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Öğe 131I labeling of tamoxifen and biodistribution studies in rats(2008) Biber Muftuler F.Z.; Unak P.; Teksoz S.; Acar C.; Yolcular S.; Yürekli Y.Tamoxifen [TAM ([Z]-2-[4-(1,2-diphenyl-1-di-butenyl)-phenoxy]-N,N-dimethylethanamine)] has been used as an antiestrogen drug for treatment and prevention of human breast cancer. Tamoxifen was labeled with 131I using iodogen as an oxidizing agent. Mass spectroscopy of the cold standard showed that the labeling occurs in ortho position to the phenyl ether position of TAM as expected. Quality control, radiochemical yield and stability were established using the radioelectrophoresis method. The radiolabeled compound maintained its stability throughout working period of 24 h. Scintigraphic imaging was performed and tissue distribution was determined in Albino Wistar rats. According to biodistribution and imaging experiments the radiolabeled compound presented estrogen receptor (ER) specificity and it was uptaken by endometrium as well as breast tissue. © 2007 Elsevier Ltd. All rights reserved.Öğe 18FDG conjugated magnetic nanoparticle probes: Synthesis and in vitro investigations on MCF-7 breast cancer cells(2013) Ozkaya F.; Unak P.; Medine E.I.; Sakarya S.; Unak G.; Timur S.18FDG conjugated magnetic iron oxide nanoparticles (MNPs) were synthesized as PET-MR hybrid imaging agent. Synthesized and characterized NPs were then applied to MCF-7 human breast cancer cells. 18FDG conjugated MNPs exhibited the cell incorporation ratio up to 30 %. As well as the characterization studies, apoptotic effects were observed depending on the cellular incorporations by the time. In conclusion, synthesized structures could have a potential as hybrid imaging agent in PET-MR imaging systems besides apoptotic effect on cancer cells. © 2012 Akadémiai Kiadó, Budapest, Hungary.Öğe 99mTc-exorphin C: A new peptide radiopharmaceutical for tumor imaging(2005) Ertay T.; Unak P.; Tasci C.; Biber F.Z.; Zihnioglu F.; Durak H.The aim of this study was to label exorphin C with 99mTc and to examine its usefulness as opioid receptor binding radiopharmaceutical in Albino Wistar rats. Exorphin C, which is a peptide with 5 aminoacids, was labeled with 99mTc using glucoheptonate (GH) as a bifunctional chelating agent. Labeling efficiency was higher than 98%. The compound was stable for at least 5 hours at room temperature. Mammary tumor bearing Albino Wistar rats were imaged using gamma-camera. Biodistribution studies were also performed. Results demonstrated that 99mTc-glucoheptonate-exorphin C ( 99mTc-GE) analogs may be useful as a new class of receptor-binding peptides for the diagnosis and therapy of some cancer diseases related with opioid receptor-expressing tissues. © 2005 Akadémiai Kiadó.Öğe 99mTc-glucoheptonate-guanine: Synthesis, biodistribution and imaging in animals(2008) Unak P.; Teksoz S.; Biber Muftuler F.Z.; Medine E.I.; Acar C.; Yurekli Y.The aim of the current study was to design a nucleotide-based radiopharmaceutical which could be labeled with 99mTc and to investigate its radiopharmaceutical efficiency and stability. GHA (glucoheptonate) was used as bifunctional chelate. GHA was labeled with 99mTc by SnCl2 reduction method first, and then G (guanine) was conjugated with 99mTc-GHA at 90°C. In order to determine its radiopharmaceutical stability, thin layer radio chromatography (TLRC) and electrophoresis were employed. In addition, the results were confirmed using high performance liquid radio chromatography (HPLRC). Scintigraphic imaging was performed on rats with mammary tumors, while tissue distribution was determined on Albino Wistar rats. Labeling yield was found to be over 95% and the labeled complex maintained its stability during the study period. The lipophilicity of the 99mTc-GHG was measured and the partition coefficient (logP) of the labeled compound calculated. The results demonstrated that the uptake of 99mTc-GHG (99mTc- glucoheptonate-guanine) reached its maximum at 3 hours p.i. in stomach and intestines. Main way of excretion was renal. Hepatobiliary excretion was also observed. In conclusion, 99mTc-GHG may be useful as a nucleotide-based radiopharmaceutical for in vivo applications. © 2008 Springer Science+Business Media, LLC.Öğe Absorbed dose estimates at the cellular level for 131I(2005) Unak P.; Cetinkaya B.Microdosimetric calculations of 131I have been evaluated for a single cell and for cell clusters. A VsBasic program has been used to calculate stopping power, linear energy transfer, range values and deposited energies per decay for beta particles, Auger and conversion electrons of 131I. The chemical composition of the cell has been taken into account in this model; results were compared with water medium. Besides, total absorbed doses have been calculated for the radionuclides distributed randomly within the cell and clusters. Cross-fire irradiation has been considered for clusters of cells. In this case, absorbed doses per cell within a cluster were found to be significantly higher than absorbed doses per single cell, depending on the cluster size. Results showed that 131I is a promising radionuclide for therapy of tumors from millimeter to centimeter dimensions. © 2004 Published by Elsevier Ltd.Öğe Absorbed dose estimates at the cellular level for 186Re and 188Re(Elsevier Ltd, 2005) Unak P.; Cetinkaya B.; Unak I.Microdosimetric calculations of 186Re and 188Re have been evaluated at the cellular level. Stopping power, LET, range values and deposited energies per decay have been calculated for beta particles, Auger and conversion electrons. In addition, total absorbed doses have been calculated for the radionuclides distributed randomly with certain activities within the cell. Results indicate 186Re and 188Re to be promising radionuclides for therapy of tumors from millimeter through centimeter dimensions. © 2004 Elsevier Ltd. All rights reserved.Öğe Affinity based laccase immobilization on modified magnetic nanoparticles: Biosensing platform for the monitoring of phenolic compounds(Taylor and Francis Inc., 2015) Babadostu A.; Guldu O.K.; Demirkol D.O.; Medine E.I.; Unak P.; Timur S.The authors report an electrochemical phenol biosensor based on the immobilization of laccase (Lac) on the surface of copper capped magnetic core-shell (Fe3O4-SiO2) nanoparticles (MNPs). After synthesis, MNP surfaces were functionalized by silanization and then, modified with histidine (His) and copper, respectively. The performance of the MNP-His/Cu/Lac biosensor has been investigated at -0.05 V versus Ag/AgCl. The proposed biosensor allowed to detect catechol and phenol in the range of 0.01-0.4 mM and 0.025-0.2 mM, respectively. Finally, phenol analysis in culture medium of P. putida adapted to phenol was successfully demonstrated with appreciable recovery values. © 2015 Copyright Taylor & Francis Group, LLC.Öğe Anti toxic effect of broccoli extract on stannous dichloride toxicity [Efeito antitóxico do extrato de brócolis na toxicidade do dicloreto de estanho](2012) Cekic B.; Muftuler F.Z.B.; Kilcar A.Y.; Gunay N.; Sakarya S.; Unak P.PURPOSE: Since Technetium-99m (99mTc) has favorable physical and chemical characteristics, it is widely used radioisotope in Nuclear Medicine. However, stannous dichloride (SnCl2) has been widely used as a reducing agent in labeling procedure of pharmaceutical with radionuclide, it has been realized that SnCl2 have genotoxic and cytotoxic effects on biological systems. In previous studies, it has been shown that some herbal extract can reduce genotoxic and cytotoxic effects of SnCl2. In the present study, it is aimed to evaluate the effect of the broccoli extract on the survival of E. coli ATCC 25922 strain against to toxic effects of SnCl2. METHODS: Broccoli was extracted with methanol extraction. HPLC and TLC analysis of broccoli extract were performed. Then antitoxicity and dose response assays were performed on bacterial strain. RESULTS: The broccoli extract had dose dependent protective effect against SnCl2 toxic effect on E. coli. CONCLUSIONS: The consumption of broccoli may alter the stannous dichloride toxicity. Broccoli extract may use as a new protective strategies against the toxic effect of SnCl2 on patients who were taken 99mTc radiopharmaceuticals.Öğe Biosensing Applications of Modified Core-Shell Magnetic Nanoparticles(2012) Ozdemir C.; Akca O.; Medine E.I.; Demirkol D.O.; Unak P.; Timur S.Fe 3O 4 magnetic nanoparticles (MNPs) were synthesized and silanized to form a core-shell (Fe 3O 4-SiO 2) structure. Afterwards, surface modification with amino silane was carried out to produce amino groups on the MNPs for the biomolecule immobilization. In order to test the performance of amino functional MNPs as immobilization platform in biosensing applications, glucose oxidase was immobilized on the surface via glutaraldehyde. Obtained Bio-MNPs were then fixed onto the carbon paste electrode by the aid of magnetic force and used as the working electrode during the amperometric measurements at -0. 7 V versus Ag/AgCl. After optimization of some parameters affecting the biosensor performance, analytical characterization was carried out. Linearity was found in the range of 0. 25-2. 0 mM glucose and defined by the equation of y = 8. 366x + 1. 819, (R 2 = 0. 996). Proposed biosensor was then applied for the glucose analysis in various beverages. Finally, data were compared with a commercial enzyme assay kit based on spectrophotometric Trinder reaction as a reference method. © 2011 Springer Science+Business Media, LLC.Öğe Cellular absorbed doses of Auger and conversion electrons from 111In(Abdus Salam International Centre for Theoretical Physics, 2011) Unak P.The purpose of this work is to calculate the microdosimetric dose distribution of the Auger and conversion electrons from 111In for both the single and cluster of cells. The total energy emitted is 32.37 keV/decay, which is the sum of Auger electron and conversion electron emission of 5.74 keV/decay and 26.63 keV/decay, respectively. The absorbed energy per decay of 111In is 5.67 keV if the chemical composition of a cell is considered. If the composition of a cell is assumed to be water, then the absorbed energy in the cell volume per decay is 3.76 keV. The absorbed dose distribution is not homogeneous, while Auger electrons deposit most of their energy within the cell, whereas conversion electrons deposit definitely less. The cluster size has little effect on the dose of the Auger electrons. However, it has a strong effect on the dose of conversion electrons. As the cluster size increases from 51 to 800 cells, the dose of conversion electrons increases by a factor of 7.8 to 14.8.Öğe A correlative study between 99mTc-ESTCPTA and 99mTc-MIBI in rats(2002) Unak P.; Enginar H.; Zümrüt Biber F.; Yurt Lambrecht F.; Aslani M.A.A.; Ozkilic H.Tissue distribution of the 99mTc labeled derivative of the estrogen compound 3,17-?-estradiolyl propyl 1,4,8,11-tetraazacyclotetradecanyl-1-(4-methylbenzoic acid) ester (ESTCPTA), which has an 3,17-?-estradiolyl propinol coupled to 1-(4-methylbenzoic acid)1,4,8,11-tetraazacyclotetradecane (CPTA), was compared to 99mTc-MIBI (methoxyisobutyl isonitrile) in female Albino Wistar rats. Tissues of interest included lung, liver, heart, kidneys, spleen, stomach, intestines, pancreas, muscle, blood, breast, ovary, fat, and uterus. 99mTc-ESTCPTA uptake by the uterus and ovary, as ER-rich tissues, was highly selective. Maximum uptakes for 99mTc-MIBI and 99mTc-ESTCPTA are 90min in breast, ovary and uterus. The pancreas also showed significant receptor saturated and unsaturated ratios for 99mTc-ESTCPTA. Results are sufficiently encouraging to generate further evaluation of these and related compounds as possible estrogen receptor based tumor imaging and therapeutic agents in estrogen-rich tissues. © 2002 Published by Elsevier Science Ltd.Öğe Detecting inflammation with 131I-labeled ornidazole(2000) Asikoglu M.; Yurt F.; Cagliyan O.; Unak P.; Ozkilic H.The aim of this study was to demonstrate the accumulation of 131I-labeled ornidazole (131I-ORN) in experimental abscesses. 131I-ORN was prepared by electrophilic radioiodination of ORN, using radioiodide in the presence of Iodogen®. An in vivo inflammation model was prepared by intramuscular injection of turpentine into the thigh of rabbits. Four days later 131I-ORN was intravenously administered to rabbits. Serial scintigrams were performed at different periods, using a Sophy DX Gamma Camera. 131I-ORN was visualized at 10 min after injection. 131I-ORN was also administered intraperitoneally to rats with turpentine-induced inflammation, for quantitative biodistribution studies. Counts of selected tissues were taken by a NaI(Tl) scintillation detector (gamma counter) after rats were decapitated. The target-to-non-target muscle ratios were 2.5, 2.6, 2.9 and 1.9 at 1, 3, 5 and 24 h, respectively. Copyright (C) 2000 Elsevier Science Ltd.Öğe Diethylenetriamine pentaacetic acid derivative of toremifene and in vitro evaluation in human breast cancer cell line MCF-7(2011) Kilcar A.Y.; Biber Muftuler F.Z.; Unak P.; Avci C.B.; Gunduz C.Cytotoxic and apoptotic effects of toremifene-diethylenetriamine pentaacetic acid (TOR-DTPA), formed by conjugation of TOR and DTPA, on the MCF-7 cell line were evaluated. TOR-DTPA was synthesized and qualified via gas chromatography-mass spectrometry system, thin layer chromatography, and high performance liquid chromatography methods. To screen the biological properties of TOR-DTPA at determined concentrations, our ongoing effort was to evaluate apoptotic and cytotoxic effects on the MCF-7 cell line. Trypan blue dye exclusion test, XTT, ELISA, and TUNEL assays were utilized to evaluate cytotoxicity and apoptosis. TOR-DTPA has no cytotoxic and limited apoptotic effect on the MCF-7 cell line according to the results of in vitro studies. It is concluded that the lack of obvious apoptotic and cytotoxic effects allows the already proposed ligand, TOR-DTPA, to be improved as a novel hydrophilic ligand for breast imaging. © Copyright 2011, Mary Ann Liebert, Inc.Öğe Effect of a plant origin drug on the biodistribution of 99mTc-DTPA in Wistar albino rats(2012) Zora H.; Biber Muftuler Z.F.; Demir I.; Kilcar A.Y.; Ichedef C.; Unak P.In recent years all over the world, medicinal plants are used quite a lot but side effects of biological and chemical contents and radiopharmaceutical interactions for each consumer in question aren't entirely well-known. The studies of plant origin drug interaction with radiopharmaceuticals are highly relevant and desired. One of them is passiflora syrup (Passiflora incarnata L., Passifloraceae) which is widely used for depression, insomnia, anxiety and menopause period. The aim of current study is to evaluate possible effects of passiflora syrup on the biodistribution of 99mTc-DTPA and its blood cells uptake. DTPA was labeled with 99mTc radionuclide. Biodistribution studies were performed on male Wistar albino rats which were treated via oral feeding-gavage-method with either passiflora syrup or 0.9 % NaCl as control group for ten days. Blood samples were obtained by cardiac blood withdrawal from the rats and they were radiolabeled. The biodistribution results showed that the passiflora syrup decreased the uptake of 99mTc-DTPA in kidneys and in blood cells. 99mTc-DTPA being used widely as a kidney diagnostic agent in nuclear medicine seems to be interacting with orally taken passiflora. Passiflora syrup may modify the uptake of 99mTc-DTPA by kidney. The knowledge of this negative effect may contribute to reduce the risk of misdiagnosis and/or repetition of the examinations in nuclear medicine.Öğe Effects of broccoli extract on biodistribution and labeling blood components with 99mTc-GH [Efeitos do extrato de brócolis na biodistribuição e marcação dos componentes do sangue com 99mTc-GH](2011) Cekic B.; Muftuler F.Z.B.; Kilcar A.Y.; Ichedef C.; Unak P.Purpose: People consume vegetables without the knowledge of the side effects of the biological and chemical contents and interactions between radiopharmaceuticals and herbal extract. To this end, current study is focused on the effects of broccoli extract on biodistribution of radiolabeled glucoheptonate (99mTc-GH) and radiolabeling of blood components. Methods: GH was labeled with 99mTc. Quality control studies were done utilizing TLC method. Biodistribution studies were performed on male rats which were treated via gavage with either broccoli extract or SF as control group for 15 days. Blood samples were withdrawn from rats' heart. Radiolabeling of blood constituents performed incubating with GH, SnCl2 and 99m Tc. Result s: Radiochemical yield of 99mTc-GH is 98.46±1.48 % (n=8). Biodistribution studies have shown that according to the control, the treated group with broccoli has approximately 10 times less uptake in kidney. The percentage of the radioactivity ratios of the blood components is found to be same in both groups. Conclusions: Although there is no considerable effect on the radiolabeling of blood components, there is an outstanding change on the biodistribution studies especially on kidneys. The knowledge of this change on kidney uptake may contribute to reduce the risk of misdiagnosis and/or repetition of the examinations in Nuclear Medicine.Öğe Enzymatic synthesis of uracil glucuronide, labeling with 125/131I, and in vitro evaluation on adenocarcinoma cells(2010) Medine I.E.; Unak P.; Sakarya S.; Toksöz F.Human UDP-glucuronosyltransferases (UGTs) are a family of membrane-bound enzymes of the endoplasmic reticulum. They catalyze the glucuronidation of various endogenous and exogenous compounds, converting them into more polar glucuronides. In this study, uracil glucuronide was enzymatically synthesized using a UGT-rich microsome preparate, which was separated from Hutu-80 cells. Two different glucuronide derivatives were obtained, with a total reaction yield of 22.95% ± 2.4% (n = 4). The glucuronide ligands were defined as uracil-n-glucuronide (UNG) and uracil-o-glucuronide (UOG). These were then analyzed by high-performance liquid chromatography-mass spectrometry and labeled with I-125 and I-131, separately. The radiolabeled 125/131I-UNG and 125/131I-UOG presented good incorporation ratios for Hutu-80, Caco-2, Detroit 562, and ACBRI 519 cells. The incorporation ratios of 125/131I-UOG were higher than those of 125/131I-UNG and of other labeled components for all cell types, and were also statistically significant compared to the values of 125/131I-UNG for primary human intestinal epithelial cells (ACBRI 519) and human intestinal adenocarcinoma cells. Cell incorporation rates of n-glucuronides and o-glucuronides were higher compared to uracil, with o-glucuronides being more selective. The results suggest that both I-125- and I-131-labeled glucuronides can be used in imaging and therapy, and further research should be done in preclinical stages. © 2010, Mary Ann Liebert, Inc. 2010.Öğe Evaluation of the efficacy of 99mTc-labeled ascorbic acid on common cold-cough drugs in rats(2007) Lambrecht F.Y.; Kayaalp E.; Unak P.; Enginar H.; Biber Muftuler F.Z.; Ilker Medine E.; Cetinkaya B.Multiple-drug therapy is common in current clinical practice. Because of this, people have been ready to embrace simplistic approaches to cold treatment, such as vitamin C and zinc. Ascorbic acid (vitamin C) is mostly administrated together with cough-cold drugs. The aim of this study was to investigate the effect of cough-cold drugs on the uptake of ascorbic acid using 99mTc-ascorbic acid (99mTc-AA) in male albino Wistar rats. Ascorbic acid was labeled with Tc-99m and the distribution of 99mTc-AA was investigated. The uptake of 99mTc-AA was evaluated when administrated alone (group I), with chlorpheniramine maleate (CPR) (group II), with phenylpropanolamine hydrochloride (PPA) (group III), and with acetaminophen (APAP) (group IV). In some organs (apart from kidneys, intestinal system, and stomach) the uptake of 99mTc-AA was not significantly affected by the administration of 99mTc with CPR or 99mTc with APAP at 120 min. On the other hand, there was significant difference in the uptake of 99mTc-AA between groups I and III. The administration of 99mTc-AA with PPA in rats caused an increase of the uptake of 99mTc-AA at 120 min in the investigated organs compared to the administration of 99mTc-AA alone. The present data show that vitamin C might be more effective for the treatment of common cold when coadministered with PPA compared to with CPR, with APAP, or alone. © 2008 Birkhäuser.Öğe Herbal infusions of black seed and wheat germ oil: Their chemical profiles, in vitro bio-investigations and effective formulations as Phyto-Nanoemulsions(Elsevier, 2015) Gumus Z.P.; Guler E.; Demir B.; Barlas F.B.; Yavuz M.; Colpankan D.; Senisik A.M.; Teksoz S.; Unak P.; Coskunol H.; Timur S.The reported studies related to black seed oil (BSO) and wheat germ oil (WGO) have illustrated that they have a wide range of biological activities. Therefore, enhancing the amount of bio-active compounds that caused higher cell based anti-oxidative effect as well as cell proliferation, etc. in seed oils, infusion of crude plant material has been gained importance as a traditional technique. Herein, we accomplished the infusion of Calendula flowers that also contains many phyto-constituents into BSO and WGO. After the infusion of oils, the change of phytochemical amount was investigated and evaluated according to the oils by chromatography, radical scavenging activity. Subsequently, for investigating the biological impact upon live cells, cytotoxicity, cell-based antioxidant capacity, wound healing and radioprotective activity were tested with monkey kidney fibroblast like cells (Vero) and HaCaT keratinocytes. In vitro cell based experiments (wound healing and radioprotective activity) confirmed that Calendula infused BSO and WGO have greater bio-activity when compared to those plain forms. The herbal oils prepared with an effective extraction technique were incorporated into nanoemulsion systems which will be then called as 'Phyto-Nanoemulsion'. After herbal oil biomolecules were encapsulated into nanoemulsion based delivery systems, the designed formulations were investigated in terms of biological activities. In conclusion, these preparations could be a good candidate as a part of dermal cosmetic products or food supplements which have the therapeutic efficiency, especially after radio- or chemotherapy. © 2015 Elsevier B.V..Öğe Hyaluronic acid-modified [19F]FDG-conjugated magnetite nanoparticles: in vitro bioaffinities and HPLC analyses in organs(Springer Netherlands, 2018) Yasakci V.; Tekin V.; Guldu O.K.; Evren V.; Unak P.In this study, we designed and synthesized [19F]FDG-(2-deoxy-2-[fluorine-19]fluoro-d-glucose) conjugated iron oxide magnetic nanoparticles ([19F]FDG-MNPs) for hybrid imaging and hyperthermia treatment. MNPs were synthesized, silica coated, and fabricated with TEOS (tetraethyl orthosilicate). They were then covered with hyaluronic acid (HA) to enhance their bioavailability. The modified MNPs were conjugated with [19F]FDG and optically labeled with ICG (indocyanine green). The in vitro bioaffinities were surveyed in MCF7 and PC3 cell lines. In vivo bioaffinies were determined using Sprague–Dawley rats. © 2018, Akadémiai Kiadó, Budapest, Hungary.Öğe Imaging of bacterial infection with 99mTc-labeled HBD-1(2008) Yurt Lambrecht F.; Yilmaz O.; Unak P.; Seyitoglu B.; Durkan K.; Yolcular S.; Baskin H.The aim of this study was to evaluate 99mTc labeled human ß-defensin-1 (HBD-1) for discrimination between bacterial infection and sterile inflammation. For this purpose, HBD-1 was radiolabeled with 99mTc and its in vivo distribution was evaluated in inflamed rats with Staphylococcus aureus (S. aureus) and sterile inflamed rats with turpentine oil. After injection into inflamed and sterile inflamed rats, 99mTc-HBD-1 was rapidly removed from the circulation via the kidneys. Binding of 99mTc-HBD-1 to inflamed muscle (T/NT = 20 at 120 min) was two times higher than binding to sterile inflamed muscle (T/NT = 10 at 120 min) of rats. It was demonstrated that 99mTc-HBD-1 can be used to detect S. aureus inflammation in rats. However, the radiolabeled antimicrobial peptide showed only poor uptake in sterile inflammation with turpentine oil in rats. As a result, 99mTc-HBD-1 can be useful for detection of bacterial inflammation. © 2008 Akadémiai Kiadó, Budapest.
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