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Permanent URI for this collectionhttps://hdl.handle.net/11443/932

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Author: search.filters.author.Unsal, Ibrahim

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    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 Biol
    BACKGROUND: 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 females
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    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 Clinical
    BACKGROUND: 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 female
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    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 Grp
    BACKGROUND: 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\%
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    Within- and between-subject biological variation data for serum zinc, copper and selenium obtained from 68 apparently healthy Turkish subjects
    (WALTER DE GRUYTER GMBH, 2022-01-01) Coskun, Abdurrahman; Carobene, Anna; Aarsand, Aasne K.; Aksungar, Fehime B.; Serteser, Mustafa; Sandberg, Sverre; Diaz-Garzon, Jorge; Fernandez-Calle, Pilar; Karpuzoglu, Fatma H.; Coskun, Cihan; Kizilkaya, Emine; Fidan, Damla; Jonker, Niels; Ugur, Esra; Unsal, Ibrahim; Chem, European Federation Clinical; Database, Task Grp Biol Variation
    Objectives Trace elements (TrEL) are nutritionally essential components in maintaining health and preventing diseases. There is a lack of reliable biological variation (BV) data for TrELs, required for the diagnosis and monitoring of TrEL disturbances. In this study, we aimed to provide updated within- and between-subject BV estimates for zinc (Zn), copper (Cu) and selenium (Se). Methods Weekly serum samples were drawn from 68 healthy subjects (36 females and 32 males) for 10 weeks and stored at -80 degrees C prior to analysis. Serum Zn, Cu and Se levels were measured using inductively-coupled plasma mass spectrometry (ICP-MS). Outlier and variance homogeneity analyses were performed followed by CV-ANOVA (Roraas method) to determine BV and analytical variation estimates with 95\% CI and the associated reference change values (RCV) for all subjects, males and females. Results Significant differences in mean concentrations between males and females were observed, with absolute and relative (\%) differences for Zn at 0.5 mu mol/L (3.5\%), Cu 2.0 mu mol/L (14.1\%) and Se 0.06 mu mol/L (6.0\%). The within-subject BV (CVI {[}95\% CI]) estimates were 8.8\% (8.2-9.3), 7.8\% (7.3-8.3) and 7.7\% (7.2-8.2) for Zn, Cu and Se, respectively. Within-subject biological variation (CVI) estimates derived for male and female subgroups were similar for all three TrELs. Marked individuality was observed for Cu and Se. Conclusions The data of this study provides updated BV estimates for serum Zn, Cu and Se derived from a stringent protocol and state of the art methodologies. Furthermore, Cu and Se display marked individuality, highlighting that population based reference limits should not be used in the monitoring of patients.
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    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 Biological
    Background: 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.
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    Personalized reference intervals - statistical approaches and considerations
    (WALTER DE GRUYTER GMBH, 2022-01-01) Coskun, Abdurrahman; Sandberg, Sverre; Unsal, Ibrahim; Yavuz, Fulya G.; Cavusoglu, Coskun; Serteser, Mustafa; Kilercik, Meltem; Aarsand, Aasne K.
    For many measurands, physicians depend on population-based reference intervals (popRI), when assessing laboratory test results. The availability of personalized reference intervals (prRI) may provide a means to improve the interpretation of laboratory test results for an individual. prRI can be calculated using estimates of biological and analytical variation and previous test results obtained in a steady-state situation. In this study, we aim to outline statistical approaches and considerations required when establishing and implementing prRI in clinical practice. Data quality assessment, including analysis for outliers and trends, is required prior to using previous test results to estimate the homeostatic set point. To calculate the prRI limits, two different statistical models based on `prediction intervals' can be applied. The first model utilizes estimates of `within-person biological variation' which are based on an individual's own data. This model requires a minimum of five previous test results to generate the prRI. The second model is based on estimates of `within-subject biological variation', which represents an average estimate for a population and can be found, for most measurands, in the EFLM Biological Variation Database. This model can be applied also when there are lower numbers of previous test results available. The prRI offers physicians the opportunity to improve interpretation of individuals' test results, though studies are required to demonstrate if using prRI leads to better clinical outcomes. We recommend that both popRIs and prRIs are included in laboratory reports to aid in evaluating laboratory test results in the follow-up of patients.
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    Melatonin in preservation solutions prevents ischemic injury in rat kidneys
    (PUBLIC LIBRARY SCIENCE, 2022-01-01) Coskun, Abdurrahman; Yegen, Cumhur; Arbak, Serap; Attaallah, Wafi; Gunal, Omer; Elmas, Merve Acikel; Ucal, Yasemin; Can, Ozge; Bas, Banu; Yildirim, Zeynep; Seckin, Ismail; Demirci, Sibel; Serteser, Mustafa; Ozpinar, Aysel; Belce, Ahmet; Basdemir, Gulcin; Moldur, Derya Emel; Derelioglu, Ecenur Izzete; Yozgatli, Tahir Koray; Erdemgil, Yigit; Unsal, Ibrahim
    Transplantation is lifesaving and the most effective treatment for end-stage organ failure. The transplantation success depends on the functional preservation of organs prior to transplantation. Currently, the University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) are the most commonly used preservation solutions. Despite intensive efforts, the functional preservation of solid organs prior to transplantation is limited to hours. In this study, we modified the UW solution containing components from both the UW and HTK solutions and analyzed their tissue-protective effect against ischemic injury. The composition of the UW solution was changed by reducing hydroxyethyl starch concentration and adding Histidine/Histidine-HCI which is the main component of HTK solution. Additionally, the preservation solutions were supplemented with melatonin and glucosamine. The protective effects of the preservation solutions were assessed by biochemical and microscopical analysis at 2, 10, 24, and 72 h after preserving the rat kidneys with static cold storage. Lactate dehydrogenase (LDH) activity in preservation solutions was measured at 2, 10, 24, and 72. It was not detectable at 2 h of preservation in all groups and 10 h of preservation in modified UW+melatonin (mUW-m) and modified UW+glucosamine (mUW-g) groups. At the 72nd hour, the lowest LDH activity (0.91 IU/g (0.63-1.17)) was measured in the mUW-m group. In comparison to the UW group, histopathological damage score was low in modified UW (mUW), mUW-m, and mUW-g groups at 10, 24, and 72 hours. The mUW-m solution at low temperature was an effective and suitable solution to protect renal tissue for up to 72 h.
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    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, Aysel
    Background: 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 levels
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    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, Ben
    Perchlorate, 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.
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    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, Ibrahim
    Analysis 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.