, Ozant; Ogut, Betul; Derici, UlverPurposeContrast-induced nephropathy (CIN) is one of the side effects of diagnostic procedures. Oxidative stress plays an important role in CIN's pathophysiology. Dexpanthenol (Dexp) is a substance with antioxidant efficacy. We investigated the likely protective effects of dexpanthenol for CIN.MethodsTwenty-four Sprague-Dawley rats were divided randomly into four groups of 6 rats; control (group 1), Dexp (group 2), CIN (group 3) and Dexp+CIN (group 4). All rats were restricted of water moderately to facilitate of nephrotoxicity. Dexp was administered into the intraperitoneally at a dose of 500mg/kg for 5days in groups 2 and 4. The same amount of saline was applied via intraperitoneally to group 1 and 3. In CIN and Dexp+CIN groups, L-NAME (10mg/kg), tenoxicam (0.5mg/kg) and sodium amidotrizoate (10ml/kg) were administered on the 4th day via the tail vein for CIN. All rats were euthanized on the 6th day and samples for biochemical and pathological evaluations were collected.ResultsWhen the Dexp+CIN group and the CIN group were compared, it was found to be provide a significant decline at the level of acute tubular injury and necrosis in kidney biopsies by dexp. Furthermore Dexp significantly reduced the serum cystatin C (Cys-C) levels, not serum creatinine. There was no statistically significant difference between the groups in total oxidant and antioxidant levels.ConclusionsDexpanthenol did not have significant effect on oxidative stress of acute kidney injury on this rat model. However, it has ameliorated serum Cys-C levels and histopathological findings of CIN.Öğe Is the Concentration of Cadmium, Lead, Mercury, and Selenium Related to Preterm Birth?(Humana Press Inc, 2019) Yildirim, Engin; Derici, Mehmet Kuersat; Demir, Emre; Apaydin, Hakan; Kocak, Ozguer; Kan, Ozguer; Gorkem, UmitEnvironmental pollution and exposure of people to heavy metals cause many bad obstetric outcomes. Our aim is to demonstrate the role of cadmium (Cd), lead (Pb), mercury (Hg), and selenium (Se) in preterm labor etiology with a case-control study. In this study, between November 2017 and April 2018, preterm delivery mothers and term delivery mothers were compared in corum, Turkey. All deliveries were performed with cesarean sections and there were 30 mothers in the control group and 20 in the study group. The maternal blood, maternal urine, umbilical cord blood, and heavy metal levels in the amnion fluid in both groups were studied. Graphite furnace atomic absorption spectrometry was used to determine the blood concentration of Cd, Pb, Hg, and Se. We found lower levels of selenium in blood and urine of preterm delivery mothers and umbilical cord and amnion fluids of preterm infants (p < 0.01). We found a statistically significant positive correlation at selenium levels between mother's blood and umbilical cord blood (r (50) = 0.896, p < 0.001) and between maternal urine and amniotic fluid (r (50) = 0.841, p < 0.001). We have not found a similar correlation between mother and fetus of other metals (p > 0.05). We found that selenium levels were lower in mothers who were preterm birth in the light of the data in our study. We could not determine the positive or negative correlation of Cd, Pb, and Hg levels in blood, urine, and amniotic fluid samples with preterm birth.Öğe Dexmedetomidine as an Alternative Anesthetic Agent for Flap Surgery: An Intravital Evaluation in the Cremaster Muscle Flap(Lippincott Williams & Wilkins, 2019) Gencay, Isin; Boybeyi, Ozlem; Unlu, Gulhan; Yazici, Ilker; Aydin, Gulcin; Buyukkocak, UnaseIntroduction: Flap surgery is one of the most commonly used techniques of reconstructive surgery for effective repair of damaged tissue. Optimal anesthetic technique and anesthetic agent plays an important role in flap perfusion. This study aimed to evaluate the effects of dexmedetomidine infusion on the microcirculation in the cremaster muscle flap by direct in vivo monitoring. Materials and Methods: We randomly divided 9 Wistar albino rats into 3 groups. The rats in the control group underwent the surgical procedure (isolation of the cremaster muscle) alone; the rats in the experimental groups 1 and 2 received an infusion of dexmedetomidine (10 and 30 min) after the surgical procedure. Results: The means of vessel diameters, number of functional capillaries, and movements of leukocytes in all groups were evaluated using intravital microscopic examination. The diameters of the arterioles and venules of the cremaster muscle significantly increased in the dexmedetomidine groups. The number of functional capillaries was higher in the dexmedetomidine groups than in the control group. No difference was observed in the movements of leukocytes between the control and experimental groups. Dexmedetomidine significantly increased the diameters of the arterioles and venules of the cremaster flap and the number of functional capillaries. Conclusion: On the basis of the effects of dexmedetomidine on microcirculation, we suggest that dexmedetomidine continue to be used as an anesthetic agent, and may be considered also for reconstructive procedures, particularly flap surgery.Öğe Autophagy: A New Therapeutic Target(Academic Press Ltd-Elsevier Science Ltd, 2018) Ceylan, Asli F.…Öğe What is the protective effect of metformin on rat ovary against ischemia-reperfusion injury?(Wiley, 2018) Sayan, Cemile Dayangan; Karaca, Gokhan; Ozkan, Zehra Sema; Tulmac, Ozlem B.; Isik, Asli Ceylan; Devrim, Tuba; Yeral, IlkinAimThe aim of this study was to investigate the protective effect of metformin on the rat ovary against ischemia-reperfusion injury. MethodsThirty-seven female Wistar albino rats were used in the study. The rats were divided into five groups, as follows: sham operation group (group 1); torsion group (group 2); torsion/detorsion+saline group (group 3); torsion/detorsion+low-dose metformin group (group 4); and torsion/detorsion+high-dose metformin group (group 5). The right ovary from each rat was evaluated histologically using hematoxylin-eosin staining, and the left ovaries were evaluated for tissue levels of the reduced-glutathione-to-oxidized-glutathione ratio, malondialdehyde (MDA), and caspase-3 activation. ResultsThe highest damage score was observed in group 3, and the lowest score was observed in group 1. The tissue caspase-3 activity levels of groups 2, 3, and 4 were significantly higher than those of group 1. The difference between group 1 and group 5 in terms of tissue caspase-3 activity was not significant (P=0.4). The reduced-glutathione-to-oxidized-glutathione ratio of group 1 was significantly higher than the ratios found in groups 2, 3, and 4. The tissue MDA level of group 1 was significantly lower than the levels found in groups 2, 3, 4, and 5. The tissue MDA level of group 5 was significantly lower than the levels in groups 3 and 4. ConclusionFrom both histopathological and biochemical analyses, the results of the study demonstrated that metformin has beneficial effects when it comes to attenuating ovarian ischemia-reperfusion injury.Öğe Usnic acid causes apoptotic-like death in Leishmania major, L. infantum and L. tropica(Springer Heidelberg, 2018) Derici, Mehmet Kursat; Cansaran-Duman, Demet; Taylan-Ozkan, AysegulLeishmaniasis, a deadly parasitic infection, threatens many people worldwide. Since the high cost, toxicity, and resistance are drawbacks of current treatment options, it is necessary to find safer and more effective new antileishmanial drugs. The aim of this study was to determine the antileishmanial activity of usnic acid and its apoptotic mechanism on Leishmania spp. promastigotes. The antileishmanial activity was evaluated by MTT assay and apoptosis-related gene expression was investigated by qRT-PCR. Usnic acid was to be effective against Leishmania major, L. infantum, and L. tropica promastigotes at IC50 =10.76 mu g/ml, 13.34 mu g/ml, and 21.06 mu g/ml, respectively. We also demonstrated a novel mechanism by which usnic acid inhibited proliferation and caused apoptosis; usnic acid upregulated p53, Bax, Casp-3, and Casp-9 gene expression and downregulated the level of Bcl-2 gene expression. Accordingly, the expression level of the P53 gene increased in L. major, L. infantum and L. tropica by 14.4-, 11.8-, and 9.5-fold, respectively, and in contrast, the Bcl-2 gene expression decreased in all three leishmaniasis by 0.8-, 0.8-, and 0.7-fold, respectively. The present study, therefore, revealed that usnic acid played a critical role in the usnic acid-induced apoptotic process in Leishmania species. Usnic acid is easily accessible and an inexpensive agent, and can be considered as an alternative therapeutic agent for Leishmania infections subject to further tests in animal models.Öğe Evaluation of in vitro Anticancer Activity of Vulpinic Acid and its Apoptotic Potential Using Gene Expression and Protein Analysis(Assoc Pharmaceutical Teachers India, 2018) Kilic, Nil; Derici, Mehmet Kursat; Buyuk, Ilker; Aydin, Semra Soydam; Aras, Sumer; Cansaran-Duman, DemetLichens and their secondary metabolite are still among the many unexamined natural sources in the drug industry. This study was designed to evaluate the cytotoxic effects of vulpinic acid lichen secondary metabolite and 6.25, 12.5, 25, 50, 100, 200 and 400 mu M concentrations that treat cancer cell lines (CaCo2, HepG2, Hep2C, RD Wehi) and normal cells (Vero and L929) by MTT assay. The aim of this study was to determine the apoptotic effect of vulpinic acid on a molecular level. The determination of apoptotic molecular patterns of vulpinic acid was performed on western blot and quantitative real-time PCR (qRT-PCR) analysis. In our study, transcriptome changes on both gene and protein levels showed similar results. The determination of, mRNA levels of Bax, Bcl-2 and P53 genes were showed by qRT-PCR in cancer and normal cell lines. The results of the study showed that IC50 value of vulpinic acid altered the mRNA levels of Bax, Bcl-2 and P53 genes in all examined cancer cells when compared to the untreated cells. When the mRNA levels of the examined genes were compared, it was observed that Box gene showed more expression increase in all cell lines when compared to Bcl-2 and P53 genes. This is the first evaluation of the apoptotic effect of vulpinic acid secondary metabolite on mRNA levels. The current study highlights some points regarding vulpinic acid and its use for cancer treatment.Öğe Synthesis, structural characterization and myorelaxant activity of 4-naphthylhexahydroquinoline derivatives containing different ester groups(Serbian Chemical Soc, 2016) Gunduz, Miyase Gozde; Albayrak, Emine; Isli, Fatma; Fincan, Gokce Sevim Ozturk; Yildirim, Seniz; Simsek, Rahime; Butcher, Ray J.The present study reports the synthesis, structural characterization and myorelaxant activity evaluation of a series of 16 novel 4-naphthylhexahydroquinoline derivatives. The compounds were achieved by one-pot microwave-assisted method via a modified Hantzsch reaction. The structures of the compounds were confirmed by various spectral methods, such as IR, 1D and 2D NMR techniques and mass analysis. X-Ray studies of compound 10 provided further evidence for the proposed structure. To evaluate their myorelaxant activities, the E-max and pD(2) values of the compounds and nifedipine were determined on isolated rabbit gastric fundus smooth muscle strips. The obtained results indicated that the introduction of long chain alkyl groups, such as the 2-methoxyethyl or 2-(methacryloyloxy)ethyl moiety, to the ester group led to the most active compounds.Öğe Effects of chronic L-DOPA administration on neurogenic and endothelium-dependent relaxation responses in rabbit corpus cavernosum(Polish Acad Sciences Inst Pharmacology, 2016) Yildirim, Seniz; Fincan, Gokce Sevim Ozturk; Isli, Fatma; Ercan, Sevim; Sarioglu, YusufBackground: Dopamine is a crucial central neurotransmitter that plays a fundamental role in the autonomic and somatic components of penile reflexes in animals and humans. Similar to the erectile responses of dopamine, systemic administration of L-DOPA induces yawning and penile erection in some species. The possible effects of L-DOPA on nitric oxide (NO)-dependent and-independent non-adrenergic non-cholinergic (NANC) relaxation responses mediated by electrical field stimulation (EFS) and endothelium-dependent relaxation were investigated in this study. Methods: Thirty-two adult albino male rabbits, in two- and four-week-treatment groups, were divided into three subgroups: control group (saline-injected) (n = 4), 3 mg/kg/day (low dose) L-DOPA-injected groups (n = 6) and 12 mg/kg/day (high dose) L-DOPA-injected groups (n = 6). After the intraperitoneal injection treatments, the corpus cavernosum tissues were placed in organ bath chambers. The EFS-mediated responses, and the concentration-response curve to carbachol, sodium nitroprusside (SNP), sildenafil were assessed. Results: The two-week treatment with high-dose L-DOPA decreased the NO-dependent NANC relaxation responses, while there was no change in the low-dose two- and four-week treatment groups. The NO independent NANC relaxation responses in the two-week groups decreased, and the responses in the four-week groups were unchanged when compared to the controls. The relaxation responses to carbachol showed no differences among all groups except for the high-dose four-week L-DOPA group. The relaxation responses of SNP and sildenafil were increased in all of the treatment groups when compared to the controls. Conclusions: The observed increases in SNP- and sildenafil-induced responses, along with the decreased EFS-mediated responses, suggest increased sensitivity in the NO-signalling pathway following L-DOPA administration. (C) 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.Öğe Role of nicotinic acetylcholine receptor subtypes on nicotine's enhancing effect on electrical field stimulation elicited contractile responses in rabbit urine bladder(Verduci Publisher, 2016) Fincan, G. S. Ozturk; Vural, I. M.; Yildirim, S. S.; Isli, F.; Dilekoz, E.; Ercan, S.; Sarioglu, Y.OBJECTIVE: This study aims to investigate the contribution of presynaptic nicotinic acetylcholine receptors (nAChRs) sub-types to nicotine-induced enhancement in electrical field stimulation (EFS) EFS-mediated contractile responses in rabbit urine bladder smooth muscle preparations. MATERIALS AND METHODS: Rabbit urine bladder smooth muscle strips were placed in organ baths containing 20 ml of an aerated Krebs-Henseleit solution, and contractions were recorded using isometric force displacement transducers. Following the acquisition of control EFS (60 V, 8 Hz, 1 ms) responses, nicotine was added to the bath at a 3x10(-5) M concentration, and EFS responses were obtained. The effect of nAChR antagonists on nicotine-induced augmentation in EFS-mediated responses was investigated in the presence of hexamethonium, dihydro-beta-erythroidine, mecamy-lamine, and alpha-bungarotoxin. RESULTS: Tetrodotoxin (TTX; 10(-6) M) completely blocked EFS-induced contractile responses in smooth muscle strips. Similarly, Atropine (10(-6) M), when administered with alpha,beta-methylene adenosine triphosphate (alpha,beta-methylene-ATP) (10(-5) M), completely blocked EFS responses. Nicotine significantly enhanced EFS-mediated contractile responses (23.67% +/- 1.75). Nicotine-induced increases in EFS responses were largely inhibited by hexamethonium, mecamylamine, and dihydro-beta-erythroidine, whereas alpha-bungarotoxin only partly inhibited these enhancements. CONCLUSIONS: These findings demonstrate that EFS-induced neurogenic contractions in rabbit urine bladder smooth muscle strips are mediated by purinergic and cholinergic transmissions, and the alpha 4 beta 2, alpha 3 beta 4, and alpha 7 sub-types of nAChRs contribute to the enhancement effect of nicotine on EFS-induced contractile responses.Öğe Effects of cell phone radiation on lipid peroxidation, glutathione and nitric oxide levels in mouse brain during epileptic seizure(Elsevier Science Bv, 2016) Esmekaya, Meric Arda; Tuysuz, Mehmet Zahid; Tomruk, Arin; Canseven, Ayse G.; Yucel, Engin; Aktuna, Zuhal; Seyhan, NesrinThe objective of the this study was to evaluate the effects of cellular phone radiation on oxidative stress parameters and oxide levels in mouse brain during pentylenetetrazole (PTZ) induced epileptic seizure. Eight weeks old mice were used in the study. Animals were distributed in the following groups: Group I: Control group treated with PTZ, Group II: 15 min cellular phone radiation + PTZ treatment + 30 min cellular phone radiation, Group III: 30 min cellular phone radiation + PTZ treatment + 30 min cellular phone radiation. The RF radiation was produced by a 900 MHz cellular phone. Lipid peroxidation, which is the indicator of oxidative stress was quantified by measuring the formation of thiobarbituric acid reactive substances (TBARS). The glutathione (GSH) levels were determined by the Ellman method. Tissue total nitric oxide (NOx) levels were obtained using the Griess assay. Lipid peroxidation and NOx levels of brain tissue increased significantly in group II and III compared to group I. On the contrary, GSH levels were significantly lower in group II and III than group I. However, no statistically significant alterations in any of the endpoints were noted between group II and Group III. Overall, the experimental findings demonstrated that cellular phone radiation may increase the oxidative damage and NOx level during epileptic activity in mouse brain. (C) 2016 Elsevier B.V. All rights reserved.
