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Öğe Assessment of Preanalytical Errors by Six Sigma Method and the Pareto Principle Analysis(2023) Oktay, Saniye Başak; Hanikoglu, FerhatAim: In this study, we aimed to evaluate the preanalytical errors over a five year period using the Six Sigma methodology and Pareto Principle in the clinical biochemistry laboratory. Methods: Five-year sample rejection data between January 2015 and December 2019 in the clinical biochemistry laboratory were analyzed and classified according to the reasons for rejection. Six Sigma levels for the total and each preanalytical error were calculated with Westgard online formula. Preanalytical errors were evaluated according to their frequencies ranks and percentages with Pareto's principle. Results: The overall rate of five-year total critical preanalytical errors was 1.91% and the sigma level was 3.6. According to Pareto's chart, the three most common errors among the five-year preanalytical rejections were clotted sample (42.49%, sigma value:4), insufficient sample (23.53%, sigma value:4.2), and wrong container (8.01%, sigma value:4.5). Conclusion: Six Sigma is a quality management methodology used to evaluate laboratory performance processes according to universal quality criteria. Calculated sigma values of preanalytical errors in our laboratory were within the acceptable range. However, planned regulatory activities for frequently observed preanalytical errors should be a laboratory management strategy to reduce these error rates and improve our laboratory performance.Öğe Can the Reduction of Cytokines Stop the Progression of Sepsis?(Springernature, 2022) Koc, Suna; Celebi, Serdar; Hanikoglu, Ferhat; Polat, Yalcin; Uysal, Betul Borku; Dokur, Mehmet; Ozer, TurkanObjective In this study, we aimed to analyze the laboratory and clinical results of cytokine hemadsorption as an immunomodulation therapy in ICU patients diagnosed with sepsis or septic shock. Methods The levels of procalcitonin (PCT) and C-reactive protein (CRP), determined to be indicators of infection/sepsis, and the levels of interleukins (IL-6, IL-8, and IL-10) and tumor necrosis factor alpha (TNF alpha), deemed as indicators of the cytokine storm, were compared among 32 patients before and after the hemadsorption procedure. Results The hemadsorption significantly reduced the levels of IL-6, IL-8, IL-10, TNF alpha, PCT, CRP, Acute Physiology and Chronic Health Evaluation (APACHE) scores, mortality rate, and Sequential Organ Failure Assessment (SOFA) scores (p<0.05). APACHE scores and the mean predicted mortality rate (PMR) of the non-survivors measured before the procedure was significantly higher than those of survivors (p=0.002 for both). IL-10, APACHE scores, and the mortality rates determined before the hemadsorption procedure were deemed significant parameters to predict the mortality among all ICU patients (p 0.05). IL-10 levels <= 125.3 ng/L, APACHE score 30, and PMR >70.33 were significantly associated with the mortality rates of all patients, indicating that these three parameters determined before the hemadsorption may be good predictors of mortality among ICU patients with sepsis. Conclusion The progression of sepsis in ICU patients may be prevented with cytokine hemadsorption applied as an immunomodulator therapy.Öğe Comparison of Cytokine Hemadsorption as an Immunomodulator Therapy in COVID-19 Patients with and without Bacterial Sepsis(Clin Lab Publ, 2022) Koc, Suna; Hanikoglu, Ferhat; Dokur, Mehmet; Polat, Yalcin; Celebi, Serdar; Koc, Sena G.; Kupeli, IlkeBackground: In this retrospective study, we aimed to compare the laboratory and clinical results of cytokine hem-adsorption as an immunomodulation therapy in COVID-19 ICU patients with or without sepsis. Methods: The levels of PCT, CRP, and ferritin were determined as indicators of infection/sepsis; the levels of in-terleukins (IL-6, IL-8 and IL-10, and TNF-??) were determined as indicators of cytokine storm were compared. APACHE score, SOFA score, and mortality rates were compared for the progression of the disease in 23 COVID-19 patients. Results: The therapy was generally successful in reducing the levels of IL-6, IL-8, IL-10, and TNF-?? but the levels measured after the procedure did not differ among the patients with or without sepsis, suggesting that the pres-ence of sepsis did not affect the efficacy and function of the cytokine hemadsorption procedure in COVID-19 pa-tients. All parameters were reduced after the procedure except the levels of PCT and ferritin and mortality rates of patients diagnosed with sepsis. The level of PCT was significantly higher in these patients compared with the patients without sepsis while the ferritin and mortality did not show any significant difference between the two groups, suggesting that the cytokine hemadsorption may be safe in the treatment of critical COVID-19 patients. Conclusions: As a result, the progression of sepsis in COVID-19 may be avoided with cytokine hemadsorption ap-plied as an immunomodulator therapy. However, this therapy should be further explored and validated prior to its introduction to everyday clinical practice when the epidemic conditions end.Öğe Effect of serum adropin levels on circulating endothelial dysfunction biomarkers in COVID-19 patients(2023) Gunesacar, Ramazan; Eksi, Durkadin Demir; Alpay, Ali Seydi; Hanikoglu, Ferhat; Erdogan, HalukPurpose: Several studies show that the symptoms of severe COVID-19 infection reflect the clinical phenotype of endothelial dysfunction and share common pathophysiological mechanisms with endothelial dysfunction. Therefore, the aim of the study was to investigate the effect of serum adropin levels on endothelial dysfunction biomarkers and determine whether adropin could be a new biomarker for COVID-19. Materials and Methods: The study included 40 patients with mild/moderate COVID-19, 48 patients with severe/critical COVID-19, and 37 controls. Serum adropin and circulating biomarkers of endothelial dysfunction including asymmetric dimethylarginine (ADMA), endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS), soluble intercellular adhesion molecule-1 (sICAM-1) and plasminogen activator inhibitor-1 (PAI-1) levels were determined by micro-ELISA. Results: Serum adropin levels were found to be significantly higher in COVID-19 patients (165.2±11.49 pg/ml) than in controls (85.46±12.08 pg/ml). Serum adropin levels of patients with severe/critical symptoms (194±16.23 pg/ml) were significantly higher than the patients with mild/moderate symptoms (130.6 ±14.53). In addition, serum ADMA, eNOS, and, ET-1 levels were significantly higher in the COVID-19 subjects (150.5±8.67 ng/ml, 172.4±14.01 pg/ml, 159.3±10.19 pg/ml, respectively) than that those in the controls (104.5±9.182 ng/ml, 141.4±17.74 pg/ml, 100.1±11.37 pg/ml, respectively). Significant positive correlations were found between adropin and ADMA, eNOS, ET-1, sICAM-1, and PAI-1 levels in the patients. Conclusion: We suggest that adropin may be a new potential biomarker for COVID-19 and an important molecule in restoring endothelial cell damage. Positive correlations between serum adropin levels and ADMA, eNOS, ET-1, sICAM-1 and PAI-1 levels in patients suggest that adropin may compensate for damage to endothelial cells.Öğe Effect of serum adropin levels on circulating endothelial dysfunction biomarkers in COVID-19 patients(Cukurova Univ, Fac Medicine, 2023) Gunesacar, Ramazan; Eksi, Durkadin Demir; Alpay, Ali Seydi; Hanikoglu, Ferhat; Erdogan, HalukPurpose: Several studies show that the symptoms of severe COVID-19 infection reflect the clinical phenotype of endothelial dysfunction and share common pathophysiological mechanisms with endothelial dysfunction. Therefore, the aim of the study was to investigate the effect of serum adropin levels on endothelial dysfunction biomarkers and determine whether adropin could be a new biomarker for COVID-19.Materials and Methods: The study included 40 patients with mild/moderate COVID-19, 48 patients with severe/critical COVID-19, and 37 controls. Serum adropin and circulating biomarkers of endothelial dysfunction including asymmetric dimethylarginine (ADMA), endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS), soluble intercellular adhesion molecule-1 (sICAM-1) and plasminogen activator inhibitor-1 (PAI-1) levels were determined by micro-ELISA. Results: Serum adropin levels were found to be significantly higher in COVID-19 patients (165.2 & PLUSMN;11.49 pg/ml) than in controls (85.46 & PLUSMN;12.08 pg/ml). Serum adropin levels of patients with severe/critical symptoms (194 & PLUSMN;16.23 pg/ml) were significantly higher than the patients with mild/moderate symptoms (130.6 & PLUSMN;14.53). In addition, serum ADMA, eNOS, and, ET-1 levels were significantly higher in the COVID-19 subjects (150.5 & PLUSMN;8.67 ng/ml, 172.4 & PLUSMN;14.01 pg/ml, 159.3 & PLUSMN;10.19 pg/ml, respectively) than that those in the controls (104.5 & PLUSMN;9.182 ng/ml, 141.4 & PLUSMN;17.74 pg/ml, 100.1 & PLUSMN;11.37 pg/ml, respectively). Significant positive correlations were found between adropin and ADMA, eNOS, ET-1, sICAM-1, and PAI-1 levels in the patients. Conclusion: We suggest that adropin may be a new potential biomarker for COVID-19 and an important molecule in restoring endothelial cell damage. Positive correlations between serum adropin levels and ADMA, eNOS, ET-1, sICAM-1 and PAI-1 levels in patients suggest that adropin may compensate for damage to endothelial cells.Öğe Evaluation of the Antioxidative and Protective Effects of Thymoquinone in a Pentylenetetrazole-induced Epilepsy Model(2025) Pala, Mukaddes; Meral, Ismail; Acikgoz, Nilgun; Hanikoglu, Ferhat; Kucukcetin, Ikbal Ozen; Ozdem, Sebahat; Yılmaz, Şenay GörücüObjective: Epilepsy is a common neurological disorder that leads to neuronal excitability and provokes various forms of cellular reorganization in the brain. We investigated the antioxidative and protective effects of thymoquinone (TQ) from the perspective of biomarkers in serum samples of rats using a pentylenetetrazol (PTZ)-induced epilepsy model. Methods: Twenty-one adult, male Wistar albino rats were randomly assigned to three groups. (1) Control (n=6); 0.5 mL saline (i.p.). (2) PTZ (n=7); 35 mg/kg PTZ (i.p.). (3) TQ+PTZ (n=8); 20 mg/kg TQ orally (p.o.)+ 35 mg/kg PTZ (i.p.). To induce kindling, PTZ was injected at a subconvulsive dose (35 mg/kg, i.p.) every other day for 24 days. Then, on the 26th day of the study, a single loading dose of PTZ (75 mg/kg) was injected into the animals. Seizure severity was evaluated with the Racine scale. Blood samples were taken from rats under anesthesia by the cardiac puncture method. The serum levels of myeloperoxidase (MPO), ischemia-modified albumin, total oxidant status (TOS), total antioxidant status (TAS), advanced oxidation protein products (AOPP), total sulfhydryl (T. sulfhydryl), and paraoxonase-1 (PON-1) were evaluated colorimetrically by the ELISA method, using a spectrophotometer. Results: A significant relationship was found between PTZ and TQ+PTZ groups for TAS (p=0.020), TOS (p=0.006), AOPP (p=0.015), and T. sulfhydryl (p=0.009). MPO and PON-1 were not significant (p>0.05). Conclusion: TQ may be used as an adjuvant agent in the regulation of epileptic seizures with its antioxidative and protective functions in the PTZ-induced epilepsy model. At the same time, serum parameters can potentially be diagnostic tools for the effective managing of treatment.Öğe Evaluation of the Antioxidative and Protective Effects of Thymoquinone in a Pentylenetetrazole-induced Epilepsy Model(Galenos Publ House, 2025) Pala, Mukaddes; Meral, Ismail; Acikgoz, Nilguen Pala; Hanikoglu, Ferhat; Kucukcetin, Ikbal oezen; Ozdem, Sebahat; Yilmaz, Senay GorucuObjective: Epilepsy is a common neurological disorder that leads to neuronal excitability and provokes various forms of cellular reorganization in the brain. We investigated the antioxidative and protective effects ofthymoquinone (TQ) from the perspective ofbiomarkers in serum samples of rats using a pentylenetetrazol (PTZ)-induced epilepsy model. Methods: Twenty-one adult, male Wistar albino rats were randomly assigned to three groups. (1) Control (n=6); 0.5 mL saline (i.p.). (2) PTZ (n=7); 35 mg/ kg PTZ (i.p.). (3) TQ+PTZ (n=8); 20 mg/kg TQ orally (p.o.)+ 35 mg/kg PTZ (i.p.). To induce kindling, PTZ was injected at a subconvulsive dose (35 mg/kg, i.p.) every other day for 24 days. Then, on the 26th day of the study, a single loading dose of PTZ (75 mg/kg) was injected into the animals. Seizure severity was evaluated with the Racine scale. Blood samples were taken from rats under anesthesia by the cardiac puncture method. The serum levels of myeloperoxidase (MPO), ischemia-modified albumin, total oxidant status (TOS), total antioxidant status (TAS), advanced oxidation protein products (AOPP), total sulfhydryl (T. sulfhydryl), and paraoxonase-1 (PON-1) were evaluated colorimetrically by the ELISA method, using a spectrophotometer. Results: A significant relationship was found between PTZ and TQ+PTZ groups for TAS (p=0.020), TOS (p=0.006), AOPP (p=0.015), and T. sulfhydryl (p=0.009). MPO and PON-1 were not significant (p>0.05). Conclusion: TQ may be used as an adjuvant agent in the regulation of epileptic seizures with its antioxidative and protective functions in the PTZ-induced epilepsy model. At the same time, serum parameters can potentially be diagnostic tools for the effective managing of treatment.Öğe Evaluation of the Relationship between Cancer and Antioxidants from an Altmetric Perspective(2022) Vardar, Gokay; Hanikoglu, Ferhat; Güney, Türkan; Dokur, Mehmet; Karadağ, MehmetObjectives: Antioxidants have been shown in research to have significant effects on serious diseases, particularly cancer. The goal of our experiment was to determine and analyzed 100 articles with the highest Altmetric attention scores (AAS) concerning antioxidants and cancer.\rMethods: Altmetric score analyzes were obtained downloading the from the Altmetric.com website. A research output's altmetric score was calculated using an algorithm based on the weighted number of all attention it receives.\rResults: The Altmetric scores of the 100 articles analyzed varied from 12 to 846. Twitter (n=86) was the most mentioned social media network in the articles. According to the research categories of the T100 articles in our analysis, the majority \rwere published in \"Medical and Health Science''. In terms of Twitter geographical breakdown, the United States leads among other nations, followed by the United Kingdom. According to Twitter demographics, the most of tweets on \rantioxidants and cancer were shared by members of the public.\rConclusion: In science and research, social media is advocated as an alternative to traditional power structures and our findings could provide a preliminary look at the social, clinical, and academic impact of antioxidant and cancer research.Öğe Investigating the Activity of Indole-2-on Derivative Src Kinase Inhibitors Against Chronic Myeloid Leukemia Cells(Bentham Science Publ Ltd, 2023) Cort-Donmez, Aysegul; Olgen, Sureyya; Guner, Ersin; Akgun-Cagliyan, Gulsum; Hanikoglu, Ferhat; Tunc-Ata, Melek; Kilic-Toprak, EmineBackground Src family tyrosine kinases play a potential role in Bcr-Abl-induced leukemogenesis. Src kinase inhibitors are reported as selective inhibitors of chronic myeloid leukemia. Objective Since Src kinase inhibitors have an inhibitive effect on chronic myeloid leukemia, indole derivatives (C-1, C-2, C-3) previously found as potent inhibitors of Src kinase were tested against chronic myeloid leukemia in this study. Methods Cell viability of K562 and R/K562 cells, antiproliferative and antioxidant effects, and inhibition profiles of Bcr-Abl kinase of indole derivatives were determined compared to dasatinib and imatinib. Results The results showed that compounds affected cell proliferation and decreased the levels of Bcr/Abl. These results confirmed that the antileukemic activity of compounds was related to Bcr/Abl expression. Docking studies also presented that compounds are inhibitors of both Src and Abl kinases. Calculation of drug-like properties showed that compounds could be potential drug candidates. Conclusion Among indole-2-on derivatives, previously identified as Src kinase inhibitors, C-2 has been discovered to be a strong anticancer drug that is active against susceptible and resistant K562 cell lines and induces apoptosis.Öğe Role of Oxidative Stress and Inflammatory Biomarkers in COVID-19 Pneumonia(2024) Ikıtımur, Hande; Kolbas, İlker; Cengiz, Mahir; Yavuzer, Serap; Yüksel, Bilge Özgür; Hanikoglu, Ferhat; Erel, OzcanIntroduction: SARS-CoV-2 causes severe lung damage and respiratory failure through oxidative stress. Biomarkers play a role in inflammation, in revealing the effects of oxidative stress, and in the regulation of treatment. The aim of our study was to reveal oxidative stress in COVID-19 patients by determining oxidative biomarkers and to examine the relationship of these parameters with lung involvement. Methods: The prospectively designed study included 45 patients hospitalized with the diagnosis of COVID-19 and 38 healthy controls. Total thiol, native thiol, disulfide, myeloperoxidase, ischaemia-modified albumin, and acute phase reactant levels to determine oxidative stress and inflammation were compared between the groups. Thorax tomography scoring was performed to determine the severity of pneumonia. The association of oxidative biomarkers with length of hospital stay and radiological score was evaluated. Results: We found that native thiol and total thiol levels decreased, and disulfide and myeloperoxidase levels increased in COVID-19 patients compared to the control group. A negative correlation was found between the duration of hospitalization and native thiol and total thiol levels (r=-0.312, p=0.043; r=-0.309, p=0.049). Native thiol and total thiol were negatively correlated with lung involvement on thorax tomography (r=-0.450, p=0.002; r=-0.436, p=0.003). MPO level was positively correlated with the duration of hospitalization (r=0.317, p=0.034). Discussion and Conclusion: These oxidative/inflammatory parameters play an important role in the lung involvement and disease monitoring of COVID-19 patients and can be used in the management of patients.
