Examınıng The Role Of Tıp60 Proteın In Repaır Of Dna Damage In Molecular Subtypes Of Breast Cancer

Kanser, kardiyovasküler hastalıklardan sonra ikinci sırada yer alan ölüm nedenidir. Dünyada kadınlarda görülen kanser türlerinin içinde akciğer kanserinden sonra ikinci sırada yer alan meme kanseri, ülkemizde ilk sırada yer almaktadır. Son yıllarda yapılan çalışmalarda, birçok tümör hücresinin DNA hasar yanıt mekanizmasını bozan mutasyonlar taşıdığı giderek daha fazla kabul görmeye başlamıştır. Bu nedenle, DNA hasarı onarım mekanizması bozuk hücrelerde, kanser tedavilerinin tasarlanmasına büyük önem verilmiştir. Çalışmamızda, meme kanserinin moleküler alt tiplerinde Tip60, ATM, p53, CHK2, BRCA1 ve H2AX mRNA ekspresyon seviyelerinin qRT-PCR ile ve protein ekspresyon seviyelerinin Western Blot metodu ile ölçülerek elde edilen sonuçları arasındaki ilişkinin tespiti amaçlanmıştır. Bu amaçla meme kanseri tanısı konan 58 hastadan doku örnekleri alınmıştır. Kontrol olarak, meme küçültme ameliyatı için kliniğe başvuran 8 sağlıklı kişi çalışmaya dahil edilmiştir. Çalışma sonuçlarına göre, Tip60 ekspresyonu hastaların %55 inde, ATM %59 unda, BRCA1 %57 sinde, H2AX %48 inde, CHK2 %66 sında ve p53 %43 ünde eşlenik normal dokuya oranla tümör dokuda azalmıştır. Moleküler alt tiplere göre değerlendirildiğinde, özellikle Luminal B ve Her2 ile zenginleştirilmiş Luminal B gruplarında yolağa ait bütün genlerin ekspresyonlarının normal dokularda tümör dokulara göre belirgin derecede yüksek bulunmuştur. Protein ekspresyonları incelendiğinde, total hasta grubunda ve Luminal A grubunda Tip60 ve H2AX düzeyleri tümör dokularda daha yüksek bulunurken, CHK2 düzeylerinin normal dokularda yüksek olduğu tespit edilmiştir. Tüm genlerin gerek normal doku gerekse tümör doku mRNA ekspresyonları arasında istatistiksel olarak anlamlı pozitif korelasyonlar gözlenmiştir (p<0.05). Genlerin mRNA ve protein ekspresyonları arasında belirgin bir korelasyon gözlenmemiştir. Sonuç olarak, Tip60 mRNA ekspresyonlarının kanserli hastalarda diğer genlere göre daha düşük olduğu ve hastaların çoğunda H2AX ve p53 hariç diğer genlerin normal dokularda tümör dokulara göre daha yüksek olduğu görülmektedir. Protein ekspresyonları ile mRNA ekspresyonları arasında korelasyon gözlenmemesinin, proteinlerin aktif olan fosforile şekillerinin ölçülmemesinden kaynaklandığını düşünmekteyiz.Cancer rows the second leading causes of death following cardiovascular diseases. Breast cancer which is the most common cancer after lung cancer in women worldwide is the first rank in our country. In recent years studies have begun to become accepted that many tumor cells carry mutations that disrupt the DNA damage response mechanism. Therefore, great importance for the design of cancer treatments in cells which with damaged DNA repair mechanism. In our study, it was aimed to determine the relationship between the mRNA expression levels of Tip60, ATM, p53, CHK2, BRCA1 and H2AX mRNA in molecular subtypes of breast cancer by qRT-PCR and the results obtained by Western blotting of protein expression levels. For that purpose, tissue and serum samples were taken from 58 patients diagnosed with breast cancer. As controls, 8 healthy persons admitted to the clinic for breast reduction surgery were also included to the study. According to the study results, tumor tissue decreased in 55% in Tip60, 59% in ATM, 57% in BRCA, 48% in H2AX, 66% in CHK2 and 43% in p53 of patients compared to the equivalent normal tissue. When evaluated according to molecular subtypes, expression of all genes in the pathway was found significantly higher in normal tissues than in tumor tissues especially in Luminal B groups and Luminal B enriched with Her2. When protein expressions are examined, the levels of Tip60 and H2AX were higher in tumor tissues and CHK2 levels were higher in normal tissues in total and Luminal A groups. Statistically significant positive correlations were observed between tumor tissue mRNA expressions of both normal and normal tissues (p <0.05)08. There was no significant correlation between the mRNA and protein expressions of the genes. As a result, the expression of Tip60 mRNA is lower in cancer patients than in other genes. In the majority of patients, other genes except H2AX and p53 are found to be higher in normal tissues than tumor tissues. No correlation was observed between protein expressions and mRNA expression and we think, it is due to the fact that the active forms of the phosphorylated proteins are not measured

Evolution from Rapid Discharge Program to ERAS Protocols in Cardiovascular Surgery

Kalp cerrahisindeki gelişmeler mortaliteyi azaltmakla beraber, komplikasyon ve maliyetleri azaltamamıştır. 1990’lı yıllarda başlatılan hızlı taburcu protokolleri yoğun bakım sürecini kısaltmasına rağmen, istenen düzeyde hastane kalış süresi ve morbiditeyi değiştirememiştir. Son yıllarda diğer cerrahi alanlarda oluşturulan ERAS porotokollerinin kalp cerrahisinde de uygulanmasına başlanmıştır. Bu çok yeni uygulamanın oluşturulmasındaki önemli noktalar ve bu konudaki tecrübeler bu derlemede ele alınarak irdelenmiştir.Although recent advances in cardiovascular surgery have decreased mortality ratse but they did not reduce complications and financial costs. Fast tract protocols proposed in 1990’s had positive have shortened ıntensive care unit stay time, they couldn’t exert changes on overall hospitalisation time and morbidity rates. Recently ERAS protocols applied for noncardiac surgery have been started to be applied for cardiovascular surgery. The important points for this new application and experiences of on this subject have been evaluated in this review

Kısa Bir Soru: Amantadin Sülfat İnfüzyonu Yoğun Bakım Ünitesinde Hayat Kurtarıcı Olur mu?

Objective: Traumatic brain injury (TBI) is one of the leading causes that cognitive and behavioral problems. Many pharmacological therapies reveal early neurochemical changes. The CRS-R is a standardized neuro-behavioral evaluation tool comprising six organized subscales (auditory, visual, motor, oromotor–verbal, communication, and arousal). We hypothesized that, the effect of amantadine sulfate infusion treatment on conscious recovery and clinical improvement in patients with severe head injury in terms of CRS-R and clinical recovery. Material and Methods: Patients’ age, gender, days of hospitalization, pre-treatment and post-treatment GCS, education level, day of amantadine sulfate, intubated or non-intubated when he/she come to intensive care unit (ICU), recovery time of conscious, discharge time, CT or MR pathology will be retrospectively recorded. Patients were aged >18 years, had brain trauma, had amantadine sulfate therapy in ICU were included the study between June 2016-June 2017. Results: A total of 40 patients using amantadine sulfate infusion were included in the study. It was determined that 13 of patients had mortality. Improvement in CT and MRI findings were detected in 21 of the living patients (77.8%). There were no differences between the mean starting time according to the clinical recovery levels and recovery status on CT-MRI. There were statistically significant differences between starting time and time of extubation and starting time of consciousness recovery and discharge time. Conclusion: In conclusion, we believe that amantadine treatment accelerates neurological recovery in terms of CRS-R and clinical recovery in TBI patients.Amaç: Travmatik beyin hasarı (TBH), bilişsel ve davranışsal sorunların önde gelen nedenlerinden biridir. Birçok farmakolojik tedavi erken nörokimyasal değişiklikleri açıklamaktadır. CRS-R, altı organize alt ölçek (işitsel, görsel, motor, oromotor-sözel, iletişim ve uyarılma) içeren standartlaştırılmış bir nöro davranışsal değerlendirme aracıdır. Biz CRS-R ve klinik iyileşme açısından ağır kafa travmalı hastalarda amantadin sülfat infüzyon tedavisinin bilinç düzeyinde ve klinik iyileşme üzerindeki etkisini sunmayı amaçladık. Gereç ve Yöntemler: Hastaların yaşı, cinsiyeti, hastanede yatış günleri, tedavi öncesi ve tedavi sonrası GKS, eğitim düzeyi, amantadin sülfat günü, entübe gelip gelmediği, bilinçte düzelme zamanı, taburculuk süresi, BT veya MR patolojileri retrospektif olarak kaydedildi. Haziran-Haziran 2017 tarihleri arasında 18 yaş üstü, beyin travması geçiren, yoğun bakımda amantadin sülfat tedavisi alan hastalar çalışmaya dahil edildi. Bulgular: Çalışmaya amantadin sülfat infüzyonu kullanan toplam 40 hasta dahil edildi. Hastaların 13’ünde mortalite olduğu tespit edildi. Yaşayan hastaların 21’inde (%77,8) BT ve MR bulgularında iyileşme saptandı. Klinik iyileşme düzeylerine ve BT-MR'da iyileşme durumuna göre ortalama başlangıç zamanı arasında fark yoktu. Başlangıç zamanı ve ekstübasyon zamanı ile bilincin düzelme ve taburculuk süresinin zamanı arasında istatistik olarak anlamlı fark gözlendi. Tartışma: Sonuç olarak, amantadin sülfat tedavisinin, CRS-R açısından da değerlendirildiğinde TBH hastalarında klinik iyileşme ve nörolojik iyileşmeyi hızlandırdığını düşünüyoruz

Cardiovascular Surgery and Interventions Case Report Open Access Coronary artery bypass graft surgery in a pediatric patient with a giant coronary aneurysm

Kawasaki disease or mucocutaneous lymph node syndrome is an acute, febrile vasculitis of unknown etiology affecting mainly infants and children under five years of age. Coronary artery involvement, which occurs in approximately 20% of such patients, may be the most important feature of this syndrome. In this paper, we report a successful coronary artery bypass graft in a nine-year-old boy with a giant coronary artery aneurysm and diffuse coronary artery disease. Keywords: Aneurysm; coronary artery bypass grafting; Kawasaki disease. Kawasaki disease (KD), previously known as mucocutaneous lymph node syndrome, is an acute, febrile, self-limiting generalized vasculitis of unknown etiology which occurs predominantly in infants and young children. It mainly affects small-and medium-sized arteries, particularly the coronary arteries, and was described by Kawasaki in 1967. [1] Gulhan et al. [2] reported a 42.4% incidence of coronary involvement in Turkish patients with KD. Kawasaki disease causes aneurysm formation at the proximal sites of the coronaries, while the distal sites are usually protected. Dilatation equal to or larger than 8 mm is categorized as a giant aneurysm, which may cause coronary artery stenosis secondary to compression or thrombosis. [3] Early diagnosis and rapid therapeutic interventions such as aspirin and intravenous gamma globulin may decrease the risk of coronary artery pathology development by approximately 20%. CASE REPORT A nine-year-old boy with KD was admitted to our institution with complaints of chest pain and fatigue. The patient&apos;s history revealed KD. He experienced the first attack at the age of two with prolonged fever. Neither intravenous gamma globulin nor steroid therapy was given. Laboratory examination showed leukocytosis, high C-reactive protein, and elevated liver enzymes. Echocardiography showed pancarditis and a giant calcified and thrombotic coronary artery aneurysm. The diameter of the left main coronary artery aneurysm was measured as 40 mm. The patient was enrolled in a treadmill exercise test according to the modified Bruce protocol. Ischemic signs were found in the anterior leads. Coronary angiography revealed a giant left main coronary artery aneurysm, a totally occluded left anterior descending artery, and a diffusely diseased circumflex arter

Patient-specific atrial hemodynamics of a double lumen neonatal cannula in correct caval position

13th International Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion -- SEP 28-30, 2017 -- Rome, ITALYWOS: 000430277400007PubMed ID: 29572879Clinical success of pediatric veno-venous (VV) extracorporeal membrane oxygenation (ECMO) is associated with the double lumen cannula cardiovascular device design as well as its anatomic orientation in the atrium. The positions of cannula ports with respect to the vena cavae and the tricuspid valve are believed to play a significant role on device hemodynamics. Despite various improvements in ECMO catheters, especially for the neonatal and congenital heart patients, it is still challenging to select a catalogue size that would fit to most patients optimally. In effect, the local unfavorable blood flow characteristics of the cannula would translate to an overall loss of efficiency of the ECMO circuit. In this study, the complex flow regime of a neonatal double lumen cannula, positioned in a patient-specific right atrium, is presented for the first time in literature. A pulsatile computational fluid dynamics (CFD) solver that is validated for cardiovascular device flow regimes was used to perform the detailed flow, oxygenated blood transport, and site-specific blood damage analysis using an integrated cannula and right atrium model. A standard 13Fr double lumen cannula was scanned using micro-CT, reconstructed and simulated under physiologic flow conditions. User defined scalar transport equations allowed the quantification of the mixing and convection of oxygenated and deoxygenated blood as well as blood residence times and hemolysis build-up. Site-specific CFD analysis provided key insight into the hemodynamic challenges encountered in cannula design and the associated intra-atrial flow patterns. Due to neonatal flow conditions, an ultra high velocity infusion jet emanated from the infusion port and created a zone of major recirculation in the atrium. This flow regime influenced the delivery of the oxygenated blood to the tricuspid valve. Elevated velocities and complex gradients resulted in higher wall shear stresses (WSS) particularly at the infusion port having the highest value followed by the aspiration hole closest to the drainage port. Our results show that, in a cannula that is perfectly oriented in the atrium, almost 38% of the oxygenated blood is lost to the atrial circulation while only half of the blood from inferior vena cava (IVC) can reach to the tricuspid valve. As such, approximately 6% of venous blood from superior vena cava (SVC) can be delivered to tricuspid. High values of hemolysis index were observed with blood damage encountered around infusion hole (0.025%). These results warrant further improvements in the cannula design to achieve optimal performance of ECMO and better patient outcomes.European Union (EU) [FP7 CIG-293931-CardioFluidMechanics]; European Research Council (ERC) Starting Grant [307460]; TUBITAK 1003 priority-research program grant [115E690]This work was supported in part by the European Union (EU) FP7 CIG-293931-CardioFluidMechanics, European Research Council (ERC) Starting Grant 307460 and TUBITAK 1003 priority-research program grant 115E690 (Principle Investigator: Kerem Pekkan). Micro-CT is kindly provided by Teknodent via Asm Horasan

mRNA Expressions of Specific Gamma-Glutamyl Transferases in Molecular Subtypes of Breast Cancer

An increased risk of breast cancer has been reported in individuals with elevated levels of gamma-glutamyl transferase (GGT). GGT1 was the only enzyme used for diagnosis in clinic and human genome contains additional related genes or sequences besides GGT1. From the perspective of amino acid sequences, genes showing substantial similarity (GGT5, GGT6, and GGT7) to GGT1 have been identified. The aim of this study was to investigate the mRNA expressions of GGT1, GGT5, GGT6, and GGT7 in 58 breast cancer patients’ tissue samples by qRT-PCR method. In total, mRNA expressions of GGT5 and GGT7 increased and GGT6 decreased in tumor tissues than those in normal tissues of the same patients (p&lt;0.145, p&lt;0.003 and p&lt;0.05, respectively). Among molecular subtypes, GGT7 expressions were significantly higher in tumor tissues than those in normal tissues of the patients in Luminal A group (p&lt;0.009). Over-expression of GGT7 was observed in almost half of the patients. The research showed mRNA expressions of GGT1, GGT5, GGT6, and GGT7 in breast cancer. Among the four genes, we obtained surprising results for GGT7 and we believe that the activity of this gene should be examined in breast cance