Tuba Candar

Behçet's: A Disease or a Syndrome? Answer from an Expression Profiling Study

Behçet’s disease (BD) is a chronic, relapsing, multisystemic inflammatory disorder with unanswered questions regarding its etiology/pathogenesis and classification. Distinct manifestation based subsets, pronounced geographical variations in expression, and discrepant immunological abnormalities raised the question whether Behçet’s is “a disease or a syndrome”. To answer the preceding question we aimed to display and compare the molecular mechanisms underlying distinct subsets of BD. For this purpose, the expression data of the gene expression profiling and association study on BD by Xavier et al (2013) was retrieved from GEO database and reanalysed by gene expression data analysis/visualization and bioinformatics enrichment tools. There were 15 BD patients (B) and 14 controls (C). Three subsets of BD patients were generated: MB (isolated mucocutaneous manifestations, n = 7), OB (ocular involvement, n = 4), and VB (large vein thrombosis, n = 4). Class comparison analyses yielded the following numbers of differentially expressed genes (DEGs); B vs C: 4, MB vs C: 5, OB vs C: 151, VB vs C: 274, MB vs OB: 215, MB vs VB: 760, OB vs VB: 984. Venn diagram analysis showed that there were no common DEGs in the intersection “MB vs C” ∩ “OB vs C” ∩ “VB vs C”. Cluster analyses successfully clustered distinct expressions of BD. During gene ontology term enrichment analyses, categories with relevance to IL-8 production (MB vs C) and immune response to microorganisms (OB vs C) were differentially enriched. Distinct subsets of BD display distinct expression profiles and different disease associated pathways. Based on these clear discrepancies, the designation as “Behçet’s syndrome” (BS) should be encouraged and future research should take into consideration the immunogenetic heterogeneity of BS subsets. Four gene groups, namely, negative regulators of inflammation (CD69, CLEC12A, CLEC12B, TNFAIP3), neutrophil granule proteins (LTF, OLFM4, AZU1, MMP8, DEFA4, CAMP), antigen processing and presentation proteins (CTSS, ERAP1), and regulators of immune response (LGALS2, BCL10, ITCH, CEACAM8, CD36, IL8, CCL4, EREG, NFKBIZ, CCR2, CD180, KLRC4, NFAT5) appear to be instrumental in BS immunopathogenesis.

Evaluation of Maternal and Fetal Stress Hormones During the Process of Birth

Objective: This study aims to determine whether mode of delivery is associated with the endocrine stress response in mother and newborn. Study Design: This prospective observational study was conducted with 86 women with a normal singleton pregnancy who delivered healthy infants between 37 and 41 weeks of gestation in a tertiary center. Study groups included; (1) women undergoing normal vaginal delivery with epidural anesthesia, (2) women undergoing vaginal delivery with immersion in water for pain relief during labor, (3) women delivered through elective caesarean section without labor. After delivery, thyroid stimulating hormone, cortisol, insulin, prolactin and Beta-endorphin levels were measured in maternal and umbilical cord serum and their relationships between modes of delivery were investigated. Results: It was found that the concentrations of cortisol and beta-endorphin after vaginal delivery with immersion in water group in both mothers and infants were higher than other two modes of delivery and these differences were statistically significant. Umbilical cord concentration of cortisol was the lowest in the caesarean section group. Conclusions: Maternal and fetal stress response was found to be associated with the mode of delivery and labor.

Ischaemia-modified albumin in preeclampsia: A critical view

Abstract The aim of the study was to compare ischaemia-modified albumin (IMA) levels, both original and corrected, in healthy pregnancies and pregnancies complicated with preeclampsia. Maternal and cord blood samples from study (n = 16) and control (n = 17) groups were collected at the time of delivery. IMA levels were given in absorbance units (ABSU). IMA levels, both original and corrected, were compared between study and control groups. No significant difference was found between maternal and cord blood IMA levels between the study and control groups [1.0 (0.3–3.5) vs 1.2 (0.2–1.4) ABSU, p = .053 and 1.0 (0.1–2.2) vs 0.9 (0.4–3.6) ABSU, p = .382, respectively]. The results were similar for maternal IMA levels, after correction of IMA levels [1.1 (0.3–5.1) vs 1.2 (0.2–1.6) ABSU, p = .292]. IMA is a novel marker for ischaemia, without precise conclusions about its value in preeclampsia. An absolute correction formula, considering all possible intervening factors, is required for more accurate results.

The prognostic value of first-trimester cystatin C levels for gestational complications

Abstract Aims: This study is designed to evaluate predictive value of first-trimester cystatin C levels for long-term pregnancy complications. Methods: The cross-sectional study population consisted of patients who admitted to outpatient clinic of a Maternity Hospital between September 2013 and December 2014. Among the 203 participants who accepted to participate in the study, 174 subjects who continued antenatal follow-up in the same clinic were included in the final analyses. Cystatin C, blood urea nitrogen, Creatinine levels and estimated glomerular filtration rates were evaluated in the first-trimester routine antenatal visit. Mode of delivery and gestational complications were noted. Results: First-trimester cystatin C levels were significantly higher in cases complicated with preterm delivery and premature rupture of membrane (PROM) compared to uncomplicated ones (0.58±0.07 vs. 0.55±0.07, P=0.041, and 0.58±0.07 vs. 0.55±0.07, P=0.036). With a cutoff value of 0.505 mg/L, sensitivity of cystatin C for preterm delivery and PROM was 91.9% and specificity was 27.7% with a negative predictive value of 92.3% and a positive predictive value of 26.6%. Conclusion: Detection of cystatin C levels in the first trimester of pregnancy for the prediction of preterm/PROM seems as a promising preliminary data. The relatively higher first-trimester cystatin C levels in complicated pregnancies are conspicuous. The results imply that in pregnancy cystatin C might be more than a marker for renal function.

The impact of nuchal cord on umbilical cord blood gas analysis and ischaemia-modified albumin levels in elective C-section

Abstract This study was designed to evaluate umbilical cord ischaemia-modified albumin (IMA) levels and the cord blood gas parameters of foetuses with or without nuchal cords, at the time of elective C-section. The cross-sectional study population consisted of the patients who were admitted to the Tertiary Care Center between February and June 2015. Women with uncomplicated single term gestations between 37 and 40 completed weeks and scheduled for elective C-sections were included in the study. Fifty cases with a nuchal cord and 50 cases without a nuchal cord were recruited. Nuchal cord blood gas analysis and the IMA levels were evaluated. The IMA levels in umbilical artery of foetuses both in the study and control groups were similar (0.714 ± 0.150 vs. 0.689 ± 0.107 ABSU, p = .340, respectively). The umbilical artery pH values of the study group were significantly lower than that in the control group (7.31 ± 0.04 vs. 7.32 ± 0.03, p = .042; respectively). The results of the current study indicate that the nuchal cord has an impact on the foetal cord blood gas parameters to some extent before the initiation of labour. Fortunately, this impact does not end up with foetal tissue ischaemia, as confirmed by the IMA levels. Impact statement What is already known on this subject? The impact of nuchal cord on perinatal outcomes has been the subject of research for many years. Although the accumulated data has pointed out some unfavourable perinatal effects, the heterogeneity of the study groups both including a vaginal delivery and C-section and the inability to adjust the interfering factors ended up with some controversies. This is why there is not much known about the effects of the nuchal cord in women who are not in the labour process. What do the results of this study add? The current study aimed to exclude the interfering effects such as the active stage of labour. In this study, elective caesarean sections were selected as the study population to evaluate the effects of the nuchal cord on cord blood gas parameters and the IMA values. pH analysis in cord blood is used to detect hypoxia and the IMA is a new ischaemia marker. The results revealed that the in utero nuchal cord is associated with a significantly higher pCO2 and lower pH values and similar IMA values. What are the implications of these findings for clinical practice and/or further research? The final outcome supports that the nuchal cord causes alterations in cord blood gas analysis but this does not reach critical levels. Therefore, the results show that there is no need to change clinical practice when the nuchal cord is detected by ultrasound in a term gestation.

Maternal serum advanced glycation end products level as an early marker for predicting preterm labor/PPROM: a prospective preliminary study

Abstract Objective: To evaluate the value of maternal serum advanced glycation end products (AGEs) level at 11–13 weeks’ gestation for the prediction of preterm labor and or preterm premature rupture of membranes (PPROM). Materials and methods: This prospective cross-sectional study is performed in a university-affiliated hospital between February and April 2016. The participants of this study are low-risk pregnant women. Blood samples for maternal AGEs level were collected in the first trimester of pregnancy and all women completed their antenatal follow-up and delivered in our center. During the follow-up 21 women developed preterm labor/PPROM. The first trimester maternal AGEs levels of preterm labor/PPROM cases were compared with uncomplicated cases (n = 25) matched for age-parity and BMI. The predictive value of AGEs levels for preterm labor/PPROM was also assessed. Results: First-trimester AGEs levels were significantly higher in cases complicated with preterm labor/PPROM (1832 (415–6682) versus 1276 (466–6445) ng/L, p = .001 and 1722 (804–6682) versus 1343 (466–6445) ng/L, p = .025). According to receiver-operating characteristic curve analysis, the calculated cut off value of AGEs was 1538 ng/L with the sensitivity 91.7%, specificity 73.8%; and the negative and positive predictive values were 91.6% and 29.5%, respectively. Conclusions: For the prediction of preterm labor/PPROM, the relatively high AGEs levels in the first trimester might be a useful marker.

Second Trimester Urinary neutrophil gelatinase-Associated lipocalin Levels in Gestational Diabetes: preliminary results

Abstract Objective: The objective of this study is to investigate the urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels in the second trimester of pregnant patients at the time of gestational diabetes mellitus (GDM) screening. Materials and methods: Urinary samples from 88 pregnant women who underwent gestational diabetes screening test were collected in late second trimester (24–28 weeks) prospectively. After an overnight fasting, 75 g GTT was performed. The blood samples were drawn for measurement of glucose, insulin, and HbA1c. The urinary and blood parameters were compared for pregnant women with or without gestational diabetes. Results: uNGAL levels were significantly elevated in pregnant women with gesting compared with the control groups (p < .014). There was a positive correlation between uNGAL and HbA1c levels (p = .001). Conclusions: In the second trimester, at the time of GDM screening, high levels of uNGAL indicate tubular injury in GDM cases which seems to be a result of hyperglycemia. uNGAL may correlate with an inflammatory renal involvement in GDM.

Flavopiridol's effects on metastasis in KRAS mutant lung adenocarcinoma cells: DOGAN TURACLI et al.

There is still no clinically approved agent for mutant KRAS, which is the most common alteration in non–small‐cell lung cancer (NSCLC). Flavopiridol is a semisynthetic flavonoid that inhibits cell growth through cyclin‐dependent kinases in G1/S or G2/M of the cell cycle and induces apoptosis. In this study, we evaluated its effect on cellular apoptosis, survival, and metastasis mechanisms on KRAS mutant A549, Calu‐1, and H2009 cell lines.

Increased anti- EBV VCA IgG antibody levels are associated with need for surgery in patients developing upper respiratory tract complications

INTRODUCTION The immune reaction developing against Ebstein-Barr virus (EBV) infection may be one of the major determinants of severe adenoid hypertrophy (AH) and chronic otitis media with effusion (COME) needing surgery. In this study, we aimed to investigate the relationship between these antibodies and the need for surgery due to complications such as severe AH and COME. METHODS Sixty consecutive patients <15 years old who were admitted to our outpatient clinics between January 2014 and December 2015 with severe AH ± COME and underwent adenoidectomy ± ventilation tube insertion and 129 control patients who had a history of EBV infection at least three months before the inclusion to the study without current symptoms of upper airway obstruction and middle ear disease were included in this study. Two groups of patients and a control group were studied: a) children who underwent adenoidectomy alone with no middle ear disease (group 1), b) children with COME and AH who underwent adenoidectomy and tympanostomy with ventilation tube insertion (group 2), and c) control group without adenoid hypertrophy or otitis media with effusion. RESULTS Patients who needed surgery (Group 1 and 2) had significantly higher levels of anti-EBV VCA IgG antibodies than control patients (19.8 ± 16.4 vs. 1.7 ± 0.8 S/CO, p < 0.001). Anti-EBV VCA IgM levels did not differ between groups. Group 2 patients had also higher levels of Anti-EBV VCA IgG antibodies than group 1 patients (35.8 ± 16.7 vs. 11.8 ± 8.5 S/CO, p < 0.001). ROC curve analysis resulted in a cut-off point of 2.92 S/CO level for anti-EBV VCA IgG antibodies for need for surgery in EBV infected patients with 97% sensitivity and 98% specificity. CONCLUSION Markedly increased serum anti-EBV VCA IgG antibodies in children who developed upper respiratory tract complications such as severe AH and COME may show the significant role of enhanced immune system reaction in the pathogenesis of these complications due to EBV infection.

Role of metformin on base excision repair pathway in p53 wild-type H2009 and HepG2 cancer cells

The antidiabetic agent metformin was shown to further possess chemopreventive and chemotherapeutic effects against cancer. Despite the advances, the underlying molecular mechanisms involved in decreasing tumor formation are still unclear. The understanding of the participation of oxidative stress in the action mechanism of metformin and its related effects on p53 and on DNA base excision repair (BER) system can help us to get closer to solve metformin puzzle in cancer. We investigated the effects of metformin in HepG2 and H2009 cells, verifying cytotoxicity, oxidative stress, antioxidant status, and DNA BER system. Our results showed metformin induced oxidative stress and reduced antioxidant capacity. Also, metformin treatment with hydrogen peroxide (H2O2) enhanced these effects. Although DNA BER enzyme activities were not changed accordantly together by metformin as a single agent or in combination with H2O2, activated p53 was decreased with increased oxidative stress in H2009 cells. Our study on the relationship between metformin/reactive oxygen species and DNA BER system in cancer cells would be helpful to understand the anticancer effects of metformin through cellular signal transduction pathways. These findings can be a model of the changes on oxidative stress that reflects p53’s regulatory role on DNA repair systems in cancer for the future studies.