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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 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, IbrahimTransplantation 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.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 Personalized Reference Intervals in Laboratory Medicine: A New Model Based on Within-Subject Biological Variation(OXFORD UNIV PRESS INC, 2021-01-01) Coskun, Abdurrahman; Sandberg, Sverre; Unsal, Ibrahim; Cavusoglu, Coskun; Serteser, Mustafa; Kilercik, Meltem; Aarsand, Aasne K.BACKGROUND: The concept of personalized medicine has received widespread attention in the last decade. However, personalized medicine depends on correct diagnosis and monitoring of patients, for which personalized reference intervals for laboratory tests may be beneficial. In this study, we propose a simple model to generate personalized reference intervals based on historical, previously analyzed results, and data on analytical and within-subject biological variation. METHODS: A model using estimates of analytical and within-subject biological variation and previous test results was developed. We modeled the effect of adding an increasing number of measurement results on the estimation of the personal reference interval. We then used laboratory test results from 784 adult patients (>18 years) considered to be in a steady-state condition to calculate personalized reference intervals for 27 commonly requested clinical chemistry and hematology measurands. RESULTS: Increasing the number of measurements had little impact on the total variation around the true homeostatic set point and using >= 3 previous measurement results delivered robust personalized reference intervals. The personalized reference intervals of the study participants were different from one another and, as expected, located within the common reference interval. However, in general they made up only a small proportion of the population-based reference interval. CONCLUSIONS: Our study shows that, if using results from patients in steady state, only a few previous test results and reliable estimates of within-subject biological variation are required to calculate personalized reference intervals. This may be highly valuable for diagnosing patients as well as for follow-up and treatment.Item 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.Item Indirect Reference Intervals Estimated from Hospitalized Population for Thyrotropin and Free Thyroxine(MEDICINSKA NAKLADA, 2010-01-01) Inal, Tamer C.; Serteser, Mustafa; Coskun, Abdurrahman; Ozpinar, Aysel; Unsal, IbrahimAim To establish indirect reference intervals from patient results obtained during routine laboratory work as an alternative to laborious and expensive producing of their own reference range values according to international instructions. Methods All results for thyrotropin (TSH) and free thyroxine (T4) that were stored in our laboratory information system between 2004 and 2008 were included in this study. After a logarithmic transformation of the raw data, outliers were excluded. Non-parametric reference intervals were estimated statistically after visual observation of the distribution using stem-and-leaf plots and histograms. A standard normal deviation test was performed to test the significance of differences between sub-groups. Results There was no significant difference in serum TSH or free T4 concentrations between male and female participants. Because no differences were found within the time span of the study, combined reference intervals were calculated. Indirect reference values were 0.43- 3.93 mU/L for TSH and 11.98-21.33 pmol/L for free T4. Conclusion Using patient laboratory data values is a relatively easy and cheap method of establishing laboratory specific reference values if skewness and kurtosis of the distribution are not too large.Item Proteins associated with neutrophil degranulation are upregulated in nasopharyngeal swabs from SARS-CoV-2 patients(PUBLIC LIBRARY SCIENCE, 2020-01-01) Akgun, Emel; Tuzuner, Mete Bora; Sahin, Betul; Kilercik, Meltem; Kulah, Canan; Cakiroglu, Hacer Nur; Serteser, Mustafa; Unsal, Ibrahim; Baykal, Ahmet TarikCOVID-19 or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared throughout the World and currently affected more than 9 million people and caused the death of around 470,000 patients. The novel strain of the coronavirus disease is transmittable at a devastating rate with a high rate of severe hospitalization even more so for the elderly population. Naso-oro-pharyngeal swab samples as the first step towards detecting suspected infection of SARS-CoV-2 provides a non-invasive method for PCR testing at a high confidence rate. Furthermore, proteomics analysis of PCR positive and negative naso-oropharyngeal samples provides information on the molecular level which highlights disease pathology. Samples from 15 PCR positive cases and 15 PCR negative cases were analyzed with nanoLC-MS/MS to identify the differentially expressed proteins. Proteomic analyses identified 207 proteins across the sample set and 17 of them were statistically significant. Protein-protein interaction analyses emphasized pathways like Neutrophil degranulation, Innate Immune System, Antimicrobial Peptides. Neutrophil Elastase (ELANE), Azurocidin (AZU1), Myeloperoxidase (MPO), Myeloblastin (PRTN3), Cathepsin G (CTSG) and Transcobalamine-1 (TCN1) were found to be significantly altered in naso-oropharyngeal samples of SARS-CoV-2 patients. The identified proteins are linked to alteration in the innate immune system specifically via neutrophil degranulation and NETosis.Item Biological variations of ADAMTS13 and von Willebrand factor in human adults(CROATIAN SOC MEDICAL BIOCHEMISTS, 2014-01-01) Kilercik, Meltem; Coskun, Abdurrahman; Serteser, Mustafa; Inan, Deniz; Unsal, IbrahimBackground: The ultra-large von Willebrand factor (vWF) multimers are very active and must be degraded by ADAMTS13 for optimal activity. A severe functional deficiency of ADAMTS13 has been associated with thrombotic thrombocytopenic purpura. The correct interpretation of patient vWF and ADAMTS13 plasma levels requires an understanding of the biological variation associated with these analytes. In the present paper, we aimed to determine the biological variation of ADAMTS13 and vWF in human adults. Materials and methods: Blood samples were collected weekly from 19 healthy subjects for 5 consecutive weeks. vWF activity and antigenicity were determined using aggregometric and immunoturbidimetric methods. ADAMTS13 antigenicity and activity were determined by ELISA. Results: The within-subject biological variations for vWF activity and antigenicity were 8.06\% and 14.37\%, respectively, while the between-subject biological variations were 18.5\% and 22.59\%, respectively. The index of individuality for vWF activity was 0.44, while vWF antigenicity was 0.64. Similarly, ADAMTS13 activity and antigenicity within-subject biological variations were 12.73\% and 9.75\%, respectively, while between-subject biological variations were 9.63\% and 6.28\%, respectively. The ADAMTS13 indexes of individuality were 1.32 and 1.55, respectively. Conclusion: We report high biological variation and individuality in vWF antigenicity and activity levels. However, ADAMTS13 antigenicity and activity displayed high biological variation, but low individuality. Thus, population-based reference intervals may be useful for monitoring ADAMTS13 antigenicity and activity, but not for vWF, which displays high individuality. These findings should be considered when determining the reference interval and other clinical variables associated with ADAMTS13 and vWF levels.