The Role of Nitric Oxide in Doxorubicin-Induced Cardiotoxicity: Experimental Study

OBJECTIVE: We evaluated the myocardial damage in rats treated with doxorubicin (DOX) alone and in combination with nitric oxide synthase (NOS) inhibitors. METHODS: Twenty-four male Sprague Dawley rats (12 weeks old, weighing 262±18 g) were randomly assigned into 4 groups (n=6). Group I was the control group. In Group II, rats were treated with intraperitoneal (ip) injections of 3 mg/kg DOX once a week for 5 weeks. In Group III, rats received weekly ip injections of 30 mg/kg L-NAME (nonspecific NOS inhibitor) 30 min before DOX injections for 5 weeks. In Group IV, rats received weekly ip injections of 3 mg/kg L-NIL (inducible NOS inhibitor) 30 min before DOX injections for 5 weeks. Rats were weighed 2 times a week. At the end of 6 weeks, hearts were excised and then fixed for light and electron microscopy evaluation and tissue lipid peroxidation (malondialdehyde). Blood samples were also obtained for measuring plasma lipid peroxidation. RESULTS: Weight loss was observed in Group II, Group III, and Group IV. Weight loss was statistically significant in the DOX group. Findings of myocardial damage were significantly higher in animals treated with DOX only than in the control group. Histopathological findings of cardiotoxicity in rats treated with DOX in combination with L-NAME and L-NIL were not significantly different compared with the control group. The level of plasma malondialdehyde in the DOX group (9.3±3.4 μmol/L) was higher than those of all other groups. CONCLUSION: Our results showed that DOX cardiotoxicity was significantly decreased when DOX was given with NO synthase inhibitors

Augmented mitochondrial cytochrome c oxidase activity in children with iron deficiency: a tandem between iron and copper?

Introduction: Dyshomeostasis of essential trace elements including iron and copper plays a key role in the pathogenesis of a myriad of serious conditions including iron deficiency (ID) anemia, in which impaired cellular energy metabolism is prominent. Although experimental studies documented decreased activity of cytochrome c oxidase (CytOx) in ID, there are not enough clinical data. The present study was conducted to determine serum copper levels and activity of mitochondrial CytOx in isolated lymphocytes of patients with iron deficiency. Material and methods: A total of 210 cases (2-17 years) were included in this prospective study. Serum iron and copper levels were measured. According to the serum iron levels, patients were allocated to iron deficient (ID, n = 70) and iron deficiency anemia (IDA, n = 70) groups, and iron-sufficient participants were allocated to the control group (n = 70). Activity of CytOx in the circulating lymphocytes was colorimetrically measured and compared with the controls. Results: The CytOx activity was significantly higher in the IDA (2.9 ±1.2 mOD/min, n = 62) group compared to the control group (2.4 ±1.3 mOD/ min, n = 68, p < 0.001). Interestingly, serum copper levels were significantly higher in both the ID (106.9 ±55.5 µg/dl, n = 64, p = 0.0001) and IDA (115.1 ±50.2 µg/dl, n = 59, p = 0.0001) groups than the control group (72.1 ±46.7 µg/dl, n = 69). Conclusions: Higher serum copper levels in patients with IDA implicate co-operative interaction between these trace elements. The elevated CytOx activity in patients with IDA is probably secondary to the normal/elevated serum copper levels

Central nervous system thrombosis in pediatric acute lymphoblastic leukemia in Turkey: A multicenter study

BackgroundIn patients with acute lymphoblastic leukemia (ALL), the risk of thromboembolism increases due to hemostatic changes secondary to the primary disease and due to treatment-related factors. In this multicenter study, we aimed to research the frequency of central nervous system (CNS) thrombosis occurring during treatment, hereditary and acquired risk factors, clinical and laboratory features of patients with thrombosis, treatment approaches, and thrombosis-related mortality and morbidity rates in pediatric ALL patients. ProcedurePediatric patients who developed CNS thrombosis during ALL treatment from 2010 to 2021 were analyzed retrospectively in 25 different Pediatric Hematology Oncology centers in Turkiye. The demographic characteristics of the patients, symptoms associated with thrombosis, the stage of the leukemia treatment during thrombosis, the anticoagulant therapy applied for thrombosis, and the final status of the patients recorded through electronic medical records were determined. ResultsData from 70 patients with CNS thrombosis during treatment, out of 3968 pediatric patients with ALL, were reviewed. The incidence of CNS thrombosis was 1.8% (venous: 1.5 %; arterial: 0.03%). Among patients with CNS thrombosis, 47 had the event in the first 2 months. Low molecular weight heparin (LMWH) was the most commonly used treatment with a median of 6 months (min-max: 3-28 months). No treatment-related complications occurred. Chronic thrombosis findings occurred in four patients (6%). In five (7%) patients who developed cerebral vein thrombosis, neurological sequelae (epilepsy and neurological deficit) remained. One patient died related to thrombosis, and the mortality rate was 1.4%. ConclusionCerebral venous thrombosis and, less frequently, cerebral arterial thrombosis may develop in patients with ALL. The incidence of CNS thrombosis is higher during induction therapy than during other courses of treatment. Therefore, patients receiving induction therapy should be monitored carefully for clinical findings suggestive of CNS thrombosis

Nabiltem Personelinin Enstrümental Uzmanlıklarının Iyileştirilmesinin Ve Laboratuvar Bünyesinde Gerçekleştirilen Analiz Hizmetlerinin Kalitesinin Ve Güvenilirliğinin Arttırılmasının Araştırılması

Namık Kemal Üniversitesi Rektörlüğü’ne bağlı olarak faaliyet gösteren Bilimsel ve Teknolojik Araştırmalar Uygulama ve Araştırma Merkezi (NABİLTEM) Üniversiteler ile Kamu Kurum ve Kuruluşlarında çalışan araştırıcılara ve çeşitli sanayi kuruluşlarının ihtiyaç duyduğu analizlerde yardımcı olmak üzere kurulmuş bir birimdir. DPT tarafından sağlanan destekle kurulan ve uluslararası kriterlere uygun analizleri gerçekleştirmek üzere yapılandırılması planlanan NABİLTEM, Namık Kemal Üniversitesinin ulusal ve uluslararası proje yürütme potansiyelini artırmayı; sanayi, özel ve kamu kuruluşlarının araştırma, ürün geliştirme ve üretim aşamalarında ihtiyaç duydukları analiz ve ölçüm isteklerini karşılamayı amaçlamaktadır. Laboratuvarımızda farklı birimlere hizmet etmek için alınmış indüktif eşleşmiş plazma- kütle spektrometresi (ICP-MS), elektron mikroskobu (SEM), atomik kuvvet mikroskobu (AFM), ultra yüksek performans sıvı kromatografi (LC-MS/MS), üç farklı dedektör sistemine sahip yüksek performans sıvı kromatografi (HPLC), gaz kromatografi kütle spektometre (GC-MS), eş zamanlı polimeraz zincir reaksiyonu (RT-PCR), DNA dizi analizleyici, floresans mikroskobu, faz kontrast mikroskobu, fourier dönüşümlü infrared spektrometresi (FT-IR), toplam organik karbon analizleyici (TOC) mevcuttur. Laboratuvarımız kadrolu elemanlarının tüm bu cihazlar konusunda uzmanlıklarının geliştirilmesi ve gerekli eğitimlerin verilmesi son derece önemlidir. Projenin amaçlarından bir tanesi personelimizin daha iyi, doğru ve güvenilir hizmet sunabilmesi için ileri düzeyde eğitilmeleri hususunda neler yapılabileceğinin araştırılması ve bunların gerçekleştirilmesidir. Yapılacak analizin tam bir güvenlik içinde, hatasız ve olabildiğince çabuk gerçekleştirilmesi gerekir. Bu da sadece çalışılan laboratuvarda çok dikkatli ve düzenli olmakla değil; uygulanacak yöntemlerin çok iyi bilinmesi, hata kaynaklarının minimuma indirilmesi, cihaza özel çalışma prensiplerine ve yazılımına hâkim olunarak özel metotların oluşturması ile başarılabilir. Bu yüzden araştırma amaçlı laboratuvar personellerinin eğitimleri; daha nitelikli araştırmaların planlanmalarına ve çeşitli platformlarda sunulan bilimsel projelerin başarılarının daha da artmasına ayrıca katkısı olacaktır.Laboratuvarımız tıp fakültesi, ziraat fakültesi, fen edebiyat fakültesi gibi interdisipliner bölümlere hizmet vereceğinden laboratuvar personelinin eğitimi verilecek analiz hizmetinin kalitesinin yapıtaşıdır.Cihazların eğitim çalışmalarının video kayıtları yapılarak hem laboratuvarda görevli uzmanların sürekli başvurabilecekleri bir cihaz eğitim arşivi oluşturulacak hem de bu kayıtların isteyen tüm akademik personele verilmesiyle öğrencilerimizin kendi disiplinlerine ait üst düzey laboratuvar cihazlarına yönelik eğitim alma olanağı hazırlanmış olacaktır. Numunelerin analize hazırlığı için gerekli ön işlemlerin yapılmasında kullanılmak üzere cam malzeme ve kimyasal sarfların ve ayrıca cihazların kalibrasyonlarının yapılması için ilgili standart çözeltilerinin temin edilmesine ihtiyaç duyulmaktadır. Dolayısıyla proje kapsamında tüm sarf malzemesi ihtiyaçlarının teminiyle analiz sayısı ve kalitesi arttırılarak daha fazla birime hizmet verilmesi de amaçlanmaktadır. Gerekli cam ve sarf malzemelerin alımı ile üniversitemize ve diğer üniversitelere analizler yapılmıştır. Aldığımız eğitimler ve yaptığımız çalışmalar aşağıda özetlenmiştir.The application and research center of scientific and technological investigations (NABILTEM) is a unit founded for researchers in universities and industrial companies in order to provide a laboratorial facility could be demanded during their works. NABILTEM was established by a grant by DPT, and is dedicated to provide a laboratorial facility useful for research and development activities of universities and isdusturial companies. Inductively Coupled Plasma – Mass Spectrometer (ICP-MS), Scanning Electron Microscope (SEM), Atomic Force Microscope AFM, High-performance Liquid Chromatography coupled with tandem Mass Spectrometry (LC-MS/MS), Highperformance Liquid Chromatography (HPLC), Gas Chromatography–Mass Spectrometry (GC-MS), Real Time PCR (RT-PCR), Otomated DNA Sequencer, Fourier Transform Infrared Spectroscopy (FT-IR), and Total Organic Carbon (TOC) are main available devices in NABILTEM in order to serve various sectors. Education of full positioned staffs of the NABILTEM on all of these devices is one of the most important points. Therefore; one of the aims of this project was to give lectures and demonstrations to the staff to provide more accurate and reliable results to customers. Serving analyses have to be done without any mistake and fast at most. This can be achieved by not only working carefully, and also by description of workflows and algorithms in advance. Thus, more successful scientific project could be performed in various platforms with well educated staffs of NABILTEM. Education of the NABILTEM personnels is the most important point for higher service quality. Video records of demonstration on devices provided in NABILTEM are very important sources for both NABILTEM and academic personnels of our university. There is a demand on standard solutions, chemical reagents and glass stuff for preparation of samples to be tested. Therefore, it is aimed to serve more departments by recruitment of all the supplies required. Set up studies for common analyses for our and other universities have been performed by having all the supplies required. The analyses performed in our laboratories and educational activities are summarizied below

The suppression of endogenous adrenalin in the prolongation of ketamine anesthesia

Cetin, Nihal/0000-0003-3233-8009; Ahiskalioglu, Ali/0000-0002-8467-8171; Ahiskalioglu, Ali/0000-0002-8467-8171; ALP, Hamit Hakan/0000-0002-9202-4944; AKSOY, Mehmet/0000-0003-0867-8660WOS: 000337884400022PubMed: 24767810This study investigated whether or not the anesthetic effect of ketamine in rats is dependent on adrenal gland hormones. the study was performed on two main rat groups, intact and adrenalectomized. Rat were divided into subgroups and given appropriate doses of ketamine, metyrapone or metyrosine. Durations of anesthesia in the groups were then recorded. Endogenous catecholamine levels were measured in samples taken from peripheral blood. This experimental results showed that ketamine did not induce anesthesia in intact rats at doses of 15 or 30 mg/kg, and that at 60 mg/kg anesthesia was established for only 11 min. However, ketamine induced significant anesthesia even at a dose of 30 mg/kg in animals in which production of endogenous catecholamine (adrenalin, noradrenalin dopamine) was inhibited with metyrosine at a level of 45-47%. Ketamine at 60 mg/kg in animals in which endogenous catecholamine was inhibited at a level of 45-47% established anesthesia for 47.6 min. However, ketamine at 30 and 60 mg/kg induced longer anesthesia in adrenalectomized rats with higher noradrenalin and dopamine levels but suppressed adrenalin production. Adrenalin plays an important role in the control of duration of ketamine anesthesia, while noradrenalin, dopamine and corticosterone have no such function. If endogenous adrenalin is suppressed, ketamine can even provide sufficient anesthesia at a 2-fold lower dose. This makes it possible for ketamine to be used in lengthy surgical procedures. (C) 2014 Elsevier Ltd. All rights reserved

Comparative investigation of protective effects of metyrosine and metoprolol against ketamine cardiotoxicity in rats

Ahiskalioglu, Ali/0000-0002-8467-8171; ALP, Hamit Hakan/0000-0002-9202-4944; Ahiskalioglu, Ali/0000-0002-8467-8171; AKSOY, Mehmet/0000-0003-0867-8660WOS: 000361605900005PubMed: 25503950This study investigated the effect of metyrosine against ketamine-induced cardiotoxicity in rats and compared the results with the effect of metoprolol. in this study, rats were divided into groups A, B and C. in group A, we investigated the effects of a single dose of metyrosine (150 mg/kg) and metoprolol (20 mg/kg) on single dose ketamine (60 mg/kg)-induced cardiotoxicity. in group B, we investigated the effect of metyrosine and metoprolol, which were given together with ketamine for 30 days. in group C, we investigated the effect of metyrosine and metoprolol given 15 days before ketamine and 30 days together with ketamine on ketamine cardiotoxicity. By the end of this process, we evaluated the effects of the levels of oxidant-antioxidant parameters such as MDA, MPO, 8-OHGua, tGSH, and SOD in addition to CK-MB and TP I on cardiotoxicity in rat heart tissue. the experimental results show that metyrosine prevented ketamine cardiotoxicity in groups A, B and C and metoprolol prevented it in only group C