Araştırma Çıktıları
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Item The EuBIVAS Project: Within- and Between-Subject Biological Variation Data for Serum Creatinine Using Enzymatic and Alkaline Picrate Methods and Implications for Monitoring(AMER ASSOC CLINICAL CHEMISTRY, 2017-01-01) Carobene, Anna; Marino, Irene; Coskun, Abdurrahman; Serteser, Mustafa; Unsal, Ibrahim; Guerra, Elena; Bartlett, William A.; Sandberg, Sverre; Aarsand, Aasne Karine; Sylte, Marit Sverresdotter; Roraas, Thomas; Solvik, Una Orvim; Fernandez-Calle, Pilar; Diaz-Garzon, Jorge; Tosato, Francesca; Plebani, Mario; Jonker, Niels; Barla, Gerhard; Ceriotti, Ferruccio; Variation, E.F.L.M. Working Grp BiolBACKGROUND: The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) European Biological Variation Study (EuBIVAS) has been established to deliver rigorously determined biological variation (BV) indices. EuBIVAS determined BV for serum creatinine using the enzymatic and alkaline picrate measurement methods. METHOD: In total, 91 healthy individuals (38 males, 53 femalesItem The EuBIVAS: Within- and Between-Subject Biological Variation Data for Electrolytes, Lipids, Urea, Uric Acid, Total Protein, Total Bilirubin, Direct Bilirubin, and Glucose(AMER ASSOC CLINICAL CHEMISTRY, 2018-01-01) Aarsand, Aasne K.; Diaz-Garzon, Jorge; Fernandez-Calle, Pilar; Guerra, Elena; Locatelli, Massimo; Bartlett, William A.; Sandberg, Sverre; Roraas, Thomas; Ceriotti, Ferruccio; Solvik, Una Orvim; Sylte, Marit Sverresdotter; Coskun, Abdurrahman; Serteser, Mustafa; Unsal, Ibrahim; Tosato, Francesca; Plebani, Mario; Jonker, Niels; Barla, Gerhard; Carobene, Anna; Chem, European Federation ClinicalBACKGROUND: The European Federation of Clinical Chemistry and Laboratory Medicine European Biological Variation Study (EuBIVAS) has been established to deliver rigorously determined data describing biological variation (BV) of clinically important measurands. Here, EuBIVAS-based BV estimates of serum electrolytes, lipids, urea, uric acid, total protein, total bilirubin, direct bilirubin, and glucose, as well as their associated analytical performance specifications (APSs), are presented. METHOD: Samples were drawn from 91 healthy individuals (38 male, 53 femaleItem Biological Variation Estimates Obtained from 91 Healthy Study Participants for 9 Enzymes in Serum(AMER ASSOC CLINICAL CHEMISTRY, 2017-01-01) Carobene, Anna; Roraas, Thomas; Solvik, Una Orvim; Sylte, Marit Sverresdotter; Sandberg, Sverre; Guerra, Elena; Marino, Irene; Jonker, Niels; Barla, Gerhard; Bartlett, William A.; Fernandez-Calle, Pilar; Diaz-Garzon, Jorge; Tosato, Francesca; Plebani, Mario; Coskun, Abdurrahman; Serteser, Mustafa; Unsal, Ibrahim; Ceriottil, Ferruccio; Biological, E.F.L.M. Working GrpBACKGROUND: We sought to develop estimates of biological variation (BV) for 9 enzymes in blood serum as part of the European Biological Variation Study. METHODS: Ninety-one healthy study participants (38 male and 53 female, 21-69 years old) were phlebotomized in each of 10 consecutive weeks at 6 European laboratories. The same preanalytical sample-handling protocol was followed at each center before transport to San Raffaele Hospital, Milan, Italy, for analysis. Sera were stored at -80 degrees C before analysis in duplicate within a single run on an ADVIA 2400 Clinical Chemistry System (Siemens Healthcare) following a protocol designed to minimize analytical imprecision. Assay traceability was established using frozen sera with target values assigned by reference methods. The results were subjected to outlier analysis before CV-ANOVA to deliver valid BV estimates. Results for 9 enzymes were subsequently partitioned for graphical display allowing visual assessment of the effects of country of origin, sex, and age on BV estimates. RESULTS: We found no effect of country upon the observed variation, but overall sex-related differences were evident for alanine amino transferase (ALT), gamma-glutamyl transferase (GGT), and creatine kinase (CK). The following estimates for within-subject BV (CVI) and between-subject BV (CVG), respectively, were obtained: ALT: 9.3\%, 28.2\%Item Within-subject and between-subject biological variation estimates of 21 hematological parameters in 30 healthy subjects(WALTER DE GRUYTER GMBH, 2018-01-01) Coskun, Abdurrahman; Carobene, Anna; Kilercik, Meltem; Serteser, Mustafa; Sandberg, Sverre; Aarsand, Aasne K.; Fernandez-Calle, Pilar; Jonker, Niels; Bartlett, William A.; Diaz-Garzon, Jorge; Huet, Sibel; Kiziltas, Cansu; Dalgakiran, Ilayda; Ugur, Esra; Unsal, Ibrahim; Varia, E.F.L.M. Working Grp BiologicalBackground: The complete blood count (CBC) is used to evaluate health status in the contexts of various clinical situations such as anemia, infection, inflammation, trauma, malignancies, etc. To ensure safe clinical application of the CBC, reliable biological variation (BV) data are required. The study aim was to define the BVs of CBC parameters employing a strict protocol. Methods: Blood samples, drawn from 30 healthy subjects (17 females, 13 males) once weekly for 10 weeks, were analyzed using a Sysmex XN 3000 instrument. The data were assessed for normality, trends, outliers and variance homogeneity prior to coefficient of variation (CV)-analysis of variance (ANOVA). Sex-stratified within-subject (CVI) and between-subjects (CVG) BV estimates were determined for 21 CBC parameters. Results: For leukocyte parameters, with the exception of lymphocytes and basophils, significant differences were found between female/male CVI estimates. The mean values of all erythrocyte-, reticulocyte- and platelet parameters differed significantly between the sexes, except for mean corpuscular hemoglobin concentration, mean corpuscular volume and platelet numbers. Most CVI and CVG estimates appear to be lower than those previously published. Conclusions: Our study, based on a rigorous protocol, provides updated and more stringent BV estimates for CBC parameters. Sex stratification of data is necessary when exploring the significance of changes in consecutive results and when setting analytical performance specifications.Item Exposure to Perchlorate in Lactating Women and Its Associations With Newborn Thyroid Stimulating Hormone(FRONTIERS MEDIA SA, 2018-01-01) Ucal, Yasemin; Sahin, Ozlem N.; Serdar, Muhittin; Blount, Ben; Kumru, Pinar; Muhcu, Murat; Eroglu, Mustafa; Akin-Levi, Cansu; Keles, Z. Zeynep Yildirim; Turam, Cem; Valentin-Blasini, Liza; Morel-Espinosa, Maria; Serteser, Mustafa; Unsal, Ibrahim; Ozpinar, AyselBackground: Perchlorate, thiocyanate, and nitrate can block iodide transport at the sodium iodide symporter (NIS) and this can subsequently lead to decreased thyroid hormone production and hypothyroidism. NIS inhibitor exposure has been shown to reduce iodide uptake and thyroid hormone levelsItem Iodine Status in Turkish Populations and Exposure to Iodide Uptake Inhibitors(PUBLIC LIBRARY SCIENCE, 2014-01-01) Ozpinar, Aysel; Kelestimur, Fahrettin; Songur, Yildiran; Can, Ozge; Valentin, Liza; Caldwell, Kathleen; Arikan, Ender; Unsal, Ibrahim; Serteser, Mustafa; Inal, Tamer; Erdemgil, Yigit; Coskun, Abdurrahman; Bakirci, Nadi; Sezgin, Ozlem; Blount, BenPerchlorate, nitrate, and thiocyanate are competitive inhibitors of the sodium iodide symporter of the thyroid membrane. These inhibitors can decrease iodine uptake by the symporter into the thyroid gland and may disrupt thyroid function. This study assesses iodine status and exposure to iodide uptake inhibitors of non-pregnant and non-lactating adult women living in three different cities in Turkey (Istanbul, Isparta and Kayseri). We measured iodine and iodide uptake inhibitors in 24-hr urines collected from study participants (N = 255). All three study populations were mildly iodine deficient, with median urinary iodine (UI) levels of 77.5 mu g/L in Istanbul, 58.8 mu g/L in Isparta, and 69.8 mu g/L in Kayseri. Perchlorate doses were higher in the study population (median 0.13 mu g/kg/day), compared with a reference population (median 0.059 mu g/kg/day), but lower than the U. S. EPA reference dose (0.7 mu g/kg/day). Urinary thiocyanate levels increased with increasing exposure to tobacco smoke, with non-smokers (268 mu g/L) significantly lower than light smokers (1110 mu g/L), who were significantly lower than heavy smokers (2410 mu g/L). This pilot study provides novel data indicating that study participants were moderately iodine deficient and had higher intakes of the iodide uptake inhibitor perchlorate compared with a reference population. Further investigation is needed to characterize the thyroid impact resulting from iodine deficiency coupled with exposure to iodide uptake inhibitors such as perchlorate, thiocyanate and nitrate.Item A Simple Method for Quantification of Five Urinary Porphyrins, Porphobilinogen and 5-Aminolevulinic Acid, Using Liquid Chromatography Tandem Mass Spectrometry(SPRINGER INDIA, 2019-01-01) Dogan, Ozlem; Serdar, Muhittin A.; Murat, Koza; Sonmez, Cigdem; Ispir, Emre; Serteser, Mustafa; Unsal, IbrahimAnalysis of porphyrins and 5-aminolevulinic acid (ALA), porphobilinogen (PBG) in physiological liquids is required for diagnosis and follow-up of porphyrias. High performance liquid chromatography (HPLC) and liquid chromatography tandem mass spectrometry (LC-MS) methods with higher specificity and sensitivity have been developed. The major disadvantage of those methods is that they require longer extraction times due to their matrix effects. The present study suggests a simple, fast, sensitive, and specific assay for determination of Coproporphyrin, 5-carboxylporphyrin, 6-carboxylporphyrin, 7-carboxylporphyrin, Uroporphyrin I and ALA, PBG in urine sample by direct injection without sample pre-treatment using LC-MS. For the purposes of the present study LC-MS device was set to multiple reaction monitoring (MRM) and positive ion mode. Porphyrins and ALA, porphobilinogen were characterized by their MS/MS product ion, spectra. ALA, PBG and 5 porphyrins were detected simultaneously. Limit of detection for Coproporphyrin, 5-carboxylporphyrin, 6-carboxylporphyrin, 7-carboxylporphyrin, Uroporphyrin I were 2nmol/L, where it was 5mol/L for ALA and 2mol/L for porphobilinogen. The present study suggests that the present method is very effective compared to many other available methods for it does not require pre-treatment, provides simultaneous results of ALA, PBG and 5 porphyrins quantitatively in a shorter span of time, and has suitable sensitivity and selectivity. LC-MS technique was used clinically for the determination of urine porphyrin levels.Item Reference interval of pregnancy-associated plasma protein-A in healthy men and non-pregnant women(ELSEVIER, 2013-01-01) Coskun, Abdurrahman; Serteser, Mustafa; Duran, Sadik; Inal, Tamer C.; Erdogan, Birsen E.; Ozpinar, Aysel; Can, Ozge; Unsal, IbrahimObjective: The serum pregnancy-associated plasma protein-A (PAPP-A) concentration is a predictor of ischemic cardiac events and renal impairment. However, the reference interval of PAPP-A has not been determined. This study determined the reference interval of PAPP-A in men and non-pregnant women. Methods: The study enrolled 126 apparently healthy individuals (52 males and 74 females). The mean age of the men and women was 34.7 (range 20-66) years and 34.6 (range 18-65) years, respectively. Serum PAPP-A concentrations were determined using an ultrasensitive enzyme-linked immunoassay kit. Reference intervals were calculated using the bootstrap method. Results: The results for three subjects were outliers, so the reference interval of PAPP-A was calculated using the data for 123 subjects. PAPP-A was undetectable in 26 subjects. The reference interval of PAPP-A for men and women (with the 90\% confidence interval) was <22.9 ng/mL (19.7-23.3) and <33.6 ng/mL (25.2-36.7), respectively. In male subjects, serum PAPP-A levels of smokers {[}3.10 (UD, 7.30) ng/mL] were significantly lower than that of non-smokers {[}11.00 (UD, 24.4) ng/mL] (p < 0.001) and there was a positive correlation between serum PAPP-A levels and subjects' age (r=0.439Item INHIBITION OF CHOLESTEROL BIOSYNTHESIS IN HYPERCHOLESTEROLEMIA - IS IT THE RIGHT CHOICE?(DE GRUYTER POLAND SP ZOO, 2013-01-01) Coskun, Abdurrahman; Serteser, Mustafa; Unsal, IbrahimCholesterol biosynthesis is a complex pathway comprising more than 20 biochemical reactions. Although the final product created in the pathway is cholesterol, the intermediate products, such as ubiquinone and dolichol, also provide vital metabolic functions. Statins are HGM-CoA reductase inhibitors that stop the production of cholesterol by directly inhibiting the mevalonate production. Mevalonate is a precursor of two additional vital molecules, squalene and ubiquinone (coenzyme Q10). We hypothesized that inhibiting the cholesterol biosynthesis with statins for an extended duration may potentiate the oxidative stress, neurodegenerative disease and cancer. Our recommendation was to measure muscle enzymes, antioxidant capacity, and ubiquinone to monitor patients receiving the statins for prolonged periods of time.Item Easy method for newborn screening of six lysosomal storage disorders using online solid-phase extraction with mass spectrometry(WALTER DE GRUYTER GMBH, 2016-01-01) Serdar, Muhittin; Lay, Incilay; Coskun, Julide; Aslan, Berna; Aslan, Huseyin; Coskun, Abdurrahman; Serteser, Mustafa; Unsal, Ibrahim; Ozpinar, AyselObjective: A modified method for screening of six lysosomal storage disorders (LSDs) by tandem mass spectrometry was presented. Methods: The enzyme activities for six LSDs (Gaucher, Pompe, Krabbe, Fabry, Niemann-Pick A/B and Mucopolysaccharidosis Type I) was measured by using ultra-HPLC and mass spectrometry. After overnight incubation of dried blood spots with three distinct reaction cocktails containing substrates and internal standards, reactions were stopped and online trapping was performed with ultra-HPLC preceding to mass spectrometry. Ultra-HPLC was equipped with online solid phase extraction and Hypersil Gold C8 analytical columns and coupled with TSQ Quantum Access Max mass spectrometry. Results: Activities of acid-ss-glucocerebrosidase (ABG), acid glucosidase (GAA), galactocerebroside-ss-galactosidase (GALC), acid-galactosidase A (GLA), acid sphingomyelinase (ASM), and alpha-L-iduronidase (IDU) were obtained from DBSs of patients and healthy individuals. The intra- and inter-assay precisions were <20\% (CV). Conclusion: Our modified method, needing less DBS punches and only three reaction coctails, with the online trapping methodology, accurately differentiates newborns with LSDs from healthy newborns.
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