Investıgatıon Of The Effect Of C1q And Complement Regulatory Proteın Cd59 On The Sh-Sy5y Cell Vıabılıty In Hyperglycemıc Condıtıons

Dopaminerjik nöronlarda yüksek glukoza maruziyet ve insülin direnci nedeni ile meydana gelen ilerleyici nöron hasarında N-metil-d-aspartat (NMDA) reseptör ve nöronal nitrik oksit sentaz aracılı oksidatif stresin azaltılmasının nöron ölümünü önleyip önlemediği bilinmemektedir. Bu çalışmanın amacı, Uluslararası Diyabet Federasyonu ölçütlerine göre yüksek glukoza maruz kalan dopaminerjik nöronlarda glukotoksisite ve insülin direnci ile ortaya çıkan oksidatif stresin sonuçlarını incelemektir. Bu bağlamda nöronal mitokondrial disfonksiyona ve bunun kompleman sistemine yansımasına, NMDA reseptör blokajı ve nöronal nitrik oksit sentaz inhibisyonunun etkileri araştırılmıştır. Bu çalışmada SH-SY5Y insan nöroblastoma dopaminerjik hücreleri 150, 200, 250mg/dL glukoz bulunan ortamda insülin, NMDA reseptör antagonisti; kinürenik asit ve nöronal nitrik oksit sentaz inhibitörü; Nω-nitro-L-arginin metilester (L-NAME) e maruz bırakılmıştır. İki hücre siklusunda oksidatif stres, total mitokondrial metabolik aktivite/hücre canlılığı (MTT), nitrik oksit, glukoz transporter 3 (GLUT3), kompleman bileşeni 1q (C1q) ve kompleman düzenleyici protein 59 (CD59) ölçülmüştür. Yüksek glukoza maruz kalan nöronlarda glukoz transportunun iki kat arttığı, ikinci hücre siklusunda hücre canlılığında azalmanın, oksidatif stres ve mitokondrial fonksiyon kaybı ile birlikte olduğu, insülin direncinin mitokondrial disfonksiyon ve nöron ölümünü hızlandırdığı tespit edilmiştir. Yüksek glukozla NMDA reseptör-aracılı olarak meydana gelen reaktif nitrojen radikallerine dayalı oksidatif streste, SH-SY5Y hücreleri tarafından sentezlenen C1q nun doğrudan katkısı olduğu, C1q ve CD59 konsantrasyonlarındaki değişikliğin nitrik oksit düzeyleri ile ilişkili olduğu anlaşılmıştır. Elde edilen sonuçlar endojen bir NMDA reseptör antagonisti olan kinürenik asitin oksidatif stresin ve mitokondrial disfonksiyonun azaltılması, insülin direncinin düzeltilmesinde LNAME e göre daha başarılı olduğu tespit edilmiştir.It is still not known whether reducing N-methyl-D-aspartate (NMDA) receptor and neuronal nitric oxide synthase-mediated oxidative stress might prevent the neuronal death caused by progressive damage of the dopaminergic neurons via exposure to high glucose and insulin resistance. The aim of this study was to investigate the effect of NMDA receptor blockage and/or inhibition of neuronal nitric oxide synthase on mitochondrial function and complement system. Dopaminergic neurons were exposed to insulin and high glucose according to the International Diabetes Federation criteria, and associated oxidative stress came up due to glucotoxicity and insulin resistance. SH-SY5Y human neuroblastoma dopaminergic cells were exposed to insulin, endogenous NMDA receptor antagonist; kynurenic acid and neuronal nitric oxide synthase inhibitor; Nω- nitro-L-arginine methyl ester (L-NAME) in cell culture media containing 150, 200, 250 mg/dL glucose. Oxidative stress, total mitochondrial metabolic activity/cell viability (MTT), nitric oxide, GLUT3, C1q and CD59 were measured at two cell cycles. In high glucose exposed neurons; glucose transport was increased by two fold, decrease in cell viability in the second cell cycle was associated with oxidative stress and loss of the mitochondrial function, insulin resistance exacerbated mitochondrial dysfunction and accelerated the neuronal cell death. C1q was found to directly contribute to the oxidative stress, originated from the reactive nitrogen radicals produced by glucose via NMDA receptors. Alteration in C1q and CD59 concentrations were related to the nitric oxide levels. These results indicated that kynurenic acid was more successful than L-NAME in suppressing the oxidative stress, decreasing mitochondrial dysfunction and ameliorating the insulin resistance

Aflatoxin and Ochratoxin in Various Types of Commonly Consumed Retail Ground Samples in Ankara, Turkey

To detect aflatoxin (AF) or ochratoxin A (OTA) contamination, 25 retail ground samples of 12 different types of seed-, pulses-. and cereal-flours and starches were randomly collected from markets and traditional bazaars in Ankara, Turkey. The levels of AF in the retail ground samples were determined by high performance liquid chromatography (HPLC) and ranged from 0.03-3.16 ppb. The percentage of contaminated samples for aflatoxin B-1, B-2, G(1), and G(2) were 64, 60, 72, and 76%, respectively. The determination of OTA level was performed by enzyme-linked immunosorbent assay (ELISA), and they were ranged between 0.27-4.07 ppb (n=24). However, the screened mycotoxin levels in the samples were under the permission limits of Turkey, the daily intake of these products corresponds to at least 50 % of daily diet in our country. Routine measurements of the toxin levels in foods and feeds should be carried out to prevent their harmful effects on health.Wo

Psöriazisli hastalarda psoriatik artrit tarama araçlarında kullanılan parametrelerin performansı: Sistematik literatür taraması

Amaç: Psöriatik artrit (PsA), farklı hastalık belirtilerine sahip heterojen bir hastalıktır. Psöriazisli hastalarda PsA taraması için çeşitli araçlar geliştirilmiştir ve her biri çalışma popülasyonuna bağlı olarak performans açısından farklılıklar göstermektedir. PsA için optimal bir tarama aracı hala karşılanmamış bir ihtiyaçtır. Bu çalışmada mevcut PsA tarama araçlarının her bir parametresinin performansının belirlenmesi hedeflenmiştir. Yöntem: PubMed’de 15 Ağustos 2020’ye kadar “psoriatic arthritis” anahtar kelimesini kullanarak sistematik bir literatür araştırması gerçekleştirdik. Başlık ve özetlerin 2 bağımsız araştırmacı tarafından taranmasının ardından, bir tarama testini bildiren İngilizce tam metinler belirlendi ve uyumsuzluklar üçüncü bir araştırmacı tarafından çözüldü. Tarama testinin her bir parametresinin duyarlılığı (Sn) ve özgüllüğünü (Sp) bildirilen çalışmalar dahil edildi. Hastalık domainleri şu şekilde gruplanmıştır; eklemler, daktilit, bel ağrısı, entezit, deri-tırnak tutulumu, sabah tutukluğu, fonksiyon, tedavi ve diğer. Hastalık domainleri açısından Sn VEYA Sp %80 olan maddeler analize alınmıştır. Bulgular: 10.754 referans arasında bir PsA tarama testini içeren 44 çalışma belirlendi ve 6 farklı aracın her bir parametresini performansını bildiren 7 çalışma dahil edilmiştir (Figür 1). Domainler için 32 farklı soru belirlenmiştir (Tablo 1). Domainler içerisinde eklemler (n=8), daktilit (n=5) ve fonksiyon (n=4) en fazla soruya sahiptir. Duyarlılığı %80’in üzerinde olan soruların dağılımı şu şekildedir; eklemler (n=2), daktilit (n=1), entezit (n=1), sabah tutukluğu (n=1), diğer (n=1). Özgünlüğü %80’in üzerinde olan soruların dağılımı şu şekildedir; eklemler (n=7), daktilit (n=4), fonksiyon (n=4), bel ağrısı (n=2), entezit (n=2), sabah tutukluğu(n=2), deri-tırnak tutulumu (n=1), diğer (n=1). Hem duyarlılığı hem de özgünlüğü %80 üzeri olan daktilit ile ilgili bir soru belirlenmiştir.Sonuç: Ülkemiz için geliştirilecek psöriazis hastalarını tarama sorgulamasında aday sorular bu literatür taraması ile belirlenmiştir. Farklı domain’lerde soruların duyarlılıkları göreceli olarak daha düşükken, özgünlükleri kabul edilir düzeyde bulunmuştur. Özellikle periferik eklemler, daktilit, fonksiyon, bel ağrısı ve entezit için olası aday sorular belirlenmiştir

Efficacy and safety profile of COVID-19 vaccine in cancer patients: A prospective, multicenter cohort study

Aim: To compare the seropositivity rate of cancer patients with non-cancer controls after inactive SARS-CoV-2 vaccination (CoronaVac) and evaluate the factors affecting seropositivity. Method: Spike IgG antibodies against SARS-CoV-2 were measured in blood samples of 776 cancer patients and 715 non-cancer volunteers. An IgG level >= 50 AU/ml is accepted as seropositive. Results: The seropositivity rate was 85.2% in the patient group and 97.5% in the control group. The seropositivity rate and antibody levels were significantly lower in the patient group (p < 0.001). Age and chemotherapy were associated with lower seropositivity in cancer patients (p < 0.001). Conclusion: This study highlighted the efficacy and safety of the inactivated vaccine in cancer patients. Clinical Trials Registration: ClinicalTrials.gov) Plain language summary Cancer patients are at high risk for infection with SARS-CoV-2 and of developing the associated disease, COVID-19, which therefore puts them in the priority group for vaccination. This study evaluated the efficacy and safety of CoronaVac, an inactivated virus vaccine, in cancer patients. The immune response rate, defined as seropositivity, was 85.2% in the cancer patient group and 97.5% in the control group. The levels of antibodies, which are blood markers of immune response to the vaccine, were also significantly lower in the patient group, especially in those older than 60 years and receiving chemotherapy. These results highlight the importance of determining the effective vaccine type and dose in cancer patients to protect them from COVID-19 without disrupting their cancer treatment.Oncological Clinical Research Association (ONKAD

Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy.

Background There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). Methods A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and >= 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. Results The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0-14.0) months in the ET arm of group A, and 5.3 (3.9-6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8-7.7) months in the ET arm of group B, and 5.7 (4.6-6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5-8.0) months in the ET arm of group C and 4.0 (3.5-4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. Conclusion Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET