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Asymmetric dimethylarginine (ADMA) in human blood: effects of extended haemodialysis in the critically ill patient with acute kidney injury, protein binding to human serum albumin and proteolysis by thermolysin
(Springer, 2015) Sitar, Mustafa Erinç; Kayaçelebi, Arslan Arınç; Beckmann, Bibiana; Kielstein, Jan T.; Tsikas, Dimitrios
Free, non-protein bound asymmetrically guanidine-dimethylated arginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthesis. Human erythrocytic membrane comprises considerable amounts of large (>50 kDa) ADMA-containing proteins. Location in the erythrocyte membrane and identity and physiological functions of ADMA-containing proteins are unrevealed. In healthy subjects, the concentration of free ADMA in heparinised plasma is almost identical to that of serum. We hypothesised that the robustness of free ADMA concentration in human blood is due to a remarkable resistance of erythrocytic ADMA-containing proteins against proteases. In vivo, we investigated the course of the concentration of ADMA in serum and EDTA plasma of a critically ill patient with acute kidney injury during extended haemodialysis. In vitro, we studied the effects of thermolysin, a useful experimental proteolytic enzyme of erythrocyte membrane proteins, on erythrocytic ADMA. The protein binding (PB) of ADMA to human serum albumin (HSA) was also determined. In these studies, ADMA was measured by a previously reported, fully validated GC–MS/MS method. We measured almost identical ADMA concentrations in plasma and serum samples of the patient. During dialysis, the circulating ADMA concentration decreased slowly and moderately indicating removal of this substance, which was however much less than expected from its low molecular weight (202 Da) and high water solubility. After dialysis, circulating ADMA concentration increased again, a phenomenon called rebound, and ADMA reached higher levels compared to the baseline. The PB value of ADMA to HSA was about 30 %. This surprisingly high PB value of ADMA to HSA may be an explanation for the rather poor dialysance of ADMA. Washed human erythrocytes suspended in phosphate-buffered physiological saline were found not to release appreciable amounts of free and ADMA-containing proteins. The lack of effect of coagulation or anticoagulation on the concentration of circulating free ADMA in humans is likely to be due to a remarkable resistance of ADMA-containing proteins in the erythrocyte membrane against proteases in vivo in humans. Our study suggests that free ADMA is released in the circulating blood at relatively high rates. The considerable PB of ADMA to HSA is likely to add to the apparently poor dialysability of ADMA. Other contributing factors could be redistribution of free ADMA between plasma and erythrocytes in favour of plasma ADMA and parallel formation of free ADMA from erythrocytic ADMA-containing proteins during haemodialysis.
Biological aging and autoimmunity
(Elsevier, 2022) Sitar, Mustafa Erinç; Rezaei, Nima
All of the functional negative changes that occur in the organism during their lifespan are called “aging.” This phenomenon is a problem as old as the human history. Academicians and authorities of the societies tried to solve the problem on behalf of humanity. Although a lot of information has been obtained about it, not all of its biological mechanisms have been explained. During this process, the changes that occur in the body can be considered holistically or separately. Our immune system, both as a single system and together with other systems like neuroendocrine system, is either directly affected by aging or directly affects aging. Many changes occur, such as elevation of clonal T-cell subsets, postpuberty thymus involution, decline of the ability to differentiate between self and nonself, alteration of the cytokine profile with a tendency to proinflammatory direction, and change in the expression of cell surface receptors. Changes that occur in human immune system, which is also called immunocenescence, are directly associated with the increased risk of autoimmune diseases and malignancies. The procedures that can be done to ensure healthy aging, prevent autoimmune diseases, and decrease the cancer risk and prolong longevity are hidden in these mechanisms.
Bir üniversite hastanesinde kandidemi olgularının retreospektif olarak değerlendirilmesi
(Türkiye Tabipleri Birliği, 2021) Karadeniz, Aslı; Öngen İpek, Belkız; Sitar, Mustafa Erinç; Hamidi, Aziz A.
Amaç: Kandidemi, hastane infeksiyonları arasında sıklığı artan; Candida albicans ve nonalbicans Candida (NAC) türleri ile gelişen ciddi bir infeksiyondur. Çalışmamızda, yatan hastalarda kandidemi etkenlerine göre klinik ve laboratuvar verilerin irdelenmesi amaçlanmıştır. Gereç ve Yöntem: Hastanemiz laboratuvarında 2017-2019 yıllarında kan kültüründe maya üremesi olan 31 hasta retrospektik olarak incelendi. Hastaların klinik ve laboratuvar verileri incelendi. C.albicans ve NAC türü maya üremesine göre gruplar arasında farklılıklar değerlendirildi. Bulgular: Olguların %58’i kadın ve % 52’sinde malignite saptandı. %48’inde kandidemi etkeni olarak C.albicans saptanırken, %52’sinde NAC üredi. Santral venöz kateter varlığı, total parenteral nutrisyon varlığı ve erken üreme oranı (<24 saat) NAC grubunda anlamlı olarak yüksek bulundu. İki grup arasında prokalsitonin, CRP, lökosit, nötrofil, lenfosit, trombosit ve albumin laboratuvar değerleri karşılaştırıldığında anlamlı farklılık saptanmadı. Sonuç: Hastanede yatışı uzamış hastalarda kandidemi önemli bir sorun olmaya devam etmektedir. Risk faktörlerini bilmek ve erken tanı yaklaşımları infeksiyonla mücadelede katkı sağlayacaktır.
Comparison of blood culture results and clinical biochemistry laboratory parameters in geriatric patients with regards to infective agents
(SelSistem, 2020) Karadeniz, Aslı; Sitar, Mustafa Erinç; Öngen İpek, Belkız
Aim: Bacterial infections can cause life-threatening sepsis and should be identified and managed accurately, especially in the elderly. We aim to examine the relationships between positive blood cultures, Gram staining pattern and biochemistry parameters, in particular, procalcitonin (ProCT) levels. Methods: This was a single center retrospective study, in which patients with positive blood cultures detected in Maltepe University Faculty of Medicine Research and Education Hospital were included. Two groups were formed according to age and evaluated with regards to bacterial Gram staining and biochemistry laboratory findings. Group 1 consisted of patients under 65 years of age (n=69) and Group 2 included those over 65 years of age (n=198). Results: Two hundred and sixty-seven episodes of bacteremia (Gram-negative: 49.43%, Gram-positive bacteremia: 50.56%) were evaluated in two groups. CRP values, lymphocyte and thrombocyte counts, creatinine, AST, ALT, albumin, CRP/albumin ratio values were similar between two groups (P>0.05 for all), while leukocyte counts, neutrophil counts and BUN values were lower in group 1 (P=0.020, P=0.020 and P<0.001 respectively) and ProCT levels were lower in group 2 (P=0.049). ProCT values (independent of age) had significantly increased in patients with Gram-negative bacteremia (P<0.001 in both group 1 and 2). Conclusion: ProCT measurement can be helpful as a distinguishing biomarker in different bloodstream infections, regardless of age.
Comparison of oxidative stress biomarkers in renal tissues of D-galactose induced, naturally aged and young rats
(Springer, 2012) Aydın, Şeval; Yanar, Karolin; Atukeren, Pınar; Dalo, Enis; Sitar, Mustafa Erinç; Uslu, Ezel; Caf, Nazlı; Çakatay, Ufuk
Ageing of kidneys is a clinical health issue of the society. Age-related renal insufficiency has important implications due to impaired redox homeostasis. We examined protein, DNA and lipid oxidation biomarkers as well as protein-bound sialic acid (SA) in the kidney tissues of D-galactose induced ageing rats, naturally aged rats and their corresponding young control group. Intraperitoneal injection of D-galactose (60 mg/kg/day) for 6 weeks to young male Sprague–Dawley rats (20-week-old) was used to establish mimetic ageing model. In this study, we investigated the levels of protein carbonyl groups (PCO), various thiol fractions such as total thiol groups (T-SH), protein (P-SH) and non-protein thiol groups (NP-SH), lipid oxidation parameters such as lipid hydroperoxides (LHP) and malondialdehyde (MDA), SA and 8-hydroxy-2?deoxyguanosine (8-OHdG) parameters for comparison of naturally aged, induced aged and young rats. In D-galactose induced aged group, PCO, LHP, MDA, and 8-OHdG concentrations were significantly higher than young control group, whereas T-SH, P-SH levels were significantly lower than the young rats. In addition, NP-SH and SA concentrations were similar between the mimetic ageing and young control groups. In naturally ageing rats, PCO and MDA levels were significantly higher, whereas T-SH, P-SH, NP-SH concentrations were low compared to young controls. On the other hand, SA and 8-OHdG levels were not different between the naturally ageing group and the young control group. Our results demonstrated that the rats in the mimetic ageing group, have significant similarities with the naturally aged rats in terms of impaired redox homeostasis and can be used as a reliable animal model for renal ageing.
A comprehensive study of myocardial redox homeostasis in naturally and mimetically aged rats
(National Library of Medicine, 2014) Cebe, Tamer; Yanar, Karolin; Atukeren, Pınar; Ozan, Tuna; Kuruç, Aylin Irmak; Kunbaz, Ahmad; Sitar, Mustafa Erinç; Mengi, Murat; Aydın, Mehmet Şerif; Eşrefoğlu, Mukaddes; Aydın, Şeval; Çakatay, Ufuk
Age-related myocardial dysfunction has important implications with impaired redox homeostasis. Current study focused on investigation of redox homeostasis and histopathological changes in the myocardium of mimetically (MA), naturally aged (NA), and young control (YC) rats. Chronic d-galactose administration to young male Wistar rats (5 months old) was used to set up experimental aging models. We investigated 16 different oxidative damage biomarkers which have evaluated redox homeostasis of cellular macromolecules such as protein, lipid, and DNA. As a protein oxidation biomarker, advanced oxidation end products, protein carbonyl groups, protein-bound advanced glycation end products, dityrosine, kynurenine, and N-formylkynurenine concentrations in MA and NA rats were found to be significantly higher compared to those in YC rats. On the other hand, the levels of protein thiol groups were not significantly different between groups, whereas lipid peroxidation biomarkers such as conjugated diens, lipid hydroperoxides, and malondialdehyde in MA and NA rats were found to be significantly higher in comparison to those in YCs. For the assessment of oxidative DNA damage, we analyzed eight hydroxy-5?-deoxyguanosine concentrations of MA and NA groups which were higher than YCs. As an antioxidant status in the MA and NA groups, Cu–Zn superoxide dismutase, ferric reducing antioxidant power, and total thiol levels were lower than those in the YCs. Only nonprotein thiol levels were not significantly different. We also observed similar histopathological changes in MA and NA rats. We concluded that the mimetic aging model could be considered as a reliable experimental model for myocardial senescence.
Crucial roles of systemic and tissue lipid peroxidation levels and anti-oxidant defences following contrast agent application
(National Library of Medicine, 2016) Sitar, Güngör; Küçük, Mehmet; Sitar, Mustafa Erinç; Yaşar, Özgür; Aydın, Şeval; Yanar, Karolin; Çakatay, Ufuk; Büyükpınarbaşılı, Nur
Background: One of the most important side effects of contrast pharmaceutical agents, which are used very common in routine radiology practice, is contrast induced nephropathy. Even ischemia, oxidative stress and osmolality related cytotoxic effects are considered, the molecular mechanisms underlying this pathology have not been identified completely yet. Objectives: The aim of the current study was to reveal the role of oxidative stress and antioxidant enzymatic defence mechanisms in the aetiopathogenesis of contrast-induced nephropathy. We also studied possible alleviating effects of N-acetylcysteine (NAC), a potent antioxidant, to obtain extra information regarding the molecular mechanisms underlying this pathology. Materials and Methods: This is an clinical-experimental study, This study was conducted of Istanbul/Turkey between September 15, 2012 and April 15, 2013. Three groups of male rats were randomly set up as a control group (C), a 100 mg/kg intraperitoneal NAC + 7 mL/kg contrast agent group (N + CIN) and a 7 mL/kg intraperitoneal contrast agent group (CIN). They were placed in individual metabolic cages 48 hours after agent administration to obtain 24-hour urine samples. Renal function tests (albumin, urea, creatinine, total protein) were conducted, oxidative stress parameters (Cu, Zn superoxide dismutase activity - Cu, Zn-SOD; advanced oxidation protein products - AOPP; protein carbonyls - PCO; total thiol groups - T-SH; and lipid hydroperoxides -LHP) were measured and tissues were analysed histopathologically. Results: Compared with the control group, groups CIN and N + CIN had significantly higher urea and LHP levels (P < 0.05 and P < 0.001, respectively) and significantly lower Cu, Zn-SOD activity and creatinine clearance (P < 0.05). There was no statistically significant difference between the groups in PCO or AOPP levels despite differences in descriptive statistics. Conclusions: Contrast-agent-induced nephropathic changes are more closely related to the magnitude of lipid peroxidation than protein oxidation.
Current aspects of ageing theories and classification according to mechanisms
(Turkish Geriatrics Society, 2013) Sitar, Mustafa Erinç; Yanar, Karolin; Aydın, Şeval; Çakatay, Ufuk
Attempts to define ageing, explain theories and classify them have always been an important issue for biogerontologists. Oxidative stress, telomeres, genetics, hormonal changes, immunity and damage accumulation over threshold values are all common theories that have been studied and modified over a long period of time. Verifications of these theories may lead to enlightenment about molecular mechanisms, and these can give rise to new research to reverse or slow age related pathological changes and increase average life span. Nowadays, an increased ratio of “successful ageing” or “healthier ageing” is a big aim for the whole society. Achieving this purpose also depends on research which studies molecular mechanisms and routine laboratory markers of ageing.
Effect of transportation and freeze-thaw procedure on hemostatic tests
(De Gruyter, 2021) Öngen İpek, Belkız; Sitar, Mustafa Erinç
Objective Coagulation tests are sensitive to pre-analytical variables. The aim of our study is to identify the effect of transportation and freeze-thaw status on for Factor VIII, Factor IX, Anti-thrombin III, Protein S, Protein C, Prothrombin time (PT) and Activated partial thromboplastin time (aPTT). Materials and methods The study was performed on 102 plasma samples obtained from 34 healthy volunteers. The samples were divided into three groups. Group A was analyzed whereas group B, C were frozen at ?20°C. After 24 h, group B and C were transported for 2 h. Following the transfer, group B was analyzed and C was frozen at ?20°C. After 24 h, group C was analyzed. Analyses of samples were performed in Thrombolyzer-XRM for PT, aPTT, Factor VIII, Factor IX, Anti-thrombin III, Protein C and Protein S. Results There were significant variations for PT, aPTT, Protein S, Factor VIII and Factor IX for group A&B and A&C comparisons in different stability criteria approaches. In significant change limit and percentage change calculations Protein S, Factor VIII and IX showed significant differences. For acceptable change limit approach, aPTT and Factor IX showed significant changes. Conclusion Laboratories should take precautions for transportation and freeze-thaw cycles to prevent inaccurate results.
Flow cytometric evaluation of cancer stem cell markers in HepG2 cells following sorafenib treatment
(Association of Clinical Biochemistry Specialists, 2021) Dönmez Çakıl, Yaprak; Sitar, Mustafa Erinç; Özünal, Zeynep Güneş; Gökçeoğlu Kayalı, Damla; Aktaş, Ranan Gülhan
Objectives: Liver cancer is a leading cause of mortality. Sorafenib resistance and cancer stem cells (CSCs) are among the factors that contribute to a poor prognosis. Different drugs enrich different CSC populations with a variety of CSC markers. This study investigated the expression of CSC markers in HepG2 cells in response to low doses of sorafenib using flow cytometry. Methods: The cytotoxicity of sorafenib was determined using a cell counting kit-8 assay. The expressions of the CSC markers CD44, CD90, and CD133 were measured with flow cytometry after treatment with sorafenib for 72 hours. Results: Sofranib inhibited cell proliferation in a dose-dependent manner. Low-dose sorafenib treatment increased CD44 expression; however, there was a decrease in the expression of CD133. An increasing trend was also seen in CD90 expression, but the difference was not significant. Conclusion: The results indicate that CSC expression varied according to the sorafenib dose administered, which supports the role of CSCs as novel pharmacological targets and highlights the importance of their characterization and the ability to identify them.
Galactose-induced aging model in rat testicular tissue
(College of Physicians & Surgeons, 2018) Aydın, Şeval; Yanar, Karolin; Şimşek, Bahadır; Cebe, Tamer; Sitar, Mustafa Erinç; Belce, Ahmet; Çakatay, Ufuk
Objective: To examine whether the D-galactose induced aging model is an appropriate model for further aging research. Study Design: Experimental study. Place and Duration of Study: Aziz Sancar Institute of Experimental Medicine, Istanbul University, Turkey, June 2015- June 2017. Methodology: The study comprises 3 groups of rats. Group I is young control (YC) 5-month-old rats. Group II is 5-monthold rats, which were mimetically aged (MA) for 6 weeks via intraperitoneal D-galactose (60 mg/kg body weight/day, 0.5 mL) administration. Group III is naturally aged (NA) 24-month-old rats. Group I and III received intraperitoneal saline (0.9% 0.5 mL) for 6 weeks as vehicle. Group I and Group II received injections at 21 weeks age and Group III rats 6 weeks before 24 months age. Tissues were harvested when rats became 6.5-month-old (Group I and Group II) and 24-month-old (Group III). Quantitative biochemical analyses of proteins, lipids, DNA biomarkers and Cu, Zn-SOD were conducted. Statistical analysis of the data was conducted using ANOVA, followed by post-hoc Bonferroni test. Results: Higher magnitude of oxidative damage and diminished antioxidant defence capacity were found in both mimetically aged and naturally aged testicular tissues. It is observed that D-galactose aging model group shares significant similarities in terms of impaired redox homeostasis with the naturally aged rats. Conclusion: D-galactose induced testicular aging model successfully mimics aging process. Therefore, D-galactose induced aging model may be used as an accelerated aging model to study the age related alterations and interventions.
Hba1c değerlerinin inflamatuar belirteçleri ile ilişkisi
(Türk Klinik Biyokimya Derneği, 2018) Öngen İpek, Belkız; Sitar, Mustafa Erinç
Amaç: Sağlıklı, prediyabetik ve diyabetik gruplarda, HbA1c ile sistemik inflamasyonun yeni belirteçlerinden kabul edilen nötrofil lenfosit oranı (NLO) ve trombosit lenfosit oranı (TLO) ile güçlü inflamasyon belirteçleri olarak kabul gören C Reaktif Protein (CRP) ve sedimantasyon arasındaki ilişkinin araştırılmasıdır. Gereç ve Yöntem: Çalışmamız hastanemize başvuran hasta sonuçlarından retrospektif olarak hazırlanmıştır. Çalışmaya glukoz, HbA1c değerleri, CRP, sedimantasyon, hemogram sonuçları olan hastalar katılmıştır. NLO tam kan sayımındaki nötrofil ve lenfosit mutlak sayısının, TLO ise kan sayımındaki trombosit ve lenfosit sayısının birbirine oranlaması ile bulunmuştur. Hastalar normal (HbA1c <6%), prediyabet (6 6.4%) ve ( ? 6.5%) diyabetik olarak 3 gruba ayrılmıştır. Bulgular: Prediyabetik, diyabetik hastalar ile kontrol grupları arasında glukoz, CRP, sedimantasyon ve nötrofil mutlak sayısı değerlerinde istatistiksel bir fark bulunurken (sırasıyla p<0.001, p<0.05, p<0.05 ve p<0.05) lenfosit mutlak sayısı, trombosit sayısı, NLO ve TLO değerlerinde ise istatistiksel anlamlı bir farklılık bulunamamıştır. Gruplar arasında fark bulunan testler için sağlıklı-prediyabetik grup ele alındığında glukoz, CRP, sedimantasyon ve nötrofil mutlak sayısı için istatistiksel fark bulunurken (p<0.05), sağlıklı-diyabetik grup ele alındığında glukoz ve CRP de istatistiksel anlamlı fark bulunmuştur (p<0.01 ve p<0.05). Prediyabetik-diyabetik grup karşılaştırıldığında ise sadece glukoz değerlerinde gruplar arasında istatistiksel anlamlı fark bulunmuştur (p<0.01). Sonuç: HbA1c değerleri ile inflamasyon belirteçleri olan NLO, TLO, CRP ve sedimantasyon arasındaki ilişki araştırılmış, HbA1c ile NLO, TLO ve sedimantasyon arasında bir ilişki saptanamazken, güçlü inflamatuar belirteç olan CRP ile HbA1c değerleri arasında ilişki saptanmıştır. Bu durum NLO ve TLO değerlerinin klinik kullanımda rutine girebilmesi için daha fazla zaman ve veriye ihtiyaç duyulduğunu göstermektedir.
Human serum albumin and its relation with oxidative stress
(Clinical Laboratory Publications GmbH, 2013) Sitar, Mustafa Erinç; Aydın, Şeval; Çakatay, Ufuk
Human serum albumin, a negative acute phase reactant and marker of nutritive status, presents at high concentrations in plasma. Albumin has always been used in many clinical states especially to improve circulatory failure. It has been showed that albumin is involved in many bioactive functions such as regulation of plasma osmotic pressure, binding and transport of various endogenous or exogenous compounds, and finally extracellular antioxidant defenses. Molecules like transferrin, caeruloplasmin, haptoglobin, uric acid, bilirubin, alpha-tocopherol, glucose, and albumin constitute extracellular antioxidant defenses in blood plasma but albumin is the most potent one. Most of the antioxidant properties of albumin can be attributed to its unique biochemical structure. The protein possesses antioxidant properties such as binding copper tightly and iron weakly, scavenging free radicals, e.g., hypochlorous acid (HOCl) and Peroxynitrite (ONOOH) and providing thiol group (-SH). Whether it is chronic or acute, during many pathological conditions, biomarkers of oxidative protein damage increase and this observation continues with considerable oxidation of human serum albumin. There is an important necessity to specify its interactions with Reactive Oxygen Species. Generally, it may lower the availability of pro-oxidants and be preferentially oxidized to protect other macromolecules but all these findings make it necessary that researchers give a more detailed explanation of albumin and its relations with oxidative stress.
Hyperoxic oxidative stress during abdominal surgery: a randomized trial
(Springer, 2016) Köksal, Güniz M.; Dikmen, Yalım; Erbabacan, Emre; Aydın, Şeval; Çakatay, Ufuk; Sitar, Mustafa Erinç; Altındaş, Fatiş
Purpose The hypothesis of our study is that during anesthesia, administration of 80 % oxygen concentration increases oxidative stress more than 40 % oxygen. Methods Forty ASA I-II patients were included in a randomized, single-blind study. Expiratory tidal volumes (ETV) were measured before induction and after extubation. After ventilation with 0.8 FiO2 and intubation, mini-bronchoalveolar lavage (mini-BAL), arterial blood gas (ABG), and blood samples were taken. Patients were randomly assigned to receive 0.8 (group I) or 0.4 (group II) FiO2 during management. Before extubation, mini-BAL, ABG, blood samples were taken. PaO2/FiO2, lactate, malondialdehyde (MDA), protein carbonyl (PCO), superoxide dismutase (SOD), total sulfhydryl (T-SH), non-protein sulfhydryl (NPSH), and protein sulfhydryl (PSH) were measured. In both groups, mean arterial pressure and heart rate values were recorded with 30-min intervals. Results ETV values were higher in group II after extubation. PaO2/FiO2 values were higher in group II after extubation compared to group I. In both groups, plasma PCO, SOD, and T-SH levels increased significantly before extubation, whereas the increase in MDA was not significant between groups. Plasma PCO, T-SH, and lactate levels were higher in group I, and plasma SOD, and PSH were higher in group I before extubation. In both groups, MDA, SOD, T-SH, and NPSH levels in mini-BAL increased significantly before extubation. Between-group comparisons, PCO, T-SH, PSH, and NPSH were significantly higher in the BAL samples of group II, and MDA levels were higher in group I. Conclusions We found that 80 % FiO2 decreased ETV and PaO2/FiO2 and increased lactate levels and oxidative stress more, inhibiting antioxidant response compared to 40 % FiO2.
Immune modulation and its role in antiaging
(Springerlink, 2018) Sitar, Mustafa Erinç; Akduman Alaşehir, Elçin; Öngen İpek, Belkız; Rizvi, Syed; Çakatay, Ufuk
Life expectancy of the communities is constantly increasing every minute, including less developed countries. That’s why application of studies to overcome and/or slow aging has always been an important and attractive issue for professional healthcare workers throughout history. There are numerous studies on different theories for explaining the aging process, but none of them can fully explain the cause. As it is known already, aging of different organs differs in a large extent. Fundamentals of this difference are mitotic activity of the tissues and resistance degree to deleterious damages. Cellular and molecular defense mechanisms clearly define resistance degree as “immunity.” Decline in immunity may cause a progressive step in aging. Inflammaging, which is low-grade chronic inflammatory status that is characteristic of the aging process, can be taught to be a biological factor responsible for the age-related diseases in the elderly. Possibility to decrease inflammaging without compromising the physiological role of inflammation can be a strategy for future perspectives. In this chapter we will focus on aging and immune system regulation together with therapies and/or modulations to rehabilitate aging.
Multidisciplinary harmonization study of a preanalytic quality indicator example in urine samples
(Association of Clinical Biochemistry Specialists, 2018) Öngen İpek, Belkız; Akduman Alaşehir, Elçin; Sitar, Mustafa Erinç; Konukoğlu, Dildar
Objectives: Usage of contamination rates as a quality indicator is a promising criterion in urine samples. A multidisciplinary approach is needed to use this quality indicator. Evaluation of urine strip and sediment according to the presence of contamination effect the rates of accurate test result, guidance of the clinician correctly, patient follow-up and requesting new sample. This feature also fulfils the rule of objectivity in quality indicators. It also plays an important role in the monitoring and effectiveness of regulatory and preventive activities. Material and Methods: Urine culture samples which were resulted as contaminated and synchronous full urinalysis test results were scanned retrospectively between July 2017 and December 2017. The patients were evaluated according to their age, sex, and being inpatient or outpatient. Strip and microscopy findings were evaluated from the results of full urine analysis. Results: 1537 urine culture test results were analyzed in 6 months for the study. Those which were considered as contamination were evaluated together with their total urine analysis at the same time. It was found that 82% were female, 18% were male, 58% were older than 65 years, 24% were between 18-65 years, 11% were <1-year-old of these patients. The test was requested 67% and 33% respectively from outpatient and inpatient. Leukocyte esterase and nitrite were found positive %33 and %16 respectively in urine strips. When urine microscopy was evaluated, 52% had abundant bacteria and 56% had more than 5 leukocytes in each area. It was found that 63.3% of the patient have no signs in microscopy or strip in <1-year-old group. Conclusions: In our study, it was found that contamination rates were higher especially over 65 years and female sex. It is important to explain the method of sampling and to be more careful when approving the test results of full urine analysis in this population. Considerations during sample collection and the selection of materials are of great importance for clinical follow-up in younger than 1-year-old population.
Oxidation scrutiny in persuaded aging and chronological aging at systemic redox homeostasis level
(Elsevier, 2014) Cebe, Tamer; Atukeren, Pınar; Yanar, Karolin; Kuruç, Aylin Irmak; Ozan, Tuna; Kunbaz, Ahmad; Sitar, Mustafa Erinç; Mirmaroufizibandeh, Reza; Aydın, Şeval; Çakatay, Ufuk
Background The effect of the natural aging process on systemic redox homeostasis is previously documented. However, none of the studies specify the effect of experimental aging on systemic redox homeostasis. The purpose of this study is to clarify the ambiguity raised in preliminary reports as to mimetic aging dependency of the type and magnitude of oxidative damage on constituents of plasma. Methods In the current study, we investigated the interrelationship among various groups of the systemic oxidative damage markers such as protein oxidation products (protein carbonyl groups, protein hydroperoxides, advanced oxidation protein products, protein thiol groups), lipid peroxidation products (malondialdehyde, lipid hydroperoxides, conjugated dienes), glycoxidation adducts (advanced glycation end products), and antioxidant capacity (ferric reducing/antioxidant power, Cu,Zn-superoxide dismutase, total thiol, non-protein thiol). All these markers were measured in plasma of mimetically aged (MA) rats (5-month-old rats subjected to d-galactose-induced experimental aging), naturally aged (NA) rats (24-month-old), and their corresponding young controls (YC) (5 months old). Results and conclusions Our current results show that systemic oxidation markers of the MA group share significant similarities in terms of impaired redox homeostasis with the NA rats and may be considered as a reliable experimental aging model for intravascular aging. Additional methodological studies including d-galactose dosage and application time are warranted to clarify the potential involvement of all these systemic redox variations as mechanistic factors in the development of mimetic aging related intravascular deterioration. Reversing or preventing systemic oxidative damage in experimental and natural aging should therefore be considered the primary target for the development of effective therapeutic strategies to prevent or treat age-related vascular disorders.
Oxidative damage parameters in renal tissues of aged and young rats based on gender
(National Library of Medicine, 2013) Uzun, Duygu; Güntaş Korkmaz, Gülcan; Sitar, Mustafa Erinç; Cebe, Tamer; Yanar, Karolin; Çakatay, Ufuk; Aydın, Şeval
Purpose Aging is characterized by a gradual functional decrease of all systems including the kidneys. Growing evidence links altered lipid protein redox-homeostasis with renal dysfunction. The effect of sexual dimorphism on the lipid protein redox-homeostasis mechanisms in the aging kidney is obscure. In the current study, we aimed to investigate redox homeostasis as it related to sexual dimorphism on protein oxidation and lipid peroxidation parameters, as protein carbonyl (PCO), total thiol (T-SH), advanced oxidation protein products (AOPP), malondialdehyde, glutathione (GSH), and superoxide dismutase (SOD) activity, as potential aging biomarkers, which may contribute to an analysis of the free radical theory of aging. Materials and methods The study was carried out with 16 naturally aged rats (24 months old; eight males and eight females) and their corresponding young rat groups as controls (6 months old; eight males and eight females). All of the aforementioned parameters (PCO, T-SH, AOPP, MDA, GSH, SOD) were measured manually instead of automated devices or ELISA kits. Results PCO, AOPP, and malondialdehyde levels in aged rats were significantly higher in the older rat group than in the younger rat group, whereas SOD activities were significantly lower in old rats. T-SH levels were not significantly different in male groups; however, T-SH levels were lower in the aged female group than in the young female control group. In addition, GSH levels were significantly different between the aged rat group and the corresponding young control group for both genders. Conclusion With respect to PCO and AOPP, impaired redox homeostasis is substantially more prominent in males than females. The decrease of G-SH levels in male groups could be attributed to stabilizing the redox status of protein thiol groups by the depletion of the GSH groups. Considering the results, the renal tissue proteins and lipids in different genders may have different susceptibilities to oxidative damage.
Procalcitonin in the diagnosis of sepsis and correlations with upcoming novel diagnostic markers
(Association of Clinical Biochemistry Specialists Turkey, 2019) Sitar, Mustafa Erinç; Öngen İpek, Belkız; Karadeniz, Aslı
Sepsis is a complex and lethal condition. For successful treatment, clinicians need high quality testing to guide the approach to pathogen identification and treatment. Medical laboratories play a vital role in the detection of infectious agents, and must continually strive to discover new and reliable tests and to analyze the reliability of existing tests in different diseases and expand their usage as appropriate. Selecting the appropriate therapy, reducing the use of antibiotics and thereby reducing antibiotic resistance are also undeniable parts of this task. The most commonly used parameters to guide infection therapy are the white blood cell count, the erythrocyte sedimentation rate, the absolute count of neutrophils, the absolute number of lymphocytes, and the level of C-reactive protein, serum amyloid A protein, ceruloplasmin, haptoglobin, fibrinogen, and procalcitonin (ProCT). Although ProCT has been accepted as quite effective in differentiating serious bacterial infections, there are unresolved questions regarding effective usage during follow-up, as there are with other markers. ProCT and other promising biomarkers in a sepsis setting were the focus of this review, beginning with the first study to define ProCT in the literature, and examining some of the studies related to the importance of the ProCT-sepsis relationship, and detailed information on candidate markers.
Ralstonia insidiosa neonatal sepsis: a case report and review of the literature
(Thieme, 2020) Akduman Alaşehir, Elçin; Öngen İpek, Belkız; Thomas, David Terence; Sitar, Mustafa Erinç; Erener Ercan, Tuğba
Introduction?Ralstonia spp. are nonfermenting gram-negative bacteria that have recently emerged as opportunistic pathogens. Previously, two case series of infection associated with Ralstonia insidiosa have been published. In this case report, R. insidiosa infection of a neonate in the neonatal intensive care unit (NICU) is presented. Case Presentation?A term male infant developed respiratory distress 2 hours after birth and was admitted to the NICU with the presumptive diagnosis of transient tachypnea of the newborn. A left apical pneumothorax was detected, requiring chest tube insertion. An umbilical catheter was placed due to poor peripheral vascular access. On the second day, blood cultures were sent from the umbilical artery and umbilical venous catheters, which showed growth of R. insidiosa. The antibiotics were changed from ampicillin and gentamicin to ampicillin–sulbactam and cefotaxime according to the antibiotic susceptibility test results. Respiratory distress symptoms resolved and the patient was extubated. The infant's clinical condition improved steadily and was discharged with breast feeding and stable vital findings, negative follow-up cultures, and C-reactive protein. Conclusion?Ralstonia insidiosa is an emerging pathogen in hospital infections due to its ability to survive in water supplies and sterilized water-based solutions. There is need for vigilance of R. insidiosa, especially in intensive care units. Awareness of rare pathogens, early detection of the bacteria, and antibiotic susceptibility test results are important in the success of treatment.

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