Berkay Saraymen

Performance of Galactomannan Antigen, Beta-d-Glucan, and Aspergillus-Lateral-Flow Device for the Diagnosis of Invasive Aspergillosis

Aspergillus lateral-flow device (LFD) was recently introduced as a practical tool for the diagnosis of invasive aspergillosis (IA). We investigated the performance of Aspergillus-LFD as a point-of-care test for the diagnosis of IA. Serum samples were collected twice weekly from patients who received intensive chemotherapy for acute leukemia, or recepients of allogeneic stem cell transplantation. Aspergillus galactomannan (GM) antigen, 1,3-beta-d-glucan and Aspergillus-LFD tests were carried out according to manufacturers’ recommendations. GM testing was repeated with a modified procedure which was proven to increase the sensitivity. Aspergillus-LFD was performed without applying any pretreatment procedure to allow the kit to fit as a point-of-care test. Fungal infections were categorized according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. A total of 75 neutropenia episodes in 64 patients were prospectively followed between February 2012 and January 2013. Probable IA was diagnosed in 11 patients, probable pulmonary fungal disease was diagnosed in one patient, and rhinocerebral aspergillosis was diagnosed in one patient. Fungemia was detected in two patients. Aspergillus-LFD was positive in serum of a patient with probable IA and in the bronchoalveolar lavage fluid of an other patient with probable IA. Aspergillus-LFD was false positive in serum of two patients. Although there was no radiological finding of IA or documented fungemia, fever resolved after empirical caspofungin therapy in one of these patients. The sensitivity of Aspergillus-LFD as a point-of-care test without any pretreatment of serum sample is low.

In the diagnosis of neonatal sepsis importance of gelsolin and relationship with mortality and morbidity

In spite of advances in neonatal care and the new generation of antibiotics, neonatal sepsis is still a major cause of morbidity and mortality. Early diagnosis of neonatal sepsis is difficult because clinical signs are non-specific. Thus, new biomarkers are still needed for diagnosis. Gelsolin is an actin-binding plasma protein. Furthermore, extracellular gelsolin binds lipopolysaccharide and lipoteichoic acid, which are major virulence factors of Gram-negative and Gram-positive bacteria. The result of this binding is the inhibition of gelsolins F-actin depolymerizing activity. Thus, gelsolin inhibits the release of IL-8 from human neutrophils subjected to lipoteichoic acid, lipopolysaccharide and heat-inactivated bacteria treatment. Our hypothesis is that pGSN levels decrease in neonatal infants with sepsis and this decrease might be used as a reliable biological marker. Forty patients who were diagnosed with severe sepsis at a neonatal intensive care unit were enrolled in the sepsis group. Twenty patients who were followed for prematurity were enrolled in the control group. The pGSN level at the time of diagnosis in the sepsis group was 33.98±11.44μg/ml, which was significantly lower than that of control group (60.05±11.3μg/ml, P<0.001) and after treatment (53.38±31.26μg/ml, P=0.003). Area under ROC curve was 0.96 (p: 0.0001, 95% CI; 0.90-0.99). Sensitivity was 90.32 (95% CI; 74.2-97.8), specificity was 95 (95% CI; 75.1-99.2). Plasma gelsolin significantly decreased in septic patient and recovery of decreased gelsolin levels correlated with clinical improvement. Thus, plasma gelsolin may be a usable marker for severe sepsis.

Serum Visfatin Levels in Ulcerative Colitis

Previous studies have suggested that adipokines play a role in inflammatory bowel disease by inducing proinflammatory cytokines, but it is uncertain whether visfatin is causally involved in ulcerative colitis (UC). We evaluated visfatin levels in patients who presented with UC flares before and after treatment.

The association of endothelial progenitor cell markers with arteriovenous fistula maturation in hemodialysis patients

AbstractAimsArteriovenous fistula (AVF) failure is one of the most important clinical problems in end-stage renal disease. Endothelial progenitor cells (EPCs) have a role on vascular angiogenesis and endothelialization. We aimed to investigate the association markers of EPCs on AVF maturation by measuring the surface expressions of CD34, CD309 and CD133 on the monocytes.MethodsThis prospective observational study was conducted in 54 voluntary patients with end-stage renal disease who were admitted for their first renal replacement therapy and were available for AVF creation. Venography was performed in all patients before AVF creation. Six patients were excluded due to inadequate veins after venographic imaging, and also seven patients were excluded due to postoperative thrombosis. The blood samples were analyzed a day before the fistula operation, and the expressions of CD34, CD133 and CD309 on the surface of monocytes were measured.ResultsPatients were divided into two groups after the evaluation of AVF maturation, as the mature group and the failure group. The CD309 expression level on the monocytes was 338.00 (35.00–479.00) in the mature group; however, it was 36.00 (5.50–237.00) (p 0.031) in the failure group. Multiple logistic regression analyses showed that both BMI and the mean fluorescence intensity level of CD309 expression on monocytes independently predicted AVF maturation.ConclusionsThe presence of DM and increased BMI negatively correlated with AVF maturation. High intensity of CD309 expression on monocytes was observed in patients with successful AVF maturation.

Evaluation of two different adjuvants with immunogenic uroplakin 3A-derived peptide for their ability to evoke an immune response in mice

RationaleOrgan- or tissue-specific antigens produced by normal tissue or by cancer cells could be used in cancer immunotherapy, to target the tumor. In our previous study, we induced T-cell-mediated, bladderspecific autoimmunity by targeting the bladder-specific protein Uroplakin 3A (UPK3A). UPK3A is a well-chosen target for developing an autoimmune response against bladder cancer since the antigen is also expressed in bladder tumors. To use this peptide, which was derived from the UPK3A protein in a bladder cancer vaccine study, it is necessary to induce a strong immune response. In this study, we aimed to develop a robust immune response in BALB/c mice using the well-characterized keyhole limpet hemocyanin (KLH)-conjugated peptide antigen (UPK3A 65-84) conjugated with an immunogenic carrier protein. In combination with the peptide, we used either Freund’s complete adjuvant (CFA) or CpG (cytosine-phosphate-guanine oligonucleotides) as effective adjuvants in order to overcome tumor tolerance.ObjectivesThe immune response evoked by UPK3A 65-84 peptide, using two different adjuvants, was compared by detection of changes in the proliferative response of immune cells, in the cytokine profile, and in the immune cell populations.FindingsWe demonstrated that CpG, combined with KLH-UPK3A 65-84, promoted a more robust immune response, via induction of higher IL-2, IFN-γ, TNF-α, IL-17 production and activation of more immune cells (CD4+ T cells, CD8+ T cells, NK cells CD11b, CD45), than CFA and the KLHUPK3A 65-84.ConclusionCpG as an adjuvant combined with KLH-UPK3A 65-84 could be used in preclinical models of bladder cancer for the development of cancer immunotherapy strategies.

Embriyonik Kök Hücreler ve İndüklenmiş Pluripotent Kök Hücreler

Embriyonik kök hücreler embriyonik blastosistlerin iç hücre kitlesinde yerleşen hücrelerden implantasyon öncesi evrede elde edilirler. Bu hücreler kendini sonsuz bir şekilde yenileyebilen ve çok sayıda farklı hücreye dönüşme (pluripotent) kabiliyetine sahip olan hücrelerdir. Bu özellikleri nedeni ile birçok dejeneratif ve genetik hastalığın tedavisinde kullanılabileceği düşünülmektedir. İnsan embriyonik kök hücreleri ile çalışmanın; etik, politik ve dini tartışmalar nedeniyle zorlaşması ve bilimsel araştırmalarda kullanımının sınırlandırılması araştırmacıları yeni arayışlara itmiştir. Japon araştırmacılar Yamanaka ve ark. 2006 yılında dört transkripsiyon faktörünü kullanarak (Oct 3⁄4, Sox-2, Klf-4, c-Myc) (OSKM faktörleri) fare ve insandan elde edilen fibroblast hücrelerini yeniden programlayarak indüklenmiş pluripotent kök (İPK) hücre elde etmeyi başarmış ve kök hücre araştırmalarında yeni bir dönemi başlatmışlardır. Elde edilen İPK hücrelerin embriyonik kök hücre ile aynı işlevlere sahip olması nedeniyle kök hücre araştırmalarında yeni bir ufuk açılmıştır. Özellikle kişiye ve hastalığa özel İPK hücre elde edilebilmesi, ilaç araştırmaları için laboratuvarda hastalık modellemesinin yapılabilmesini sağlayarak hücre düzeyinde araştırmalar için yeni bir alan açmıştır. ABSTRACT

PO-0539 Preliminary Study: Is Gelsolin Possible An Early Diagnostic Biomarker For Neonatal Sepsis?

Background and aims Gelsolin is an actin-binding plasma protein that has a protective role against tissue injuries. Studies of sepsis are shown that diminish of plasma gelsolin (pGSN) correlates with elevated circulating levels of actin and pGSN changes correlation with clinical improvement in septic patients. The aim of this study investigate pGSN’s importance in preterm infant with sepsis and related with mortality and morbidity. Methods Thirty-one patients who were diagnosed with severe sepsis at neonatal intensive care unit were enrolled in sepsis group, twenty patients who were followed for prematurity were enrolled in control group. Plasma gelsolin levels were measured using an enzyme-linked immunosorbent assay from whole blood samples. Result The pGSN level at the time of diagnosis in the severe sepsis group was 33.98 ± 11.44 µg/ml, which was significantly lower than that of 20 nonseptic preterm neonates (60.05 ± 11.3 µg/ml, p < 0.001) and after treatment (53,38 ± 31.26 µg/ml, p = 0.003). Tollner scors in severe sepsis patients were 12.3 ± 4 and there were negatif correlation with gelsolin level. But, it did not detect correlation betwen postnatal age, gestational age, birth weight, gender and pGSN level in sepsis and control groups. Conclusion Plasma gelsolin may be a usable marker for severe sepsis. Recovery of decreased gelsolin levels correlated with clinical improvement.