Browsing by Author "Özarda, Yeşim"
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Item A global multicenter study on reference values: 2. Exploration of sources of variation across the countries(Elsevier, 2017-04) Ichihara, Kiyoshi; Barth, Julian H; Klee, George; Shimizu, Yoshihisa; Xia, Liangyu; Hoffmann, Mariza; Shah, Swarup; Matsha, Tandi; Wassung, Janette; Smit, Francois; Ruzhanskaya, Anna; Straseski, Joely; Bustos, Daniel N; Kimura, Shogo; Takahashi, Aki; Özarda, Yeşim; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyokimya Anabilim Dalı.; AAL-8873-2021; 35741320500Objectives: The intent of this study, based on a global multicenter study of reference values (RVs) for serum analytes was to explore biological sources of variation (SVs) of the RVs among 12 countries around the world. Methods: As described in the first part of this paper, RVs of 50 major serum analytes from 13,396 healthy individuals living in 12 countries were obtained. Analyzed in this study were 23 clinical chemistry analytes and 8 analytes measured by immunoturbidimetry. Multiple regression analysis was performed for each gender, country by country, analyte by analyte, by setting four major SVs (age, BMI, and levels of drinking and smoking) as a fixed set of explanatory variables. For analytes with skewed distributions, log-transformation was applied. The association of each source of variation with RVs was expressed as the partial correlation coefficient (rp). Results: Obvious gender and age-related changes in the RVs were observed in many analytes, almost consistently between countries. Compilation of age-related variations of RVs after adjusting for between-country differences revealed peculiar patterns specific to each analyte. Judged from the rp, BMI related changes were observed for many nutritional and inflammatory markers in almost all countries. However, the slope of linear regression of BMI vs. RV differed greatly among countries for some analytes. Alcohol and smoking-related changes were observed less conspicuously in a limited number of analytes. Conclusion: The features of sex, age, alcohol, and smoking-related changes in RVs of the analytes were largely comparable worldwide. The finding of differences in BMI-related changes among countries in some analytes is quite relevant to understanding ethnic differences in susceptibility to nutritionally related diseases.Item Bursa ilinde 18-45 yaş arası sağlıklı bireylerde vitaminlerin ve antioksidan parametrelerin referans aralıklarının belirlenmesi(Uludağ Üniversitesi, 2006) Hızlı, Zafer Banu; Özarda, Yeşim; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.Tıbbi kararda gerekli olan referans aralıklarının hesaplanması için çeşitli öneriler bulunmaktadır. Sağlıklı referans bireylerden elde edilen sonuçlardan “ABD Ulusal Klinik Laboratuvar Standartları Komitesi (NCCLS)” ve “Uluslararası Klinik Kimya ve Laboratuvar Tıbbı Federasyonu (IFCC)”nun önerilerine göre parametrik ve parametrik olmayan yöntem ile yapılan hesaplamalar yanında laboratuvara başvuran bireylerin sonuçlarından da hesaplama yapılabilmektedir. Populasyon, diyet, teknik ve referans grubun seçimine bağlı olarak laboratuvarlar ve bölgeler arası oluşan farklardan dolayı her laboratuvarın kendi referans aralıklarını belirlemesi son derece önemlidir. Oksidatif stres birçok hastalığın patogenezinde kritik rol oynamaktadır. Reaktif oksijen türlerinin biyolojik etkileri çeşitli antioksidan savunma sistemleri kontrol altında tutulmaktadır. Süperoksit dismutaz (SOD), glutatyon peroksidaz (GPx), glutatyon redüktaz (GR) gibi antioksidan enzimler, A, E, C, B grubu vitaminler ile çeşitli biyolojik moleküllerden oluşmaktadır. Bu antioksidan savunma sistemleri birbiriyle ilişkili reaksiyonlarla oksidatif stres hasarını ortadan kaldırmaya çalışırlar. Antioksidan parametrelerin ve vitamin düzeylerinin, biyolojik değişkenliklerinin yüksek olması nedeniyle “topluma dayalı referans aralıklar” gözönüne alınarak değerlendirilmesi gereklidir. Bu çalışmada referans aralıklarını belirlemek amacıyla Bursa ilinde, Uludağ Üniversitesi Tıp Fakültesi Tıbbi Tahliller, Eğitim ve Araştırma Merkez laboratuarında 18 – 45 yaşları arasındaki 407 bireyden 12 – 14 saatlik açlık sonrasında kanlar alındı. SOD, GPx, GR ve vitamin A, E, C, B1, B2, B6 düzeyleri analiz edildi. Referans değerler NCCLS’nin önerdiği C 28-A prosedürüne göre belirlendi. % 95 referans aralıkları parametrik olmayan yöntem ile hesaplandı. Üretici firmanın vermiş olduğu ve literatürlerden elde edilen referans aralıkları ile karşılaştırıldı. Çalışmamızın sonuçları Türkiye’de yapılan diğer çalışmaların sonuçları ile karşılaştırılabilir ve tüm bölgelerden elde edilen veriler ile birleştirilip Türkiye için ortak referans aralıkların belirlenmesi sağlanabilir.Item Changes of plasma free choline and choline-containing compounds' concentrations and choline loss during hemodialysis in ESRD patients(Pergamon-Elsevier Science, 2002-05) Özarda, Yeşim; Dilek, Kamil; Yurtkuran, Mustafa Abbas; Ulus, İsmail Hakkı; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; AAL-8873-2021; D-5340-2015; 55665181500; 56005080200; 7003389525; 7004271086Objectives: This study was undertaken to determine the changes in plasma free choline and choline-containing compounds in end stage renal disease (ESRD) and to determine if they were lost into the dialysate during hemodialysis. Design and methods: Plasma and dialysate free choline, phosphocholine and phospholipid, phosphatidylcholine-, sphingomyelin-bound choline were measured before, during and after hemodialysis. Results: Plasma free and bound choline concentrations (mean +/- standard error of the mean) were 12.9 +/- 0.6 and 2697 +/- 57 muM or 37.3 +/- 0.9 and 2792 +/- 98 muM in controls or in ESRD patients, respectively. Free choline concentrations were correlated (r = 0.598 p < 0.001) with the time the patients were subjected to hemodialysis. Plasma free choline and phosphocholine concentrations a-re decreased by a total of -8.1 +/- 0.6 μmol/L and -88 +/- 8 μmol/L, respectively: phospholipid- phosphatidylcholine- and sphingomyelin-bound choline are increased, during hemodialysis. Patients lost about 350 μmoles of choline into the dialysate during hemodialysis. Conclusion: Plasma free choline concentrations are elevated in ESRD. and a considerable amount of choline is lost into the hemodialysate.Item Choline status in newborns, infants, children, breast-feeding women, breast-fed infants and human breast milk(Elsevier Science, 2005-08) Özarda, Yeşim; Özbek, Resul; Hamurtekin, Emre; Ulus, Ismail H.; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi.; Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji ve Klinik Farmakoloji Anabilim Dalı.; AAL-8873-2021; D-5340-2015This study assessed the choline status in newborns, infants, children, breast-feeding women, breast milk, infant forinula, breast-fed and formula-fed infants. The serum free choline level was 35.1 +/- 1.1 mu mol/L at birth and decreased to 24.2 +/- 1.6, 18.1 +/- 0.8, 16.3 +/- 0.9, 14.3 +/- 0.8, 12.9+0.6 or 10.9 +/- 0.6 mu mol/L at 22-28, 151-180, 331-365, 571-730, 731-1095 or 4016-4380 days after birth, respectively. The serum phospholipid-bound choline level was 1997 +/- 75 mu mol/L at birth and increased gradually to 2315 +/- 190 or 2572 +/- 100 mu mol/L at 571-730 or 4016-4380 days after birth, respectively. In breast-feeding women, serum free and phospholipid-bound choline levels were doubled at 12-28 days after birth, they decreased toward the control values with time. Free choline, phosphocholine and glycerophosphocholine were major choline compounds in breast milk. Their concentrations in mature milk were much greater than in colostrum and serum. Choline contents of breast milk varied greatly between mothers, and milk free choline levels were correlated with serum free choline (r.541; P <.001), phospholipid-bound choline (r=.527; P <.001) and glycerophosphocho line (r=.299-1 P <.01) concentrations and lactating days (r=.520 - P <.001). In breast-fed infants, serum free choline concentrations were correlated with free choline (r.47; P <.001), phosphocholine (r=.345; P <.002), glycerophosphocholine (r=.311; P <.01) and total choline (r=.306; P <.01) contents of breast milk. Serum free choline concentration in formula-fed infants was lower than breast-fed infants. These data show that (a) circulating choline status is elevated during infancy and lactation, (b) choline contents of breast milk vary between mothers and milk free choline contents are influenced by maternal circulating choline status, and (c) the choline contents of breast milk can influence infants' circulating choline status.Item Common reference intervals for aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) in serum: results from an IFCC multicenter study(Walter de Gruyter, 2010-11) Ceruotti, Ferruccio; Henny, Joseph; Queralto, Josep; Ziyu, Shen; Chen, Baorong; Boyd, James C.; Panteghini, Mauro; Özarda, Yeşim; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya ve Klinik Biyokimya Anabilim Dalı.; AAL-8873-2021; 35741320500Background: Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) measurements are important for the assessment of liver damage. The aim of this study was to define the reference intervals (RIs) for these enzymes in adults, paying attention to standardization of the methods used and careful selection of the reference population. Methods: AST, ALT and GGT were measured with commercial analytical systems standardized to the IFCC-recommended reference measurement systems. Three centers (two in Italy and one in China) measured their own freshly collected samples; one of these centers also measured frozen samples from the Nordic Countries RI Project and from a Turkish center. RIs were generated using non-parametric techniques from the results of 765 individuals (411 females and 354 males, 18-85 years old) selected on the basis of the results of other laboratory tests and a specific questionnaire. Results: AST results from the four regions (Milan, Beijing, Bursa and Nordic Countries) were statistically different, but these differences were too small to be clinically relevant. Likewise, differences between the upper reference limits for genders was only 1.7 U/L (0.03 mu kat/L), allowing a single RI of 11-34 U/L (0.18-0.57 mu kat/L) to be defined. Inter-regional differences were not statistically significant for ALT, but partitioning was required due to significant gender differences. RIs for ALT were 8-41 U/L (0.13-0.68 mu kat/L) for females and 9-59 U/L (0.15-0.99 mu kat/L) for males, respectively. The upper reference limits for GGT from the Nordic Country population were higher than those from the other three regions and results from this group were excluded from final calculations. The GGT RIs were 6-40 U/L (0.11-0.66 mu kat/L) for females and 12-68 U/L (0.20-1.13 mu kat/L) for males, respectively. Conclusions: For AST and ALT, the implementation of common RIs appears to be possible, because no differences between regions were observed. However, a common RI for GGT that is applicable worldwide appears unlikely due to differences among populations. Clin Chem Lab Med 2010;48:1593-601.Item Comparison of clinical and laboratory outcomes of three different lipid emulsions in pediatric parenteral nutrition(Lippincott Williams & Wilkins, 2007-05) Başarır, Özkan T.; Çakır, Esra; Özarda, Yeşim; Erdemir, Gülin; Uludağ Üniversitesi/Tıp Fakültesi/Pediatri Gastroenteroloji Hepatoloji ve Beslenme Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; AAL-8873-2021Item Comparison of pre-and postpartum serum leptin, ghrelin, and lipid levels in sheep(Bilimsel ve Teknolojik Araştırma Kurumu, 2018-03-29) Temizel, Ethem Mutlu; Cihan, Hüseyin; Levent, Pınar; Sarıl, Ahmet; Özarda, Yeşim; Yılmaz, Zeki; Uludağ Üniversitesi/Veteriner Fakültesi/İç Hastalıkları Anabilim Dalı.; Uludağ Üniversitesi/Veteriner Fakültesi/Biyokimya Anabilim Dalı.; 0000-0001-9836-0749; 0000-0003-1544-6438; A-9637-2008; AAL-8873-2021; T-4585-2019; ABH-3742-2020; 26430270100; 6602381681; 56690616700; 57202390224; 35741320500; 35944810500Serum leptin and ghrelin play important roles in energy metabolism and inducing appetite during pregnancy and lactation. We investigated the serum levels of leptin and ghrelin and their relationship with the duration of lactation and serum biochemical responses during the prepartum (last week before lambing) and postpartum periods in sheep. They were also evaluated between pregnant and nonpregnant (control ewes) ewes. For these purposes, pregnant (n = 15) and control Awassi ewes (n = 15) that were 2 years of age were used in this study. Blood samples were collected 1 week before the expected date of lambing (baseline) and for 12 weeks after parturitions. Serum leptin, ghrelin, cholesterol, triglyceride, VLDL, LDL, HDL, NEFA, and phospholipid levels were assayed. Leptin and ghrelin levels of the prepartum period in pregnant and control ewes were 4.5 ng/mL and 3.4 ng/mL (P < 0.05) and 75 pg/mL and 166 pg/ mL (P < 0.01), respectively. The baseline value of ghrelin (81 pg/mL) decreased to 43 pg/mL within 1 week after parturition (P < 0.01). Serum ghrelin levels increased after 1 week. There was also a significant difference in serum ghrelin levels between control ewes and those a week before parturition in pregnant ewes (P < 0.001). The NEFA level was higher in pregnant than in control sheep (P < 0.001). In conclusion, leptin levels tended to decrease during the lactation period, which could be associated with a negative energy balance. Additionally, ghrelin levels tended to gradually increase during lactation to adapt to a negative energy balance. We think that variations in serum leptin and ghrelin might be used to monitor metabolic adaptation during lactation.Publication Comparison of reference intervals derived by direct and indirect methods based on compatible datasets obtained in Turkey(Elsevier, 2021-05-26) Özarda, Yeşim; Ichihara, Kiyoshi; Jones, Graham; Streichert, Thomas; Ahmadian, Robab; Ahmadian, Robab; Bursa Uludağ Üniversitesi/Tıp Fakültesi/İstatistik Anabilim Dalı.; 0000-0003-1550-639X; AAE-5602-2019Background: Indirect derivation of reference intervals (RIs) from the laboratory information system (LIS) has been recently pursued. We aimed at evaluating the accuracy of indirectly predicted RIs compared to the RIs established directly from healthy subjects in the nationwide RI study in Turkey, targeting 25 major chemistry analytes.Methods: LIS data were retrieved from the laboratory that performed measurements for the direct study. They were cleaned by limiting to outpatients with age 18-65 years, and by allowing only one record per year per patient. Evaluated were four indirect methods of univariate approach: Hoffmann, Bhattacharya, Arzideh, and Wosniok methods. Power transformation of the LIS dataset was performed either using the power (lambda) reported by the IFCC global RI study (the first two methods) or using a lambda predicted (the last two).Results: Compared to the direct study dataset, the LIS dataset showed a variable degree of alterations in peak location and shape. Consequently, lower-side peak-shifts observed in sodium, albumin, etc. led to lowered RI limits, whereas higher-side peak-shift observed in triglyceride, low-density lipoprotein cholesterol, etc. led to raised RI limits. Overall, 72% (62-81) of the RI limits predicted by indirect methods showed significant biases from direct RIs. However, the biases observed in total cholesterol, lactic dehydrogenase, etc. were attributed to a higher-side age-bias in LIS dataset. After excluding them, the overall proportion of biased RIs was reduced to 47% (38-54).Conclusion: To reduce prediction biases that remained after age adjustment, it is necessary to apply more rigorous data-cleaning before applying indirect methods.Item The concentration of adiponectin in breast milk is related to maternal hormonal and inflammatory status during 6 months of lactation(Walter de Gruyter Gmbh, 2012-05) Özarda, Yeşim; Güneş, Yeliz; Tuncer, Gül Özlem; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; AAL-8873-2021; 35741320500; 54913156100; 54910813000Background: Varying concentrations of adiponectin are present in human breast milk. This study aimed to determine the relationship between milk adiponectin concentration and the hormonal and inflammatory status of breast-feeding women. Methods: Blood and breast milk samples were collected from 157 breast-feeding women enrolled at 1-180 post-partum lactation days. The milk and serum adiponectin concentrations were measured by radioimmunoassays. The serum oestradiol, prolactin, thyroxine, triiodothyronine, cortisol and insulin concentrations were measured by the chemiluminescent immunometric method. The leptin, resistin and ghrelin concentrations were measured by the immunometric methods. Results: The milk, but not serum, adiponectin concentration increased during the 180-day lactation period and displayed a positive correlation (r=0.748; p<0.001) to the lactation day. The milk adiponectin concentration was positively correlated to the maternal serum ghrelin concentration (r=0.299; p<0.001) and inversely to the maternal serum oestradiol (r=-0.366; p<0.001), prolactin (r=-0.444; p<0.001), thyroxine (r=-0.355; p<0.001), triiodothyronine (r=-0.291; p<0.001), cortisol (r=-0.537; p<0.001), and C-reactive protein (r=-0.483; p<0.001) concentrations. The milk adiponectin concentration was positively correlated to the milk leptin (r=0.344; p<0.001) and ghrelin (r=0.458; p<0.001) concentrations, and inversely to milk resistin concentration (r=-0.518; p<0.001). The serum adiponectin concentration in breastfed infants was positively correlated (r=0.711; p<0.001) to the adiponectin concentration in the consumed breast milk. Conclusions: The adiponectin concentration in breast milk increases over time during lactation and is affected by the maternal hormonal and inflammatory status.Item Demonstration of reciprocal diurnal variation in human serum T3 and rT3 concentration demonstrated by mass spectrometric analysis and establishment of thyroid hormone reference intervals(SAGE Publications, 2020-05) Sun, Qian; Avallone, Livia; Stolze, Brian; Araque, Katherine Andrea; Jonklaas, Jacqueline; Parikh, Toral; Welsh, Kerry; Masika, Likhona; Soldin, Steven J.; Özarda, Yeşim; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; AAL-8873-2021; 35741320500Background: There has been a wide range of reference intervals proposed in previous literature for thyroid hormones due to large between-assay variability of immunoassays, as well as lack of correction for collection time. We provided the diurnal reference intervals for five thyroid hormones, namely total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), free triiodothyronine (FT3), and reverse T3 (rT3), measured in serum samples of healthy participants using a liquid chromatography/tandem mass spectrometry (LC-MS/MS) method. Methods: Couplet serum samples (a.m. and p.m.) were collected from 110 healthy females and 49 healthy males. Healthy volunteers were recruited from four participating centers between 2016 and 2018. Measurements of thyroid hormones were obtained by LC-MS/MS analysis. Results: Our study revealed significant uptrend in AM to PM FT4 (p < 0.0001) samples, downtrend in AM to PM TT3 (p = 0.0004) and FT3 samples (p < 0.0001), and AM to PM uptrend in rT3 samples (p < 0.0001). No difference was observed for TT4 between AM and PM. No significant sex differences were seen for any of the five thyroid hormones. Conclusion: When diagnosing thyroid disorders, it is important to have accurate measurement of thyroid hormones, and to acknowledge the diurnal fluctuation found, especially for FT3. Our study highlights the importance of standardization of collection times and implementation of LC-MS/MS in thyroid hormone measurement.Item Determining the indirect reference intervals for complete blood count parameters in Bursa, Turkey(Wiley, 2016-09) Özarda, Yeşim; Uludağ Üniversitesi/Tıp Fakültesi/Temel Tıp Bilimleri Anabilim Dalı.; AAL-8873-2021Item Diurnal variation of steroid hormones and their reference intervals using mass spectrometric analysis(BioScientifica, 2018-12) Parikh, T. P.; Stolze, B.; Jonklaas, J.; Welsh, K.; Masika, L.; Hill, M.; DeCherney, A.; Soldin, S. J.; Özarda, Yeşim; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyokimya Anabilim Dalı.; AAL-8873-2021; 35741320500Objective: Accurate measurement of steroid hormones remains challenging. Mass spectrometry affords a reliable means for quantitating steroid profiles accurately. Our objective was to establish and define (1) the extent of diurnal fluctuations in steroid concentrations that potentially necessitate strict adherence to time of sample acquisition and (2) time-dependent steroid reference intervals. Design: Nine steroid markers were examined in couplets in males and females. Methods: Using isotope dilution high-performance liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis, we developed a multi-steroid profile requiring only a minimal volume of serum (0.1 mL). Couplet (AM and PM) measurements of steroid hormones for 120 healthy females (F) and 62 healthy males (M) were obtained. Patients were recruited from several participating centers. Results: The following diurnal values were noted to be significantly different in both females and males: cortisone, cortisol, corticosterone, 11 deoxycortisol (11 DOC), androstenedione, 17a-hydroxyprogesterone (17 OHP) and dehydroepiandrosterone (DHEA). Testosterone was only found to have significant diurnal variance in males. Progesterone showed no significant difference in AM and PM values for either groups and thus may provide an internal control. Conclusions: When diagnosing endocrine disorders, it is imperative to acknowledge the 24-h diurnal variation of the biochemical steroid markers. We highlight the importance of standardization of collection times and appropriate implementation of reference intervals. Precis: We identify diurnal fluctuations in steroid concentrations with time of day and emphasize the importance of adhering to firm time of sample acquisition.Item Endotoxin increases plasma leptin and ghrelin levels in dogs(Lippincott Williams & Wilkins, 2008-03) Yılmaz, Zeki; Özarda, Yeşim; Ulus, İsmail Hakkı; Uludağ Üniversitesi/Tıp Fakültesi/İç Hastalıkları Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Temel Tıp Bilimleri Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji ve Klinik Farmakoloji Anabilim Dalı.; 0000-0001-9836-0749; D-5340-2015; A-9637-2008; AAL-8873-2021; 35944810500; 35741320500; 7004271086Objective. Evaluations of plasma leptin and ghrelin levels and their relations with circulating levels of proinflammatory mediators, stress hormones, and biochemical markers of hepatorenal injury during experimental endotoxemia in dogs. Setting: Uludag University. Design: Placebo-controlled animal study. Animals, Adult mongrel dogs (n = 16). Interventions. Intravenous injection of endotoxin (1 mg/kg) and blood sample withdrawal before and at 0.5-48 hrs posttreatment. Measurements and Main Results. Mean baseline plasma leptin and ghrelin levels were 2.4 +/- 0.1 ng/mL and 867 +/- 58 pg/mL, respectively. Plasma leptin and ghrelin increased significantly by 16% (p <.05) and 72% (p <.001) at 0.5 hr, and they remained elevated by 33-41 % (p <.001) and 59-74% (p <.001) at 48 hrs after administration of endotoxin, respectively. There was positive correlation (r =.844; p <.001) between plasma leptin and ghrelin levels in endotoxin-treated dogs. Endotoxemia was associated with several-fold elevations in circulating levels of stress hormones, proinflammatory mediators, and hepatorenal injury markers. Plasma leptin and ghrelin levels in endotoxin-treated dogs were correlated with serum nitric oxide (r =.955 and r =.890; p <.001), procalcitonin (r =.825 and r =.716; p <.001), cortisol (r =.823 and r =.786; p <.001), and hepatorenal injury markers (r =.580 to.745 and r =.393 to.574; p <.05 to.01). Conclusions. Circulating leptin and. ghrelin levels increase during endotoxemia, and these increases are associated with elevated levels of proinflarnmatory mediators, stress hormones, and serum biochemical markers for hepatorenal dysfunction.Item Establishing and using reference intervals(Walter de Gruyter, 2020-01-18) Özarda, Yeşim; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Klinik Biyokimya Anabilim Dalı.; AAL-8873-2021; 35741320500Reference intervals (RIs) and clinical decision limits (CDLs) are fundamental tools used by healthcare and laboratory professionals to interpret patient laboratory test results. The traditional method for establishing RIs, known as the direct approach, is based on collecting samples from members of a preselected reference population, making the measurements and then determining the intervals. For challenging groups such as pediatric and geriatric age groups, indirect methods are appointed for the derivation of RIs in the EP28-A3c guideline. However, there has been an increasing demand to use the indirect methods of deriving RIs by the use of routine laboratory data stored in the laboratory information system. International Federation of Clinical Chemistry (IFCC), Committee on Reference Intervals and Decision Limits (C-RIDL) is currently working on the study for the comparison of the conventional (direct) and alternative (indirect) approaches for the determination of reference intervals. As a matter of fact that, the process of developing RIs is often beyond the capabilities of an individual laboratory due to the complex, expensive and time-consuming process to develop them. Therefore, a laboratory can alternatively transfer and verify RIs established by an external source (i.e. manufacturers' package inserts, publications). IFCC, C-RIDL has focused primarily on RIs and has performed multicenter studies to obtain common RIs in recent years. However, as the broader responsibility of the Committee, from its name, includes "decision limits", the C-RIDL also emphasizes the importance of the correct use of both RIs and CDLs and to encourage laboratories to specify the appropriate information to clinicians as needed.Item Hyperglycemia induced by intracerebroventricular choline: Involvement of the sympatho-adrenal system(Elsevier, 2002-03-08) Taga, Yavuz; Gürun, Mine Sibel; Özarda, Yeşim; Ulus, İsmail Hakkı; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji ve Klinik Farmakoloji Anabilim Dalı.; AAL-8873-2021; D-5340-2015; AAG-8716-2019; 55664349700; 35741320500; 7004271086Intracerebroventricular (i.c.v.) injection of choline (75-300 mug) produced a dose-dependent increase in blood glucose levels. Pretreatment with the nicotinic acetylcholine receptor antagonist, mecamylamine (50 mug, i.c.v.) blocked the hyperglycemia induced by choline (150 mug, i.c.v.), but the response was not affected by pre-treatment with the muscarinic acetylcholine receptor antagonist, atropine (10 mug, i.c.v.). Pre-treatment with the neuronal choline uptake inhibitor, hemicholinium-3 (20 mug, i.c.v.), attenuated the hyperglycemia induced by choline. The hyperglycemic response to choline was associated increased plasma levels of adrenaline and noradrenaline. The hyperglycemia elicited by choline was greatly attenuated by bilateral adrenalectomy, and entirely blocked by either surgical transection of the splanchnic nerves or by pre-treatment with the a-adrenoceptor antagonist, phentolamine. These data show that choline, a precursor of acetylcholine, increases blood glucose and this effect is mediated by central nicotinic acetylcholine receptor activation. An increase in sympatho-adrenal activity appears to be involved in the hyperglycemic effect of choline.Item Indirect methods for reference interval determination - Review and recommendations(Walter de Gruyter, 2019-01) Jones, Graham R. D.; Haeckel, Rainer; Loh, Tze Ping; Sikaris, Ken; Streichert, Thomas; Katayev, Alex; Barth, Julian H; Özarda, Yeşim; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; 0000-0003-0532-789X; AAL-8873-2021; 35741320500Reference intervals are a vital part of the information supplied by clinical laboratories to support interpretation of numerical pathology results such as are produced in clinical chemistry and hematology laboratories. The traditional method for establishing reference intervals, known as the direct approach, is based on collecting samples from members of a preselected reference population, making the measurements and then determining the intervals. An alternative approach is to perform analysis of results generated as part of routine pathology testing and using appropriate statistical techniques to determine reference intervals. This is known as the indirect approach. This paper from a working group of the International Federation of Clinical Chemistry (IFCC) Committee on Reference Intervals and Decision Limits (C-RIDL) aims to summarize current thinking on indirect approaches to reference intervals. The indirect approach has some major potential advantages compared with direct methods. The processes are faster, cheaper and do not involve patient inconvenience, discomfort or the risks associated with generating new patient health information. Indirect methods also use the same preanalytical and analytical techniques used for patient management and can provide very large numbers for assessment. Limitations to the indirect methods include possible effects of diseased subpopulations on the derived interval. The IFCC C-RIDL aims to encourage the use of indirect methods to establish and verify reference intervals, to promote publication of such intervals with clear explanation of the process used and also to support the development of improved statistical techniques for these studies.Item Intraperitoneal administration of choline increases serum glucose in rat: Involvement of the sympathoadrenal system(George Thieme Verlag, 2002-06) Özarda, Yeşim; Taga, Yavuz; Gürun, Mine Sibel; Ulus, İsmail Hakkı; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji ve Klinik Farmakoloji Anabilim Dalı.; AAL-8873-2021; D-5340-2015; AAG-8716-2019; 55664349700; 7004271086Intraperitoneal injection of choline (40, 80 or 120 mg/kg) produced a dose-dependent increase in serum glucose and choline levels in rats. The increases in serum glucose and choline were associated with an increase of serum insulin as well as plasma levels of epinephrine and norepinephrine. The increases in serum glucose and plasma catecholamine concentrations induced by choline (120 mg/kg) were blocked by pretreatment with the ganglionic nicotinic receptor antagonist hexamethonium (15 mg/kg), but were not affected by pretreatment with atropine (5 mg/kg). The choline-induced rise in serum insulin was blocked by pretreatment with atropine and with hexamethonium each. The increase in serum glucose evoked by choline (120 mg/kg) was blocked by alpha-adrenoceptor blockade and bilateral adrenalectomy each. Blockade of beta-adrenoceptor by propranolol or chemical sympathectomy by 6-hydroxydopamine failed to alter the hyperglycemic response to choline. These results show that choline, a precursor of the neurotransmitter acetylcholine, increases serum glucose and insulin levels. The effect of choline on serum insulin is mediated by both muscarinic and nicotinic acetylcholine receptors, whereas the effect of choline on serum glucose is mediated solely by nicotinic receptors. The stimulation of adrenal medullary catecholamine release and subsequent activation of alpha-adrenoceptors apparently mediates the hyperglycemic effect of choline.Item İskemi modifiye albumin düzeylerinde biyolojik değişkenliklerin saptanması, referans değişim değeri ve Türk toplumundaki referans değerlerinin hesaplanması(Uludağ Üniversitesi, 2014) Tuncer, Gül Özlem; Özarda, Yeşim; Uludağ Üniversitesi/Sağlık Bilimleri Enstitüsü/Biyokimya Anabilim Dalı.Biyolojik varyasyon (BV) birey içi (CVI) ve bireyler arası (CVG) varyasyondan oluşmaktadır. Bu BV bileşenleri analitik kalite özelliklerini ve hedeflerini belirlemek, seri analit ölçümlerindeki değişiklikleri incelemek ve referans aralıkların (RA) klinik açıdan yararlılığını değerlendirmek amacıyla kullanılmaktadır. Popülasyona dayalı RA, CVI > CVG durumunda geçerli olmakta, CVI < CVG bulunması, hastalıkların belirlenmesinde bireye dayalı RA'nı daha duyarlı hale getirmektedir. Bireysellik indeksi (II), RA'ların klinik yararlılığının değerlendirilmesinde objektif bir kriter olarak sunulmaktadır. Bireye dayalı RA ve CVI kullanılarak ardışık ölçüm sonuçları arasındaki anlamlı farklılıkları ifade eden Referans Değişim Değeri (RCV) belirlenebilmektedir. Son yıllarda miyokardiyal iskemi belirteçleri potansiyel bir ilgi alanı olmaktadır. Bu belirteçler arasında İskemi Modifiye Albumin (İMA) FDA onayı almış ilk kardiyak iskemi belirteci olarak dikkat çekmektedir. Bu çalışmada sabah 12-14 saatlik açlık sonrası, İMA BV bileşenlerinin belirlenmesi amacıyla 24-50 yaş aralığındaki 21 (11 kadın, 10 erkek) sağlıklı gönüllüden ayın 0.,1., 2., 7.,14., 21. ve 28. günlerinde toplam 7; RA'ın belirlenmesi için 24-52 yaş aralığındaki 260 (130 kadın, 130 erkek) sağlıklı bireyden bir adet kan örneği alınmıştır. İMA kolorimetrik yöntemle ve Albumin- Kobalt Bağlanma (ACB) testiyle ölçülmüştür. ACB testi için analitik varyasyon (CVA) değerleri ve analitik kalite özellikleri (doğruluktan sapma ve ölçüm belirsizliği) belirlenmiştir. Her iki cinsiyet ve tüm grup için CVI, CVG, II, RCV ve RA değerleri hesaplanmıştır. İMA CVI ve CVG sonuçlarıyla belirlenen II değeri (1.5), hesapladığımız RA'larını klinik açıdan yararlı hale getirmektedir. Çalışmamıza ait BV bileşenleri ve RCV'nin, hesaplanan RA'lar ile beraber klinik kullanıma sunulabilir, konuyla ilgili yapılmış diğer çalışma verileriyle karşılaştırılabilir ve mümkünse birleştirilebilir olduğu kanısındayız.Item Metoclopramida e ondansetrona alteram o bloqueio neuromuscular induzido por mivacúrio? - um estudo randomizado(Elsevier, 2013-04-01) Tercan, Mehmet; Mercanoglu Efe, Esra; Türker, Gürkan; Kaya, Fatma Nur; Yavaşçaoğlu, Belgin; Özarda, Yeşim; Başağan Moğol, Elif; Uludağ Üniversitesi/Tıp Fakültesi/Anestezi ve Reanimasyon Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; 0000-0003-0736-0490; 0000-0002-3019-581X; AAM-6282-2020; AAG-9356-2021; AAL-8873-2021; AAI-7914-2021; AAI-6642-2021Background: We aimed to investigate the effects of metoclopramide and ondansetrone on mivacurium neuromuscular blockade. Methods: Seventy five, ASA I-II patients, aged 18-65 and scheduled for elective surgery requiring tracheal intubation were included in the study. The patients received metoclopramide 10 mg, ondansetrone 4 mg or normal saline 5 mL; group M, group O, group NS (n = 25), respectively. Before anesthesia study drugs were administered in a volume of 5 mL. The level of plasma cholinesterase were obtained before and 5 minutes after the administration of study drugs and5 minutes after the administration of mivacurium. Onset time, T25, T75, T25-75, T90 levelswere compared with each other and differences between each patients were investigated. After recording T90, the study was terminated and surgery was started. Results: Onset time was significantly shorter in group M, than the other two groups. Onset time in group O was significantly shorter than in group NS. In Group M T25, T75, T90 and recovery indices were significantly greater than in Group NS (p < 0.001). In Group O T25, T75 were greater than Group NS (p < 0.01 and p < 0.05, respectively). In Group M T75, T90 and emergence indices were significantly higher than Group O (p < 0.001, p < 0.01, p < 0.001, respectively). In Groups M and O, plasma cholinesterase levels decreased significantly (p < 0.001) after administration of study drugs and mivacurium. Plasma cholinesterase also was reduced in Group NS 5 minutes after the administration of mivacurium (p < 0.001). Conclusion: Ondansetrone is believed to be more reliable agent than metoclopramide when used with mivacurium.Item A nationwide multicentre study in Turkey for establishing reference intervals of haematological parameters with novel use of a panel of whole blood(Croatian Soc Medical Biochemistry & Laboratory Medicine, 2017) Özarda, Yeşim; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyokimya Anabilim Dalı.; AAL-8873-2021; 35741320500Introduction: A nationwide multicentre study was conducted to establish well-defined reference intervals (Rls) of haematological parameters for the Turkish population in consideration of sources of variation in reference values (RVs). Materials and methods: K2-EDTA whole blood samples (total of 3363) were collected from 12 laboratories. Sera were also collected for measurements of iron, UIBC, TIBC, and ferritin for use in the latent abnormal values exclusion (LAVE) method. The blood samples were analysed within 2 hours in each laboratory using Cell Dyn and Ruby (Abbott), LH780 (Beckman Coulter), or XT-2000i (Sysmex). A panel of freshly prepared blood from 40 healthy volunteers was measured in common to assess any analyser-dependent bias in the measurements. The SD ratio (SDR) based on ANOVA was used to judge the need for partitioning RVs. Rls were computed by the parametric method with/without applying the LAVE method. Results: Analyser-dependent bias was found for basophils (Bas), MCHC, RDW and MPV from the panel test results and thus those Rls were derived for each manufacturer. Rls were determined from all volunteers' results for WBC, neutrophils, lymphocytes, monocytes, eosinophils, MCV, MCH and platelets. Gender-specific Rls were required for RBC, haemoglobin, haematocrit, iron, UIBC and ferritin. Region-specific Rls were required for RBC, haemoglobin, haematocrit, UIBC, and TIBC. Conclusions: With the novel use of a freshly prepared blood panel, manufacturer-specific Rls' were derived for Bas, Bas%, MCHC, RDW and MPV. Regional differences in Rls were observed among the 7 regions of Turkey, which may be attributed to nutritional or environmental factors, including altitude.
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